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1. Hara I, Miyake H, Yamada Y, Yamanaka K, Furukawa J, Kumano M, Takenaka A, Fujisawa M: Feasibility and usefulness of high-dose chemotherapy (high-dose ifosfamide, carboplatin and etoposide) combined with peripheral blood stem cell transplantation for male germ cell tumor: a single-institute experience. Anticancer Drugs; 2006 Oct;17(9):1057-66
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  • [Source] The source of this record is MEDLINE®, a database of the U.S. National Library of Medicine.
  • [Title] Feasibility and usefulness of high-dose chemotherapy (high-dose ifosfamide, carboplatin and etoposide) combined with peripheral blood stem cell transplantation for male germ cell tumor: a single-institute experience.
  • Although the usefulness of high-dose chemotherapy with peripheral blood stem cell transplantation for advanced germ cell tumor is still under evaluation in phase III randomized controlled studies, this approach is currently used as one treatment option for relapsed or advanced male germ cell tumor.
  • Clinical outcomes of high-dose chemotherapy for a single institute from Japan are presented herein.
  • We administered 63 courses of high-dose ifosfamide, carboplatin and etoposide chemotherapy (1250 mg/m carboplatin; 1500 mg/m etoposide; 7.5 g/m ifosfamide) to 34 men with germ cell tumors.
  • Of these, 27 patients underwent high-dose ifosfamide, carboplatin and etoposide as first-line therapy after 2-3 courses of conventional bleomycin, etoposide and cisplatin chemotherapy, and seven patients underwent high-dose ifosfamide, carboplatin and etoposide for relapsed germ cell tumor.
  • Peripheral blood stem cells were harvested during previous chemotherapy and sufficient CD34 cells were harvested for transplantation.
  • Although all patients experienced grade 4 hemotoxicity, leukocyte counts recovered to above 1000/mul within 8-11 days after peripheral blood stem cell transplantation.
  • No treatment-related deaths occurred.
  • High-dose ifosfamide, carboplatin and etoposide could be performed safely, and could offer an effective means of treating advanced or refractory germ cell tumors in men.
  • [MeSH-major] Antineoplastic Combined Chemotherapy Protocols / therapeutic use. Neoplasms, Germ Cell and Embryonal / therapy. Peripheral Blood Stem Cell Transplantation. Testicular Neoplasms / therapy
  • [MeSH-minor] Adolescent. Adult. Bleomycin / administration & dosage. Carboplatin / administration & dosage. Cisplatin / administration & dosage. Combined Modality Therapy. Etoposide / administration & dosage. Germinoma / therapy. Humans. Ifosfamide / administration & dosage. Male. Middle Aged

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  • (PMID = 17001179.001).
  • [ISSN] 0959-4973
  • [Journal-full-title] Anti-cancer drugs
  • [ISO-abbreviation] Anticancer Drugs
  • [Language] eng
  • [Publication-type] Journal Article
  • [Publication-country] England
  • [Chemical-registry-number] 11056-06-7 / Bleomycin; 6PLQ3CP4P3 / Etoposide; BG3F62OND5 / Carboplatin; Q20Q21Q62J / Cisplatin; UM20QQM95Y / Ifosfamide; BEP protocol
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2. Beyrouthy MJ, Garner KM, Hever MP, Freemantle SJ, Eastman A, Dmitrovsky E, Spinella MJ: High DNA methyltransferase 3B expression mediates 5-aza-deoxycytidine hypersensitivity in testicular germ cell tumors. Cancer Res; 2009 Dec 15;69(24):9360-6
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  • [Title] High DNA methyltransferase 3B expression mediates 5-aza-deoxycytidine hypersensitivity in testicular germ cell tumors.
  • Testicular germ cell tumors (TGCT) are the most common solid tumors of 15- to 35-year-old men.
  • TGCT patients are frequently cured with cytotoxic cisplatin-based therapy.
  • However, TGCT patients refractory to cisplatin-based chemotherapy have a poor prognosis, as do those having a late relapse.
  • Pluripotent embryonal carcinomas (EC) are the malignant counterparts to embryonic stem cells and are considered the stem cells of TGCTs.
  • Here, we show that human EC cells are highly sensitive to 5-aza-deoxycytidine (5-aza-CdR) compared with somatic solid tumor cells.
  • Decreased proliferation and survival with low nanomolar concentrations of 5-aza-CdR is associated with ATM activation, H2AX phosphorylation, increased expression of p21, and the induction of genes known to be methylated in TGCTs (MGMT, RASSF1A, and HOXA9).
  • Notably, 5-aza-CdR hypersensitivity is associated with markedly abundant expression of the pluripotency-associated DNA methyltransferase 3B (DNMT3B) compared with somatic tumor cells.
  • Intriguingly, cisplatin-resistant EC cells retain an exquisite sensitivity to low-dose 5-aza-CdR treatment, and pretreatment of 5-aza-CdR resensitizes these cells to cisplatin-mediated toxicity.
  • These novel findings indicate that high expression of DNMT3B, a likely byproduct of their pluripotency and germ cell origin, sensitizes TGCT-derived EC cells to low-dose 5-aza-CdR treatment.

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  • (PMID = 19951990.001).
  • [ISSN] 1538-7445
  • [Journal-full-title] Cancer research
  • [ISO-abbreviation] Cancer Res.
  • [Language] ENG
  • [Grant] United States / NCI NIH HHS / CA / R21 CA124817; United States / NCI NIH HHS / CA / R01-CA087546; United States / NCI NIH HHS / CA / R21 CA124817-02; United States / NCI NIH HHS / CA / CA104312-05; United States / NCI NIH HHS / CA / R01 CA111422; United States / NCI NIH HHS / CA / CA124817-02; United States / NCI NIH HHS / CA / R01-CA111422; United States / NCI NIH HHS / CA / P30 CA023108; United States / NCI NIH HHS / CA / R01-CA104312; United States / NCI NIH HHS / CA / CA087546-09; United States / NCI NIH HHS / CA / R01 CA087546; United States / NCI NIH HHS / CA / CA111422-04; United States / NCI NIH HHS / CA / R01 CA087546-09; United States / NCI NIH HHS / CA / R01 CA104312-05; United States / NCI NIH HHS / CA / R01 CA111422-04; United States / NCI NIH HHS / CA / R21 R21CA124817; United States / NCI NIH HHS / CA / R01 CA104312
  • [Publication-type] Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't
  • [Publication-country] United States
  • [Chemical-registry-number] 0 / Cell Cycle Proteins; 0 / DNA-Binding Proteins; 0 / H2AFX protein, human; 0 / Histones; 0 / RNA, Small Interfering; 0 / Tumor Suppressor Proteins; 776B62CQ27 / decitabine; EC 2.1.1.37 / DNA (Cytosine-5-)-Methyltransferase; EC 2.1.1.37 / DNA methyltransferase 3B; EC 2.7.11.1 / ATM protein, human; EC 2.7.11.1 / Ataxia Telangiectasia Mutated Proteins; EC 2.7.11.1 / Protein-Serine-Threonine Kinases; M801H13NRU / Azacitidine; Q20Q21Q62J / Cisplatin
  • [Other-IDs] NLM/ NIHMS152147; NLM/ PMC2795063
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3. You YN, Leibovitch BC, Que FG: Hepatic metastasectomy for testicular germ cell tumors: is it worth it? J Gastrointest Surg; 2009 Apr;13(4):595-601
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  • [Title] Hepatic metastasectomy for testicular germ cell tumors: is it worth it?
  • BACKGROUND: Chemotherapy is highly effective for metastatic germ cell tumor (GCT), but experience with resection of hepatic metastases from GCT is limited.
  • Pre-resection therapy, surgical pathology, and operative outcomes were reviewed.
  • Hepatic histology included: necrosis (33%), viable tumor (27%), mature teratoma (13%), and benign histology (27%).
  • Concomitant resection of extrahepatic disease (14 patients, 93%) found necrosis (53%), mature teratoma (27%), and viable tumor (13%).
  • At 8.2 years (mean) from resection, 11 patients (73%) were alive: five with no evidence of disease, two with elevated tumor marker only, and four with gross disease.
  • CONCLUSION: Resection of post-chemotherapy hepatic disease is safe, even when combined with resection of extrahepatic residual disease.
  • [MeSH-major] Hepatectomy. Liver Neoplasms / secondary. Liver Neoplasms / surgery. Neoplasms, Germ Cell and Embryonal / secondary
  • [MeSH-minor] Adolescent. Adult. Choriocarcinoma / secondary. Choriocarcinoma / surgery. Female. Humans. Male. Middle Aged. Prognosis. Retrospective Studies. Survival Analysis. Testicular Neoplasms / pathology. Young Adult

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  • (PMID = 19190967.001).
  • [ISSN] 1873-4626
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  • [ISO-abbreviation] J. Gastrointest. Surg.
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  • [Publication-type] Journal Article
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4. Fosså SD, Paluchowska B, Horwich A, Kaiser G, de Mulder PH, Koriakine O, van Oosterom AT, de Prijck L, Collette L, de Wit R, EORTC GU Group: Intensive induction chemotherapy with C-BOP/BEP for intermediate- and poor-risk metastatic germ cell tumours (EORTC trial 30948). Br J Cancer; 2005 Nov 28;93(11):1209-14
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  • [Title] Intensive induction chemotherapy with C-BOP/BEP for intermediate- and poor-risk metastatic germ cell tumours (EORTC trial 30948).
  • New chemotherapy regimens are continuously explored in patients with high-risk malignant germ cell tumours (MGCTs).
  • This multicentre phase II trial assessed the efficacy and toxicity of C-BOP/BEP chemotherapy in intermediate and poor prognosis MGCT (IGCCCG criteria).
  • C-BOP/BEP treatment consisted of cycles of cisplatin, vincristine, bleomycin and carboplatin, followed by one cycle of vincristine and bleomycin and three cycles of BEP (bleomycon, etoposide, cisplatin).
  • The trial was designed to demonstrate a 1-year progression-free survival rate of 80%, that is, to exclude a 1-year rate of 70% or less, with a one-sided significance level of 5%.
  • After a median observation time of 40.4 months (range: 13.7-66.3), the 1-year progression-free survival rate was 81.8% 95% CI: 72.5-91.1%).
  • With an 82% 1-year progression-free survival and a lower limit of the 95% CI above 70%, the efficacy of C-BOP/BEP is comparable to that of published alternative chemotherapy schedules in high-risk MGCT patients.
  • The treatment's toxicity is manageable in a multicentre setting.
  • In poor prognosis patients, C-BOP/BEP should be compared to standard chemotherapy of four cycles of BEP.
  • [MeSH-major] Antineoplastic Combined Chemotherapy Protocols / therapeutic use. Neoplasms, Germ Cell and Embryonal / drug therapy. Ovarian Neoplasms / drug therapy. Testicular Neoplasms / drug therapy
  • [MeSH-minor] Adolescent. Adult. Bleomycin / administration & dosage. Carboplatin / administration & dosage. Cisplatin / administration & dosage. Disease Progression. Etoposide / administration & dosage. Female. Humans. Male. Middle Aged. Neoplasm Metastasis. Prognosis. Risk Assessment. Survival Analysis. Treatment Outcome. Vincristine / administration & dosage

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  • (PMID = 16251877.001).
  • [ISSN] 0007-0920
  • [Journal-full-title] British journal of cancer
  • [ISO-abbreviation] Br. J. Cancer
  • [Language] eng
  • [Publication-type] Clinical Trial, Phase II; Journal Article; Multicenter Study
  • [Publication-country] England
  • [Chemical-registry-number] 11056-06-7 / Bleomycin; 5J49Q6B70F / Vincristine; 6PLQ3CP4P3 / Etoposide; BG3F62OND5 / Carboplatin; Q20Q21Q62J / Cisplatin; BEP protocol
  • [Other-IDs] NLM/ PMC2361516
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5. Regadera J, Blánquez MJ, González-Peramato P, Nistal M, Miller JC, Tirado OM, Notario V: PCPH expression is an early event in the development of testicular germ cell tumors. Int J Oncol; 2006 Mar;28(3):595-604
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  • [Title] PCPH expression is an early event in the development of testicular germ cell tumors.
  • Testicular germ cell tumors (TGCTs) include various malignancies with distinct pathologies that share a common precursor lesion (intratubular germ cell neoplasia, unclassified, ITGCNU, or carcinoma in situ, CIS).
  • TGCTs, as a whole, represent a highly curable tumor paradigm, with high sensitivity to radiotherapy and, especially, to cisplatin-based chemotherapy.
  • However, a percentage of cases display therapeutic resistance, and the molecular mechanisms underlying such resistant phenotype remain to be elucidated.
  • We put forward the notion that expression of oncogenic forms of the PCPH gene, which are known to confer resistance to radiation and chemotherapeutic drugs, including cisplatin, may be expressed in TGCTs, and thus contribute to the development of therapeutic resistance.
  • To begin testing this concept, we studied PCPH expression in human TGCT cell lines and in 54 solid tumors by RT-PCR, western immunoblot and immunohistochemistry.
  • The results demonstrated that: i) PCPH is expressed in TGCT cell lines and tumors, including CIS;.
  • ii) its expression levels vary among different TGCT pathologies, being generally higher in well differentiated regions and lower in areas of predominant proliferation;.
  • iii) PCPH expression is substantially increased in tumors relative to matched normal testicular tissue;.
  • iv) tumor samples express PCPH polypeptides of low molecular mass, consistent with the known size of the PCPH oncoprotein, that are either absent from, or markedly reduced in, matched normal tissue.
  • Collectively, these results positively identify PCPH as a good early molecular marker for testicular neoplasms, and strongly indicate that immunodetection of truncated PCPH polypeptides may be a useful diagnostic tool for TGCT.
  • [MeSH-major] Neoplasms, Germ Cell and Embryonal / pathology. Oncogene Proteins / genetics. Testicular Neoplasms / pathology
  • [MeSH-minor] Adolescent. Adult. Blotting, Western. Cell Line, Tumor. Child. Gene Expression Regulation, Neoplastic. Humans. Immunohistochemistry. Male. Middle Aged. Molecular Weight. Protein Isoforms / chemistry. Protein Isoforms / genetics. Protein Isoforms / metabolism. Pyrophosphatases. RNA, Messenger / genetics. RNA, Messenger / metabolism. Reverse Transcriptase Polymerase Chain Reaction. Seminoma / genetics. Seminoma / metabolism. Seminoma / pathology

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  • (PMID = 16465363.001).
  • [ISSN] 1019-6439
  • [Journal-full-title] International journal of oncology
  • [ISO-abbreviation] Int. J. Oncol.
  • [Language] eng
  • [Grant] United States / PHS HHS / / R01-64472
  • [Publication-type] Comparative Study; Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't
  • [Publication-country] Greece
  • [Chemical-registry-number] 0 / Oncogene Proteins; 0 / Protein Isoforms; 0 / RNA, Messenger; EC 3.6.1.- / ENTPD5 protein, human; EC 3.6.1.- / Pyrophosphatases
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6. Gotto GT, Carver BS, Sogani P, Sheinfeld J: Surgery for retroperitoneal relapse in the setting of a prior retroperitoneal lymph node dissection for germ cell tumor. Indian J Urol; 2010 Jan-Mar;26(1):102-7
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  • [Title] Surgery for retroperitoneal relapse in the setting of a prior retroperitoneal lymph node dissection for germ cell tumor.
  • Recognition of the therapeutic role of retroperitoneal lymph node dissection (RPLND) in the setting of testicular germ cell tumors (GCTs) is of utmost importance.
  • Despite the advent of effective cisplatin-based chemotherapy for testicular GCTs, patients who have undergone suboptimal surgery at the time of initial RPLND are compromised.
  • Patients with retroperitoneal relapse following initial RPLND should be treated with reoperative RPLND and chemotherapy and can expect long term survival rates nearing 70% when treated in tertiary centers by experienced surgeons.

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  • (PMID = 20535295.001).
  • [ISSN] 1998-3824
  • [Journal-full-title] Indian journal of urology : IJU : journal of the Urological Society of India
  • [ISO-abbreviation] Indian J Urol
  • [Language] eng
  • [Publication-type] Journal Article
  • [Publication-country] India
  • [Other-IDs] NLM/ PMC2878419
  • [Keywords] NOTNLM ; Recurrence / relapse / reoperative / retroperitoneal lymph node dissection / testicular cancer
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7. Durand X, Avances C, Flechon A, Mottet N, sous-comité OGE du comité de cancérologie de l'Association française d'urologie: [Testicular germ cell tumors late relapses]. Prog Urol; 2010 Jun;20(6):416-24
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  • [Title] [Testicular germ cell tumors late relapses].
  • [Transliterated title] Récidives tardives des tumeurs germinales du testicule.
  • The late relapses (LR) of germinal cells tumors occur by definition more than two years after a succesful initial care.
  • These rare situations have a poor prognosis with a median survival of 23.9 months after chemotherapy.
  • The risk is increased by the arising of a first relapse in the first two years which follow the initial treatment.
  • The LR group includes two very different clinical situations: the LR of the initially watched GCT, treatment of which bases on the standards of first-line stage II tumor treatment; and the LR of NSGCT after a first line chemotherapy, treatment of which bases mainly on surgery which allows a long-term complete remission in more than 50%.
  • Other situations (multifocal, non extirpable tumors) require therapeutic associations and impact the prognosis.
  • The knowledge of particular genetic profiles could allow in the future to identify the germinal tumors at risk of RT and to propose adapted watching.
  • [MeSH-major] Neoplasm Recurrence, Local. Neoplasms, Germ Cell and Embryonal. Testicular Neoplasms
  • [MeSH-minor] Humans. Male. Risk Factors. Time Factors

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  • [Copyright] Copyright 2010 Elsevier Masson SAS. All rights reserved.
  • (PMID = 20538205.001).
  • [ISSN] 1166-7087
  • [Journal-full-title] Progrès en urologie : journal de l'Association française d'urologie et de la Société française d'urologie
  • [ISO-abbreviation] Prog. Urol.
  • [Language] fre
  • [Publication-type] English Abstract; Journal Article; Review
  • [Publication-country] France
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8. Sonpavde G, Hutson TE, Roth BJ: Management of recurrent testicular germ cell tumors. Oncologist; 2007 Jan;12(1):51-61
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  • [Title] Management of recurrent testicular germ cell tumors.
  • Although front-line chemotherapy cures most men with testicular germ cell tumors, salvage therapy is still important in a small but significant minority.
  • Second-line conventional-dose or high-dose chemotherapy with stem cell rescue may cure 25%-50% of patients.
  • New chemotherapeutic agents, including the taxanes gemcitabine and oxaliplatin, have added to the therapeutic armamentarium.
  • Cisplatin-refractory patients have a poor prognosis with current therapy, and novel chemotherapeutic and biologic agents need to be discovered for such patients.
  • [MeSH-major] Neoplasm Recurrence, Local / therapy. Neoplasms, Germ Cell and Embryonal / therapy. Salvage Therapy / methods. Testicular Neoplasms / therapy
  • [MeSH-minor] Humans. Male. Prognosis. Stem Cell Transplantation. Treatment Outcome

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  • (PMID = 17227900.001).
  • [ISSN] 1083-7159
  • [Journal-full-title] The oncologist
  • [ISO-abbreviation] Oncologist
  • [Language] eng
  • [Publication-type] Journal Article; Review
  • [Publication-country] United States
  • [Number-of-references] 72
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9. Oldenburg J, Wahlqvist R, Fosså SD: Late relapse of germ cell tumors. World J Urol; 2009 Aug;27(4):493-500
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  • [Title] Late relapse of germ cell tumors.
  • OBJECTIVE: To assess the main characteristics of late relapsing malignant germ cell tumors (MGCTs).
  • These tumors are rare and occur by definition 2 years or later after successful treatment.
  • METHODS: We present relevant literature on relapsing MGCT in order to highlight the following issues: incidence, impact of initial treatment on the subsequent risk of late relapse, treatment, and survival.
  • RESULTS: A pooled analysis of 5,880 patients with MGCT revealed late relapses in 119 of 3,704 (3.2%) and in 31 of 2,176 (1.4%) patients with non-seminoma and seminoma, respectively.
  • The retroperitoneal space is the predominant site of relapse in both histological types.
  • The initial treatment is important for the risk and localization of late relapses.
  • Patients with single site teratoma are usually cured by surgery alone, whereas viable MGCT or teratoma with malignant transformation may require multimodal treatment with chemo- and/or radiotherapy as well as surgery.
  • Surgery is the most important part in the treatment of late relapses.
  • Salvage chemotherapy should, if feasible, be based on a representative biopsy.
  • CONCLUSIONS: Treatment of late relapsing MGCT patients is challenging and should be performed in experienced centers only.
  • Referral of late relapsing patients to high-volume institutions ensures the best chances of cure and enables multimodal treatment, and contributes to increased knowledge of tumor biology as well experience with the clinical course of these patients.
  • [MeSH-major] Neoplasm Recurrence, Local / surgery. Neoplasms, Germ Cell and Embryonal / surgery. Retroperitoneal Neoplasms / surgery. Seminoma / surgery
  • [MeSH-minor] Combined Modality Therapy. Humans. Male. Teratoma / drug therapy. Teratoma / secondary. Teratoma / surgery. Testicular Neoplasms / drug therapy. Testicular Neoplasms / pathology. Testicular Neoplasms / surgery

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  • (PMID = 19373473.001).
  • [ISSN] 1433-8726
  • [Journal-full-title] World journal of urology
  • [ISO-abbreviation] World J Urol
  • [Language] eng
  • [Publication-type] Journal Article; Research Support, Non-U.S. Gov't; Review
  • [Publication-country] Germany
  • [Number-of-references] 58
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10. Meattini I, Scotti V, Pescini F, Livi L, Sulprizio S, Palumbo V, Sarti C, Biti G: Ischemic stroke during cisplatin-based chemotherapy for testicular germ cell tumor: case report and review of the literature. J Chemother; 2010 Apr;22(2):134-6
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  • [Title] Ischemic stroke during cisplatin-based chemotherapy for testicular germ cell tumor: case report and review of the literature.
  • Testicular germ-cell tumors are the most common solid tumor in young men, with an incidence peak between the ages of 20 and 35 years.
  • Even if rare, arterial thromboembolism is a serious and possible complication during cisplatin-based chemotherapy in young patients.
  • The strong association between rapid treatment and favorable outcome is well known.
  • We report the management of a young patient affected by non seminomatous testicular neoplasm without cardiovascular risk factors who developed an ischemic stroke during cisplatin-based treatment.
  • [MeSH-major] Antineoplastic Agents / adverse effects. Brain Ischemia / chemically induced. Cisplatin / adverse effects. Neoplasms, Germ Cell and Embryonal / drug therapy. Stroke / chemically induced. Testicular Neoplasms / drug therapy
  • [MeSH-minor] Adult. Antineoplastic Combined Chemotherapy Protocols / adverse effects. Antineoplastic Combined Chemotherapy Protocols / therapeutic use. Humans. Male


11. Escalera Almendros C, Chiva Robles V, Pascual Mateo C, Rodríguez García N, García Tello A, Berenguer Sánchez A: [Post chemotherapy laparoscopic retroperitoneal lymph node dissection]. Arch Esp Urol; 2006 Jun;59(5):517-23
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  • [Title] [Post chemotherapy laparoscopic retroperitoneal lymph node dissection].
  • OBJECTIVES: To describe the laparoscopic excision of a postchemotherapy retroperitoneal residual mass in a patient with mixed germ cell testicular tumor.
  • METHODS/RESULTS: We report the operative technique of laparoscopic excision of a retroperitoneal mass in a 33 year old patient with mixed germ cell testicular tumor.
  • CONCLUSION: The laparoscopic approach is another option for the surgical treatment of residual masses after chemotherapy in testicular tumors.
  • [MeSH-major] Laparoscopy. Lymph Node Excision / methods. Neoplasms, Germ Cell and Embryonal / drug therapy. Neoplasms, Germ Cell and Embryonal / surgery. Testicular Neoplasms / drug therapy. Testicular Neoplasms / surgery
  • [MeSH-minor] Adult. Combined Modality Therapy. Humans. Male. Neoplasm, Residual. Retroperitoneal Space

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  • (PMID = 16903554.001).
  • [ISSN] 0004-0614
  • [Journal-full-title] Archivos españoles de urología
  • [ISO-abbreviation] Arch. Esp. Urol.
  • [Language] spa
  • [Publication-type] Case Reports; English Abstract; Journal Article
  • [Publication-country] Spain
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12. Mueller S, Schittenhelm M, Honecker F, Malenke E, Lauber K, Wesselborg S, Hartmann JT, Bokemeyer C, Mayer F: Cell-cycle progression and response of germ cell tumors to cisplatin in vitro. Int J Oncol; 2006 Aug;29(2):471-9
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  • [Title] Cell-cycle progression and response of germ cell tumors to cisplatin in vitro.
  • Testicular germ cell tumors (GCTs) are highly sensitive to cisplatin-based chemotherapy.
  • It has been suggested that the chemosensitivity of GCTs can be partially attributed to the preference of apoptosis induction over a p21-mediated G1/S phase cell-cycle arrest following induction of p53.
  • Since cell-cycle progression can be manipulated by a growing number of targeted agents, a thorough understanding of the impact of cell-cycle progression on drug-induced cell death might help to enhance the efficacy of chemotherapy.
  • The aim of this study was to assess the cell-cycle dependence of cisplatin-induced cell death in an in vitro model of GCTs.
  • Cell-cycle progression and induction of apoptosis were assessed by flow cytometry and Western blot analysis of PARP cleavage in the GCT derived cell lines, NT2 and 2102 EP, and compared with the breast carcinoma cell line MCF-7.
  • Response to treatment was assessed in different phases of the cell cycle after synchronization by serum depletion and contact inhibition.
  • A 2-h exposure of cells in G2/M with 10 microM cisplatin resulted in a higher apoptotic index 70 h after treatment (74 and 70% for NT2 and 2102 EP, respectively) compared to treatment in G1/S (34 and 38%).
  • Synchronized cells treated in G1 showed PARP cleavage after 48 h following cisplatin exposure, whereas treatment in G2 resulted in PARP cleavage already after 24 h.
  • Cisplatin-induced cell death in GCTs is highly dependent on cell-cycle phase.
  • All crucial events are restricted to the G2/M phase: cisplatin-induced DNA-damage is sensed, the apoptotic process is initiated and eventually executed in this phase of the cell cycle.
  • The cells are most sensitive to cisplatin in this phase of the cell cycle.
  • As far as the development of targeted agents is concerned, inhibition of the cell cycle in G1/S phase is likely to result in a protective effect against cisplatin, whereas agents arresting cells in G2/M may exert a synergistic effect.
  • [MeSH-major] Antineoplastic Agents / pharmacology. Cisplatin / pharmacology. Neoplasms, Germ Cell and Embryonal / drug therapy. Neoplasms, Germ Cell and Embryonal / pathology
  • [MeSH-minor] Apoptosis. Cell Cycle. Cell Line, Tumor. DNA Damage. Drug Resistance, Neoplasm. Humans. In Vitro Techniques. Poly(ADP-ribose) Polymerases / metabolism

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  • (PMID = 16820891.001).
  • [ISSN] 1019-6439
  • [Journal-full-title] International journal of oncology
  • [ISO-abbreviation] Int. J. Oncol.
  • [Language] eng
  • [Publication-type] Journal Article; Research Support, Non-U.S. Gov't
  • [Publication-country] Greece
  • [Chemical-registry-number] 0 / Antineoplastic Agents; EC 2.4.2.30 / Poly(ADP-ribose) Polymerases; Q20Q21Q62J / Cisplatin
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13. Pectasides D, Farmakis D, Pectasides M: The management of stage I nonseminomatous testicular germ cell tumors. Oncology; 2006;71(3-4):151-8
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  • [Title] The management of stage I nonseminomatous testicular germ cell tumors.
  • Testicular germ cell tumors represent the most common malignancies in young males; 70% of patients with seminomas and 50% of those with nonseminomatous germ cell tumors (NSGCT) have clinical stage I at diagnosis.
  • Lymphovascular invasion, embryonal-cell carcinoma component, absence of yolk sac histology and MIB1 proliferation rate represent predictors of micrometastatic diseasein stage I NSGCT.
  • Therapeutic options following orchiectomy in patients with stage I NSGCT comprise nerve-sparing retroperitoneal lymph node dissection, surveillance or adjuvant cisplatin-based chemotherapy.
  • All available treatment modalities produce excellent results, with a long-term survival of almost 100%.
  • Consequently, therapy-induced toxicity is an important concern in the management of these patients.
  • An individually tailored approach that takes into account the prognostic factor profile as well as the patient's preferences and their ability to comply with each one of the modalities is the key to the management of stage I testicular cancer.
  • [MeSH-major] Neoplasms, Germ Cell and Embryonal / therapy. Testicular Neoplasms / therapy
  • [MeSH-minor] Chemotherapy, Adjuvant. Humans. Lymph Node Excision. Male. Orchiectomy. Prognosis

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  • (PMID = 17646698.001).
  • [ISSN] 1423-0232
  • [Journal-full-title] Oncology
  • [ISO-abbreviation] Oncology
  • [Language] eng
  • [Publication-type] Journal Article; Review
  • [Publication-country] Switzerland
  • [Number-of-references] 49
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14. Badawi JK, Kittner T, Manseck A, Wirth MW: Intraluminal tumour thrombus of a mixed non-seminomatous germ cell tumour of testis within the inferior vena cava. Onkologie; 2005 Feb;28(2):98-100
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  • [Title] Intraluminal tumour thrombus of a mixed non-seminomatous germ cell tumour of testis within the inferior vena cava.
  • BACKGROUND: Intracaval tumour thrombus developed per continuitatem from a primary testicular tumour is rare.
  • CASE REPORT: A patient with metastatic mixed non-seminomatous germ cell tumour of the testis extending into the inferior vena cava (IVC) is presented.
  • He belonged to the intermediate-risk group according to the IGCCCG (International Germ Cell Cancer Collaborative Group) classification.
  • Computed tomography revealed the tumour thrombus as filling defect in the IVC extending nearly to the right renal vein.
  • Combination chemotherapy led to regression of pulmonal metastases and the intraluminal tumour thrombus.
  • The thrombus originated from the ostium of the right testicularis vein in the IVC.
  • Histological examination revealed no vital tumour tissue.
  • CONCLUSION: In patients with testicular cancer information about pathological processes of the IVC is important for therapeutic management.
  • Testicular tumours seldom extend up the IVC.
  • [MeSH-major] Neoplasms, Germ Cell and Embryonal / diagnosis. Neoplasms, Germ Cell and Embryonal / therapy. Testicular Neoplasms / diagnosis. Testicular Neoplasms / therapy. Vascular Neoplasms / diagnosis. Vascular Neoplasms / therapy
  • [MeSH-minor] Adult. Humans. Lung Neoplasms / complications. Lung Neoplasms / diagnosis. Lung Neoplasms / drug therapy. Lung Neoplasms / secondary. Male. Neoplasm Invasiveness. Treatment Outcome. Vena Cava, Inferior / pathology. Vena Cava, Inferior / radiography. Vena Cava, Inferior / surgery

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  • (PMID = 15665558.001).
  • [ISSN] 0378-584X
  • [Journal-full-title] Onkologie
  • [ISO-abbreviation] Onkologie
  • [Language] eng
  • [Publication-type] Case Reports; Journal Article
  • [Publication-country] Switzerland
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15. Heidenreich A, Thüer D, Polyakov S: Postchemotherapy retroperitoneal lymph node dissection in advanced germ cell tumours of the testis. Eur Urol; 2008 Feb;53(2):260-72
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  • [Title] Postchemotherapy retroperitoneal lymph node dissection in advanced germ cell tumours of the testis.
  • OBJECTIVES: To review the role of postchemotherapy retroperitoneal lymph node dissection (PC-RPLND) in patients with advanced testicular germ cell tumours (TGCT) with special attention towards the indication, surgical technique, and oncological outcome.
  • RESULTS: According to current guidelines and recommendations, PC-RPLND in advanced seminomas with residual tumours is indicated only if a PET scan performed 6-8 wk after chemotherapy is positive.
  • In nonseminomatous TGCT, PC-RPLND is indicated for all residual radiographic lesions with negative or plateauing markers.
  • Patients with increasing markers should undergo salvage chemotherapy.
  • CONCLUSION: PC-RPLND represents a major part of the management of advanced TGCT undergoing inductive chemotherapy.
  • Complete resection of all residual masses after primary chemotherapy results in a long-term disease-free survival of 95%.
  • [MeSH-major] Lymph Node Excision. Seminoma / surgery. Teratoma / surgery. Testicular Neoplasms / surgery
  • [MeSH-minor] Antineoplastic Combined Chemotherapy Protocols / therapeutic use. Cisplatin / administration & dosage. Combined Modality Therapy. Humans. Lymphatic Metastasis. Male. Neoplasm Staging. Neoplasm, Residual. Prognosis. Retroperitoneal Space

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  • [CommentIn] Eur Urol. 2008 Feb;53(2):272-3 [18045771.001]
  • [CommentIn] Eur Urol. 2008 Oct;54(4):954-5 [18572303.001]
  • [CommentIn] Eur Urol. 2008 Feb;53(2):273-4 [18045772.001]
  • (PMID = 18045770.001).
  • [ISSN] 0302-2838
  • [Journal-full-title] European urology
  • [ISO-abbreviation] Eur. Urol.
  • [Language] eng
  • [Publication-type] Journal Article; Review
  • [Publication-country] Switzerland
  • [Chemical-registry-number] Q20Q21Q62J / Cisplatin
  • [Number-of-references] 61
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16. Suita S, Shono K, Tajiri T, Takamatsu T, Mizote H, Nagasaki A, Inomata Y, Hara T, Okamura J, Miyazaki S, Kawakami K, Eguchi H, Tsuneyoshi M, Committee for Pediatric Solid Malignant Tumors in the Kyushu Area: Malignant germ cell tumors: clinical characteristics, treatment, and outcome. A report from the study group for Pediatric Solid Malignant Tumors in the Kyushu Area, Japan. J Pediatr Surg; 2002 Dec;37(12):1703-6
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  • [Title] Malignant germ cell tumors: clinical characteristics, treatment, and outcome. A report from the study group for Pediatric Solid Malignant Tumors in the Kyushu Area, Japan.
  • PURPOSE: This study aims to assess the prognostic factors and optimal treatments for malignant germ cell tumors (MGCT) in childhood.
  • METHODS: Among 117 MGCT, the clinical features were analyzed.
  • The prognostic factors and treatments were assessed based on the 5-year survival rate. RESULTS:.
  • (1) Stage: 100% for stage I (n = 54), 75.0% for stage II (n = 4), 67.3% for stage III (n = 14), and 54.8% for stage IV (n = 33); Unknown: n = 12. (2) Primary site: 93.4% for the testis (n = 52), 86.7% for the ovary (n = 31), 56.9% for the sacrococcygeal (n = 21), and 60.6% for others (n = 12); unknown: n = 1. (3) Surgical intervention for primary tumor: 100% for stage I with a complete resection (n = 53), 78.4% for stage III, IV with a complete resection (n = 26), and 33.3% for stage III, IV with an incomplete resection (n = 21). (4) Type of chemotherapy for the stage III and IV: 83.9% for the PVB (cisplatin, vinblastin, bleomycin; n = 13), 66.7% for the VAC (vincristine, actinomycin D, cyclophosphamide; n = 6), and 47.1% for other regimens (n = 25).
  • Radical complete resection alone is a sufficient treatment for localized MGCT.
  • The PVB regimen is optimal chemotherapy for advanced MGCT; however, high-risk cases still may require more aggressive treatment.
  • [MeSH-major] Germinoma / diagnosis. Germinoma / therapy
  • [MeSH-minor] Adolescent. Antineoplastic Combined Chemotherapy Protocols / therapeutic use. Child. Child, Preschool. Female. Humans. Incidence. Infant. Infant, Newborn. Liver Neoplasms / secondary. Lung Neoplasms / secondary. Male. Neoplasm Staging. Ovarian Neoplasms / diagnosis. Ovarian Neoplasms / epidemiology. Ovarian Neoplasms / surgery. Prognosis. Retrospective Studies. Survival Rate. Testicular Neoplasms / diagnosis. Testicular Neoplasms / epidemiology. Testicular Neoplasms / surgery. Treatment Outcome

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  • [Copyright] Copyright 2002, Elsevier Science (USA). All rights reserved.
  • [CommentIn] J Urol. 2003 Sep;170(3):1040 [12926414.001]
  • (PMID = 12483635.001).
  • [ISSN] 1531-5037
  • [Journal-full-title] Journal of pediatric surgery
  • [ISO-abbreviation] J. Pediatr. Surg.
  • [Language] eng
  • [Publication-type] Journal Article; Research Support, Non-U.S. Gov't
  • [Publication-country] United States
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17. Rogers PC, Olson TA, Cullen JW, Billmire DF, Marina N, Rescorla F, Davis MM, London WB, Lauer SJ, Giller RH, Cushing B, Pediatric Oncology Group 9048, Children's Cancer Group 8891: Treatment of children and adolescents with stage II testicular and stages I and II ovarian malignant germ cell tumors: A Pediatric Intergroup Study--Pediatric Oncology Group 9048 and Children's Cancer Group 8891. J Clin Oncol; 2004 Sep 1;22(17):3563-9
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  • [Title] Treatment of children and adolescents with stage II testicular and stages I and II ovarian malignant germ cell tumors: A Pediatric Intergroup Study--Pediatric Oncology Group 9048 and Children's Cancer Group 8891.
  • PURPOSE: To determine whether children with localized gonadal malignant germ cell tumors (MGCT) stage II testicular and stages I and II ovarian treated with four cycles of standard-dose cisplatin combined with etoposide and low-dose bleomycin (PEB) have an event-free survival (EFS) of at least 85% without significant toxicity.
  • PATIENTS AND METHODS: Between May 1990 and July 1995, eligible pediatric patients with stage II or recurrent from stage I (as a stage II) testicular MGCT and stages I and II ovarian MGCT were enrolled onto this Pediatric Oncology Group and Children's Cancer Group study.
  • PEB chemotherapy consisted of bleomycin 15 U/m2 on day 1, cisplatin 20 mg/m2/d on days 1 to 5, and etoposide 100 mg/m2/d on days 1 to 5.
  • Patients received four cycles of therapy at 21-day intervals.
  • RESULTS: Seventy-four patients with a median age of 10.5 years (range, 8.7 months to 16.7 years) were enrolled.
  • Primary sites included: stage II testicular (n = 17), stage I ovarian (n = 41), and stage II ovarian MGCT (n = 16).
  • Treatment with standard PEB resulted in 6-year EFS of 95% and overall survival (OS) of 95.7%.
  • EFS and OS by primary site were as follows: stage II testicular, 100% and 100%; stage I ovarian, 95.1% and 95.1%; and stage II ovarian, 87.5% and 93.8%, respectively.
  • CONCLUSION: Combination chemotherapy with PEB results in excellent EFS and OS with minimal toxicity in children and adolescents with localized gonadal MGCT.
  • [MeSH-major] Antineoplastic Combined Chemotherapy Protocols / therapeutic use. Bleomycin / therapeutic use. Cisplatin / therapeutic use. Etoposide / therapeutic use. Ovarian Neoplasms / drug therapy. Testicular Neoplasms / drug therapy
  • [MeSH-minor] Adolescent. Adult. Child. Combined Modality Therapy. Disease-Free Survival. Female. Germinoma / drug therapy. Germinoma / surgery. Humans. Male. Neutropenia

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  • (PMID = 15337806.001).
  • [ISSN] 0732-183X
  • [Journal-full-title] Journal of clinical oncology : official journal of the American Society of Clinical Oncology
  • [ISO-abbreviation] J. Clin. Oncol.
  • [Language] eng
  • [Grant] United States / NCI NIH HHS / CA / CA13539; United States / NCI NIH HHS / CA / U10 CA29139
  • [Publication-type] Clinical Trial; Journal Article; Research Support, U.S. Gov't, P.H.S.
  • [Publication-country] United States
  • [Chemical-registry-number] 11056-06-7 / Bleomycin; 6PLQ3CP4P3 / Etoposide; Q20Q21Q62J / Cisplatin; BEP protocol
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18. Schrader M, Muller M, Straub B, Miller K: Testicular sperm extraction in azoospermic patients with gonadal germ cell tumors prior to chemotherapy--a new therapy option. Asian J Androl; 2002 Mar;4(1):9-15
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  • [Title] Testicular sperm extraction in azoospermic patients with gonadal germ cell tumors prior to chemotherapy--a new therapy option.
  • BACKGROUND: In view of the high cure rates in patients with testicular germ cell tumors (TGCT), increasing clinical importance is attached to protection of fertility.
  • Long-term infertility due to cytostatic therapy may be expected in more than 50% of the patients at a cumulative dose of cisplatin > 0.6 g/m2.
  • The standard procedure for fertility protection in cancer patients includes cryopreservation of ejaculated spermatozoa.
  • Considering that some patients have tumor-induced azoospermia, we examined the usefulness of testicular sperm extraction before therapy.
  • METHOD: A survey of the literature served as a basis for investigating biological and clinical aspects of the impact of chemotherapy on male fertility.
  • A study of our patient population also enabled us to explore the option of extracting sperm from the contralateral healthy testis prior to treatment in 14 azoospermic patients with testicular germ cell tumors.
  • RESULTS: We were able to successfully recover haploid germ cells in 6/14 testicular biopsies from azoospermic patients with testicular germ cell cancer prior to treatment.
  • Maturation arrest was found in 3/14 cases and Sertoli-cell-only syndrome in the rest.
  • None of the patients had secondary healing or a treatment delay because of the testicular biopsy.
  • CONCLUSION: Since the post-therapeutic fertility status is difficult to predict in cancer patients, we think that TESE should be regarded as a general option prior to cancer treatment and offered to azoospermic cancer patients.
  • [MeSH-major] Germinoma / pathology. Infertility, Male / therapy. Oligospermia / pathology. Spermatozoa / cytology. Testicular Neoplasms / pathology
  • [MeSH-minor] Antineoplastic Agents / adverse effects. Humans. Male

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  • (PMID = 11907623.001).
  • [ISSN] 1008-682X
  • [Journal-full-title] Asian journal of andrology
  • [ISO-abbreviation] Asian J. Androl.
  • [Language] eng
  • [Publication-type] Journal Article; Review
  • [Publication-country] China
  • [Chemical-registry-number] 0 / Antineoplastic Agents
  • [Number-of-references] 54
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19. Verdonk RC, Rutgers B, Hospers GA: Celiac trunk thrombosis and splenic infarction during chemotherapy for a testicular germ cell tumor. Urology; 2008 Apr;71(4):602
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  • [Title] Celiac trunk thrombosis and splenic infarction during chemotherapy for a testicular germ cell tumor.
  • [MeSH-major] Antineoplastic Combined Chemotherapy Protocols / adverse effects. Celiac Artery. Neoplasms, Germ Cell and Embryonal / drug therapy. Splenic Infarction / radiography. Testicular Neoplasms / drug therapy. Thrombosis / radiography
  • [MeSH-minor] Adult. Bleomycin / adverse effects. Cisplatin / adverse effects. Etoposide / adverse effects. Humans. Male. Tomography, X-Ray Computed

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  • (PMID = 18295315.001).
  • [ISSN] 1527-9995
  • [Journal-full-title] Urology
  • [ISO-abbreviation] Urology
  • [Language] eng
  • [Publication-type] Case Reports; Journal Article
  • [Publication-country] United States
  • [Chemical-registry-number] 11056-06-7 / Bleomycin; 6PLQ3CP4P3 / Etoposide; Q20Q21Q62J / Cisplatin; BEP protocol
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20. Inoue T, Habuchi T, Shimoda N, Satoh S, Sato K, Kato T, Minamiya Y, Ogawa J, Matuo S, Sasaki S: [A case of long-term remission with salvage surgeries for chemotherapy-resistant germ cell tumor of testis]. Nihon Hinyokika Gakkai Zasshi; 2002 Sep;93(6):715-8
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  • [Title] [A case of long-term remission with salvage surgeries for chemotherapy-resistant germ cell tumor of testis].
  • A patient with non-seminomatous germ cell tumor of testis underwent operations for metastases in the lung and mediastinum three times, when the serum AFP level remained remarkably high despite of intensive chemotherapy, and has been disease-free for three years after the last treatment.
  • Our experience illustrates that the salvage surgery even under high serum marker levels may provide a beneficial outcome for selected cases of chemotherapy-resistant germ cell tumors.
  • [MeSH-major] Germinoma / secondary. Germinoma / surgery. Lung Neoplasms / secondary. Lung Neoplasms / surgery. Mediastinal Neoplasms / secondary. Mediastinal Neoplasms / surgery. Salvage Therapy / methods. Testicular Neoplasms / pathology. Testicular Neoplasms / surgery
  • [MeSH-minor] Adult. Biomarkers, Tumor / blood. Drug Resistance, Neoplasm. Humans. Male. Remission Induction. Time Factors. alpha-Fetoproteins / analysis

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  • (PMID = 12385098.001).
  • [ISSN] 0021-5287
  • [Journal-full-title] Nihon Hinyōkika Gakkai zasshi. The japanese journal of urology
  • [ISO-abbreviation] Nippon Hinyokika Gakkai Zasshi
  • [Language] jpn
  • [Publication-type] Case Reports; English Abstract; Journal Article
  • [Publication-country] Japan
  • [Chemical-registry-number] 0 / Biomarkers, Tumor; 0 / alpha-Fetoproteins
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21. Noel EE, Yeste-Velasco M, Mao X, Perry J, Kudahetti SC, Li NF, Sharp S, Chaplin T, Xue L, McIntyre A, Shan L, Powles T, Oliver RT, Young BD, Shipley J, Berney DM, Joel SP, Lu YJ: The association of CCND1 overexpression and cisplatin resistance in testicular germ cell tumors and other cancers. Am J Pathol; 2010 Jun;176(6):2607-15
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  • [Title] The association of CCND1 overexpression and cisplatin resistance in testicular germ cell tumors and other cancers.
  • Development of chemoresistance limits the clinical efficiency of platinum-based therapy.
  • Although many resistance mechanisms have been demonstrated, genetic/molecular alterations responsible for drug resistance in the majority of clinical cases have not been identified.
  • We analyzed three pairs of testicular germ cell tumor cell lines using Affymetrix expression microarrays and revealed a limited number of differentially expressed genes across the cell lines when comparing the parental and resistant cells.
  • Analysis of testicular germ cell tumor clinical samples by quantitative reverse transcription PCR analysis revealed that overall expression of CCND1 was significantly higher in resistant cases compared with sensitive samples (P < 0.0001).
  • Finally combined CCND1 knockdown using small-interfering RNA and cisplatin treatment inhibited cell growth in vitro significantly more effectively than any of these single treatments.
  • Therefore, deregulation of CCND1 may be a major cause of cisplatin resistance in testicular germ cell tumors and may also be implicated in ovarian and prostate cancers.
  • CCND1 could be potentially used as a marker for treatment stratification and as a molecular target to improve the treatment of platinum-resistant tumors.

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  • (PMID = 20395447.001).
  • [ISSN] 1525-2191
  • [Journal-full-title] The American journal of pathology
  • [ISO-abbreviation] Am. J. Pathol.
  • [Language] ENG
  • [Grant] United Kingdom / Cancer Research UK / /
  • [Publication-type] Journal Article; Research Support, Non-U.S. Gov't
  • [Publication-country] United States
  • [Chemical-registry-number] 0 / Antineoplastic Agents; 0 / RNA, Small Interfering; 136601-57-5 / Cyclin D1; Q20Q21Q62J / Cisplatin
  • [Other-IDs] NLM/ PMC2877824
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22. Dieckmann KP, Albers P, Classen J, De Wit M, Pichlmeier U, Rick O, Müllerleile U, Kuczyk M: Late relapse of testicular germ cell neoplasms: a descriptive analysis of 122 cases. J Urol; 2005 Mar;173(3):824-9
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  • [Title] Late relapse of testicular germ cell neoplasms: a descriptive analysis of 122 cases.
  • PURPOSE: The problem of late relapse of testicular germ cell tumor (GCT) is poorly understood.
  • In the present study we increased the understanding of L/R by analyzing these events in a large patient sample.
  • MATERIALS AND METHODS: Late relapse was defined as recurrence of disease more than 2 years after completion of primary treatment.
  • Several parameters were analyzed including age, clinical stage, treatment at primary presentation, occurrence of prior early relapse, interval to L/R, tumor markers, site of relapse, and mode and outcome of L/R treatment.
  • Possible effects of various clinical parameters on treatment results were studied by multivariate statistical analysis.
  • A total of 75% of nonseminomas but only 20% of seminomas had disseminated disease at first presentation, while 51 patients with nonseminoma had initially received chemotherapy. alpha-Fetoprotein was increased in 45 patients (of 59 eligible) with nonseminoma at L/R, human chorionic gonadotropin in 12 cases. alpha-Fetoprotein levels greater than 100 U/l indicated poor prognosis.
  • Treatment should include surgery in nonseminoma.
  • Seminomas and otherwise chemotherapy naive cases might respond to chemotherapy only.
  • Particular risk groups for late relapse are nonseminoma with prior early relapse, patients receiving chemotherapy for disseminated disease at first presentation and those with pure teratoma.
  • [MeSH-major] Germinoma / epidemiology. Neoplasm Recurrence, Local / epidemiology. Testicular Neoplasms / epidemiology
  • [MeSH-minor] Adolescent. Adult. Humans. Male. Middle Aged. Retrospective Studies. Time Factors

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  • (PMID = 15711278.001).
  • [ISSN] 0022-5347
  • [Journal-full-title] The Journal of urology
  • [ISO-abbreviation] J. Urol.
  • [Language] eng
  • [Publication-type] Journal Article
  • [Publication-country] United States
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23. Dieckmann KP, Classen J, Souchon R, Loy V: [Management of testicular intraepithelial neoplasia (TIN)--a review based on the principles of evidence-based medicine]. Wien Klin Wochenschr; 2001 Jan 15;113(1-2):7-14
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  • [Title] [Management of testicular intraepithelial neoplasia (TIN)--a review based on the principles of evidence-based medicine].
  • [Transliterated title] Therapie der testikulären intraepithelialen Neoplasie (TIN)--eine Ubersicht auf Grundlage der evidenzbasierten Medizin (EBM).
  • Testicular intraepithelial neoplasia (TIN; also called carcinoma in situ of the testis) is the uniform precursor of testicular germ cell tumors.
  • There is general agreement on the biological significance of TIN, however, the treatment is still a matter of dispute.
  • The present review summarizes the treatment options currently available.
  • Therefore, fertility aspects should be considered before any kind of treatment is employed.
  • Nonetheless, individual patients may qualify for sperm banking or cryopreservation of testicular tissue for future sperm extraction (TESE) and assisted fertilization.
  • The most common clinical situation is the case of contralateral TIN in the presence of unilateral testicular cancer.
  • Low dose radiotherapy to the testis with 18 Gy is the standard management option in these patients.
  • The same procedure may be applied to solitary testicles after partial orchiectomy for germ cell tumors.
  • If chemotherapy is required due to metastatic disease of the primary tumor management of TIN should be deferred.
  • After chemotherapy 30% of TIN cases will persist and approximately 42% will recur in the later course.
  • Repeat biopsy should be done six months after completion of chemotherapy or later.
  • If one testicle is afflicted with TIN while the other testis is in healthy condition (conceivable in infertility cases or patients with primary extragonadal germ cell tumors), then the TIN-bearing testis should be excised.
  • Radiotherapy is not feasible in these cases because of shielding problems with the healthy testis.
  • [MeSH-major] Carcinoma / diagnosis. Carcinoma / therapy. Orchiectomy / adverse effects. Testicular Neoplasms / diagnosis. Testicular Neoplasms / therapy. Testis / pathology
  • [MeSH-minor] Biopsy. Diagnosis, Differential. Evidence-Based Medicine. Humans. Infertility, Male / etiology. Male. Radiotherapy / adverse effects

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  • (PMID = 11233474.001).
  • [ISSN] 0043-5325
  • [Journal-full-title] Wiener klinische Wochenschrift
  • [ISO-abbreviation] Wien. Klin. Wochenschr.
  • [Language] ger
  • [Publication-type] English Abstract; Journal Article; Review
  • [Publication-country] Austria
  • [Number-of-references] 67
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24. Salazar Soler R, Maroto Rey P, Solà Rocabert C, López López JJ: [Rescue chemotherapy in testicular germ cell tumors]. Arch Esp Urol; 2000 Jul-Aug;53(6):554-64
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  • [Title] [Rescue chemotherapy in testicular germ cell tumors].
  • [Transliterated title] Quimioterapia de rescate en tumores de células germinales testiculares.
  • OBJECTIVE: To review the different salvage chemotherapy regimens according to the prognostic factors based on the response to the different therapeutic alternatives.
  • METHODS: The conventional rescue chemotherapy regimens, as well as the role of surgery, new drugs and therapeutic modalities, particularly high dose second and third line chemotherapy, were reviewed.
  • RESULTS/CONCLUSIONS: Germ cell testicular tumor is the paradigm of curable tumors of the adult.
  • Whereas the cure rate for stage I tumors is higher than 98%, patients with advanced stage tumors have a lower cure rate.
  • Approximately 10% of the patients with good-prognosis factors and 30%-50% of those with poor-prognosis factors show tumor progression or recurrence after first line chemotherapy using cisplatin-based combinations.
  • Patients who have recurrence after first line chemotherapy have a 40% probability of achieving second complete remission with second line chemotherapy, but will be sustained in only 20% of the patients, although rare cases of advanced pure seminoma that recurred have shown a cure rate of 55% with second line chemotherapy.
  • New strategies have been developed using new drugs such as taxanes or high doses of well-known chemotherapeutic agents with autologous hematopoietic rescue that have been utilized with success in patients with refractory germ cell testicular tumors.
  • A global analysis of the patients treated with third line chemotherapy shows a sustained complete remission rate of 22%.
  • [MeSH-major] Antineoplastic Agents / therapeutic use. Germinoma / drug therapy. Testicular Neoplasms / drug therapy
  • [MeSH-minor] Humans. Male. Neoplasm Recurrence, Local / epidemiology. Prognosis

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  • (PMID = 11002524.001).
  • [ISSN] 0004-0614
  • [Journal-full-title] Archivos españoles de urología
  • [ISO-abbreviation] Arch. Esp. Urol.
  • [Language] spa
  • [Publication-type] English Abstract; Journal Article; Review
  • [Publication-country] SPAIN
  • [Chemical-registry-number] 0 / Antineoplastic Agents
  • [Number-of-references] 88
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25. Rescorla F, Billmire D, Vinocur C, Colombani P, London W, Giller R, Cushing B, Lauer S, Cullen J, Davis M, Hawkins E: The effect of neoadjuvant chemotherapy and surgery in children with malignant germ cell tumors of the genital region: a pediatric intergroup trial. J Pediatr Surg; 2003 Jun;38(6):910-2
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  • [Title] The effect of neoadjuvant chemotherapy and surgery in children with malignant germ cell tumors of the genital region: a pediatric intergroup trial.
  • PURPOSE: This study was designed to evaluate (1) the efficacy of standard or high-dose cisplatin with etoposide and bleomycin and (2) the role of surgical resection in infants and children with malignant germ cell tumors (MGCT) of the genital region.
  • METHODS: Fourteen of 317 children enrolled in to the Pediatric Oncology Group/Children's Cancer Group intergroup study of MGCT from 1990 through 1996 had genital tumors.
  • The initial procedure was biopsy in 11 and subtotal resection in 2.
  • Two with relapse were saved with additional therapy, and one with progressive disease died.
  • (1) the current survival rate for genital MGCT is excellent, (2) delayed surgical resection with organ preservation is not associated with an adverse outcome, and (3) the treatment comparison of the effect of cisplatin dose was inconclusive in this small study population.
  • [MeSH-major] Antineoplastic Combined Chemotherapy Protocols / therapeutic use. Germinoma / drug therapy. Germinoma / surgery. Neoadjuvant Therapy / methods. Urogenital Neoplasms / drug therapy. Urogenital Neoplasms / surgery
  • [MeSH-minor] Bleomycin / administration & dosage. Child, Preschool. Cisplatin / administration & dosage. Disease-Free Survival. Etoposide / administration & dosage. Female. Humans. Infant. Male. Neoplasms, Germ Cell and Embryonal. Penile Neoplasms / diagnosis. Penile Neoplasms / drug therapy. Penile Neoplasms / mortality. Penile Neoplasms / surgery. Survival Rate. Treatment Outcome. Uterine Neoplasms / diagnosis. Uterine Neoplasms / drug therapy. Uterine Neoplasms / mortality. Uterine Neoplasms / surgery. Vaginal Neoplasms / diagnosis. Vaginal Neoplasms / drug therapy. Vaginal Neoplasms / mortality. Vaginal Neoplasms / surgery

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  • (PMID = 12778391.001).
  • [ISSN] 1531-5037
  • [Journal-full-title] Journal of pediatric surgery
  • [ISO-abbreviation] J. Pediatr. Surg.
  • [Language] eng
  • [Publication-type] Clinical Trial; Journal Article; Randomized Controlled Trial
  • [Publication-country] United States
  • [Chemical-registry-number] 11056-06-7 / Bleomycin; 6PLQ3CP4P3 / Etoposide; Q20Q21Q62J / Cisplatin
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26. Witjes JA, Spermon JR: Prognostic factors in clinical stage 1 non-seminomatous testicular tumours. Curr Opin Urol; 2001 Sep;11(5):531-4
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  • [Title] Prognostic factors in clinical stage 1 non-seminomatous testicular tumours.
  • For patients with a clinical stage 1 non-seminomatous germ cell tumour of the testis cure rates should be close to 100%, whether surveillance, primary surgery, primary chemotherapy or a combination is chosen.
  • Even with the best predictive factors currently available (vascular invasion and percentage embryonal cell carcinoma in the primary tumour), the identification of micro-metastases is no better than the flip of a coin.
  • [MeSH-major] Antineoplastic Combined Chemotherapy Protocols / administration & dosage. Germinoma / pathology. Germinoma / therapy. Testicular Neoplasms / pathology. Testicular Neoplasms / therapy
  • [MeSH-minor] Biopsy, Needle. Combined Modality Therapy. Humans. Male. Neoplasm Staging. Prognosis. Survival Rate. Treatment Outcome. Urogenital Surgical Procedures / methods

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  • (PMID = 11493776.001).
  • [ISSN] 0963-0643
  • [Journal-full-title] Current opinion in urology
  • [ISO-abbreviation] Curr Opin Urol
  • [Language] eng
  • [Publication-type] Comparative Study; Journal Article; Review
  • [Publication-country] United States
  • [Number-of-references] 15
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27. Katz MH, McKiernan JM: Treatment of nonretroperitoneal residual germ cell tumor masses. Urol Oncol; 2005 Nov-Dec;23(6):431-9
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  • [Title] Treatment of nonretroperitoneal residual germ cell tumor masses.
  • The appropriate treatment of residual disease outside the retroperitoneum after chemotherapy is a crucial component of the comprehensive approach to treating advanced testicular germ cell tumors (GCT).
  • Therefore, in patients with normalized serum tumor markers, we recommend resection of all sites of residual disease outside the retroperitoneum.
  • After excision of residual viable GCT, evidence suggests that at least intermediate-risk patients who have received only induction chemotherapy will benefit from further systemic treatment.
  • Patients with residual nonretroperitoneal viable GCT after salvage chemotherapy receive no benefit from additional systemic chemotherapy.
  • [MeSH-major] Neoplasms, Germ Cell and Embryonal / drug therapy. Neoplasms, Germ Cell and Embryonal / surgery
  • [MeSH-minor] Humans. Survival Rate. Time Factors. Treatment Outcome

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  • [CommentIn] Urol Oncol. 2005 Nov-Dec;23(6):439-40 [16301124.001]
  • (PMID = 16301123.001).
  • [ISSN] 1078-1439
  • [Journal-full-title] Urologic oncology
  • [ISO-abbreviation] Urol. Oncol.
  • [Language] eng
  • [Publication-type] Journal Article; Review
  • [Publication-country] United States
  • [Number-of-references] 40
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28. Zurita AJ, Diestra JE, Condom E, García Del Muro X, Scheffer GL, Scheper RJ, Pérez J, Germà-Lluch JR, Izquierdo MA: Lung resistance-related protein as a predictor of clinical outcome in advanced testicular germ-cell tumours. Br J Cancer; 2003 Mar 24;88(6):879-86
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  • [Title] Lung resistance-related protein as a predictor of clinical outcome in advanced testicular germ-cell tumours.
  • This study was undertaken to investigate the expression and predictive value for outcome of multidrug resistance-associated (MDR) proteins P-glycoprotein (Pgp), MRP1, BCRP, and LRP, in advanced testicular germ-cell tumours (TGCT).
  • Paraffin-embedded sections from 56 previously untreated patients with metastatic TGCT were immunostained for Pgp, MRP1, BCRP, and LRP.
  • All patients received platinum-based chemotherapy after orchidectomy.
  • Immunostaining was related to clinicopathological parameters, response to chemotherapy, and outcome.
  • P-glycoprotein and MRP1 associated, respectively, to low AFP (P=0.026) and high LDH levels (P=0.014), whereas LRP expression associated with high beta-hCG levels (P=0.003) and stage IV tumours (P=0.029).
  • No correlation was found between Pgp, MRP1, and BCRP expression and response to chemotherapy and survival.
  • In contrast, patients with LRP-positive tumours (strong or intermediate expression) had shorter progression-free (P=0.0006) and overall survival (P=0.0116) than LRP-negative patients, even after individual log-rank adjustments by statistically associated variables.
  • Our data suggest that a positive LRP immunostaining at the time of diagnosis in metastatic TGCT is associated with an adverse clinical outcome.
  • [MeSH-major] Drug Resistance, Multiple. Gene Expression Regulation, Neoplastic. Germinoma / drug therapy. Germinoma / genetics. Neoplasm Proteins / biosynthesis. Testicular Neoplasms / drug therapy. Testicular Neoplasms / genetics. Vault Ribonucleoprotein Particles / biosynthesis
  • [MeSH-minor] Adolescent. Adult. Antineoplastic Combined Chemotherapy Protocols. Cisplatin / administration & dosage. Disease-Free Survival. Humans. Immunohistochemistry. Male. Middle Aged. Orchiectomy. P-Glycoprotein / analysis. P-Glycoprotein / biosynthesis. Prognosis

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  • (PMID = 12644825.001).
  • [ISSN] 0007-0920
  • [Journal-full-title] British journal of cancer
  • [ISO-abbreviation] Br. J. Cancer
  • [Language] eng
  • [Publication-type] Journal Article; Research Support, Non-U.S. Gov't
  • [Publication-country] England
  • [Chemical-registry-number] 0 / Neoplasm Proteins; 0 / P-Glycoprotein; 0 / Vault Ribonucleoprotein Particles; 0 / major vault protein; Q20Q21Q62J / Cisplatin
  • [Other-IDs] NLM/ PMC2377094
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29. Ohyama C, Kyan A, Satoh M, Saito S, Nishimura Y, Imai Y, Oikawa K, Yokoyama J, Suzuki K, Takeuchi M, Hoshi S, Orikasa S: Bilateral testicular tumors: a report of nine cases with long-term follow-up. Int J Urol; 2002 Mar;9(3):173-7
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  • [Title] Bilateral testicular tumors: a report of nine cases with long-term follow-up.
  • BACKGROUND: The incidence and clinical features of bilateral germ cell testicular tumor (GCTT) in the Japanese population are not fully characterized.
  • The median age of the first tumor was 29 (range 21-75) years.
  • In the case of metachronous tumor, the median interval between first and contralateral tumor was 8 (range 2-25) years.
  • Standard treatment was defined as surveillance policy in stage I, chemotherapy for higher stages of non-seminoma, and radiotherapy for stage II seminoma.
  • The significance of HLA-A24 for bilateral testicular tumor is equivocal in the Japanese population.
  • [MeSH-major] Germinoma. Testicular Neoplasms
  • [MeSH-minor] Adult. Aged. Androgens / therapeutic use. Follicle Stimulating Hormone / blood. Follow-Up Studies. HLA Antigens / blood. Humans. Incidence. Male. Middle Aged. Orchiectomy. Testosterone / blood

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  • (PMID = 12010330.001).
  • [ISSN] 0919-8172
  • [Journal-full-title] International journal of urology : official journal of the Japanese Urological Association
  • [ISO-abbreviation] Int. J. Urol.
  • [Language] eng
  • [Publication-type] Case Reports; Journal Article
  • [Publication-country] Australia
  • [Chemical-registry-number] 0 / Androgens; 0 / HLA Antigens; 3XMK78S47O / Testosterone; 9002-68-0 / Follicle Stimulating Hormone
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30. Ozen H, Ekici S, Sozen S, Ergen A, Tekgül S, Kendi S: Resection of residual masses alone: an alternative in surgical therapy of metastatic testicular germ cell tumors after chemotherapy. Urology; 2001 Feb;57(2):323-7
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  • [Title] Resection of residual masses alone: an alternative in surgical therapy of metastatic testicular germ cell tumors after chemotherapy.
  • OBJECTIVES: The standard approach in postchemotherapy surgery of testicular cancer is retroperitoneal lymph node dissection.
  • METHODS: Seventy-five patients underwent resection of residual masses after chemotherapy.
  • After tumor marker levels returned to normal, patients with residual lymph nodes greater than 2 cm in nonseminomatous germ cell tumors and greater than 4 cm in seminomas and any resectable parenchymal lesions were candidates for the limited surgery.
  • [MeSH-major] Germinoma / drug therapy. Germinoma / surgery. Testicular Neoplasms / drug therapy. Testicular Neoplasms / surgery
  • [MeSH-minor] Adolescent. Adult. Ejaculation. Fibrosis. Humans. Liver Neoplasms / secondary. Lymphatic Metastasis. Male. Middle Aged. Necrosis. Postoperative Complications. Retroperitoneal Neoplasms / secondary. Retrospective Studies. Survival Rate. Thoracic Neoplasms / secondary

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  • (PMID = 11182346.001).
  • [ISSN] 1527-9995
  • [Journal-full-title] Urology
  • [ISO-abbreviation] Urology
  • [Language] eng
  • [Publication-type] Journal Article
  • [Publication-country] United States
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31. Curtin JC, Spinella MJ: p53 in human embryonal carcinoma: identification of a transferable, transcriptional repression domain in the N-terminal region of p53. Oncogene; 2005 Feb 24;24(9):1481-90
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  • [Title] p53 in human embryonal carcinoma: identification of a transferable, transcriptional repression domain in the N-terminal region of p53.
  • Testicular germ cell tumors (TGCTs) arise despite possessing high levels of wild-type p53, suggesting p53 latency.
  • We have previously shown that p53 repression in TGCT-derived human embryonal carcinoma (EC) is relieved upon treatment with all-trans retinoic acid (RA), resulting in enhanced p53 transactivation activity.
  • Progressively, larger truncations were made in the C- or N-terminal direction.
  • Deletion of residues toward the C-terminus of p53 as far as residue 354 did not affect either the basal or RA-inducible activity of gal4-p53.
  • When a small region in the N-terminus was deleted (residues 105-116), relief of the basal repression of p53 activity characteristic of EC was observed.
  • Owing to its location in the N-terminal half of p53, we have named this region the p53 N-terminal Repression Domain (p53-NRD).
  • The p53-NRD mediated repression in a variety of cell lines, with the most prominent repression observed in human EC cells.
  • In contrast, NRD-mediated repression was not sensitive to RA and TSA in a derived RA-resistant cell line with a retinoic acid receptor gamma (RARgamma) defect, but sensitivity could be restored with transfection of RARgamma.
  • These data indicate that a unique repressor domain resides in p53 at residues 90-116 whose activity can be modulated in the presence of 'differentiation therapy' and 'transcription therapy' agents.

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  • (PMID = 15674351.001).
  • [ISSN] 0950-9232
  • [Journal-full-title] Oncogene
  • [ISO-abbreviation] Oncogene
  • [Language] ENG
  • [Grant] United States / NCI NIH HHS / CA / K01 CA075154; United States / NCI NIH HHS / CA / K01-CA75154
  • [Publication-type] Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, P.H.S.
  • [Publication-country] England
  • [Chemical-registry-number] 0 / Tumor Suppressor Protein p53; 5688UTC01R / Tretinoin
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32. Oliver T: Conservative management of testicular germ-cell tumors. Nat Clin Pract Urol; 2007 Oct;4(10):550-60
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  • [Source] The source of this record is MEDLINE®, a database of the U.S. National Library of Medicine.
  • [Title] Conservative management of testicular germ-cell tumors.
  • Cure rates of germ-cell cancer have been greater than 95% for the last decade; therefore, over the past few years there has been a greater focus on 'conservative' approaches to treatment.
  • The increased incidence of late non-germ-cell cancers in the era of radiotherapy and the incidence of subclinical testicular deficiency and metabolic syndrome in cured patients have accelerated this trend.
  • Taking account of the increase in cure rates of primary chemotherapy failures from 5% to 60% with intensification of chemotherapy and surgery, this Review focuses on three areas: lessons from the initial failed trials of less-intensive treatment (i.e. bleomycin withdrawal and carboplatin substitution) that emphasised the need for improved salvage therapy; successes of reducing treatment of patients with metastases classed as good-risk from four cycles(20 days) to three cycles(9 days) and using 1 day carboplatin instead of 21 day radiotherapy as adjuvant for stage 1 seminoma; and the unexpected finding at 5 years of a 72% reduction of contralateral second germ-cell cancer.
  • This finding provides the stimulus for the next generation of conservative trials using organ preservation, aiming to reduce occurrence of metabolic syndrome and using new radiological and minimal surgery techniques to accelerate the assessment of less toxic drugs and new approaches for combined medial and surgical treatment.
  • [MeSH-major] Germinoma / therapy. Testicular Neoplasms / therapy
  • [MeSH-minor] Antineoplastic Agents / therapeutic use. Clinical Trials as Topic / methods. Disease Management. Humans. Male

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  • (PMID = 17921970.001).
  • [ISSN] 1743-4289
  • [Journal-full-title] Nature clinical practice. Urology
  • [ISO-abbreviation] Nat Clin Pract Urol
  • [Language] eng
  • [Publication-type] Journal Article; Review
  • [Publication-country] United States
  • [Chemical-registry-number] 0 / Antineoplastic Agents
  • [Number-of-references] 86
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33. Dalmau J, Porta-Etessam J: [Paraneoplastic cerebral syndromes with oto-neuro-ophthalomologic manifestations]. Rev Neurol; 2000 Dec 16-31;31(12):1213-9
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  • There is no ocular movement abnormality which can be considered pathognomonic of a paraneoplastic disorder, but opsoclonus-myoclonus of infancy is often associated with neuroblastoma.
  • The management of these syndromes depends on their rapid identification as paraneoplastic disorders and on the early diagnosis and treatment of the cancer.
  • Patients with anti-Ta (or anti Ma-2) antibodies may improve with treatment of the cancer, usually a germ-cell tumor of the testis.
  • Paraneoplastic opsoclonus-myoclonus of infancy usually improves with treatment that combines chemotherapy, steroids, and intravenous immunoglobulins, although neurological sequelae (psychomotor and language retardation) are frequent.
  • Detection of antineuronal antibodies facilitates the early identification of some of these syndromes and associated tumors.
  • In general, the management of these syndromes is based on treatment of the associated cancer.
  • [MeSH-minor] Antibodies, Neoplasm / immunology. Autoantibodies / immunology. Autoantigens / immunology. Hearing Loss, Sensorineural / etiology. Hearing Loss, Sensorineural / immunology. Humans. Lambert-Eaton Myasthenic Syndrome / etiology. Lambert-Eaton Myasthenic Syndrome / immunology. Neoplasm Proteins / immunology. Neoplasms / complications. Neoplasms / immunology. Nerve Tissue Proteins / immunology. Neurons / immunology. Ophthalmoplegia / etiology. Ophthalmoplegia / immunology. Paraneoplastic Cerebellar Degeneration / etiology. Paraneoplastic Cerebellar Degeneration / immunology

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  • (PMID = 11205562.001).
  • [ISSN] 0210-0010
  • [Journal-full-title] Revista de neurologia
  • [ISO-abbreviation] Rev Neurol
  • [Language] spa
  • [Publication-type] English Abstract; Journal Article; Review
  • [Publication-country] Spain
  • [Chemical-registry-number] 0 / Antibodies, Neoplasm; 0 / Autoantibodies; 0 / Autoantigens; 0 / Neoplasm Proteins; 0 / Nerve Tissue Proteins
  • [Number-of-references] 44
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34. Langenstroer P, Rosen MA, Griebling TL, Thrasher JB: Ejaculatory function in stage T1 nonseminomatous germ cell tumors: retroperitoneal lymph node dissection versus surveillance--a decision analysis. J Urol; 2002 Oct;168(4 Pt 1):1396-401
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  • [Source] The source of this record is MEDLINE®, a database of the U.S. National Library of Medicine.
  • [Title] Ejaculatory function in stage T1 nonseminomatous germ cell tumors: retroperitoneal lymph node dissection versus surveillance--a decision analysis.
  • PURPOSE: Ejaculatory function remains a major concern for patients with low stage nonseminomatous germ cell tumors of the testis.
  • To compare ejaculatory function for surveillance protocols to primary retroperitoneal lymph node dissection appropriately, we constructed a decision analysis model mimicking the standard treatment algorithm for stage 1 nonseminomatous germ cell tumor of the testis.
  • Based on this model, we established that a primary nerve sparing retroperitoneal dissection must be performed with a 96.8% ejaculatory function rate to be recommended as the appropriate therapy.
  • However, if a highly skilled surgeon routinely performs post-chemotherapy dissection with an ejaculatory function rate of 69.2% or greater, surveillance should be offered as the primary treatment modality.
  • This result simply demonstrates a high skill level to allow the surgeon to salvage ejaculatory function in post-chemotherapy retroperitoneal lymph node dissection settings.
  • If we account for a 10% loss of ejaculatory function from primary chemotherapy, the minimum ejaculatory function rate for primary retroperitoneal dissection decreases to 95.7%.
  • RESULTS: In the post-chemotherapy setting an 85.7% ejaculatory function rate must be achieved for surveillance to be considered the optimal choice.
  • Clearly, less surgical rigor is needed with a primary retroperitoneal lymph node dissection when correcting for the effects of chemotherapy on ejaculatory function.
  • Despite this fact, 1-way sensitivity analysis revealed that our model is insensitive to the ejaculatory function effects of chemotherapy.
  • CONCLUSIONS: Thus, to maximize ejaculatory function for patients with stage 1 nonseminomatous germ cell tumor a nerve sparing primary retroperitoneal lymph node dissection should always be performed, unless the likelihood of recurrence on surveillance is low or the surgical skill level allows for a highly successful post chemotherapy nerve sparing dissection.
  • [MeSH-major] Ejaculation / physiology. Lymph Node Excision. Neoplasms, Germ Cell and Embryonal / surgery. Postoperative Complications / physiopathology. Testicular Neoplasms / surgery
  • [MeSH-minor] Adult. Chemotherapy, Adjuvant / adverse effects. Clinical Competence. Combined Modality Therapy. Decision Trees. Humans. Lymph Nodes / pathology. Lymphatic Metastasis. Male. Neoplasm Staging. Retroperitoneal Space. Risk Assessment

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  • [CommentIn] J Urol. 2002 Oct;168(4 Pt 1):1405 [12352403.001]
  • (PMID = 12352401.001).
  • [ISSN] 0022-5347
  • [Journal-full-title] The Journal of urology
  • [ISO-abbreviation] J. Urol.
  • [Language] eng
  • [Publication-type] Journal Article
  • [Publication-country] United States
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35. Fosså SD, Aass N, Harvei S, Tretli S: Increased mortality rates in young and middle-aged patients with malignant germ cell tumours. Br J Cancer; 2004 Feb 9;90(3):607-12
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  • [Title] Increased mortality rates in young and middle-aged patients with malignant germ cell tumours.
  • Cisplatin-based chemotherapy of malignant germ cell tumours (MGCT) has been reported to increase the risk of cardiovascular morbidity.
  • A high incidence of second nongerm cell malignancies is well documented in MGCT survivors.
  • The death risk due to these conditions is, however, more unknown in MGCT patients.
  • Standard mortality rates (SMRs) were established in 3378 Norwegian MGCT patients treated from 1962 to 1997 aged <or=55 years.
  • The patients represented three principal treatment strategies: 1962/1969 (period 1): radiotherapy only; 1970/1979 (period 2): radiotherapy with or without noncisplatin-containing chemotherapy; 1980/1997 (period 3): surgery only or radiotherapy or cisplatin-based chemotherapy.
  • Patients not dying from MGCT displayed significantly increased SMRs for respectively diseases of the circulatory system (SMR: 1.2, 95% confidence interval (CI): 1.0-1.5), benign gastrointestinal disorders (SMR: 2.1, 95% CI: 1.1-3.5) and nongerm cell malignancies (SMR: 2.0, 95% CI: 1.7-2.4).
  • The risk of dying from a nongerm cell malignancy was increased both in periods 2 and 3.
  • In conclusion, although the overall SMR for diseases of the circulatory system is increased in MCGT survivors, the introduction of cisplatin-based chemotherapy into the treatment of MGCT has so far not resulted in increased death rates due to these conditions.
  • Patients with MGCT have a significantly increased relative death risk due to a second nongerm cell cancer, even after the introduction of modern treatment principles with overall reduction of radiotherapy.
  • [MeSH-major] Antineoplastic Combined Chemotherapy Protocols / therapeutic use. Cardiovascular Diseases / chemically induced. Cardiovascular Diseases / mortality. Cisplatin / therapeutic use. Neoplasms, Germ Cell and Embryonal / drug therapy. Neoplasms, Germ Cell and Embryonal / mortality. Registries / statistics & numerical data
  • [MeSH-minor] Adolescent. Adult. Age Factors. Combined Modality Therapy. Female. Follow-Up Studies. Humans. Male. Middle Aged. Mortality / trends. Neoplasms, Second Primary / etiology. Neoplasms, Second Primary / mortality. Radiation Injuries / mortality. Risk Factors. Survival Analysis

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  • (PMID = 14760372.001).
  • [ISSN] 0007-0920
  • [Journal-full-title] British journal of cancer
  • [ISO-abbreviation] Br. J. Cancer
  • [Language] eng
  • [Publication-type] Journal Article; Research Support, Non-U.S. Gov't
  • [Publication-country] England
  • [Chemical-registry-number] Q20Q21Q62J / Cisplatin
  • [Other-IDs] NLM/ PMC2409607
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36. Dohle GR: Male infertility in cancer patients: Review of the literature. Int J Urol; 2010 Apr;17(4):327-31
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  • [Title] Male infertility in cancer patients: Review of the literature.
  • The number of men surviving cancer at a young age has increased dramatically in the past 20 years as a result of early detection and improved cancer treatment protocols; more than 75% of young cancer patients nowadays are long-term survivors.
  • The commonest cancers in patients of reproductive age are leukaemia, Hodgkin's lymphomas and testicular germ cell tumors.
  • Fertility is often impaired after chemotherapy and radiation therapy.
  • Cryopreservation of semen before cancer treatment starts is currently the only method to preserve future male fertility.
  • In some malignancies, especially in germ cell tumors, sperm quality is already abnormal at the time of diagnosis.
  • In approximately 12% of men, no viable spermatozoa are present for cryopreservation before the start of chemotherapy.
  • Cytotoxic therapy influences spermatogenesis at least temporarily and in some cases permanently.
  • The amount of damage inflicted by chemotherapy on spermatogenesis depends on the combination of drugs used and on the cumulative dose given for cancer treatment.
  • Alkylating agents, such as cyclophosphamide and procarbazine, are most detrimental to germ cells.
  • Radiation therapy, especially whole-body irradiation, is also associated with the risk of permanent sterility.
  • Besides the cancer treatment, tumor type and pretreatment fertility are of prognostic value for future fertility in male cancer survivors.
  • After cancer treatment, many men need artificial reproductive techniques to achieve fatherhood; usually in vitro fertilization (IVF) or intracytoplasmic sperm injection (ICSI) is indicated for successful treatment.
  • About 15% of men will use their cryopreserved semen because of persistent azoospermia after cancer treatment.
  • Treatment results with cryopreserved semen are generally good and comparable to general IVF and ICSI results.
  • So far, no studies have reported an increased rate of congenital abnormalities or malignancies in children born from fathers who had cancer treatment is the past, but close follow up is warranted, especially in children born after IVF/ICSI.
  • [MeSH-major] Drug-Related Side Effects and Adverse Reactions. Infertility, Male / etiology. Neoplasms / therapy. Radiotherapy / adverse effects
  • [MeSH-minor] Cryopreservation. Humans. Male. Spermatozoa


37. Ishibashi M, Nakayama K, Oride A, Yeasmin S, Katagiri A, Iida K, Nakayama N, Miyazaki K: [A case of PEP(BEP)-resistant ovarian dysgerminoma successfully treated by VeIP therapy]. Gan To Kagaku Ryoho; 2009 Mar;36(3):513-7
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  • [Title] [A case of PEP(BEP)-resistant ovarian dysgerminoma successfully treated by VeIP therapy].
  • Ovarian germ cell tumors are malignant tumors which commonly develop during childhood, and which are sensitive to chemotherapy.
  • We have had a case of germ cell tumors which showed resistance to first-line PEP(BEP)chemotherapy.
  • As second-line chemotherapy, VeIP therapy was used, because it is possible that this therapy is effective against recurrent testicular germ cell tumors.
  • She experienced acute abdominal pain and visited the hospital, where she was diagnosed with torsion of an ovarian tumor.
  • Then she received chemotherapy PEP(BEP), but after eight months of PEP (BEP), her serum hCG-CTP was again elevated to 14.5 mIU/mL.
  • After the operation, the patient again underwent chemotherapy.
  • After 6 courses of this therapy, she had a follow-up operation.
  • She remains without recurrence of this disease 24 months after VeIP therapy.
  • This case suggests that VeIP therapy might be an effective second-line therapy for patients with PEP(BEP)-resistant ovarian dysgerminoma.
  • [MeSH-major] Antineoplastic Combined Chemotherapy Protocols / therapeutic use. Drug Resistance, Neoplasm / drug effects. Dysgerminoma / drug therapy. Dysgerminoma / pathology. Ovarian Neoplasms / drug therapy. Ovarian Neoplasms / pathology
  • [MeSH-minor] Adolescent. Bleomycin / therapeutic use. Cisplatin / therapeutic use. Female. Humans. Magnetic Resonance Imaging. Positron-Emission Tomography. Remission Induction. Tomography, X-Ray Computed. Treatment Outcome

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  • (PMID = 19295284.001).
  • [ISSN] 0385-0684
  • [Journal-full-title] Gan to kagaku ryoho. Cancer & chemotherapy
  • [ISO-abbreviation] Gan To Kagaku Ryoho
  • [Language] jpn
  • [Publication-type] Case Reports; English Abstract; Journal Article
  • [Publication-country] Japan
  • [Chemical-registry-number] 11056-06-7 / Bleomycin; Q20Q21Q62J / Cisplatin
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38. Giménez Bachs JM, Salinas Sánchez AS, Ruíz Mondéjar R, Lorenzo Romero JG, Donate Moreno MJ, Segura Martín M, Hernández Millán IR, Cañamares Pabolaza L, Virseda Rodríguez JA: [Surgery of large residual mass after chemotherapy in advanced testicular germ cell tumor]. Actas Urol Esp; 2004 Mar;28(3):230-3
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  • [Title] [Surgery of large residual mass after chemotherapy in advanced testicular germ cell tumor].
  • [Transliterated title] Cirugía de gran masa residual tras quimioterapia en tumor germinal testicular avanzado.
  • Treatment for testicular tumours has progress in such a manner in the last years that high cure percentages can at present be achieved.
  • After chemotherapy, in most cases, residual mass can appear.
  • In this cases surgery is considered a viable therapeutic option although it implies an advanced surgical training since it is a complex technique and implies serious implications.
  • We submit the case of a patient who presented a large residual mass from a testicular germ cell tumour after being treated with orquiectomía and chemotherapy.
  • [MeSH-major] Germinoma / surgery. Testicular Neoplasms / surgery
  • [MeSH-minor] Adult. Disease Progression. Humans. Male. Neoplasm, Residual

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  • (PMID = 15141420.001).
  • [ISSN] 0210-4806
  • [Journal-full-title] Actas urologicas espanolas
  • [ISO-abbreviation] Actas Urol Esp
  • [Language] spa
  • [Publication-type] Case Reports; English Abstract; Journal Article
  • [Publication-country] Spain
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39. Sperlongano P, Pisaniello D, Di Mauro U, Pone D, Casoli E: Management of testicular seminoma. Our experience. Ann Ital Chir; 2000 Jan-Feb;71(1):127-30
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  • [Title] Management of testicular seminoma. Our experience.
  • MATERIALS: They examine 12 cases of seminoma among a series of 19 patients with testicular germ cell tumours observed at the Second Surgical Department of the Second University of Naples.
  • RESULTS: Their results showed a better prognosis for patients in early stage of the disease who underwent surgery and adjuvant prophylactic radiotherapy; good survival rates for patients in advanced stages of the disease were achieved by the combined use of surgery, adjuvant radiotherapy and chemotherapy.
  • DISCUSSION: The authors discuss risk factors, clinical and diagnostic features of seminomas, relating their prognosis with the combined use of both surgery and adjuvant therapies.
  • They consider total orchiectomy, followed by prophylactic radiotherapy, the treatment of choice, especially in stages IA and IIA.
  • [MeSH-major] Seminoma / therapy. Testicular Neoplasms / therapy
  • [MeSH-minor] Adolescent. Adult. Chemotherapy, Adjuvant. Humans. Lymph Node Excision. Male. Neoplasm Staging. Orchiectomy. Postoperative Care. Preoperative Care. Radiotherapy, Adjuvant. Risk Factors

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  • (PMID = 10829535.001).
  • [ISSN] 0003-469X
  • [Journal-full-title] Annali italiani di chirurgia
  • [ISO-abbreviation] Ann Ital Chir
  • [Language] eng
  • [Publication-type] Journal Article
  • [Publication-country] ITALY
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40. Ulbright TM, Hattab EM, Zhang S, Ehrlich Y, Foster RS, Einhorn LH, Cheng L: Primitive neuroectodermal tumors in patients with testicular germ cell tumors usually resemble pediatric-type central nervous system embryonal neoplasms and lack chromosome 22 rearrangements. Mod Pathol; 2010 Jul;23(7):972-80
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  • [Title] Primitive neuroectodermal tumors in patients with testicular germ cell tumors usually resemble pediatric-type central nervous system embryonal neoplasms and lack chromosome 22 rearrangements.
  • Primitive neuroectodermal tumors (PNETs) are one of the most frequent types of 'non-germ cell' tumor in patients with testicular germ cell tumors and have a guarded prognosis when present in metastatic sites after cisplatin-based chemotherapy.
  • Improved treatments, including targeted therapy, require understanding the biology of these neoplasms.
  • We therefore analyzed the morphologic, immunohistochemical and molecular biologic features of 14 PNETs from 14 patients with concurrent or previous testicular germ cell tumors; 12 tumors were from metastatic sites and 2 were primary in the testis.
  • Using standard light microscopic criteria for central nervous system and peripheral PNETs, we classified nine tumors as medulloepithelioma, three as medulloblastoma/supratentorial PNET, one as neuroblastic tumor with abundant neuropil and true rosettes and one as small cell embryonal tumor/PNET (Ewing sarcoma-like).
  • INI1 was diffusely and strongly positive in all tumors whereas the other stains, except for cytoplasmic WT1 (which showed substantial reactivity in most tumors), were mostly focal to negative, including CD99 (eight negative, six focal) and Fli-1 (all negative).
  • Only 1 tumor, classified as medulloepithelioma, was scored positive for chromosome 22 translocation (22% rearranged cells) and the remaining 13 were negative, including the one case that resembled peripheral PNET.
  • We conclude that PNETs derived from testicular germ cell tumors mostly resemble central nervous system PNETs and generally lack the chromosome 22 translocation of peripheral PNETs.
  • Future treatment strategies should take these findings into account.
  • [MeSH-major] Neoplasms, Germ Cell and Embryonal / pathology. Neoplasms, Multiple Primary / pathology. Neuroectodermal Tumors, Primitive, Peripheral / pathology. Testicular Neoplasms / pathology
  • [MeSH-minor] Adult. Biomarkers, Tumor / analysis. Chromosomes, Human, Pair 22 / genetics. Gene Rearrangement. Humans. Immunohistochemistry. In Situ Hybridization, Fluorescence. Male. Young Adult

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  • (PMID = 20348883.001).
  • [ISSN] 1530-0285
  • [Journal-full-title] Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc
  • [ISO-abbreviation] Mod. Pathol.
  • [Language] eng
  • [Publication-type] Journal Article
  • [Publication-country] United States
  • [Chemical-registry-number] 0 / Biomarkers, Tumor
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41. Thijssens K, Vaneerdeweg W, Schrijvers D, Eyskens E, Van Oosterom A: Retroperitoneal lymph node dissection as adjuvant therapy in the treatment of non-seminomatous testicular cancer. Acta Chir Belg; 2003 Nov-Dec;103(6):599-602
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  • [Title] Retroperitoneal lymph node dissection as adjuvant therapy in the treatment of non-seminomatous testicular cancer.
  • OBJECTIVE: To assess the results of retroperitoneal lymph node dissection (RPLND) of residual masses in patients with disseminated non-seminomatous germ cell tumour treated with cisplatin-based chemotherapy, both in terms of extension of surgery, morbidity and survival.
  • PATIENTS AND METHODS: Retrospectively, all patients treated for non-seminomatous germ cell tumour at the University Hospital of Antwerp were studied from January 1987 till December 1997.
  • In patients with non-seminomatous testicular cancer more than stage I, the 'wait and see' strategy changed and patients were treated with chemotherapy.
  • Patients were assessed at the end of chemotherapy and if a residual masses persisted, a RPLND was performed.
  • RESULTS: Sixty patients had a non-seminomatous germ cell tumor of the testis and were analysed.
  • Forty-seven patients were treated with cisplatin-based chemotherapy.
  • A complete response was observed in sixteen patients (34%), while 31 patients (66%) achieved a partial response and were treated with a RPLND.
  • In two patients malignant cells or fibrotic tissue were found above the renal trunk and bilateral.
  • In five patients viable tumour cells were found in the region below the renal trunk.
  • Sixteen patients underwent RPLND below the level of the renal trunk, of which nine had a unilateral resection, containing viable tumour in two patients.
  • The survival of the patients treated with a RPLND was 97% and in the whole group of patients with a non-seminomatous testicular cancer 98%.
  • CONCLUSION: RPLND has a place in the treatment of patients with non-seminomatous testicular cancer after chemotherapy in case of residual masses.
  • [MeSH-major] Germinoma / secondary. Germinoma / surgery. Lymph Node Excision. Testicular Neoplasms / pathology. Testicular Neoplasms / surgery
  • [MeSH-minor] Adult. Belgium. Chemotherapy, Adjuvant. Cohort Studies. Disease-Free Survival. Follow-Up Studies. Humans. Lymph Nodes / pathology. Lymph Nodes / surgery. Lymphatic Metastasis. Male. Middle Aged. Neoplasm Staging. Retrospective Studies. Risk Assessment. Sensitivity and Specificity. Survival Rate. Treatment Outcome

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  • (PMID = 14743567.001).
  • [ISSN] 0001-5458
  • [Journal-full-title] Acta chirurgica Belgica
  • [ISO-abbreviation] Acta Chir. Belg.
  • [Language] eng
  • [Publication-type] Journal Article
  • [Publication-country] Belgium
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42. Hara I, Miyake H, Yamada Y, Takenaka A, Fujisawa M: High-dose chemotherapy for male germ cell tumor. Int J Urol; 2006 Aug;13(8):1037-44
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  • [Title] High-dose chemotherapy for male germ cell tumor.
  • Today, 20-30% of male patients with advanced germ cell tumor (GCT) do not have durable, complete remission in spite of cis-platinum (CDDP)-based chemotherapy.
  • High-dose chemotherapy (HDCT) has been tried in CDDP refractory GCT patients.
  • However, the clinical outcome was not good and the treatment-related death rate was not ignorable.
  • Therefore, earlier introduction of HDCT with peripheral blood stem cell transplantation was preferable as it renders HDCT more effective and less toxic, and multicycle HDCT is feasible.
  • HDCT is also performed as first line chemotherapy for poor prognosis GCT patients.
  • Induction chemotherapy followed by multicycles of HDCT was tried.
  • The durable free rate of recent HDCT as first line chemotherapy is 43-73%.
  • Although previous reports suggest the superiority of HDCT, one recent randomized controlled trial (RCT) failed to show an improvement with one cycle of HDCT followed by three cycles of standard-dose chemotherapy (SDCT) compared with four cycles of SDCT.
  • [MeSH-major] Antineoplastic Agents / therapeutic use. Antineoplastic Combined Chemotherapy Protocols / therapeutic use. Neoplasms, Germ Cell and Embryonal / drug therapy. Testicular Neoplasms / drug therapy
  • [MeSH-minor] Bone Marrow Transplantation. Clinical Trials as Topic. Humans. Male. Paclitaxel / therapeutic use. Peripheral Blood Stem Cell Transplantation

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  • (PMID = 16903926.001).
  • [ISSN] 0919-8172
  • [Journal-full-title] International journal of urology : official journal of the Japanese Urological Association
  • [ISO-abbreviation] Int. J. Urol.
  • [Language] eng
  • [Publication-type] Journal Article; Review
  • [Publication-country] Australia
  • [Chemical-registry-number] 0 / Antineoplastic Agents; P88XT4IS4D / Paclitaxel
  • [Number-of-references] 76
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43. Mottet N, Rousmans S, Culine S: [Systematic review 2007: Primary treatments of testicular germ cell tumors after radical orchydectomy]. Bull Cancer; 2008 Feb;95(2):205-34
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  • [Title] [Systematic review 2007: Primary treatments of testicular germ cell tumors after radical orchydectomy].
  • [Transliterated title] Synthèse méthodique des données scientifiques 2007: Traitements de première intention des tumeurs germinales du testicule après orchidectomie totale.
  • In this context, the SOR, in collaboration with the French Association of Urology (AFU), has developed a systematic review on the management of nonseminomatous (NSTGC) or seminomatous(STGC) testicular germ cell cancer treated with primary radiotherapy (RT), chemotherapy (CT) or surveillance (SV) after radical orchidectomy.
  • Today, 80 % of patients with testicular germ cell cancer, including metastatic stage, can be cured.
  • Actual challenges are to limit morbidity and late sequels of treatments while maintaining their therapeutic efficacy.
  • Following this goal, surveillance, considered as a therapeutic option, is being broadly developed particularly for localised tumours.
  • CONCLUSIONS: The choice of risk-adapted treatment for patients with locally NSTGC of the testis seems to be appropriate: SV for low risk patients and CT for others.
  • For local STGC, the choice of SV or CT versus RT needs to be confirmed by RCT with prolonged follow-up according to promising results in term of toxicity obtained with carboplatine or lower irradiation dose (20 Gy instead of 30 Gy).
  • Finally, for advanced STGC, the utility of carboplatine single agent treatment versus cisplatin-based combination chemotherapy has not been proved.
  • [MeSH-major] Neoplasms, Germ Cell and Embryonal. Testicular Neoplasms
  • [MeSH-minor] Humans. Lymph Node Excision. Male. Neoplasm Recurrence, Local / prevention & control. Neoplasm Staging. Neoplasm, Residual. Orchiectomy. Practice Guidelines as Topic. Randomized Controlled Trials as Topic. Risk Assessment. Seminoma / drug therapy. Seminoma / pathology. Seminoma / radiotherapy. Seminoma / therapy. Treatment Outcome

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  • (PMID = 18330045.001).
  • [ISSN] 1769-6917
  • [Journal-full-title] Bulletin du cancer
  • [ISO-abbreviation] Bull Cancer
  • [Language] fre
  • [Publication-type] English Abstract; Journal Article; Meta-Analysis; Review
  • [Publication-country] France
  • [Number-of-references] 126
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44. Wang JW, Yang L, Wang JY, Qu T, Cai RG, Huang J, Sun Y: [Long-term results of multimodality therapy of testicular germ cell tumor]. Zhonghua Zhong Liu Za Zhi; 2003 Jul;25(4):382-5
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  • [Title] [Long-term results of multimodality therapy of testicular germ cell tumor].
  • OBJECTIVE: To study the clinical characteristics, outcome, prognostic factors and survival of patients with testicular germ cell tumors (TGCTs).
  • METHODS: 107 TGCT patients received chemotherapy after orchiectomy.
  • Seventy-four patients had non-seminomatous germ cell tumors (NSGCTT) with 21 (28.4%) stage I lesions.
  • Therapy including chemotherapy, radiation and necessary salvage operation were performed after orchiectomy.
  • RESULTS: Clinical stage and pathological type were the main prognostic factors.
  • Seventeen (26.6%) patients achieved CR by chemotherapy alone and an additional 8 patients (12.5%) achieved CR by chemotherapy plus salvage operation or radiation.
  • CONCLUSION: The long-term outcome for stage I germ cell tumors is excellent.
  • The treatment outcome and survival in patients with metastatic TGCTs can be greatly improved by adopting multi-modality therapy with combined chemotherapy as the chief means.
  • [MeSH-major] Germinoma / surgery. Orchiectomy. Seminoma / surgery. Testicular Neoplasms / surgery
  • [MeSH-minor] Adolescent. Adult. Antineoplastic Combined Chemotherapy Protocols / therapeutic use. Bleomycin / therapeutic use. Child. Child, Preschool. Cisplatin / therapeutic use. Combined Modality Therapy. Etoposide / therapeutic use. Follow-Up Studies. Humans. Lung Neoplasms / drug therapy. Lung Neoplasms / secondary. Male. Middle Aged. Neoplasm Staging. Survival Rate. Treatment Outcome

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  • (PMID = 12921572.001).
  • [ISSN] 0253-3766
  • [Journal-full-title] Zhonghua zhong liu za zhi [Chinese journal of oncology]
  • [ISO-abbreviation] Zhonghua Zhong Liu Za Zhi
  • [Language] chi
  • [Publication-type] Clinical Trial; Comparative Study; English Abstract; Journal Article
  • [Publication-country] China
  • [Chemical-registry-number] 11056-06-7 / Bleomycin; 6PLQ3CP4P3 / Etoposide; Q20Q21Q62J / Cisplatin; BEP protocol
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45. Aparicio J, Germà JR: Treatment of stage I testicular germ-cell tumors. Med Oncol; 2006;23(3):305-15
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  • [Title] Treatment of stage I testicular germ-cell tumors.
  • More than a half of patients with testicular cancer are diagnosed with clinical stage I disease.
  • In this setting, definitive cure is the rule.
  • However, there is no consensus on the optimal treatment choice.
  • A literature review (1990-2005) was performed in order to identify the pros and the cons associated with each therapy, as well as their long-term outcomes.
  • Several treatment alternatives yield similar efficacy results.
  • Thus, therapy-related morbidity, economic costs, quality-of-life issues, and patient preferences should be considered.
  • Refinement in the knowledge of predictive factors for relapse and amounting experience with both surveillance and adjuvant chemotherapy have led to consideration of risk-adapted treatment policies as an alternative to more traditional approaches (i.e., prophylactic irradiation for seminomas and retroperitoneal lymph node dissection for non-seminomas).
  • In conclusion, with cure rates approaching 100%, close surveillance for low-risk patients and adjuvant chemotherapy for those at high risk of relapse seems the preferred option for clinical stage I testicular cancer, in both seminoma and non-seminoma cases.
  • [MeSH-major] Medical Oncology / methods. Neoplasms, Germ Cell and Embryonal / therapy. Testicular Neoplasms / therapy
  • [MeSH-minor] Chemotherapy, Adjuvant / methods. Humans. Lymph Node Excision. Lymph Nodes / surgery. Male. Prognosis. Radiotherapy, Adjuvant / methods. Recurrence. Risk. Seminoma / therapy. Treatment Outcome

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  • (PMID = 17018887.001).
  • [ISSN] 1559-131X
  • [Journal-full-title] Medical oncology (Northwood, London, England)
  • [ISO-abbreviation] Med. Oncol.
  • [Language] eng
  • [Publication-type] Journal Article; Review
  • [Publication-country] United States
  • [Number-of-references] 78
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46. Sundar S, Decatris MP, Kumar DM: Cure without complications: a population-based analysis of treatment intensity and survival in testicular germ cell tumours. Clin Oncol (R Coll Radiol); 2003 Apr;15(2):84-5
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  • [Title] Cure without complications: a population-based analysis of treatment intensity and survival in testicular germ cell tumours.
  • [MeSH-major] Drug-Related Side Effects and Adverse Reactions. Germinoma / mortality. Germinoma / therapy. Radiotherapy / adverse effects. Testicular Neoplasms / mortality. Testicular Neoplasms / therapy
  • [MeSH-minor] Adolescent. Adult. Aged. Aged, 80 and over. Cohort Studies. Drug Therapy / methods. Humans. Male. Middle Aged. Population Surveillance

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  • (PMID = 12708717.001).
  • [ISSN] 0936-6555
  • [Journal-full-title] Clinical oncology (Royal College of Radiologists (Great Britain))
  • [ISO-abbreviation] Clin Oncol (R Coll Radiol)
  • [Language] eng
  • [Publication-type] Comparative Study; Letter
  • [Publication-country] England
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47. Sakamoto H, Oohta M, Inoue K, Fuji K, Fukagai T, Yoshida H: Testicular sperm extraction in patients with persistent azoospermia after chemotherapy for testicular germ cell tumor. Int J Urol; 2007 Feb;14(2):167-70
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  • [Title] Testicular sperm extraction in patients with persistent azoospermia after chemotherapy for testicular germ cell tumor.
  • Sperm cryopreservation before chemotherapy in young males is recommended because of chemotherapy's gonadotoxic effects.
  • Two azoospermic patients presented to us after chemotherapy, and we obtained sperm from them by testicular sperm extraction (TESE).
  • One patient was 32 years old and had been treated with six cycles of cisplatin, etoposide and bleomycin (BEP) chemotherapy and one cycle of high-dose chemotherapy for stage III non-seminoma.
  • Histopathology of the testicular specimen showed germinal aplasia with focal islands of full spermatogenesis.
  • The other patient was 33 years old who was treated with four cycles of BEP chemotherapy for stage II seminoma.
  • Histopathology of the testicular specimen showed Sertoli-cell-only syndrome.
  • TESE should be considered in patients with persistent azoospermia after chemotherapy if frozen sperm samples are not available.
  • [MeSH-major] Azoospermia / etiology. Neoplasms, Germ Cell and Embryonal / drug therapy. Spermatozoa. Testicular Neoplasms / drug therapy. Tissue and Organ Harvesting
  • [MeSH-minor] Adult. Humans. Male

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  • (PMID = 17302578.001).
  • [ISSN] 0919-8172
  • [Journal-full-title] International journal of urology : official journal of the Japanese Urological Association
  • [ISO-abbreviation] Int. J. Urol.
  • [Language] eng
  • [Publication-type] Case Reports; Journal Article
  • [Publication-country] Australia
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48. Ishioka J, Kageyama Y, Ichiyanagi N, Fukuda H, Higashi Y: Incorporation of TIP (paclitaxel, ifosfamide, cisplatin) into first-line therapy for intermediate to poor risk testicular germ cell tumors with unfavorable marker decline after initial two cycles chemotherapy: a report of three cases. Int J Urol; 2007 May;14(5):455-7
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  • [Title] Incorporation of TIP (paclitaxel, ifosfamide, cisplatin) into first-line therapy for intermediate to poor risk testicular germ cell tumors with unfavorable marker decline after initial two cycles chemotherapy: a report of three cases.
  • Three patients of advanced-non-seminomatous germ cell tumors (International Germ Cell Cancer Collaborative Group classification: poor risk, 2; intermediate, 1) without evidence of a second primary germ cell tumor were treated.
  • The patients received two cycles of standard BEP (bleomycin, etopside, cisplatin) or VIP/VB (etoposide, ifosphamide, cisplatin/vinblastine, bleomycin) therapy first.
  • All patients in this trial showed unfavorable marker response to these therapies and received four cycles of TIP subsequently.
  • [MeSH-major] Antineoplastic Combined Chemotherapy Protocols / therapeutic use. Neoplasms, Germ Cell and Embryonal / drug therapy. Testicular Neoplasms / drug therapy
  • [MeSH-minor] Adult. Biomarkers, Tumor / blood. Cisplatin / administration & dosage. Humans. Ifosfamide / administration & dosage. Male. Middle Aged. Paclitaxel / administration & dosage. Risk Factors

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  • (PMID = 17511735.001).
  • [ISSN] 0919-8172
  • [Journal-full-title] International journal of urology : official journal of the Japanese Urological Association
  • [ISO-abbreviation] Int. J. Urol.
  • [Language] eng
  • [Publication-type] Journal Article
  • [Publication-country] Australia
  • [Chemical-registry-number] 0 / Biomarkers, Tumor; P88XT4IS4D / Paclitaxel; Q20Q21Q62J / Cisplatin; UM20QQM95Y / Ifosfamide
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49. Azak A, Oksüzoğlu B, Deren T, Oneç BM, Zengin N: Cerebrovascular accident during cisplatin-based combination chemotherapy of testicular germ cell tumor: an unusual case report. Anticancer Drugs; 2008 Jan;19(1):97-8
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  • [Title] Cerebrovascular accident during cisplatin-based combination chemotherapy of testicular germ cell tumor: an unusual case report.
  • Even though testicular nonseminomatous germ cell tumors (NSGCTs) usually have a good prognosis and high curability rates, unpredicted complications owing to chemotherapy regimens might complicate the course.
  • Thromboembolism, which is infrequently associated with germ cell tumors and the vascular toxicity of chemotherapeutics, causes morbidity and mortality.
  • We report a young testicular NSGCT patient, without any known underlying risk factor, who experienced an unpredicted cerebrovascular accident after he received cisplatin-based combination chemotherapy.
  • [MeSH-major] Antineoplastic Agents / adverse effects. Cisplatin / adverse effects. Neoplasms, Germ Cell and Embryonal / complications. Stroke / etiology. Testicular Neoplasms / complications
  • [MeSH-minor] Adolescent. Antineoplastic Combined Chemotherapy Protocols / adverse effects. Antineoplastic Combined Chemotherapy Protocols / therapeutic use. Blood Coagulation Tests. Cerebral Infarction / chemically induced. Cerebral Infarction / etiology. Fatal Outcome. Humans. Male. Thromboembolism / chemically induced. Thromboembolism / etiology. Tomography, X-Ray Computed

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  • (PMID = 18043135.001).
  • [ISSN] 0959-4973
  • [Journal-full-title] Anti-cancer drugs
  • [ISO-abbreviation] Anticancer Drugs
  • [Language] eng
  • [Publication-type] Case Reports; Journal Article
  • [Publication-country] England
  • [Chemical-registry-number] 0 / Antineoplastic Agents; Q20Q21Q62J / Cisplatin
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50. Heidenreich A: [Therapeutical options for seminomas at clinical stage I-IIA/B]. Urologe A; 2004 Nov;43(11):1435-44; quiz 1445
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  • [Transliterated title] Therapieoptionen des Seminoms im klinischen Stadium I-IIA/B.
  • Seminomas represent the most common histological subgroup of all testicular germ cell tumors.
  • About 75% of all seminomas present as clinical stage I disease at time of initial diagnosis and exhibit a long-term cure rate of 99%.
  • Currently, three treatment strategies are available for stage I seminomas: surveillance, radiotherapy and chemotherapy.
  • Pathohistological prognostic factors allow an individualized risk-adapted therapeutic approach.
  • Tumor size < or =4 cm and absence of rete testis invasion define a low-risk group with a recurrence rate of 12% being best managed by surveillance.
  • Tumor size >4 cm and presence of rete testis invasion define a high-risk with a 35% risk of relapse, best managed by active therapy.
  • Active treatment either consists of radiation of the ipsilateral paracaval or paraaortic lymph nodes with 20 Gy or of adjuvant chemotherapy with 2 cycles of carboplatin.
  • [MeSH-major] Carboplatin / therapeutic use. Practice Guidelines as Topic. Radiotherapy, Computer-Assisted / methods. Risk Assessment / methods. Testicular Neoplasms / pathology. Testicular Neoplasms / therapy
  • [MeSH-minor] Antineoplastic Agents / therapeutic use. Germany. Humans. Male. Neoplasm Staging. Practice Patterns, Physicians'. Risk Factors. Treatment Outcome

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  • (PMID = 15526184.001).
  • [ISSN] 0340-2592
  • [Journal-full-title] Der Urologe. Ausg. A
  • [ISO-abbreviation] Urologe A
  • [Language] ger
  • [Publication-type] English Abstract; Journal Article; Review
  • [Publication-country] Germany
  • [Chemical-registry-number] 0 / Antineoplastic Agents; BG3F62OND5 / Carboplatin
  • [Number-of-references] 18
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51. Schrader M, Müller M, Sofikitis N, Straub B, Krause H, Miller K: "Onco-tese": testicular sperm extraction in azoospermic cancer patients before chemotherapy-new guidelines? Urology; 2003 Feb;61(2):421-5
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  • [Source] The source of this record is MEDLINE®, a database of the U.S. National Library of Medicine.
  • [Title] "Onco-tese": testicular sperm extraction in azoospermic cancer patients before chemotherapy-new guidelines?
  • OBJECTIVES: To examine the usefulness of pretreatment testicular sperm extraction because some patients have tumor-induced azoospermia.
  • In view of the high cure rates for testicular germ cell tumors and malignant lymphomas, increasing clinical importance is attached to protecting fertility.
  • High-dose cytostatic therapy may be expected to cause long-term infertility.
  • Thus, the standard procedure for fertility protection is cryopreservation of ejaculated spermatozoa before therapy.
  • METHODS: Contralateral testicular biopsies were taken from 14 azoospermic patients with malignant testicular germ cell tumors.
  • In addition, 17 patients with malignant lymphomas underwent unilateral (n = 6) or bilateral (n = 11) testicular biopsy.
  • The tissue specimens were cryopreserved, and the histologic workup was performed at the same time.
  • RESULTS: Of the 14 patients with malignant testicular germ cell tumors, 6 had spermatozoa in their testicular biopsies.
  • Sertoli cell-only syndrome was found in 5 patients, and 3 had maturation arrest without detection of spermatozoa.
  • Successful sperm recovery was possible in 8 of the 17 patients with malignant lymphoma, 4 had Sertoli cell-only syndrome, and 5 had maturation arrest.
  • None of the patients had evidence of secondary wound healing or treatment delay because of the testicular biopsy.
  • CONCLUSIONS: Our results show that testicular sperm extraction is a useful technique for obtaining spermatozoa before cytotoxic therapy in azoospermic cancer patients.
  • This procedure should be considered as an option for fertility preservation in azoospermic cancer patients, because high cumulative cytostatic doses can cause irreversible fertility alterations.
  • [MeSH-major] Antineoplastic Agents / adverse effects. Antineoplastic Agents / therapeutic use. Germinoma / drug therapy. Oligospermia / chemically induced. Spermatozoa / physiology. Testicular Neoplasms / drug therapy. Testis / surgery. Tissue and Organ Harvesting / methods
  • [MeSH-minor] Biopsy, Needle. Cryopreservation / methods. Humans. Lymphoma / pathology. Male. Sertoli Cell Tumor / drug therapy. Sertoli Cell Tumor / pathology. Sperm Count


52. Kalaitzis C, Bantis A, Tsakaldimis G, Giannakopoulos S, Sivridis E, Touloupidis S: Osteolytic bone destruction resulting from relapse of a testicular tumour 23 years after inguinal orchiectomy and adjuvant chemotherapy: a case report. J Med Case Rep; 2009;3:8702
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  • [Title] Osteolytic bone destruction resulting from relapse of a testicular tumour 23 years after inguinal orchiectomy and adjuvant chemotherapy: a case report.
  • INTRODUCTION: Late relapse of a testicular germ cell tumour is an uncommon occurrence.
  • We report a case of osteolytic bone metastasis appearing 23 years after the initial treatment of a metastatic testicular mixed tumour (choriocarcinoma and embryonal carcinoma).
  • This is one of the longest periods of recurrence reported for testicular germ cell tumours.
  • CASE PRESENTATION: A 52-year-old Caucasian man who underwent a right inguinal orchiectomy due to testicular tumour in 1984 presented to our outpatient clinic in a generally bad condition of health and with severe pain of his right hip joint and os ischii caused by osteolytic metastasis.
  • CONCLUSIONS: This case emphasizes the need for a life-long follow-up of patients with primary metastatic testicular cancer.

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  • (PMID = 19830236.001).
  • [ISSN] 1752-1947
  • [Journal-full-title] Journal of medical case reports
  • [ISO-abbreviation] J Med Case Rep
  • [Language] eng
  • [Publication-type] Journal Article
  • [Publication-country] England
  • [Other-IDs] NLM/ PMC2737795
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53. Kempkensteffen C, Hinz S, Jäger T, Weikert S, Krause H, Schostak M, Christoph F, Strenziok R, Miller K, Schrader M: [Expression levels of the IAP antagonists XAF1, Smac/DIABLO and HtrA2 in testicular germ cell tumours]. Aktuelle Urol; 2008 Nov;39(6):436-41
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  • [Title] [Expression levels of the IAP antagonists XAF1, Smac/DIABLO and HtrA2 in testicular germ cell tumours].
  • [Transliterated title] Expression der pro-apoptotischen Apoptoseinhibitor-(IAP)Antagonisten XAF1, Smac/DIABLO und HtrA2 in Keimzelltumoren des Hodens.
  • We examined the mRNA-expression of these pro-apoptotic parameters in testicular germ cell tumors (TGCT) and normal testicular tissue and correlated their expression levels to clinicopathological tumour features.
  • MATERIAL AND METHODS: Real-time RT-PCR was used to quantify the mRNA-expression of XAF1, Smac/DIABLO and HtrA2 in normal testicular tissue (n = 18), carcinoma in situ (n = 4), seminomas (n = 64), and non-seminomatous germ cell tumors (n = 35).
  • RESULTS: Compared to normal testicular tissue, the expression levels of XAF1 were increased in TGCT (p < 0.001), whereas those of Smac/DIABLO and HtrA2 were decreased (p < 0.001 and p < 0.001).
  • Smac/DIABLO expression levels showed a significant trend towards a gradual decrease from normal testicular tissue to CIS and seminomas and finally to NSGCT (p < 0.001).
  • Moreover, XAF1 and HtrA2 expression levels gradually increased with progression of clinical tumour stage in seminoma patients (p = 0.001 and p = 0.018), their expression levels being strongly intercorrelated (Spearman rho correlation coefficient: 0.674; p < 0.001).
  • CONCLUSION: These data suggest that a down-regulation of Smac/DIABLO and HtrA2 is implicated in the development and progression of TGCT, whereas overexpression of XAF1 in TGCT might contribute to their extraordinary sensitivity to chemotherapy.
  • Regarding the additional correlation of XAF1 and HtrA2 expression with clinical tumour stage in seminoma patients, it appears reasonable to further evaluate these three IAP antagonists as molecular parameters for the prediction of treatment response and prognosis of TGCT patients.
  • [MeSH-major] Gene Expression Regulation, Neoplastic / genetics. Inhibitor of Apoptosis Proteins / antagonists & inhibitors. Inhibitor of Apoptosis Proteins / genetics. Intracellular Signaling Peptides and Proteins / genetics. Mitochondrial Proteins / genetics. Neoplasm Proteins / genetics. Neoplasms, Germ Cell and Embryonal / genetics. Serine Endopeptidases / genetics. Testicular Neoplasms / genetics
  • [MeSH-minor] Biopsy. Carcinoma in Situ / genetics. Carcinoma in Situ / pathology. Carcinoma, Embryonal / genetics. Carcinoma, Embryonal / pathology. Disease Progression. Down-Regulation / genetics. Humans. Male. Prognosis. RNA, Messenger / genetics. Reverse Transcriptase Polymerase Chain Reaction. Seminoma / genetics. Seminoma / pathology. Teratocarcinoma / genetics. Teratocarcinoma / pathology. Testis / pathology

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  • (PMID = 18979398.001).
  • [ISSN] 1438-8820
  • [Journal-full-title] Aktuelle Urologie
  • [ISO-abbreviation] Aktuelle Urol
  • [Language] ger
  • [Publication-type] English Abstract; Journal Article
  • [Publication-country] Germany
  • [Chemical-registry-number] 0 / DIABLO protein, human; 0 / Inhibitor of Apoptosis Proteins; 0 / Intracellular Signaling Peptides and Proteins; 0 / Mitochondrial Proteins; 0 / Neoplasm Proteins; 0 / RNA, Messenger; 0 / XAF1 protein, human; EC 3.4.21.- / Omi serine protease; EC 3.4.21.- / Serine Endopeptidases
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54. Kollmannsberger C, Moore C, Chi KN, Murray N, Daneshmand S, Gleave M, Hayes-Lattin B, Nichols CR: Non-risk-adapted surveillance for patients with stage I nonseminomatous testicular germ-cell tumors: diminishing treatment-related morbidity while maintaining efficacy. Ann Oncol; 2010 Jun;21(6):1296-301
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  • [Title] Non-risk-adapted surveillance for patients with stage I nonseminomatous testicular germ-cell tumors: diminishing treatment-related morbidity while maintaining efficacy.
  • BACKGROUND: With treatment leading to nearly uniform cure in clinical stage I nonseminomatous testicular cancer (CSI-NSGCT), diminishing treatment-related morbidity has become the primary concern.
  • This study examined feasibility and outcome of active surveillance as treatment in an unselected CSI patient population.
  • MATERIALS AND METHODS: All patients with CSI-NSGCT referred from 1998 to 2007 to the British Columbia Cancer Agency and the Oregon Testis Cancer Program were retrospectively reviewed.
  • All relapses were in long-term remission following chemotherapy with or without retroperitoneal lymph node dissection (RPLND).
  • No patient has required second-line chemotherapy.
  • CONCLUSIONS: Active surveillance for all CSI-NSGCT patients is associated with excellent outcomes comparable with the best results reported with primary RPLND or adjuvant chemotherapy.
  • Nearly 75% of patients are spared any therapy after orchiectomy.

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  • (PMID = 19875756.001).
  • [ISSN] 1569-8041
  • [Journal-full-title] Annals of oncology : official journal of the European Society for Medical Oncology
  • [ISO-abbreviation] Ann. Oncol.
  • [Language] ENG
  • [Publication-type] Evaluation Studies; Journal Article
  • [Publication-country] England
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55. Michael H, Lucia J, Foster RS, Ulbright TM: The pathology of late recurrence of testicular germ cell tumors. Am J Surg Pathol; 2000 Feb;24(2):257-73
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  • [Title] The pathology of late recurrence of testicular germ cell tumors.
  • A total of 91 men had histologically documented late recurrences of testicular germ cell tumors characterized by a complete response to treatment with a subsequent disease-free interval of at least 2 years and no evidence of a second primary lesion.
  • Ninety percent of the patients for whom information was available received chemotherapy shortly after their initial diagnosis of testicular germ cell tumors; most of the other patients were known to have stage I disease initially.
  • Thus, teratoma was the most common type of neoplasm in late recurrences.
  • Excluding teratoma coexisting with other types of neoplasms, yolk sac tumor was the most frequent type of tumor in patients with late recurrence.
  • It occurred in 47% of patients, either alone or with teratoma, another nonteratomatous germ cell tumor type, or a "nongerm cell malignant tumor."
  • Unusual types of yolk sac tumor, including glandular, parietal, clear cell, and pleomorphic patterns, were seen frequently in late recurrences and often raised differential diagnostic problems with "nongerm cell" carcinomas.
  • A smaller number of late recurrences consisted of other types of neoplasms.
  • Twenty percent of patients with late recurrence had a nonteratomatous germ cell tumor other than yolk sac tumor, either alone, with yolk sac tumor, or with a "nongerm cell malignant tumor."
  • Most of these nonteratomatous germ cell tumors other than yolk sac tumor were embryonal carcinoma, although rarely seminoma and choriocarcinoma were encountered.
  • "Nongerm cell malignant tumors," including both sarcomas and carcinomas of various types, occurred in 23% of late-recurrence patients, either alone or with a nonteratomatous germ cell tumor.
  • Patients whose late recurrences consisted of pure "nongerm cell malignant tumor" or pure germ cell tumor (yolk sac tumor or other types) had a much worse prognosis: Only 36% to 37% were alive with no evidence of disease.
  • Patients with two different types of nonteratomatous malignancies in their late recurrences had a dismal clinical course: Only 17% with both yolk sac tumor and other nonteratomatous germ cell tumor had no evidence of disease, whereas no patient with both nonteratomatous germ cell tumor and "nongerm cell malignant tumor" was disease free.
  • Furthermore, late recurrence is not likely to respond to chemotherapy and is best treated by surgical excision when possible.
  • [MeSH-major] Germinoma / pathology. Neoplasm Recurrence, Local / pathology. Testicular Neoplasms / pathology
  • [MeSH-minor] Adolescent. Adult. Carcinoma, Embryonal / complications. Carcinoma, Embryonal / pathology. Carcinoma, Embryonal / therapy. Choriocarcinoma / complications. Choriocarcinoma / pathology. Choriocarcinoma / therapy. Endodermal Sinus Tumor / complications. Endodermal Sinus Tumor / pathology. Endodermal Sinus Tumor / therapy. Fluorescent Antibody Technique, Direct. Humans. Male. Neoplasm Staging. Neoplasms, Second Primary / pathology. Neoplasms, Second Primary / therapy. Sarcoma / complications. Sarcoma / pathology. Sarcoma / therapy. Seminoma / complications. Seminoma / pathology. Seminoma / therapy. Teratoma / complications. Teratoma / pathology. Teratoma / therapy

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  • (PMID = 10680894.001).
  • [ISSN] 0147-5185
  • [Journal-full-title] The American journal of surgical pathology
  • [ISO-abbreviation] Am. J. Surg. Pathol.
  • [Language] eng
  • [Publication-type] Journal Article
  • [Publication-country] UNITED STATES
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56. Looijenga LH, Gillis AJ, Stoop HJ, Hersmus R, Oosterhuis JW: Chromosomes and expression in human testicular germ-cell tumors: insight into their cell of origin and pathogenesis. Ann N Y Acad Sci; 2007 Dec;1120:187-214
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  • [Title] Chromosomes and expression in human testicular germ-cell tumors: insight into their cell of origin and pathogenesis.
  • Human germ-cell tumors (GCTs) are a heterogeneous group of neoplasms.
  • Within the testis, three types of GCTs can be diagnosed: type I (teratomas and yolk-sac tumors of neonates and infants); type II (seminomas and nonseminomas); type III (spermatocytic seminomas).
  • Here the focus is on the type II GCTs, the most frequent type in the adult testis (so-called TGCTs).
  • They can also be diagnosed in dysgenetic gonads (an incomplete or defective formation of the gonad, caused by a disturbed process of migration of the germ cells and/or their correct organization in their fetal gonadal ridge), the anterior mediastinum, and pineal/suprasellar region.
  • In the testis, they originate from the malignant counterpart of primordial germ cells/gonocytes, referred to as carcinoma in situ (CIS)/intratubular germ-cell neoplasia unclassified (ITGCNU).
  • With the exception of teratomas, most histological elements of TGCTs are sensitive for (cisplatin-based) chemotherapy; CIS/ITGCNU and seminoma cells are also sensitive to DNA damage induced by irradiation.
  • Moreover, the genetic constitution of TGCTs (low incidence of mutations and frequent uniparental disomies) can also be linked to characteristics of ES cells, likely related to their specific inability to repair DNA damage and their high sensitivity to apoptotic cell death.
  • The unusual presence of wild-type P53 in TGCTs is explained by specific expression of a cluster of micro-RNAs (miRNAs), that is, hsa-miR 371-373, also expressed in ES cells, which prevents P53-driven cellular senescence upon oncogenic stress.
  • Many characteristics of human TGCTs reflect the nonmalignant counterparts from which they originate.
  • The conclusion is that TGCTs are embryonic cancers found in adults.
  • [MeSH-major] Chromosomes, Human. Gene Expression Regulation, Neoplastic. Neoplasms, Germ Cell and Embryonal / etiology. Neoplasms, Germ Cell and Embryonal / genetics. Neoplastic Stem Cells / physiology. Testicular Neoplasms / etiology. Testicular Neoplasms / genetics
  • [MeSH-minor] Animals. Disease Progression. Embryonal Carcinoma Stem Cells. Epigenesis, Genetic / physiology. Humans. Male. Models, Biological. Stem Cells / physiology

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  • (PMID = 17911410.001).
  • [ISSN] 0077-8923
  • [Journal-full-title] Annals of the New York Academy of Sciences
  • [ISO-abbreviation] Ann. N. Y. Acad. Sci.
  • [Language] eng
  • [Publication-type] Journal Article; Research Support, Non-U.S. Gov't; Review
  • [Publication-country] United States
  • [Number-of-references] 206
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57. Mannuel HD, Hussain A: Update on testicular germ cell tumors. Curr Opin Oncol; 2010 May;22(3):236-41
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  • [Title] Update on testicular germ cell tumors.
  • PURPOSE OF REVIEW: To discuss several important developments in testicular germ cell tumors in the past year.
  • RECENT FINDINGS: Genomic studies are examining gene expression as possible markers for disease relapse and chemotherapy resistance.
  • Optimal treatment strategies for early-stage nonseminomatous tumors continue to evolve and patient compliance with posttreatment surveillance schedules remains problematic.
  • Advanced and platinum-refractory disease states continue to be challenging entities in terms of optimizing therapy and outcome.
  • SUMMARY: Significant challenges remain for treatment of certain categories of testicular germ cell tumors.
  • Treatment and surveillance paradigms continue to be defined and refined as research in these areas continues.
  • [MeSH-major] Neoplasms, Germ Cell and Embryonal / pathology. Testicular Neoplasms / pathology
  • [MeSH-minor] Combined Modality Therapy. Gene Expression. Gene Expression Profiling. Humans. Male. Prognosis

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  • (PMID = 20401976.001).
  • [ISSN] 1531-703X
  • [Journal-full-title] Current opinion in oncology
  • [ISO-abbreviation] Curr Opin Oncol
  • [Language] eng
  • [Publication-type] Journal Article; Review
  • [Publication-country] United States
  • [Number-of-references] 22
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58. Wilson C, Yang J, Strefford JC, Summersgill B, Young BD, Shipley J, Oliver T, Lu YJ: Overexpression of genes on 16q associated with cisplatin resistance of testicular germ cell tumor cell lines. Genes Chromosomes Cancer; 2005 Jun;43(2):211-6
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  • [Title] Overexpression of genes on 16q associated with cisplatin resistance of testicular germ cell tumor cell lines.
  • Testicular germ-cell tumors (TGCTs) show exquisite sensitivity to cisplatin-based chemotherapy, and therefore this is considered a good model system for studying the mechanism of chemotherapy resistance.
  • Although the genetic alterations related to TGCT have been well studied, little is known about the genetic basis of chemotherapy resistance, which occurs in a small proportion of TGCTs.
  • Comparative genomic hybridization (CGH) analysis on chromosomes revealed genetic differences between the resistant and parent cell lines in each pair, but did not show any consistent chromosome changes in all three lines.
  • Microarray CGH analysis generated some additional information of DNA copy number gains and losses including some important oncogenes, tumor-suppressor genes, and drug-resistance-related genes.
  • However, no consistent genomic region changes were found in the three cell lines.
  • Further definition of genes in this chromosomal region will aid our understanding of the mechanism of cisplatin resistance and may offer novel therapeutic targets.
  • [MeSH-major] Antineoplastic Agents / pharmacology. Chromosomes, Human, Pair 16. Cisplatin / pharmacology. Germinoma / genetics. Testicular Neoplasms / genetics
  • [MeSH-minor] Cell Line, Tumor. Humans. Male

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  • [Copyright] Copyright 2005 Wiley-Liss, Inc.
  • (PMID = 15761863.001).
  • [ISSN] 1045-2257
  • [Journal-full-title] Genes, chromosomes & cancer
  • [ISO-abbreviation] Genes Chromosomes Cancer
  • [Language] eng
  • [Publication-type] Journal Article; Research Support, Non-U.S. Gov't
  • [Publication-country] United States
  • [Chemical-registry-number] 0 / Antineoplastic Agents; Q20Q21Q62J / Cisplatin
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59. Tan A, Gilligan T: Controversies in the management of early-stage germ cell tumors. Curr Oncol Rep; 2009 May;11(3):235-43
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  • [Title] Controversies in the management of early-stage germ cell tumors.
  • The optimal management of clinical stage I testicular germ cell tumors remains controversial despite a cure rate of 99%.
  • Alternatives for stage I nonseminomas include close surveillance, retroperitoneal lymph node dissection, and chemotherapy.
  • For pure seminomas, the options are surveillance, chemotherapy, and radiation.
  • [MeSH-major] Neoplasms, Germ Cell and Embryonal / drug therapy. Testicular Neoplasms / drug therapy. Testicular Neoplasms / radiotherapy
  • [MeSH-minor] Antineoplastic Agents / therapeutic use. Carboplatin / therapeutic use. Humans. Male. Neoplasm Recurrence, Local. Neoplasm Staging. Risk Factors. Seminoma / drug therapy. Seminoma / prevention & control. Seminoma / radiotherapy

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  • (PMID = 19336016.001).
  • [ISSN] 1534-6269
  • [Journal-full-title] Current oncology reports
  • [ISO-abbreviation] Curr Oncol Rep
  • [Language] eng
  • [Publication-type] Journal Article; Review
  • [Publication-country] United States
  • [Chemical-registry-number] 0 / Antineoplastic Agents; BG3F62OND5 / Carboplatin
  • [Number-of-references] 49
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60. Hussain SA, Ma YT, Palmer DH, Hutton P, Cullen MH: Biology of testicular germ cell tumors. Expert Rev Anticancer Ther; 2008 Oct;8(10):1659-73
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  • [Source] The source of this record is MEDLINE®, a database of the U.S. National Library of Medicine.
  • [Title] Biology of testicular germ cell tumors.
  • Germ cell tumors are derived from cells of the germ cell lineage and are the most common solid malignancies to affect young Caucasian men between the ages of 15 and 40 years.
  • All testicular germ cell tumors develop from the same precursor lesion, intratubular germ cell neoplasia unclassified, which in turn is thought to arise from malignant transformation of a primordial germ cell or gonocyte.
  • These tumors are characterized by extreme chemosensitivity and are considered a model for curative disease.
  • In spite of this, a small subset of patients with metastatic disease fail to achieve a complete response with cisplatin-based chemotherapy or relapse from complete remission.
  • Understanding the molecular biology may help the design of new therapies for those patients with a poor prognosis and could also improve the treatment of cancer in general.
  • Current understanding of the role of genetic and epigenetic factors in the etiology of germ cell tumors and the biochemical mechanisms underlying chemotherapy sensitivity and resistance is discussed in detail in this review.
  • [MeSH-major] Neoplasms, Germ Cell and Embryonal / pathology. Testicular Neoplasms / pathology
  • [MeSH-minor] Adolescent. Adult. Apoptosis. Cell Lineage. DNA Damage. Drug Resistance, Neoplasm. Epigenesis, Genetic. Gene Expression Profiling. Humans. Male. Neoplasm Invasiveness

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  • (PMID = 18925857.001).
  • [ISSN] 1744-8328
  • [Journal-full-title] Expert review of anticancer therapy
  • [ISO-abbreviation] Expert Rev Anticancer Ther
  • [Language] eng
  • [Publication-type] Journal Article; Review
  • [Publication-country] England
  • [Number-of-references] 180
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61. Boeck S, Metzeler KH, Hausmann A, Baumann A, Gallmeier E, Parhofer KG, Stemmler HJ: Cisplatin-based chemotherapy for pulmonary metastasized germ cell tumors of the testis--be aware of acute respiratory distress syndrome. Onkologie; 2009 Mar;32(3):125-8
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  • [Title] Cisplatin-based chemotherapy for pulmonary metastasized germ cell tumors of the testis--be aware of acute respiratory distress syndrome.
  • BACKGROUND: Cisplatin-based combination chemotherapy is regarded as standard of care for patients with advanced germ cell tumors.
  • In patients with lung metastases and a high tumor load, an association between induction chemotherapy and the development of a 'tumorassociated' acute respiratory distress syndrome (ARDS) has been hypothesized.
  • CASE REPORT: We report the clinical course of a 19-year-old patient who rapidly developed fatal ARDS during the first cycle of chemotherapy using the PEI regimen (cisplatin, etoposide and ifosfamide) for a metastasized (lung, liver, lymph nodes) germ cell tumor of the testis.
  • CONCLUSION: Further clinical research in order to better define risk factors for developing ARDS in this patient population as well as novel strategies for the prevention and treatment of ARDS in those patients are necessary.
  • [MeSH-major] Cisplatin / administration & dosage. Cisplatin / adverse effects. Giant Cell Tumors / drug therapy. Giant Cell Tumors / secondary. Lung Neoplasms / secondary. Respiratory Distress Syndrome, Adult / chemically induced. Testicular Neoplasms / drug therapy. Testicular Neoplasms / secondary
  • [MeSH-minor] Antineoplastic Agents / administration & dosage. Antineoplastic Agents / adverse effects. Humans. Male. Treatment Outcome. Young Adult


62. Kopp HG, Kuczyk M, Classen J, Stenzl A, Kanz L, Mayer F, Bamberg M, Hartmann JT: Advances in the treatment of testicular cancer. Drugs; 2006;66(5):641-59
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  • [Title] Advances in the treatment of testicular cancer.
  • Testicular cancer is the most common solid tumour in young men, and the treatment of testicular germ cell tumours (TGCT) has been called a success story of medical oncology, germ cell cancer being regarded as the "model of a curable neoplasm".
  • Even with metastatic disease, high cure rates can be achieved: the overall 5-year survival for all stages of TGCT is approximately 80%.
  • Today, elaborate systems for prognostic evaluation for gonadal and extragonadal germ cell tumours facilitate the choice of the most appropriate therapy for individual patients.
  • In doing so, the ultimate goal of treatment is tumour-free survival for any patient with TGCT.
  • This goal has already been reached for >99% of the patients with early-stage tumours, as well as for the majority of patients with advanced disease (56% of patients with metastases are considered to have a good prognosis at the time of diagnosis; the 5-year survival rate for this group is 90%).
  • However, patients with 'intermediate' or 'poor' prognosis at the time of diagnosis, as well as patients with relapsed disease after cisplatin-containing therapy, still have an unsatisfactorily low 5-year survival rate after standard therapy with PEB (cisplatin, etoposide, bleomycin) of only 80%, 45-55% and 20-25%, respectively.Therefore, our goals must be (i) to limit acute and chronic toxicity by avoiding overtreatment for patients with localised disease and/or good prognosis with advanced disease; and (ii) to identify patients with poor prognosis and treat them in specialised centres, where not only is optimal interdisciplinary care available but new treatment strategies are being applied.
  • For example, tandem high-dose chemotherapy regimens might be effective in achieving higher cure rates in these patients.
  • [MeSH-major] Antineoplastic Combined Chemotherapy Protocols / therapeutic use. Seminoma / drug therapy. Testicular Neoplasms / drug therapy
  • [MeSH-minor] Brain Neoplasms / drug therapy. Brain Neoplasms / radiotherapy. Brain Neoplasms / secondary. Combined Modality Therapy. Humans. Liver Neoplasms / drug therapy. Liver Neoplasms / secondary. Liver Neoplasms / surgery. Male. Neoplasm Staging. Orchiectomy. Prognosis. Salvage Therapy

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  • (PMID = 16620142.001).
  • [ISSN] 0012-6667
  • [Journal-full-title] Drugs
  • [ISO-abbreviation] Drugs
  • [Language] eng
  • [Publication-type] Journal Article; Review
  • [Publication-country] New Zealand
  • [Number-of-references] 172
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63. Noel EE, Perry J, Chaplin T, Mao X, Cazier JB, Joel SP, Oliver RT, Young BD, Lu YJ: Identification of genomic changes associated with cisplatin resistance in testicular germ cell tumor cell lines. Genes Chromosomes Cancer; 2008 Jul;47(7):604-13
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  • [Title] Identification of genomic changes associated with cisplatin resistance in testicular germ cell tumor cell lines.
  • Since the introduction of cisplatin into the clinic, the treatment of patients with a variety of solid tumors including testicular germ cell tumors, ovarian and lung cancers, has dramatically improved.
  • One of the main causes for therapeutic failure in these malignancies is the development of drug resistance.
  • Testicular germ cell tumors (TGCTs), the most common malignancy in young men, exhibit extreme sensitivity to cisplatin-based chemotherapy, making them an ideal model for investigating the mechanisms of cisplatin chemo-sensitivity and resistance.
  • TGCT development and pathogenesis have been well studied but little is known about the genetic background in chemo-resistant cases.
  • We investigated genomic differences between three TGCT parental cell lines and their cisplatin resistant derivatives.
  • Using 10K single nucleotide polymorphism (SNP) microarray analysis, we identified two small chromosomal regions with consistent copy number changes across all three pairs of resistant cell lines.
  • The significance of these regions should be further investigated as they may contain key genes involved in the development of chemo- resistance to cisplatin-based treatment in TGCTs and other cancers.
  • [MeSH-major] Antineoplastic Agents / therapeutic use. Chromosome Aberrations. Cisplatin / therapeutic use. Drug Resistance, Neoplasm / genetics. Testicular Neoplasms / drug therapy. Testicular Neoplasms / genetics
  • [MeSH-minor] Gene Dosage. Humans. In Situ Hybridization, Fluorescence. Male. Microarray Analysis. Polymorphism, Single Nucleotide. Tumor Cells, Cultured

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  • [Copyright] (c) 2008 Wiley-Liss, Inc.
  • (PMID = 18384131.001).
  • [ISSN] 1098-2264
  • [Journal-full-title] Genes, chromosomes & cancer
  • [ISO-abbreviation] Genes Chromosomes Cancer
  • [Language] eng
  • [Grant] United Kingdom / Cancer Research UK / / A6438; United Kingdom / Cancer Research UK / / A6789
  • [Publication-type] Journal Article; Research Support, Non-U.S. Gov't
  • [Publication-country] United States
  • [Chemical-registry-number] 0 / Antineoplastic Agents; Q20Q21Q62J / Cisplatin
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64. Barlow LJ, Badalato GM, McKiernan JM: Serum tumor markers in the evaluation of male germ cell tumors. Nat Rev Urol; 2010 Nov;7(11):610-7
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  • [Title] Serum tumor markers in the evaluation of male germ cell tumors.
  • Serum tumor markers play a critical role in the diagnosis, staging, risk stratification, and surveillance of patients with testicular germ cell tumors (GCTs).
  • Production of the oncofetal substances α fetoprotein and human chorionic gonadotropin can aid the diagnosis of testicular GCTs, and specific patterns of marker elevation can be used to determine the type of tumor, particularly as it pertains to nonseminoma.
  • These markers, in addition to lactate dehydrogenase, have been incorporated in the standard TNM staging system for testicular tumors; the S stage category corresponds to serum elevation of these proteins.
  • Furthermore, the degree of serum tumor marker elevation has been incorporated into standardized patient risk groupings, which are used to guide therapeutic management.
  • The rate of tumor marker decay after radical orchiectomy is an important index to monitor, as a slow decline might be indicative of metastatic disease and should prompt a thorough systemic survey.
  • The rate of tumor marker decline is already being utilized in the setting of metastatic GCTs to determine response to chemotherapy, and has been used in some scenarios to individualize the type of chemotherapy patients received.
  • Compared to any other solid organ malignancy, the role of serum tumor markers in GCT is unprecedented; these markers are instrumental in the diagnosis and management of testicular GCT.
  • [MeSH-major] Biomarkers, Tumor / blood. Neoplasms, Germ Cell and Embryonal / blood. Neoplasms, Germ Cell and Embryonal / diagnosis. Testicular Neoplasms / blood. Testicular Neoplasms / diagnosis
  • [MeSH-minor] Diagnosis, Differential. Humans. Male

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  • (PMID = 21068762.001).
  • [ISSN] 1759-4820
  • [Journal-full-title] Nature reviews. Urology
  • [ISO-abbreviation] Nat Rev Urol
  • [Language] eng
  • [Publication-type] Journal Article; Review
  • [Publication-country] England
  • [Chemical-registry-number] 0 / Biomarkers, Tumor
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65. Lifschitz-Mercer B, Elliott DJ, Leider-Trejo L, Schreiber-Bramante L, Hassner A, Eisenthal A, Maymon BB: Absence of RBM expression as a marker of intratubular (in situ) germ cell neoplasia of the testis. Hum Pathol; 2000 Sep;31(9):1116-20
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  • [Title] Absence of RBM expression as a marker of intratubular (in situ) germ cell neoplasia of the testis.
  • RBM (RNA-binding motif) protein is a marker of male germ cells.
  • This protein is encoded by the Azoospermia factor region-b (AZF-b) of the human Y chromosome and is expressed exclusively in the male germ cell line, that is, spermatogonia, spermatocytes, and round spermatids.
  • The authors analyzed the expression of the RBM gene in germ cell tumors and in the seminiferous tubules in the vicinity of these tumors to identify the presence of IGCN.
  • Sections from testicular germ cell tumors of 21 patients were stained with anti-RBM antibody by using an immunohistochemical method.
  • Distal tubules showing spermatogenesis were immunopositive for RBM protein.
  • All of the germ cell tumors studied were completely immunonegative for RBM.
  • Tubules with spermatocyte-like cells, which were expected to express RBM, did not express this protein.
  • This result enabled the identification of tubules as being IGCN.
  • RBM is a novel marker consistently expressed in normal male germ cells but not in malignant germ cell tumors or IGCN.
  • Thus, the absence of RBM expression in germ cells provides a new diagnostic tool of preinvasive malignancy of the testis.
  • [MeSH-major] RNA-Binding Proteins / metabolism. Seminoma / metabolism. Testicular Neoplasms / metabolism
  • [MeSH-minor] Adult. Biomarkers, Tumor / metabolism. Fluorescent Antibody Technique, Indirect. Humans. Male. Middle Aged. Seminiferous Tubules / metabolism. Seminiferous Tubules / pathology

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  • (PMID = 11014580.001).
  • [ISSN] 0046-8177
  • [Journal-full-title] Human pathology
  • [ISO-abbreviation] Hum. Pathol.
  • [Language] eng
  • [Publication-type] Journal Article
  • [Publication-country] UNITED STATES
  • [Chemical-registry-number] 0 / Biomarkers, Tumor; 0 / RNA-Binding Proteins
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66. Spermon JR, De Geus-Oei LF, Kiemeney LA, Witjes JA, Oyen WJ: The role of (18)fluoro-2-deoxyglucose positron emission tomography in initial staging and re-staging after chemotherapy for testicular germ cell tumours. BJU Int; 2002 Apr;89(6):549-56
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  • [Title] The role of (18)fluoro-2-deoxyglucose positron emission tomography in initial staging and re-staging after chemotherapy for testicular germ cell tumours.
  • OBJECTIVE: To investigate the role of 18fluoro-2-deoxyglucose positron emission tomography (FDG-PET) in the initial staging of clinical stage I and II nonseminomatous germ cell tumours (NSGCTs) and in re-staging (non)seminomatous GCTs after chemotherapy.
  • Stage I patients underwent a retroperitoneal lymph node dissection because of vascular invasion in the primary tumour.
  • Thirty-eight scans were taken after completing chemotherapy (28 NSGCTs and 10 seminomatous GCTs), and validated by histology or clinical follow-up.
  • RESULTS: In stage I NSGCT, FDG-PET staging was equivalent to computed tomography (CT) staging.
  • In stage II NSGCT, FDG-PET missed two lesions (mature teratoma and retroperitoneal mass with a small component of embryonal cell carcinoma) whereas CT correctly classified all.
  • In 20 of 28 patients with NSGCT, histology was obtained after chemotherapy.
  • In four of five patients with necrosis after chemotherapy the PET result was correctly negative.
  • Interestingly, of the 12 patients with a correct negative PET result, 11 had no mature teratoma in their primary tumour.
  • Moreover, it could be useful to predict fibrotic residual mass in NSGCT in those patients with no teratoma component in their primary tumour.
  • [MeSH-major] Fluorodeoxyglucose F18. Germinoma / radionuclide imaging. Neoplasm Staging / methods. Radiopharmaceuticals. Testicular Neoplasms / radionuclide imaging
  • [MeSH-minor] Adolescent. Adult. Follow-Up Studies. Humans. Lymphatic Metastasis. Male. Middle Aged. Tomography, Emission-Computed / methods

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  • (PMID = 11942962.001).
  • [ISSN] 1464-4096
  • [Journal-full-title] BJU international
  • [ISO-abbreviation] BJU Int.
  • [Language] eng
  • [Publication-type] Journal Article
  • [Publication-country] England
  • [Chemical-registry-number] 0 / Radiopharmaceuticals; 0Z5B2CJX4D / Fluorodeoxyglucose F18
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67. Ray-Coquard I, Pautier P, Pujade-Lauraine E, Méeus P, Morice P, Treilleux I, Duvillard P, Alexandre J, Lhommé C, Selle F, Guastalla J: [Rare ovarian tumours: therapeutic strategies in 2010, national website observatory for rare ovarian cancers and delineation of referent centers in France]. Bull Cancer; 2010 Jan;97(1):123-35
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  • [Title] [Rare ovarian tumours: therapeutic strategies in 2010, national website observatory for rare ovarian cancers and delineation of referent centers in France].
  • [Transliterated title] Les tumeurs rares de l'ovaire: stratégies thérapeutiques en 2010, Observatoire francophone des tumeurs rares de l'ovaire et émergence des centres de références.
  • Majorities of the rare ovarian cancers were represented by germ cell tumours and sex cords ovarian tumours with borderline tumours, clear cell carcinoma and mucinous carcinoma and are extremely rare malignant diseases of the ovaries.
  • Tumors of the stromal (Leydig cells) and/or sex cords (Sertoli cells) represent approximately 7% of ovarian cancers and develop from the conjunctive tissue (respectively, interstitial and nurse cells) of the ovaries.
  • All together, they represented less than 5% of the adult malignant and non malignant ovarian tumours.
  • Treatment of rare ovarian tumors is currently as follows.
  • Surgery is the same as that for ovarian adenocarcinoma, with one major difference: conservation of reproductive function in women of reproductive age is usual case for this type of tumor.
  • Chemotherapy for germ cell and sex cords tumors, based on data reported in the literature is the same as that prescribed for testicular germ-cell tumors.
  • For rare epithelial carcinoma, carboplatin plus paclitaxel remains the standard attitude with a well-known less efficiency than for other epithelial subtypes.
  • Surgery, chemotherapy and possible surgical intervention for residual lesions are highly complex.
  • Too rare to be included in randomized studies, treatment of these tumors has benefited from the therapeutic advancements made against testicular germ-cell tumors or with publications using retrospective data.
  • Because of the rarity of these tumours a specialized website (www.ovaire-rare.org) was developed in France in 2002.
  • The website provides very interesting data for a better knowledge of these rare tumors and will possibly help improve medical practice.
  • Since 2008, referent centers were delineated to promote optimal management of these tumors, organization of clinical and molecular research at a national or international level and to elaborate guidelines.
  • The other new scientific data concern surgical procedures for sex cords tumors, evidence for presence of FOXL2 mutation in adult granulosa cell tumors, the use of paclitaxel plus carboplatin for sex cords tumors.
  • [MeSH-major] Cancer Care Facilities / organization & administration. Ovarian Neoplasms / therapy
  • [MeSH-minor] Adenocarcinoma, Clear Cell / pathology. Adenocarcinoma, Clear Cell / therapy. Adenocarcinoma, Mucinous / pathology. Adenocarcinoma, Mucinous / therapy. Adult. Antineoplastic Agents / therapeutic use. Female. France. Humans. Neoplasms, Germ Cell and Embryonal / pathology. Neoplasms, Germ Cell and Embryonal / therapy. Rare Diseases / pathology. Rare Diseases / therapy. Sarcoma / pathology. Sarcoma / therapy. Sex Cord-Gonadal Stromal Tumors / pathology. Sex Cord-Gonadal Stromal Tumors / therapy

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  • (PMID = 20007069.001).
  • [ISSN] 1769-6917
  • [Journal-full-title] Bulletin du cancer
  • [ISO-abbreviation] Bull Cancer
  • [Language] fre
  • [Publication-type] English Abstract; Journal Article
  • [Publication-country] France
  • [Chemical-registry-number] 0 / Antineoplastic Agents
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68. Gilbert DC, Van As NJ, Huddart RA: Reducing treatment toxicities in the management of good prognosis testicular germ cell tumors. Expert Rev Anticancer Ther; 2009 Feb;9(2):223-33
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  • [Title] Reducing treatment toxicities in the management of good prognosis testicular germ cell tumors.
  • Testicular germ cell tumors are the most frequent solid tumor to affect young adult males and are increasing in incidence for reasons that are poorly understood.
  • However, toxicities from treatment are increasingly recognized, with patients experiencing increased rates of second malignancies, cardiovascular disease and a range of circulatory, neurological and endocrine sequelae.
  • High cure rates in a young population make reducing this long-term treatment-related morbidity and mortality imperative.
  • In stage I disease, options following orchidectomy range from surveillance to adjuvant therapy, in the form of carboplatin or para-aortic radiotherapy for seminoma, and combination chemotherapy for nonseminoma.
  • Metastatic disease requires combination chemotherapy with the exception of low-volume para-aortic nodal disease in seminoma, where radiotherapy with or without carboplatin may be curative.
  • These various treatment options are discussed with a focus on reducing long-term treatment-related toxicities while preserving the high rates of long-term disease control.
  • [MeSH-major] Germinoma / therapy. Testicular Neoplasms / therapy
  • [MeSH-minor] Antineoplastic Agents / adverse effects. Antineoplastic Agents / therapeutic use. Clinical Trials as Topic. Combined Modality Therapy. Humans. Male. Neoplasm Metastasis. Neoplasm Staging. Orchiectomy. Prognosis. Seminoma / therapy. Survival Rate. Young Adult

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  • (PMID = 19192960.001).
  • [ISSN] 1744-8328
  • [Journal-full-title] Expert review of anticancer therapy
  • [ISO-abbreviation] Expert Rev Anticancer Ther
  • [Language] eng
  • [Publication-type] Journal Article; Review
  • [Publication-country] England
  • [Chemical-registry-number] 0 / Antineoplastic Agents
  • [Number-of-references] 75
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69. Heim KC, White KA, Deng D, Tomlinson CR, Moore JH, Freemantle SJ, Spinella MJ: Selective repression of retinoic acid target genes by RIP140 during induced tumor cell differentiation of pluripotent human embryonal carcinoma cells. Mol Cancer; 2007 Sep 19;6:57
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  • [Title] Selective repression of retinoic acid target genes by RIP140 during induced tumor cell differentiation of pluripotent human embryonal carcinoma cells.
  • Cell-and context-specific activities of nuclear receptors may be in part due to distinct coregulator complexes recruited to distinct subsets of target genes.
  • We had previously shown that RIP140 limits RA induced tumor cell differentiation of embryonal carcinoma; the pluriopotent stem cells of testicular germ cell tumors.
  • This implies that RIP140 represses key genes required for RA-mediated tumor cell differentiation.
  • RESULTS: To begin to address this issue, microarray technology was employed to elucidate in a de novo fashion the global role of RIP140 in RA target gene regulation of embryonal carcinoma.
  • In general, RIP140-dependent gene expression was consistent with RIP140 functioning to limit RA signaling and tumor cell differentiation.
  • CONCLUSION: Together the data demonstrates that RIP140 has profound effects on RA-mediated gene expression in this cancer stem cell model.
  • The RIP140-dependent RA target genes identified here may be particularly important in mediating RA-induced tumor cell differentiation and the findings suggest that RIP140 may be an attractive target to sensitize tumor cells to retinoid-based differentiation therapy.

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  • (PMID = 17880687.001).
  • [ISSN] 1476-4598
  • [Journal-full-title] Molecular cancer
  • [ISO-abbreviation] Mol. Cancer
  • [Language] ENG
  • [Grant] United States / NCI NIH HHS / CA / R01 CA104312; United States / NCI NIH HHS / CA / R01-CA104312
  • [Publication-type] Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, Non-P.H.S.
  • [Publication-country] England
  • [Chemical-registry-number] 0 / Adaptor Proteins, Signal Transducing; 0 / Neoplasm Proteins; 0 / Nuclear Proteins; 0 / RNA, Small Interfering; 0 / Receptors, Retinoic Acid; 0 / nuclear receptor interacting protein 1; 0 / retinoic acid receptor beta; 5688UTC01R / Tretinoin
  • [Other-IDs] NLM/ PMC2034384
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70. Detti B, Elliott PA, McLaren DB, Howard GC: Late Relapse and Follow-up Protocols in Testicular Germ Cell Tumours: The Edinburgh Cancer Centre Experience and Review of the Literature. Clin Med Oncol; 2008;2:19-25
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  • [Title] Late Relapse and Follow-up Protocols in Testicular Germ Cell Tumours: The Edinburgh Cancer Centre Experience and Review of the Literature.
  • AIMS: To identify clinicopathological features and outcomes in patients with late relapse (LR) of testicular germ cell tumours (GCTs) in order to guide follow-up policy.
  • MATERIALS AND METHODS: The Edinburgh Cancer Centre (ECC) database identified all patients diagnosed with testicular GCT between 1988 and 2002.
  • Of 703 patients, six relapsed more than 24 months after their initial treatment.
  • A retrospective casenote review was performed to extract clinical, pathological, treatment and outcome data.
  • All patients presented initially with stage I disease and five were classified as good risk (International Germ Cell Consensus Classification, IGCCC).
  • Median time to LR was 31 months.
  • Markers at the time of relapse were normal in all patients.
  • Three patients were treated with chemotherapy alone, two patients underwent surgical resection and one patient received combined treatment.
  • All patients obtained a complete response and all remain disease free with a median follow-up of 52 months.
  • Chemo-naive patients with LR were successfully salvaged with chemotherapy alone and patients previously exposed to cisplatin-based chemotherapy were salvaged with complete surgical excision.
  • The optimal length of follow-up in patients with testicular germ cell tumours is not known and practice varies widely.

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  • (PMID = 21892262.001).
  • [ISSN] 1177-9314
  • [Journal-full-title] Clinical medicine. Oncology
  • [ISO-abbreviation] Clin Med Oncol
  • [Language] eng
  • [Publication-type] Journal Article
  • [Publication-country] New Zealand
  • [Other-IDs] NLM/ PMC3161629
  • [Keywords] NOTNLM ; follow-up / germ cell tumors / late relapse
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71. di Pietro A, Vries EG, Gietema JA, Spierings DC, de Jong S: Testicular germ cell tumours: the paradigm of chemo-sensitive solid tumours. Int J Biochem Cell Biol; 2005 Dec;37(12):2437-56
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  • [Title] Testicular germ cell tumours: the paradigm of chemo-sensitive solid tumours.
  • Testicular germ cell tumours (TGCTs) are the most frequent solid malignant tumour in men 20-40 years of age and the most frequent cause of death from solid tumours in this age group.
  • The majority of metastatic testicular cancer patients, in contrast to most other metastatic solid tumours, can be cured with highly effective cisplatin-based chemotherapy.
  • From a genetic point of view, almost all TGCTs in contrast to solid tumours are characterised by the presence of wild type p53.
  • Expression levels of other proteins involved in the regulation of cell cycle progression indicate a deregulated G1-S phase checkpoint in TGCTs.
  • After cisplatin-induced DNA damage, the increasing levels of p53 lead to the trans-activation of a number of genes but not of p21(Waf1/Cip1), preferentially directing TGCT cells into apoptosis or programmed cell death, both via the mitochondrial and the death receptor apoptosis pathways.
  • The sensitivity of TGCTs to chemotherapeutic drugs may lay in the susceptibility of germ cells to apoptosis.
  • Taken together, this provides TGCT as a tumour type model to investigate and understand the molecular determinants of chemotherapy sensitivity of solid tumours.
  • This review aims to summarise the current knowledge on the biological basis of cisplatin-induced apoptosis and response to chemotherapy in TGCTs.
  • [MeSH-major] Cisplatin / therapeutic use. Germinoma / drug therapy. Testicular Neoplasms / drug therapy
  • [MeSH-minor] Adult. Animals. Apoptosis. Carcinoma in Situ / physiopathology. Cell Cycle / physiology. Cell Line, Tumor. DNA-Binding Proteins / physiology. Genes, Neoplasm. Genes, Tumor Suppressor / physiology. Humans. Male. Membrane Proteins / physiology. Mice. Nuclear Proteins / physiology. Testis / cytology. Tumor Suppressor Protein p53 / genetics. Tumor Suppressor Protein p53 / metabolism. Tumor Suppressor Proteins

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  • (PMID = 16099193.001).
  • [ISSN] 1357-2725
  • [Journal-full-title] The international journal of biochemistry & cell biology
  • [ISO-abbreviation] Int. J. Biochem. Cell Biol.
  • [Language] eng
  • [Publication-type] Journal Article; Research Support, Non-U.S. Gov't; Review
  • [Publication-country] England
  • [Chemical-registry-number] 0 / CKAP4 protein, human; 0 / DNA-Binding Proteins; 0 / Membrane Proteins; 0 / Nuclear Proteins; 0 / Tumor Suppressor Protein p53; 0 / Tumor Suppressor Proteins; 0 / tumor suppressor protein p73; Q20Q21Q62J / Cisplatin
  • [Number-of-references] 202
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72. Masters JR, Köberle B: Curing metastatic cancer: lessons from testicular germ-cell tumours. Nat Rev Cancer; 2003 Jul;3(7):517-25
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  • [Title] Curing metastatic cancer: lessons from testicular germ-cell tumours.
  • More than 80% of patients with metastatic testicular germ-cell tumours (TGCTs), however, can be cured using cisplatin-based combination chemotherapy.
  • Why are TGCTs more sensitive to chemotherapeutics than most other tumour types?
  • Answers to this question could lead to new treatments for metastatic cancers.
  • [MeSH-major] Neoplasm Metastasis / physiopathology. Neoplasm Metastasis / therapy. Neoplasms, Germ Cell and Embryonal / drug therapy. Testicular Neoplasms / drug therapy
  • [MeSH-minor] Antineoplastic Agents / therapeutic use. Cisplatin / therapeutic use. Humans. Male


73. Nonomura N, Nagahara A, Oka D, Mukai M, Nakai Y, Nakayama M, Nishimura K, Kakimoto K, Nakamura T, Usami M, Okuyama A, Miki T: Brain metastases from testicular germ cell tumors: a retrospective analysis. Int J Urol; 2009 Nov;16(11):887-93
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  • [Title] Brain metastases from testicular germ cell tumors: a retrospective analysis.
  • OBJECTIVES: To review our series of testicular germ cell tumors with brain metastases and to establish an optimal treatment strategy for them.
  • METHODS: Twenty-seven cases of testicular germ cell tumors from three institutions were retrospectively reviewed.
  • RESULTS: Twenty-six were non-seminomatous tumors and only one was a seminoma.
  • Based on the International Germ Cell Consensus Classification, two cases were classified as good prognosis, seven as intermediate prognosis and 18 as poor prognosis.
  • Chemotherapy was carried out in all patients.
  • Three patients received chemotherapy only.
  • The prognosis of those with brain metastases at the time of diagnosis tended to be better than those developing brain metastases during treatment.
  • Those with a single brain metastasis showed significantly better survival than those with multiple brain metastases.
  • CONCLUSION: Testicular germ cell tumors with brain metastases can be managed with the combination of whole-brain radiotherapy, stereotactic radiotherapy, and/or surgical resection in combination with chemotherapy.
  • [MeSH-major] Brain Neoplasms / secondary. Neoplasms, Germ Cell and Embryonal / secondary. Testicular Neoplasms / pathology
  • [MeSH-minor] Adult. Humans. Male. Retrospective Studies. Young Adult

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  • (PMID = 19863625.001).
  • [ISSN] 1442-2042
  • [Journal-full-title] International journal of urology : official journal of the Japanese Urological Association
  • [ISO-abbreviation] Int. J. Urol.
  • [Language] eng
  • [Publication-type] Journal Article
  • [Publication-country] Australia
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74. Amato RJ, Ro JY, Ayala AG, Swanson DA: Risk-adapted treatment for patients with clinical stage I nonseminomatous germ cell tumor of the testis. Urology; 2004 Jan;63(1):144-8; discussion 148-9
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  • [Title] Risk-adapted treatment for patients with clinical stage I nonseminomatous germ cell tumor of the testis.
  • OBJECTIVES: To evaluate whether two courses of chemotherapy after orchiectomy in patients with clinical Stage I nonseminomatous germ cell testicular tumor at high risk of relapse will spare patients additional chemotherapy or surgery.
  • METHODS: High-risk patients had one or more of the following: preorchiectomy alpha-fetoprotein level of 80 ng/dL or greater, 80% embryonal cell carcinoma or greater, or vessel invasion in the primary tumor.
  • High-risk patients were offered two 21-day courses of outpatient chemotherapy consisting of carboplatin, etoposide, and bleomycin.
  • Low-risk patients and high-risk patients not receiving chemotherapy were observed.
  • All but eight of the high-risk patients received chemotherapy.
  • No patient who underwent chemotherapy developed relapse, although 1 patient with normal biomarkers and a late-appearing mass underwent retroperitoneal lymphadenectomy for mature teratoma.
  • Two of the 23 low-risk patients had disease relapse; both successfully underwent chemotherapy.
  • The nonhematologic toxicity was mild in patients receiving chemotherapy, and no patient required hospitalization.
  • CONCLUSIONS: Two courses of postorchiectomy adjuvant chemotherapy were safe and well tolerated and markedly decreased the relapse rate in high-risk patients with clinical Stage I nonseminomatous germ cell testicular tumor without additional surgery or more protracted chemotherapy.
  • [MeSH-major] Antineoplastic Combined Chemotherapy Protocols / therapeutic use. Chemotherapy, Adjuvant. Germinoma / drug therapy. Orchiectomy. Testicular Neoplasms / drug therapy
  • [MeSH-minor] Biomarkers, Tumor / blood. Bleomycin / administration & dosage. Carboplatin / administration & dosage. Carcinoma, Embryonal / drug therapy. Carcinoma, Embryonal / pathology. Carcinoma, Embryonal / surgery. Combined Modality Therapy. Disease-Free Survival. Drug Administration Schedule. Etoposide / administration & dosage. Humans. Lymph Node Excision. Male. Neoplasm Invasiveness. Neoplasm Proteins / analysis. Neoplasm Staging. Neoplasms, Multiple Primary / drug therapy. Neoplasms, Multiple Primary / pathology. Neoplasms, Multiple Primary / surgery. Neoplasms, Second Primary / drug therapy. Neoplasms, Second Primary / pathology. Neoplasms, Second Primary / surgery. Prognosis. Risk Factors. Seminoma / drug therapy. Seminoma / pathology. Seminoma / surgery. Teratoma / drug therapy. Teratoma / pathology. Teratoma / surgery. Treatment Outcome. alpha-Fetoproteins / analysis

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  • (PMID = 14751368.001).
  • [ISSN] 1527-9995
  • [Journal-full-title] Urology
  • [ISO-abbreviation] Urology
  • [Language] eng
  • [Publication-type] Comparative Study; Journal Article
  • [Publication-country] United States
  • [Chemical-registry-number] 0 / Biomarkers, Tumor; 0 / Neoplasm Proteins; 0 / alpha-Fetoproteins; 11056-06-7 / Bleomycin; 6PLQ3CP4P3 / Etoposide; BG3F62OND5 / Carboplatin
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75. Weissbach L, Bussar-Maatz R, Flechtner H, Pichlmeier U, Hartmann M, Keller L: RPLND or primary chemotherapy in clinical stage IIA/B nonseminomatous germ cell tumors? Results of a prospective multicenter trial including quality of life assessment. Eur Urol; 2000 May;37(5):582-94
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  • [Source] The source of this record is MEDLINE®, a database of the U.S. National Library of Medicine.
  • [Title] RPLND or primary chemotherapy in clinical stage IIA/B nonseminomatous germ cell tumors? Results of a prospective multicenter trial including quality of life assessment.
  • BACKGROUND: In order to reduce therapy-related morbidity in patients with nonseminomatous testicular germ cell tumors in clinical stage IIA/B, we performed a prospective multicenter trial comparing the standard retroperitoneal lymph node dissection (RPLND) +2 cycles of chemotherapy (arm A) with 3-4 cycles of primary chemotherapy (arm B).
  • 109 received primary RPLND and 78 primary chemotherapy.
  • Two different chemotherapies were applied (PEB and CEB as adjuvant or inductive treatment).
  • The quality of life (QoL), therapy-related morbidity, suspected predictive factors (histology and size of metastases), and outcome were assessed.
  • In arm B, 67% achieved complete remission with chemotherapy alone, 33% required a secondary RPLND.
  • Two patients died due to complications of chemotherapy.
  • Acute toxicity of chemotherapy was higher in the group receiving primary chemotherapy.
  • CONCLUSION: We recommend primary RPLND because adjuvant chemotherapy can be spared in PS I, two cycles of chemotherapy are less toxic than 3 or 4 cycles, the primary operation is associated with less complications than that following chemotherapy and, with modern surgical procedures, ejaculation can be preserved in most of the patients, provided that the operation is carried out by an experienced surgeon.
  • No statistically significant differences in the QoL outcome occurred between the treatment groups, suggesting that chemotherapy alone is not superior to primary or secondary RPLND in this respect.
  • [MeSH-major] Antineoplastic Combined Chemotherapy Protocols / therapeutic use. Germinoma / drug therapy. Germinoma / surgery. Lymph Node Excision. Quality of Life. Testicular Neoplasms / drug therapy. Testicular Neoplasms / surgery
  • [MeSH-minor] Bleomycin / administration & dosage. Carboplatin / administration & dosage. Cisplatin / administration & dosage. Etoposide / administration & dosage. Humans. Male. Neoplasm Staging. Retroperitoneal Space

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  • (PMID = 10765098.001).
  • [ISSN] 0302-2838
  • [Journal-full-title] European urology
  • [ISO-abbreviation] Eur. Urol.
  • [Language] eng
  • [Publication-type] Clinical Trial; Journal Article; Multicenter Study; Randomized Controlled Trial
  • [Publication-country] SWITZERLAND
  • [Chemical-registry-number] 11056-06-7 / Bleomycin; 6PLQ3CP4P3 / Etoposide; BG3F62OND5 / Carboplatin; Q20Q21Q62J / Cisplatin; BEP protocol; JEB protocol
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76. Heidenreich A: Clinical stage I nonseminomatous testicular germ-cell tumors: surgery or watchful waiting, still an issue? Curr Opin Urol; 2002 Sep;12(5):427-30
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  • [Title] Clinical stage I nonseminomatous testicular germ-cell tumors: surgery or watchful waiting, still an issue?
  • PURPOSE OF REVIEW: The optimal management for clinical stage I nonseminomatous testicular germ-cell tumors is still a subject open to controversy.
  • It is the purpose, here, to present a critical review of recent developments concerning primary therapy for clinical stage I nonseminomatous testicular germ-cell tumors and to identify potential new prognostic risk factors predicting occult metastatic retroperitoneal lymph node disease.
  • RECENT FINDINGS: In accordance with the primary goal to improve quality of life, to protect fertility and to reduce long-term toxicity in survivors of testicular cancer, the major advantage of surveillance protocols is that adjuvant therapy will be administered only to those patients who require therapy.
  • Primary nerve-sparing retroperitoneal lymph-node dissection has diagnostic and therapeutic capabilities in low-volume disease; as local relapses are extremely rare, an effective and cost-saving follow-up concentrating on pulmonary recurrences can be initiated.
  • Nerve-sparing retroperitoneal lymph node dissection represents the initial approach for mature teratomas; patients with purely embryonal carcinoma have a high risk for systemic relapses and might be better served by primary chemotherapy.
  • The advantages and disadvantages of both treatment modalities must be discussed extensively with the patient, and it will be basically his decision as to which therapeutic approach is chosen.
  • [MeSH-major] Germinoma / pathology. Germinoma / therapy. Testicular Neoplasms / pathology. Testicular Neoplasms / therapy
  • [MeSH-minor] Humans. Lymphatic Metastasis. Male. Neoplasm Staging. Prognosis. Risk Factors

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  • (PMID = 12172431.001).
  • [ISSN] 0963-0643
  • [Journal-full-title] Current opinion in urology
  • [ISO-abbreviation] Curr Opin Urol
  • [Language] eng
  • [Publication-type] Journal Article; Review
  • [Publication-country] United States
  • [Number-of-references] 27
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77. Mueller T, Mueller LP, Holzhausen HJ, Witthuhn R, Albers P, Schmoll HJ: Histological evidence for the existence of germ cell tumor cells showing embryonal carcinoma morphology but lacking OCT4 expression and cisplatin sensitivity. Histochem Cell Biol; 2010 Aug;134(2):197-204
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  • [Title] Histological evidence for the existence of germ cell tumor cells showing embryonal carcinoma morphology but lacking OCT4 expression and cisplatin sensitivity.
  • The biological basis for manifestation of chemotherapy resistance in metastatic testicular germ cell tumors (GCT) remains obscure and is of particular clinical interest.
  • In the xenograft model, the cisplatin-sensitive cell line H12.1 gives rise to xenografts where EC structures are mainly composed of OCT4-positive cells, whereas xenografts from the resistant cell line 1411HP exclusively comprise OCT4-negative EC areas.
  • We found that post-chemotherapy residual metastatic tumors of patients can be comprised of exclusively OCT4-negative EC, whereas the matched testicular primary tumor harbors OCT4-positive EC.
  • Thorough histological analyses revealed a few examples of such OCT4-negative EC cells also in the testicular primary tumor as well as in xenografts from the cisplatin-sensitive NSGCT-cell line.
  • This challenges the use of the term EC cell.
  • The data also support our hypothesis that malignant growth of resistant NSGCT may be driven by this cell type.
  • [MeSH-major] Cisplatin / pharmacology. Drug Resistance, Neoplasm. Embryonal Carcinoma Stem Cells / pathology. Neoplasms, Germ Cell and Embryonal / pathology. Octamer Transcription Factor-3 / deficiency
  • [MeSH-minor] Animals. Cell Line, Tumor. Female. Histology. Humans. Immunohistochemistry. Male. Mice. Mice, Nude. Stem Cells. Transplantation, Heterologous / pathology

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  • (PMID = 20532795.001).
  • [ISSN] 1432-119X
  • [Journal-full-title] Histochemistry and cell biology
  • [ISO-abbreviation] Histochem. Cell Biol.
  • [Language] eng
  • [Publication-type] Journal Article; Research Support, Non-U.S. Gov't
  • [Publication-country] Germany
  • [Chemical-registry-number] 0 / Octamer Transcription Factor-3; Q20Q21Q62J / Cisplatin
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78. Clevenger JA, Foster RS, Ulbright TM: Differentiated rhabdomyomatous tumors after chemotherapy for metastatic testicular germ-cell tumors: a clinicopathological study of seven cases mandating separation from rhabdomyosarcoma. Mod Pathol; 2009 Oct;22(10):1361-6
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  • [Title] Differentiated rhabdomyomatous tumors after chemotherapy for metastatic testicular germ-cell tumors: a clinicopathological study of seven cases mandating separation from rhabdomyosarcoma.
  • To gain insight concerning prognosis, we investigated seven cases of post-chemotherapy retroperitoneal lymph-node dissections from patients with testicular germ-cell tumors that contained sizable nodules of differentiated skeletal muscle, but that lacked both a primitive cellular component and mitotic activity.
  • The patients were 18-28 years old at the time of retroperitoneal lymph-node dissection.
  • All had a previous non-seminomatous germ-cell tumor of the testis, five of which had a teratoma component.
  • In one the testicular tumor had foci of embryonal rhabdomyosarcoma.
  • The retroperitoneal lymph-node dissections were performed 0.2-4.7 years after orchiectomy, all following cisplatin-based chemotherapy, and contained rhabdomyomatous tumors that ranged from 0.8-5 cm.
  • These consisted of nodular to diffuse aggregates of fetal-type rhabdomyocytes with central to peripheral nuclei and abundant, eosinophilic, fibrillary cytoplasm with occasional cross striations.
  • Follow-up in six patients showed three were disease free at 2.2-3.4 years; two developed recurrent teratoma at 1.3-3.7 years; and a sixth developed recurrent teratoma at 0.5 and 2 years, followed at 17 years by progressive tumor with elevated alpha-fetoprotein.
  • No patient with available follow-up developed progressive sarcoma.
  • We conclude that rhabdomyomatous tumors in retroperitoneal lymph-node dissection specimens after chemotherapy for metastatic testicular germ-cell tumors show clinical behavior similar to teratoma rather than rhabdomyosarcoma.
  • We believe the most likely explanation for the finding of pure rhabdomyomatous tumors in this setting, a phenomenon sometimes termed 'cytodifferentiation,' is selective persistence of differentiated tumor cells because of chemotherapy.
  • [MeSH-major] Antineoplastic Combined Chemotherapy Protocols / therapeutic use. Cell Differentiation / drug effects. Lymph Nodes / pathology. Neoplasms, Germ Cell and Embryonal / secondary. Rhabdomyosarcoma, Embryonal / secondary. Teratoma / secondary. Testicular Neoplasms / pathology
  • [MeSH-minor] Adolescent. Adult. Chemotherapy, Adjuvant. Cisplatin / administration & dosage. Disease-Free Survival. Humans. Lymph Node Excision. Lymphatic Metastasis. Male. Orchiectomy. Retrospective Studies. Time Factors. Treatment Outcome. Young Adult

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  • (PMID = 19633644.001).
  • [ISSN] 1530-0285
  • [Journal-full-title] Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc
  • [ISO-abbreviation] Mod. Pathol.
  • [Language] eng
  • [Publication-type] Journal Article
  • [Publication-country] United States
  • [Chemical-registry-number] Q20Q21Q62J / Cisplatin
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79. McGurk CJ, Cummings M, Köberle B, Hartley JA, Oliver RT, Masters JR: Regulation of DNA repair gene expression in human cancer cell lines. J Cell Biochem; 2006 Apr 1;97(5):1121-36
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  • [Title] Regulation of DNA repair gene expression in human cancer cell lines.
  • Although most advanced cancers are incurable, the majority of testicular germ cell tumors can be cured using cisplatin-based combination chemotherapy.
  • The nucleotide excision repair (NER) pathway removes most DNA adducts produced by cisplatin, and the low levels of NER in testis tumor cells may explain why these cancers are curable.
  • Three NER proteins: ERCC1, XPF, and XPA, are present at low levels in testis tumor cell lines, and addition of these proteins to protein extracts of testis tumor cells increases their in vitro DNA repair capacity to normal levels.
  • The levels of the mRNA transcripts for ERCC1, XPF, and XPA were measured in a panel of 14 different human cancer cell lines, using real-time PCR.
  • Three alternative transcription start points (TSPs) were identified for ERCC1 but none were testis-specific.
  • The significantly lower levels of ERCC1, XPF, and XPA protein in testis tumor cell lines cannot be explained solely by differences in transcriptional efficiency or mRNA stability.
  • For ERCC1, post-transcriptional control by alternative splicing does not account for the testis-specific low levels of protein expression.
  • Pulse-chase experiments showed that the half-life of ERCC1 protein in a testis tumor cell line was not significantly different to that in a prostate cancer cell line.
  • [MeSH-major] Cisplatin / pharmacology. DNA Repair / physiology. DNA-Binding Proteins / genetics. Endonucleases / genetics. Gene Expression Regulation. Neoplasms / genetics. RNA, Messenger / metabolism
  • [MeSH-minor] 3' Untranslated Regions. 5' Untranslated Regions. Alternative Splicing. Blotting, Northern. Cell Line, Tumor. Humans. Male. Promoter Regions, Genetic. Protein Biosynthesis / genetics. Repressor Proteins / genetics. Transcription Initiation Site. Transcription, Genetic. Xeroderma Pigmentosum Group A Protein / metabolism

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  • [Copyright] (c) 2005 Wiley-Liss, Inc.
  • (PMID = 16315315.001).
  • [ISSN] 0730-2312
  • [Journal-full-title] Journal of cellular biochemistry
  • [ISO-abbreviation] J. Cell. Biochem.
  • [Language] eng
  • [Publication-type] Journal Article; Research Support, Non-U.S. Gov't
  • [Publication-country] United States
  • [Chemical-registry-number] 0 / 3' Untranslated Regions; 0 / 5' Untranslated Regions; 0 / DNA-Binding Proteins; 0 / RNA, Messenger; 0 / Repressor Proteins; 0 / XPA protein, human; 0 / Xeroderma Pigmentosum Group A Protein; 0 / xeroderma pigmentosum group F protein; EC 3.1.- / ERCC1 protein, human; EC 3.1.- / Endonucleases; Q20Q21Q62J / Cisplatin
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80. Kim C, McGlynn KA, McCorkle R, Zheng T, Erickson RL, Niebuhr DW, Ma S, Zhang Y, Bai Y, Dai L, Graubard BI, Kilfoy B, Barry KH, Zhang Y: Fertility among testicular cancer survivors: a case-control study in the U.S. J Cancer Surviv; 2010 Sep;4(3):266-73
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  • [Title] Fertility among testicular cancer survivors: a case-control study in the U.S.
  • INTRODUCTION: Testicular germ cell tumors (TGCT) disproportionately affect men between the ages of 15 and 49 years, when reproduction is typical.
  • Although TGCT treatment directly affects gonadal tissues, it remains unclear whether there are long-term effects on fertility.
  • METHODS: To examine post-TGCT treatment fertility, study participants in a previously conducted case-control study were contacted.
  • The men were initially enrolled in the US Servicemen's Testicular Tumor Environmental and Endocrine Determinants (STEED) study between 2002 and 2005.
  • A total of 246 TGCT cases and 236 controls participated in the current study and completed a self-administered questionnaire in 2008-2009.
  • RESULTS: TGCT cases were significantly more likely than controls to experience fertility distress (OR 5.23; 95% CI 1.99-13.76) and difficulty in fathering children (OR 6.41; 2.72-15.13).
  • These findings were predominantly observed among nonseminoma cases and cases treated with surgery only or surgery-plus-chemotherapy.
  • DISCUSSION: While expressing greater fertility distress, higher likelihood of fertility testing, and difficulty fathering children, these data suggest that TGCT survivors are no less likely to father children than are other men.
  • It is possible that treatment for TGCT does not permanently affect fertility or, alternatively, that TGCT survivors attempt to father children with greater persistence or at younger ages than do other men.

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  • (PMID = 20571931.001).
  • [ISSN] 1932-2267
  • [Journal-full-title] Journal of cancer survivorship : research and practice
  • [ISO-abbreviation] J Cancer Surviv
  • [Language] ENG
  • [Grant] United States / NCRR NIH HHS / RR / UL1 RR024139; United States / FIC NIH HHS / TW / D43 TW007864-04; United States / NCI NIH HHS / CA / T32 CA105666; United States / NCI NIH HHS / CA / CA130110-02; United States / NCI NIH HHS / CA / CA130110; United States / Intramural NIH HHS / / ZIA CP010126-15; United States / FIC NIH HHS / TW / D43 TW007864; United States / FIC NIH HHS / TW / D43 TW008323; United States / FIC NIH HHS / TW / TW008323-03; United States / NCI NIH HHS / CA / R03 CA130110; United States / NCRR NIH HHS / RR / UL1 RR024139-05; United States / NCI NIH HHS / CA / R03 CA130110-02; United States / NCRR NIH HHS / RR / RR024139-05; United States / FIC NIH HHS / TW / 1D43TW008323-01; United States / FIC NIH HHS / TW / D43 TW008323-03; United States / FIC NIH HHS / TW / TW007864-04; United States / FIC NIH HHS / TW / 1D43TW007864-01
  • [Publication-type] Comparative Study; Journal Article; Research Support, N.I.H., Extramural
  • [Publication-country] United States
  • [Other-IDs] NLM/ NIHMS267469; NLM/ PMC3057887
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81. Schweyer S, Soruri A, Meschter O, Heintze A, Zschunke F, Miosge N, Thelen P, Schlott T, Radzun HJ, Fayyazi A: Cisplatin-induced apoptosis in human malignant testicular germ cell lines depends on MEK/ERK activation. Br J Cancer; 2004 Aug 2;91(3):589-98
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  • [Title] Cisplatin-induced apoptosis in human malignant testicular germ cell lines depends on MEK/ERK activation.
  • Testicular germ cell tumours (TGCT) represent the most common malignancies in young males.
  • Whereas in 1970s, the survival rate in patients with metastatic testicular tumours was only 5%, these days, 80% of the patients treated by modern chemotherapy will survive their disease.
  • The drug that revolutionised the cure rate for patients with metastatic testicular tumours was cisdiamminedichloroplatinum (cisplatin, CDDP).
  • In vitro experiments on neoplastic germ cell lines showed that their exquisite sensitivity to CDDP could be attributed to p53-dependent and -independent pathways.
  • For this purpose, we used the human TGCT cell line NCCIT, the mutated p53 of which is known to remain inactive during the course of CDDP-induced apoptosis.
  • Interestingly, experiments with the human malignant germ cell line NTERA, which is known to possess wild-type p53, revealed the same results.
  • Thus, our data suggest that CDDP mediates its p53-independent apoptosis-inducing effect on the malignant human testicular germ cells--at least partially--through activation of the MEK-ERK signalling pathway. July 2004
  • [MeSH-major] Antineoplastic Agents / pharmacology. Apoptosis / drug effects. Cisplatin / pharmacology. Gene Expression Profiling. Genes, p53. MAP Kinase Signaling System / physiology. Mitogen-Activated Protein Kinase Kinases / biosynthesis. Neoplasms, Germ Cell and Embryonal / pathology. Testicular Neoplasms / pathology
  • [MeSH-minor] Blotting, Western. Cell Cycle. Humans. Male. Oligonucleotide Array Sequence Analysis. Phosphorylation. Reverse Transcriptase Polymerase Chain Reaction. Signal Transduction. Tumor Cells, Cultured

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  • (PMID = 15266324.001).
  • [ISSN] 0007-0920
  • [Journal-full-title] British journal of cancer
  • [ISO-abbreviation] Br. J. Cancer
  • [Language] eng
  • [Publication-type] Journal Article
  • [Publication-country] England
  • [Chemical-registry-number] 0 / Antineoplastic Agents; EC 2.7.12.2 / Mitogen-Activated Protein Kinase Kinases; Q20Q21Q62J / Cisplatin
  • [Other-IDs] NLM/ PMC2409982
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82. Oldenburg J, Alfsen GC, Waehre H, Fosså SD: Late recurrences of germ cell malignancies: a population-based experience over three decades. Br J Cancer; 2006 Mar 27;94(6):820-7
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  • [Title] Late recurrences of germ cell malignancies: a population-based experience over three decades.
  • The purpose of this study was to explore the incidence of late relapse in patients with malignant germ cell tumour (MGCT) in a population-based series, with emphasis on the mode of detection, survival, and the relevance of histological findings.
  • Twenty-five patients developed a late relapse.
  • All 10 seminoma patients, but only eight of 15 non-seminoma patients relapsed with vital malignant tumour (P=0.02).
  • Teratoma or necrosis was found in seven of nine primarily chemotherapy-treated non-seminoma patients with normal tumour markers at late relapse.
  • Six of nine patients operated with limited retroperitoneal lymph node dissection as part of the primary treatment had relapsed retroperitoneally outside the original operation field.
  • The 10-year cause-specific survival was 68% in all patients, 50% in patients relapsing with vital malignant tumour and 100% in those with teratoma/ necrosis before or after salvage chemotherapy.
  • The 10-year incidence rate of late relapses of 1.3% might reflect the true incidence rate in a population-based cohort of MGCT patients, with cure in at least half of them.
  • [MeSH-major] Neoplasm Recurrence, Local / epidemiology. Neoplasms, Germ Cell and Embryonal / pathology. Seminoma / pathology. Testicular Neoplasms / pathology
  • [MeSH-minor] Adult. Aged. Cohort Studies. Humans. Incidence. Male. Middle Aged. Necrosis. Time Factors


83. Spierings DC, de Vries EG, Vellenga E, de Jong S: The attractive Achilles heel of germ cell tumours: an inherent sensitivity to apoptosis-inducing stimuli. J Pathol; 2003 Jun;200(2):137-48
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  • [Title] The attractive Achilles heel of germ cell tumours: an inherent sensitivity to apoptosis-inducing stimuli.
  • Testicular germ cell tumours (TGCTs) are extremely sensitive to cisplatin-containing chemotherapy.
  • The rapid time course of apoptosis induction after exposure to cisplatin suggests that TGCT cells are primed to undergo programmed cell death as an inherent property of the cell of origin.
  • In fact, apoptosis induction of germ cells in the testis is an important physiological mechanism to control the quality and quantity of the gametes produced.
  • Although p53 protein is highly expressed in the majority of TGCTs, almost no p53 mutations have been detected.
  • Interestingly, p53 overexpression is associated with loss of p21 and gain of mdm2 expression, which might indicate a partial loss in functionality of the p53 regulatory pathway in TGCTs.
  • Besides p21, TGCTs often show low expression of other proteins involved in the regulation of cell cycle progression, such as the retinoblastoma protein and members of the INK4 family.
  • It can be postulated that the deregulated G(1)-S phase checkpoint results in premature entry into the S phase upon DNA damage.
  • In addition to Bcl-2 family members that are involved in the regulation of germ cell apoptosis in the normal testis via the mitochondrial death pathway, the Fas death pathway is also known to regulate apoptosis of germ cells in the testis.
  • Since chemotherapy has been shown to activate the Fas death pathway and TGCTs co-express both Fas and its ligand FasL, TGCT cells might undergo apoptosis upon cisplatin treatment via autocrine or paracrine activation of the Fas system by FasL.
  • The hypothesis suggested here is that the lack of cell cycle arrest following a cisplatin-containing treatment, together with the activation of the Fas death pathway and the mitochondrial death pathway, explains the rapid and efficient apoptosis of TGCT cells.
  • Defining the mechanisms involved in the cisplatin sensitivity of TGCTs will provide tools to increase cisplatin sensitivity in other human tumours with acquired or intrinsic resistance.
  • [MeSH-major] Apoptosis. Germinoma / pathology. Testicular Neoplasms / pathology
  • [MeSH-minor] Antigens, CD95 / physiology. Cell Cycle. Cyclin-Dependent Kinase Inhibitor p21. Cyclins / physiology. Humans. Male. Neoplasm Proteins / physiology. Proto-Oncogene Proteins c-bcl-2 / physiology

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  • [Copyright] Copyright 2003 John Wiley & Sons, Ltd.
  • (PMID = 12754734.001).
  • [ISSN] 0022-3417
  • [Journal-full-title] The Journal of pathology
  • [ISO-abbreviation] J. Pathol.
  • [Language] eng
  • [Publication-type] Journal Article; Research Support, Non-U.S. Gov't; Review
  • [Publication-country] England
  • [Chemical-registry-number] 0 / Antigens, CD95; 0 / CDKN1A protein, human; 0 / Cyclin-Dependent Kinase Inhibitor p21; 0 / Cyclins; 0 / Neoplasm Proteins; 0 / Proto-Oncogene Proteins c-bcl-2
  • [Number-of-references] 159
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84. Detti B, Livi L, Scoccianti S, Meattini I, Gacci M, Lapini A, Biti G: Late relapse in testicular germ cell tumors. Tumori; 2007 Sep-Oct;93(5):428-31
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  • [Title] Late relapse in testicular germ cell tumors.
  • AIMS AND BACKGROUND: Analysis of patients with late relapse of testicular germ cell tumors (GCTs) with reports on clinicopathological features and outcomes.
  • METHODS: We identified all patients diagnosed with testicular GCTs at our Institute between 1988 and 2004 who developed relapse > or = 24 months after completion of primary therapy.
  • A retrospective case-note review was performed to extract clinical, pathological, treatment and outcome data.
  • RESULTS: Six patients (1.25%) developed late relapse.
  • All patients presented with stage I disease and were classified as "good risk" according to the International Germ Cell Consensus Classification.
  • Mean time to late relapse was 48 months.
  • Five patients were managed by chemotherapy alone while one underwent combined treatment with surgery followed by chemotherapy.
  • All patients obtained a complete response and all remained free from recurrence with a mean follow-up of 115 months.
  • Chemonaive patients with late relapse were successfully salvaged with chemotherapy alone or surgical excision followed by cisplatin-based chemotherapy.
  • The optimal duration of follow-up in patients with testicular GCTs is not known and practice varies widely.
  • At our Institute we advise lifelong follow-up of all patients with malignant GCTs of the testis.
  • [MeSH-major] Neoplasm Recurrence, Local / epidemiology. Testicular Neoplasms / epidemiology
  • [MeSH-minor] Adult. Antineoplastic Combined Chemotherapy Protocols / therapeutic use. Humans. Male. Mediastinal Neoplasms / drug therapy. Mediastinal Neoplasms / secondary. Mediastinal Neoplasms / surgery. Medical Records. Middle Aged. Outcome Assessment (Health Care). Retroperitoneal Neoplasms / drug therapy. Retroperitoneal Neoplasms / secondary. Retroperitoneal Neoplasms / surgery. Retrospective Studies. Teratocarcinoma / drug therapy. Teratocarcinoma / secondary. Teratocarcinoma / surgery

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  • (PMID = 18038873.001).
  • [ISSN] 0300-8916
  • [Journal-full-title] Tumori
  • [ISO-abbreviation] Tumori
  • [Language] eng
  • [Publication-type] Journal Article
  • [Publication-country] United States
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85. Anthoney DA, McKean MJ, Roberts JT, Hutcheon AW, Graham J, Jones W, Paul J, Kaye SB: Bleomycin, vincristine, cisplatin/bleomycin, etoposide, cisplatin chemotherapy: an alternating, dose intense regimen producing promising results in untreated patients with intermediate or poor prognosis malignant germ-cell tumours. Br J Cancer; 2004 Feb 9;90(3):601-6
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  • [Title] Bleomycin, vincristine, cisplatin/bleomycin, etoposide, cisplatin chemotherapy: an alternating, dose intense regimen producing promising results in untreated patients with intermediate or poor prognosis malignant germ-cell tumours.
  • Patients with poor and intermediate prognosis metastatic germ-cell tumours (MGCTs) are at a significant risk of relapse after standard platinum-based chemotherapy.
  • Novel treatment regimens are required to improve survival.
  • Dose intense, alternating combinations of drugs with known activity in germ-cell tumours represents one approach.
  • In all, 43 patients with IGCCCG intermediate/poor prognosis MGCT were treated with a dose intense regimen alternating bleomycin, vincristine, cisplatin (BOP) with bleomycin, etoposide, cisplatin (BEP) to a maximum of three cycles.
  • The complete response rate was 58%; a further 7% of patients being rendered disease free by resection of viable residual tumour.
  • With a median follow-up of more than 4 years in surviving patients, 3-year OS and PFS rates of 81% (95% CI: 66-91%) and 72% (95% CI: 56-83%) are seen, respectively.
  • Bleomycin, vincristine, cisplatin (BOP)/bleomycin, etoposide, cisplatin (BEP) represents a practicable, well-tolerated, dose intense chemotherapy regimen with significant activity in intermediate and poor prognosis MGCT.
  • [MeSH-major] Antineoplastic Combined Chemotherapy Protocols / therapeutic use. Neoplasms, Germ Cell and Embryonal / drug therapy
  • [MeSH-minor] Adolescent. Adult. Bleomycin / administration & dosage. Cisplatin / administration & dosage. Dose-Response Relationship, Drug. Drug Administration Schedule. Etoposide / administration & dosage. Female. Humans. Infusions, Intravenous. Injections, Intramuscular. Middle Aged. Neutropenia / chemically induced. Prognosis. Survival Analysis. Treatment Outcome. Vincristine / administration & dosage

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  • (PMID = 14760371.001).
  • [ISSN] 0007-0920
  • [Journal-full-title] British journal of cancer
  • [ISO-abbreviation] Br. J. Cancer
  • [Language] eng
  • [Publication-type] Clinical Trial; Journal Article; Multicenter Study
  • [Publication-country] England
  • [Chemical-registry-number] 11056-06-7 / Bleomycin; 5J49Q6B70F / Vincristine; 6PLQ3CP4P3 / Etoposide; Q20Q21Q62J / Cisplatin; BEP protocol; COB protocol
  • [Other-IDs] NLM/ PMC2409589
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86. Holley A, Cartner M, Lipman J: Acute respiratory distress in a bleomycin primed patient: a new use for nitric oxide. Anaesth Intensive Care; 2007 Feb;35(1):86-90
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  • A 27-year-old male, previously treated with bleomycin for a testicular germ cell tumour presented with severe acute respiratory distress syndrome on the second postoperative day following an extensive retroperitoneal dissection.
  • [MeSH-major] Antineoplastic Combined Chemotherapy Protocols / adverse effects. Nitric Oxide / therapeutic use. Respiratory Distress Syndrome, Adult / drug therapy
  • [MeSH-minor] Adult. Bleomycin / adverse effects. Cisplatin / adverse effects. Etoposide / adverse effects. Humans. Male. Neoplasm Invasiveness. Neoplasm Recurrence, Local / drug therapy. Neoplasms, Germ Cell and Embryonal / drug therapy. Neoplasms, Germ Cell and Embryonal / pathology. Neoplasms, Germ Cell and Embryonal / surgery. Retroperitoneal Neoplasms / drug therapy. Retroperitoneal Neoplasms / secondary. Retroperitoneal Neoplasms / surgery. Testicular Neoplasms / drug therapy. Testicular Neoplasms / pathology. Testicular Neoplasms / surgery

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  • (PMID = 17323672.001).
  • [ISSN] 0310-057X
  • [Journal-full-title] Anaesthesia and intensive care
  • [ISO-abbreviation] Anaesth Intensive Care
  • [Language] eng
  • [Publication-type] Case Reports; Journal Article
  • [Publication-country] Australia
  • [Chemical-registry-number] 11056-06-7 / Bleomycin; 31C4KY9ESH / Nitric Oxide; 6PLQ3CP4P3 / Etoposide; Q20Q21Q62J / Cisplatin; BEP protocol
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87. Gilligan T: Changing management of clinical low-stage testicular cancer. ScientificWorldJournal; 2005 Oct 16;5:852-67
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  • [Title] Changing management of clinical low-stage testicular cancer.
  • Stage I and II testicular germ cell tumors (GCTs) are almost always cured with appropriate treatment and most ongoing research regarding these tumors focuses on minimizing treatment toxicity.
  • The management of clinical stage I testicular GCTs has grown more complicated due to the emergence of a brief course of chemotherapy as an additional treatment option for stage I seminomas and stage I nonseminomas.
  • In addition, growing concern about radiation-induced cancers and other late toxicity has dulled enthusiasm for radiotherapy as a treatment for stage I seminomas.
  • At this point in history, stage I patients have three treatment options following radical orchiectomy: adjuvant (sometimes called "primary") chemotherapy (carboplatin for seminomas and the combined regimen of bleomycin, etoposide, and cisplatin for nonseminomas), surveillance, and either retroperitoneal lymph node dissection (for nonseminomas) or radiotherapy (for pure seminomas).
  • Clinical studies have made it possible to identify subgroups of patients at high and low risk for relapse and this has made it possible to tailor treatment decisions to the individual patient's postorchiectomy relapse risk.
  • [MeSH-major] Testicular Neoplasms / pathology. Testicular Neoplasms / therapy
  • [MeSH-minor] Carboplatin / administration & dosage. Carboplatin / therapeutic use. Dose-Response Relationship, Radiation. Humans. Male. Neoplasm Recurrence, Local. Neoplasm Staging. Neoplasms, Germ Cell and Embryonal / drug therapy. Neoplasms, Germ Cell and Embryonal / pathology. Neoplasms, Germ Cell and Embryonal / radiotherapy. Neoplasms, Germ Cell and Embryonal / therapy

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  • (PMID = 16244754.001).
  • [ISSN] 1537-744X
  • [Journal-full-title] TheScientificWorldJournal
  • [ISO-abbreviation] ScientificWorldJournal
  • [Language] eng
  • [Publication-type] Journal Article; Review
  • [Publication-country] England
  • [Chemical-registry-number] BG3F62OND5 / Carboplatin
  • [Number-of-references] 100
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88. Bauer S, Mühlenberg T, Leahy M, Hoiczyk M, Gauler T, Schuler M, Looijenga L: Therapeutic potential of Mdm2 inhibition in malignant germ cell tumours. Eur Urol; 2010 Apr;57(4):679-87
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  • [Title] Therapeutic potential of Mdm2 inhibition in malignant germ cell tumours.
  • BACKGROUND: Inadequate response to cisplatin-based chemotherapy is associated with poor prognosis in patients with advanced malignant testicular germ cell tumours (TGCTs), especially of the nonseminomatous type.
  • The majority of these tumours express low levels of p53, and TP53 mutations are rarely observed.
  • Murine double minute 2 (Mdm2) inhibitors enhance apoptosis in tumours harbouring wild-type p53.
  • OBJECTIVE: We sought to investigate the potential therapeutic value of Mdm2 in TGCT-derived cell lines with the histology of nonseminoma.
  • DESIGN, SETTING, AND PARTICIPANTS: The Mdm2 inhibitor nutlin-3 was evaluated alone and in combination with cisplatin in a panel of germ cell tumour (GCT)-derived cell lines (embryonal carcinomas, being the nonseminomatous stem-cell component) with wild-type (NT2 and 2102EP cells) and mutant (NCCIT cells) p53 status.
  • MEASUREMENTS: Biological consequences of Mdm2 inhibition were determined by analysis of the p53 pathway, cell proliferation, and apoptosis.
  • RESULTS AND LIMITATIONS: Nutlin-3 exhibited significant activity (IC50 2.8 μM) in NT2 and 2102EP (wild-type p53) but not in p53-mutant NCCIT cells (<10% inhibition at 10 μM).
  • CONCLUSIONS: These results provide strong evidence for further development of pharmacologic Mdm2 inhibition for the treatment of patients suffering from high-risk nonseminomatous TGCT with wild-type p53 status.
  • [MeSH-major] Antineoplastic Combined Chemotherapy Protocols / pharmacology. Carcinoma, Embryonal / enzymology. Proto-Oncogene Proteins c-mdm2 / antagonists & inhibitors. Testicular Neoplasms / enzymology
  • [MeSH-minor] Apoptosis / drug effects. Cell Line, Tumor. Cell Proliferation / drug effects. Cell Survival / drug effects. Cisplatin / pharmacology. Cyclin-Dependent Kinase Inhibitor p21 / metabolism. Dose-Response Relationship, Drug. Drug Resistance, Neoplasm. Enzyme Inhibitors / pharmacology. Humans. Imidazoles / pharmacology. Inhibitory Concentration 50. Male. Mutation. Piperazines / pharmacology. Tumor Suppressor Protein p53 / genetics. Tumor Suppressor Protein p53 / metabolism

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  • [Copyright] Copyright © 2009 European Association of Urology. Published by Elsevier B.V. All rights reserved.
  • (PMID = 19560254.001).
  • [ISSN] 1873-7560
  • [Journal-full-title] European urology
  • [ISO-abbreviation] Eur. Urol.
  • [Language] eng
  • [Publication-type] Journal Article
  • [Publication-country] Switzerland
  • [Chemical-registry-number] 0 / CDKN1A protein, human; 0 / Cyclin-Dependent Kinase Inhibitor p21; 0 / Enzyme Inhibitors; 0 / Imidazoles; 0 / Piperazines; 0 / TP53 protein, human; 0 / Tumor Suppressor Protein p53; 0 / nutlin 3; EC 6.3.2.19 / MDM2 protein, human; EC 6.3.2.19 / Proto-Oncogene Proteins c-mdm2; Q20Q21Q62J / Cisplatin
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89. Heidenreich A, Krege S, Flasshove M: [Interdisciplinary cooperation in the treatment of complex patients with advanced testicular germ cell tumor]. Urologe A; 2004 Dec;43(12):1521-30
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  • [Title] [Interdisciplinary cooperation in the treatment of complex patients with advanced testicular germ cell tumor].
  • [Transliterated title] Interdisziplinäre Kooperation in der Therapie von komplexen Patienten mit fortgeschrittenem testikulärem Keimzelltumor.
  • Testicular germ cell tumors represent the classic example of a curable solid cancer even in the metastatic stage.
  • Cure rates are as high as 95% and 80-85% in patients with good and intermediate prognosis; even in patients with poor prognosis cure rates of 50% have been achieved by interdisciplinary collaboration of all specialties involved in the management of testis cancer.
  • Standardization of diagnosis and therapy should be further optimized due to the recently published interdisciplinary national and European guidelines.
  • Besides realization of standardized guidelines, treatment of patients with extensive primary disease or recurrent germ cell tumors following standard therapy requires comprehensive knowledge in conservative and surgical management, which is basically only available at specialized cancer centers.
  • Patients with complex findings, especially if associated with a poor prognosis according to IGCCCG, should be referred to specialized tertiary referral centers at a very early stage, since the cure rates depend not only on the consideration of guidelines but also on the expertise of the attending oncologist and surgeon.
  • When treating these patients, one has to consider that inadequately administered chemotherapy (dosage, length of cycles, number of cycles) cannot be compensated for by surgery and that inadequately performed retroperitoneal lymphadenectomy or residual tumor resection cannot be compensated for by chemotherapy.
  • In any case, suboptimal primary therapy will result in inferior cure rates and an unnecessarily increased mortality rate.
  • [MeSH-major] Lymph Node Excision / methods. Neoplasms, Germ Cell and Embryonal / secondary. Neoplasms, Germ Cell and Embryonal / therapy. Patient Care Team / organization & administration. Practice Patterns, Physicians' / organization & administration. Testicular Neoplasms / drug therapy. Testicular Neoplasms / surgery
  • [MeSH-minor] Adult. Combined Modality Therapy / methods. Cooperative Behavior. European Union. Germany. Humans. Lymphatic Metastasis. Male. Middle Aged. Peritoneal Neoplasms / drug therapy. Peritoneal Neoplasms / secondary. Peritoneal Neoplasms / surgery. Peritoneum / surgery. Practice Guidelines as Topic. Severity of Illness Index. Treatment Outcome

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  • (PMID = 15592709.001).
  • [ISSN] 0340-2592
  • [Journal-full-title] Der Urologe. Ausg. A
  • [ISO-abbreviation] Urologe A
  • [Language] ger
  • [Publication-type] English Abstract; Journal Article; Review
  • [Publication-country] Germany
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90. Feldman DR, Bosl GJ, Sheinfeld J, Motzer RJ: Medical treatment of advanced testicular cancer. JAMA; 2008 Feb 13;299(6):672-84
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  • [Title] Medical treatment of advanced testicular cancer.
  • CONTEXT: The medical treatment of advanced testicular germ cell tumors has changed over the past 30 years, with long-term survival now achieved in the majority of patients.
  • Clinicians need to be familiar with the available treatment regimens for testicular cancer and their associated toxic effects.
  • OBJECTIVE: To review the treatments used for advanced testicular germ cell tumors and their associated short-term and long-term complications.
  • EVIDENCE ACQUISITION: A search was performed of all English-language literature (1966 to October 2007) within the MEDLINE database using the terms neoplasms, germ cell, or embryonal or testicular neoplasms restricted to humans, drug therapy, complications, and mortality.
  • The Cochrane Register of Controlled Trials Databases (through October 2007) was also searched using the terms testicular cancer or germ cell tumors.
  • One hundred eighty-six articles were selected based on pertinence to advanced testicular cancer treatment, associated complications, and late relapses with an emphasis on randomized controlled trials.
  • DATA SYNTHESIS: The treatment of advanced testicular germ cell tumors with cisplatin combination chemotherapy is based on risk stratification (good, intermediate, or poor prognosis) according to pretreatment clinical features of prognostic value.
  • Complete responses are achieved less frequently for patients with intermediate- and poor-risk germ cell tumors, in whom 4 cycles of bleomycin, etoposide, and cisplatin remains the standard of care.
  • Second- and third-line programs, including high-dose chemotherapy, also have curative potential.
  • Chronic toxicities associated with therapy include cardiovascular disease, infertility, and secondary malignancies.
  • CONCLUSIONS: Clinical trials have led to evidence-based treatment recommendations for advanced testicular cancer based on risk stratification.
  • Clinicians should be familiar with the potential complications of these therapies.

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  • (PMID = 18270356.001).
  • [ISSN] 1538-3598
  • [Journal-full-title] JAMA
  • [ISO-abbreviation] JAMA
  • [Language] ENG
  • [Publication-type] Journal Article; Research Support, Non-U.S. Gov't; Review
  • [Publication-country] United States
  • [Chemical-registry-number] 0 / Antineoplastic Agents
  • [Number-of-references] 202
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91. Khurana K, Gilligan TD, Stephenson AJ: Management of poor-prognosis testicular germ cell tumors. Indian J Urol; 2010 Jan-Mar;26(1):108-14
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  • [Source] The source of this record is MEDLINE®, a database of the U.S. National Library of Medicine.
  • [Title] Management of poor-prognosis testicular germ cell tumors.
  • Currently, the outcome of patients with intermediate-and poor-risk germ cell tumors at diagnosis is optimized by the use of risk-appropriate chemotherapy and post-chemotherapy surgical resection of residual masses.
  • Currently, there is no role for high-dose chemotherapy in the first-line setting.
  • Patients who progress on first-line chemotherapy or who relapse after an initial complete response also have a poor prognosis.
  • In the setting of early relapse, the standard approach at most centers is conventional-dose, ifosfamide-based regimens and post-chemotherapy resection of residual masses.
  • The treatment of patients with late relapse is complete surgical resection whenever feasible.
  • Salvage chemotherapy for late relapse may be used prior to surgery in patients where a complete resection is not feasible.
  • A complete surgical resection of all residual sites of disease after chemotherapy is critical for the prevention of relapse and the long-term survival of patients with advanced germ cell tumors.

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