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1. Takeda K, Nemoto K, Saito H, Ogawa Y, Takai Y, Yamada S: Predictive factors for acute esophageal toxicity in thoracic radiotherapy. Tohoku J Exp Med; 2006 Apr;208(4):299-306
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  • Previous studies demonstrated several clinical and dosimetric parameters of AET in patients with lung cancer.
  • However, there are few reports dealing with these variables in intra-thoracic malignancies, including lung cancer and other thoracic malignancy.
  • We examined 61 patients with intra-thoracic malignancies treated with radiotherapy: 34 patients with non-small-cell lung cancer (55%), 9 cases with small-cell lung cancer (15%), 7 cases with thymic cancer (11%), 4 thymomas (7%), 2 malignant lymphomas (3%), one seminoma (2%), one liposarcoma (2%), and 3 cases of other malignancies (5%).
  • Radiotherapy was performed with a median dose of 60 Gray (Gy) (range 40-67 Gy).
  • AET was graded according to the Radiation Therapy Oncology Group (RTOG) criteria.
  • The following parameters were analyzed with respect to associations with AET by univariate and multivariate analyses: age, gender, thoracic surgery before radiotherapy, concurrent chemotherapy, duration of radiotherapy, maximum esophageal dose, mean esophageal dose, and percentage of esophageal volume receiving from 10 Gy (V10) to 65 Gy (V65), in 5-Gy increments.
  • 43 patients (70%) developed AET: 36 patients (59%) with AET of RTOG Grade 1, 7 patients (11%) with Grade 2, and no patients (0%) with Grade 3 or worse.
  • Our findings provide a better understanding of the factors related to AET, and might be useful in designing a treatment plan to prevent severe esophageal toxicity.
  • [MeSH-minor] Adult. Aged. Aged, 80 and over. Antineoplastic Combined Chemotherapy Protocols / therapeutic use. Carcinoma / radiotherapy. Combined Modality Therapy. Female. Humans. Japan / epidemiology. Lung Neoplasms / radiotherapy. Male. Middle Aged. Neoplasm Staging. Radiotherapy Dosage

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  • (PMID = 16565592.001).
  • [ISSN] 0040-8727
  • [Journal-full-title] The Tohoku journal of experimental medicine
  • [ISO-abbreviation] Tohoku J. Exp. Med.
  • [Language] eng
  • [Publication-type] Journal Article
  • [Publication-country] Japan
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2. Walter MA, Hildebrandt IJ, Hacke K, Kesner AL, Kelly O, Lawson GW, Phelps ME, Czernin J, Weber WA, Schiestl RH: Small-animal PET/CT for monitoring the development and response to chemotherapy of thymic lymphoma in Trp53-/- mice. J Nucl Med; 2010 Aug;51(8):1285-92
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  • [Title] Small-animal PET/CT for monitoring the development and response to chemotherapy of thymic lymphoma in Trp53-/- mice.
  • Transgenic mouse models of human cancers represent one of the most promising approaches to elucidate clinically relevant mechanisms of action and provide insights into the treatment efficacy of new antitumor drugs.
  • The use of Trp53 transgenic mice (Trp53 knockout [Trp53(-/-)] mice) for these kinds of studies is, so far, restricted by limitations in detecting developing tumors and the lack of noninvasive tools for monitoring tumor growth, progression, and treatment response.
  • METHODS: We hypothesized that quantitative small-animal PET with (18)F-FDG was able to detect the onset and location of tumor development, follow tumor progression, and monitor response to chemotherapy.
  • To test these hypotheses, C57BL/6J Trp53(-/-) mice underwent longitudinal small-animal PET during lymphoma development and gemcitabine treatment.
  • Trp53 wild-type (Trp53(+/+)) mice were used as controls, and histology after full necropsy served as the gold standard.
  • RESULTS: In Trp53(+/+) mice, the thymic standardized uptake value (SUV) did not exceed 1.0 g/mL, with decreasing (18)F-FDG uptake over time.
  • Conversely, all Trp53(-/-) mice that developed thymic lymphoma showed increasing thymic glucose metabolism, with a mean SUV doubling time of 9.0 wk (range, 6.0-17.5 wk).
  • Using an SUV of 3.0 g/mL as a criterion provided a sensitivity of 78% and a specificity of 100% for the detection of thymic lymphoma.
  • Treatment monitoring with (18)F-FDG PET correctly identified all histologic responses and relapses to gemcitabine.
  • CONCLUSION: (18)F-FDG small-animal PET can be used to visualize onset and progression of thymic lymphomas in Trp53(-/-) mice and monitor response to chemotherapy.
  • [MeSH-major] Lymphoma / drug therapy. Lymphoma / radionuclide imaging. Thymus Neoplasms / drug therapy. Thymus Neoplasms / radionuclide imaging. Tumor Suppressor Protein p53 / genetics
  • [MeSH-minor] Aging / physiology. Animals. Antimetabolites, Antineoplastic / therapeutic use. Antineoplastic Agents / therapeutic use. Cell Proliferation. Deoxycytidine / analogs & derivatives. Deoxycytidine / therapeutic use. Disease Progression. Fluorodeoxyglucose F18. Image Processing, Computer-Assisted. Mice. Mice, Knockout. Mitotic Index. Positron-Emission Tomography. Radiopharmaceuticals. Tomography, Emission-Computed

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  • (PMID = 20660381.001).
  • [ISSN] 1535-5667
  • [Journal-full-title] Journal of nuclear medicine : official publication, Society of Nuclear Medicine
  • [ISO-abbreviation] J. Nucl. Med.
  • [Language] eng
  • [Publication-type] Journal Article; Research Support, Non-U.S. Gov't
  • [Publication-country] United States
  • [Chemical-registry-number] 0 / Antimetabolites, Antineoplastic; 0 / Antineoplastic Agents; 0 / Radiopharmaceuticals; 0 / Tumor Suppressor Protein p53; 0W860991D6 / Deoxycytidine; 0Z5B2CJX4D / Fluorodeoxyglucose F18; B76N6SBZ8R / gemcitabine
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3. Teoh DC, El-Modir A: Managing a locally advanced malignant thymoma complicated by nephrotic syndrome: a case report. J Med Case Rep; 2008;2:89
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  • [Title] Managing a locally advanced malignant thymoma complicated by nephrotic syndrome: a case report.
  • INTRODUCTION: The management of locally advanced inoperable malignant thymoma is difficult as there are no large randomized clinical trial data to guide treatment.
  • However various case series have shown that malignant thymoma is often a chemosensitive disease.
  • Cisplatin-based chemotherapy has been the gold-standard in the management of these patients.
  • However when thymic cancers are complicated by paraneoplastic syndromes that damage kidney and neurological function, cisplatin use is often contraindicated.
  • CASE PRESENTATION: We report a case of a 37 year old man with locally advanced malignant thymoma complicated by significant nephrotic syndrome and renal impairment.
  • He responded to a novel combination of carboplatin, epirubicin and cyclophosphamide chemotherapy used as first line therapy.
  • CONCLUSION: The treatment with chemotherapy of locally advanced malignant thymoma complicated by nephrotic syndrome and renal impairment is difficult due to the increase of toxicity.
  • In this case, a novel chemotherapy combination with lesser toxicity was used successfully.
  • In addition this chemotherapy combination did not impede the later use of conventional cisplatin-based chemotherapy.
  • Therefore we suggest a course of carboplatin-based chemotherapy for locally advanced malignant thymoma in patients who are unsuitable for cisplatin.

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  • (PMID = 18353189.001).
  • [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/ PMC2278156
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4. Qian H, Jiang G, He S, Wang L, Fu X, Gong Q: [The effect of whole pleural cavity irradiation with combined 60Co and electron beam plus local biological agents on malignant pleural effusion]. Zhongguo Fei Ai Za Zhi; 2000 Oct 20;3(5):336-9
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  • [Title] [The effect of whole pleural cavity irradiation with combined 60Co and electron beam plus local biological agents on malignant pleural effusion].
  • BACKGROUND: To study the effect and complications of combined 60Co γ ray and electron beam irradiation to malignant pleural effusion.
  • METHODS: From January,1996 to December,1998,55 patients with malignant pleural effusion (unilateral; 49 cases of primary lung cancer,4 breast cancer and 2 thymic tumor) received whole pleural cavity irradiation of 60Co γ ray with centrally placed lead blocks to protect the vital organs and normal lung tissue,and the electron beam irradiation at the area which was covered by lead blocks in 60Co γ ray irradiation.The pleural effusion was completely drained before radiotherapy,and dose distribution of middle level was calculated by TPS using EXT 2.4 version software (Multidata Co.USA).The 100% isodose curve was 2Gy,15 fractions were given and another 20Gy/10Fx irradiation was added to the visible tumor.All patients received sequential chemotherapy for 3-6 cycles (cisplatin-based regimens for lung cancer and thymic tumor,cyclophosphamide and adriamycin and fluoracil for breast cancer).Kaplan-Meier curve was used to evaluate the pleural effusion control rate and survival rate of patients.
  • RESULTS: Complete remission of the malignant pleural effusion was seen in 9 patients and partial in 46 when treatment completed.The 6-,12-,18-month pleural effusion control rate and survival rate of the patients were 76%,53%,44% and 64%,34%,26%,respectively.The median control time of effusion and survival time were 14 months (2-32 months) and 9 months (4-32 months) respectively.We did not find any abnormality in liver function as well as in kidney function before and after treatment.Myelosuppression was the main side effect after combined chemotherapy and radiotherapy.Nineteen patients suffered from acute oesophagitis in grade 1-2,and 3 serious pleural fibrosis.There was no acute irradiation pneumonitis.
  • CONCLUSIONS: The treatment for malignant pleural effusion with combined 60Co γ ray and electron beam irradiation is tolerable and effective in clinical use.

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  • (PMID = 20979716.001).
  • [ISSN] 1009-3419
  • [Journal-full-title] Zhongguo fei ai za zhi = Chinese journal of lung cancer
  • [ISO-abbreviation] Zhongguo Fei Ai Za Zhi
  • [Language] chi
  • [Publication-type] English Abstract; Journal Article
  • [Publication-country] China
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5. Huang EY, Madireddi MT, Gopalkrishnan RV, Leszczyniecka M, Su Z, Lebedeva IV, Kang D, Jiang H, Lin JJ, Alexandre D, Chen Y, Vozhilla N, Mei MX, Christiansen KA, Sivo F, Goldstein NI, Mhashilkar AB, Chada S, Huberman E, Pestka S, Fisher PB: Genomic structure, chromosomal localization and expression profile of a novel melanoma differentiation associated (mda-7) gene with cancer specific growth suppressing and apoptosis inducing properties. Oncogene; 2001 Oct 25;20(48):7051-63
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  • [Title] Genomic structure, chromosomal localization and expression profile of a novel melanoma differentiation associated (mda-7) gene with cancer specific growth suppressing and apoptosis inducing properties.
  • Abnormalities in cellular differentiation are frequent occurrences in human cancers.
  • Treatment of human melanoma cells with recombinant fibroblast interferon (IFN-beta) and the protein kinase C activator mezerein (MEZ) results in an irreversible loss in growth potential, suppression of tumorigenic properties and induction of terminal cell differentiation.
  • Ectopic expression of mda-7 by means of a replication defective adenovirus results in growth suppression and induction of apoptosis in a broad spectrum of additional cancers, including melanoma, glioblastoma multiforme, osteosarcoma and carcinomas of the breast, cervix, colon, lung, nasopharynx and prostate.
  • Hu-mda-7 mRNA is stably expressed in the thymus, spleen and peripheral blood leukocytes.
  • De novo mda-7 mRNA expression is also detected in human melanocytes and expression is inducible in cells of melanocyte/melanoma lineage and in certain normal and cancer cell types following treatment with a combination of IFN-beta plus MEZ.
  • Mda-7 expression is also induced during megakaryocyte differentiation induced in human hematopoietic cells by treatment with TPA (12-O-tetradecanoyl phorbol-13-acetate).
  • In contrast, de novo expression of mda-7 is not detected nor is it inducible by IFN-beta+MEZ in a spectrum of additional normal and cancer cells.
  • No correlation was observed between induction of mda-7 mRNA expression and growth suppression following treatment with IFN-beta+MEZ and induction of endogenous mda-7 mRNA by combination treatment did not result in significant intracellular MDA-7 protein.
  • Mda-7 represents a differentiation, growth and apoptosis associated gene with potential utility for the gene-based therapy of diverse human cancers.
  • [MeSH-major] Antigens, Neoplasm / genetics. Apoptosis / genetics. Chromosomes, Human, Pair 1 / genetics. Diterpenes. Genes. Growth Substances / genetics. Interleukins. Neoplasm Proteins / genetics. Neoplasms / genetics
  • [MeSH-minor] Base Sequence. Carcinoma / pathology. Cell Differentiation / drug effects. Cell Differentiation / genetics. Cell Division / genetics. Cloning, Molecular. Dimethyl Sulfoxide / pharmacology. Female. Gene Expression Regulation, Neoplastic / drug effects. Genes, Tumor Suppressor. Glioblastoma / pathology. HL-60 Cells / metabolism. HL-60 Cells / pathology. Humans. Interferon Type I / pharmacology. K562 Cells / metabolism. K562 Cells / pathology. Male. Melanocytes / metabolism. Melanoma / chemistry. Melanoma / genetics. Melanoma / pathology. Molecular Sequence Data. Molecular Weight. Organ Specificity. Osteosarcoma / pathology. RNA, Messenger / biosynthesis. RNA, Messenger / genetics. RNA, Neoplasm / biosynthesis. RNA, Neoplasm / genetics. Recombinant Fusion Proteins / physiology. Recombinant Proteins. Terpenes / pharmacology. Tetradecanoylphorbol Acetate / pharmacology. Transfection. Tumor Cells, Cultured / pathology

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  • (PMID = 11704829.001).
  • [ISSN] 0950-9232
  • [Journal-full-title] Oncogene
  • [ISO-abbreviation] Oncogene
  • [Language] eng
  • [Grant] United States / NCI NIH HHS / CA / CA35675; United States / NCI NIH HHS / CA / CA80826; United States / NIAMS NIH HHS / AR / P30-AR44535
  • [Publication-type] Comparative Study; Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, Non-P.H.S.; Research Support, U.S. Gov't, P.H.S.
  • [Publication-country] England
  • [Chemical-registry-number] 0 / Antigens, Neoplasm; 0 / Diterpenes; 0 / Growth Substances; 0 / Interferon Type I; 0 / Interleukins; 0 / Neoplasm Proteins; 0 / RNA, Messenger; 0 / RNA, Neoplasm; 0 / Recombinant Fusion Proteins; 0 / Recombinant Proteins; 0 / Terpenes; 0 / interleukin-24; 34807-41-5 / mezerein; NI40JAQ945 / Tetradecanoylphorbol Acetate; YOW8V9698H / Dimethyl Sulfoxide
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6. Tsurusaki M, Mimura F, Sugihara R, Okada M: [A case of advanced thymic cancer successfully treated with neoadjuvant intra-arterial infusion chemotherapy]. Gan To Kagaku Ryoho; 2003 Nov;30(12):1959-62
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  • [Title] [A case of advanced thymic cancer successfully treated with neoadjuvant intra-arterial infusion chemotherapy].
  • We report the case of a 68-year-old man with advanced thymic cancer who was diagnosed as having squamous cell carcinoma by percutaneous needle biopsy.
  • The CT scan showed pre-cardiac and pulmonary invasion, therefore the tumor was classified as Masaoka's stage III.
  • Induction systemic chemotherapy consisting of CDDP (70 mg/m2, day 1), ADM (40 mg/m2, day 1) and ETP (70 mg/m2, day 1-3) was performed for the purpose of reducing the tumor size; however, the tumor's size did not shrink.
  • Therefore, second line chemotherapy combined with selective intra-arterial infusion chemotherapy and systemic chemotherapy consisting of CDDP (70 mg/m2, day 1; intra-arterial), ADM (30 mg/m2, day 1; intra-arterial), VCR (0.5 mg/m2, day 3; systemic) and CPA (500 mg/m2, day 3; systemic) was performed.
  • After this treatment, the tumor was reduced in size, and an extended thymectomy was subsequently performed.
  • The histological diagnosis of the resected tumor was squamous cell carcinoma.
  • Examination of the resected tumor revealed extensive necrosis and only a few cancer cells.
  • These results show that intra-arterial infusion chemotherapy may be effective for local control of advanced thymic cancer.
  • [MeSH-major] Antineoplastic Combined Chemotherapy Protocols / therapeutic use. Carcinoma, Squamous Cell / drug therapy. Thymectomy. Thymus Neoplasms / drug therapy
  • [MeSH-minor] Aged. Cisplatin / administration & dosage. Cyclophosphamide / administration & dosage. Doxorubicin / administration & dosage. Drug Administration Schedule. Etoposide / administration & dosage. Humans. Infusions, Intra-Arterial. Infusions, Intravenous. Male. Neoadjuvant Therapy. Vincristine / administration & dosage

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  • (PMID = 14650967.001).
  • [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] 5J49Q6B70F / Vincristine; 6PLQ3CP4P3 / Etoposide; 80168379AG / Doxorubicin; 8N3DW7272P / Cyclophosphamide; Q20Q21Q62J / Cisplatin
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7. Chen T, Li D, Fu YL, Hu W: Screening of QHF formula for effective ingredients from Chinese herbs and its anti-hepatic cell cancer effect in combination with chemotherapy. Chin Med J (Engl); 2008 Feb 20;121(4):363-8
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  • [Title] Screening of QHF formula for effective ingredients from Chinese herbs and its anti-hepatic cell cancer effect in combination with chemotherapy.
  • BACKGROUND: Recent studies have shown that effective ingredients of Chinese herbs are used more and more widely in the treatment or co-treatment of cancers, however, they are usually used separately and there has been limited research about joint application of Chinese herbs in multi-modal treatment.
  • The aim of this study was to screen a QHF (Q: Qingrejiedu, H: Huoxuehuayu and F: Fuzhengguben) formula for effective ingredients from Chinese medicines and assess its anti-hepatic cell cancer (HCC) effect in combination with chemotherapy.
  • The QHF formula and the best ratio of ingredients were evaluated in H(22) mouse (KM) models with solid tumors and ascites tumors by uniform design and monitoring inhibition of tumor growth and survival.
  • We then observed the anti-hepatic cell cancer (HCC) effect of QHF when combined with cisplatin (DDP) in H(22) mouse (Balb/c) models with solid tumors and ascites tumors.
  • Evaluating of the therapeutic effect included the general condition of the mice, inhibition of tumor growth, survival, changes in body weight, thymus index, spleen index and WBC counts.
  • RESULTS: The optimal QHF dose ratio for anti-hepatic cell cancer treatment was: 800 mg/kg Cinobufotalin, 14 mg/kg Ginsenosides Rg3, 5.5 mg/kg PNS and 100 mg/kg Lentinan.
  • Treatment was more efficient in inhibiting the growth of transplanted tumors in H(22) mice when using the QHF formula (55.91%) than using Cinobufotalin (33.25%), Ginsenosides Rg3 (35.11%), PNS (27.12%) or Lentinan (4.97%) separately.
  • QHF also prolonged the life of H(22) ascites hepatic cancer mice more efficiently (38.13%) than Cinobufotalin (25.00%), Ginsenosides Rg3 (27.27%), PNS (23.30%) or Lentinan (24.43%).
  • QHF combined with DDP could reduce DDP-induced leucopenia, spleen and thymus atrophy and other toxic reactions.
  • Combining QHF with DDP the tumor growth inhibition reached 82.54% with a 66.83% increase in survival.
  • CONCLUSIONS: QHF is more efficient in anti-hepatic cell cancer treatment than the single drugs that constitute the formula.
  • QHF combined with DDP can attenuate tumor growth and suppresses the DDP-induced toxic reactions.
  • [MeSH-major] Antineoplastic Agents, Phytogenic / administration & dosage. Antineoplastic Combined Chemotherapy Protocols / therapeutic use. Drugs, Chinese Herbal / administration & dosage. Liver Neoplasms, Experimental / drug therapy. Phytotherapy
  • [MeSH-minor] Animals. Body Weight / drug effects. Cisplatin / administration & dosage. Male. Mice. Mice, Inbred BALB C. Organ Size / drug effects

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  • (PMID = 18304471.001).
  • [ISSN] 0366-6999
  • [Journal-full-title] Chinese medical journal
  • [ISO-abbreviation] Chin. Med. J.
  • [Language] eng
  • [Publication-type] Journal Article
  • [Publication-country] China
  • [Chemical-registry-number] 0 / Antineoplastic Agents, Phytogenic; 0 / Drugs, Chinese Herbal; Q20Q21Q62J / Cisplatin
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8. Hasegawa S, Ito H, Kojima Y, Nakayama H, Wada N, Inui K, Imoto K, Rino Y, Takanashi Y: [A case of thymic cancer with pericardial tamponade as initial manifestation]. Gan To Kagaku Ryoho; 2006 Jan;33(1):79-82
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  • [Title] [A case of thymic cancer with pericardial tamponade as initial manifestation].
  • We report a case of thymic cancer with pericardial tamponade in a 70-year-old woman.
  • The effusion was serous fluid, not bloody, and no malignant cells were found.
  • The patient underwent a tumor resection, and the final pathological diagnosis was squamous cell carcinoma of the thymus.
  • In a review of 14 cases of thymic tumor with pericardial tamponade as initial manifestations in the Japanese literature,there were only three cases of thymic cancer.
  • The prognosis was reported to be extremely poor.Some reports showed the effectiveness of chemotherapy and irradiation therapy.
  • We should keep looking for the best treatment for this disease.
  • [MeSH-major] Carcinoma, Squamous Cell / complications. Cardiac Tamponade / etiology. Thymus Neoplasms / complications
  • [MeSH-minor] Aged. Bone Neoplasms / secondary. Combined Modality Therapy. Female. Humans. Liver Neoplasms / secondary. Pericardial Effusion / etiology

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  • (PMID = 16410702.001).
  • [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
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9. Aspinall R, Andrew D: Thymic atrophy in the mouse is a soluble problem of the thymic environment. Vaccine; 2000 Feb 25;18(16):1629-37
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  • [Title] Thymic atrophy in the mouse is a soluble problem of the thymic environment.
  • The clinical presentations of such immune dysfunction are an age-related increased susceptibility to certain infections, and an increased incidence of autoimmune disease and certain cancers.
  • These manifestations are thought to be causally linked to an age associated involution of the thymus, which precedes the onset of immune dysfunction.
  • Hypotheses to account for the age-related changes in the thymus include: (i) an age related decline in the supply of T cell progenitors from the bone marrow (ii) an intrinsic defect in the marrow progenitors, or (iii) problems with rearrangement of the TCR beta chain because of a defect in the environment provided by the thymus.
  • The results from these studies reveal no age related decline either in the number of function of T cell progenitors in the thymus, but changes in the thymic environment in terms of the cytokines produced.
  • We have shown that specific cytokine replacement therapy leads to an increase in thymopoiesis in old animals.
  • [MeSH-major] Aging / immunology. Aging / pathology. Thymus Gland / immunology. Thymus Gland / pathology
  • [MeSH-minor] Animals. Atrophy. Gene Rearrangement, beta-Chain T-Cell Antigen Receptor. Hematopoiesis / drug effects. Hematopoietic Stem Cells / immunology. Hematopoietic Stem Cells / pathology. Interleukin-7 / metabolism. Interleukin-7 / pharmacology. Mice. Models, Biological. Receptors, Antigen, T-Cell, alpha-beta / metabolism. T-Lymphocyte Subsets / immunology. T-Lymphocyte Subsets / pathology

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  • (PMID = 10689140.001).
  • [ISSN] 0264-410X
  • [Journal-full-title] Vaccine
  • [ISO-abbreviation] Vaccine
  • [Language] eng
  • [Publication-type] Journal Article; Research Support, Non-U.S. Gov't; Review
  • [Publication-country] ENGLAND
  • [Chemical-registry-number] 0 / Interleukin-7; 0 / Receptors, Antigen, T-Cell, alpha-beta
  • [Number-of-references] 68
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10. Michalak EM, Vandenberg CJ, Delbridge AR, Wu L, Scott CL, Adams JM, Strasser A: Apoptosis-promoted tumorigenesis: gamma-irradiation-induced thymic lymphomagenesis requires Puma-driven leukocyte death. Genes Dev; 2010 Aug 1;24(15):1608-13
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  • [Title] Apoptosis-promoted tumorigenesis: gamma-irradiation-induced thymic lymphomagenesis requires Puma-driven leukocyte death.
  • Although tumor development requires impaired apoptosis, we describe a novel paradigm of apoptosis-dependent tumorigenesis.
  • Because DNA damage triggers apoptosis through p53-mediated induction of BH3-only proteins Puma and Noxa, we explored their roles in gamma-radiation-induced thymic lymphomagenesis.
  • Tumor suppression by Puma deficiency reflected its protection of leukocytes from gamma-irradiation-induced death, because their glucocorticoid-mediated decimation in Puma-deficient mice activated cycling of stem/progenitor cells and restored thymic lymphomagenesis.
  • Our demonstration that cycles of cell attrition and repopulation by stem/progenitor cells can drive tumorigenesis has parallels in human cancers, such as therapy-induced malignancies.

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  • (PMID = 20679396.001).
  • [ISSN] 1549-5477
  • [Journal-full-title] Genes & development
  • [ISO-abbreviation] Genes Dev.
  • [Language] ENG
  • [Grant] United States / NCI NIH HHS / CA / R01 CA043540; United States / NCI NIH HHS / CA / R01 CA043540-22; United States / NCI NIH HHS / CA / CA043540
  • [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 / Antineoplastic Agents, Hormonal; 0 / Apoptosis Regulatory Proteins; 0 / PUMA protein, mouse; 0 / Pmaip1 protein, mouse; 0 / Proto-Oncogene Proteins c-bcl-2; 0 / Tumor Suppressor Protein p53; 0 / Tumor Suppressor Proteins; 7S5I7G3JQL / Dexamethasone
  • [Other-IDs] NLM/ PMC2912558
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11. Matsuoka T, Kobayashi S, Oka K, Sakano H, Kawano K, Katoh T: [Thymic cancer with superior vena cava invasion reconstructed by ready-made Y-graft]. Kyobu Geka; 2010 May;63(5):379-81
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  • [Title] [Thymic cancer with superior vena cava invasion reconstructed by ready-made Y-graft].
  • Computed tomography (CT) showed the lobulated tumor suspected of superior vena cava (SVC) invasion, located in the anterior mediastinum, 5 x 3 cm in size.
  • Histopathological diagnosis was thymic cancer, poorly differentiated squamous cell carcinoma.
  • Postoperative radiotherapy (RT : 12.6 Gy) was canceled for the side effect.
  • Alternatively, adjuvant chemotherapy [carboplatin (CBDCA) +paclitaxel (PTX)] was administered.
  • Additional RT (50 Gy) was given to the lesion of local recurrence 1 and half year after the operation.
  • [MeSH-major] Carcinoma, Squamous Cell / pathology. Neoplasm Invasiveness / pathology. Thymus Neoplasms / pathology. Vena Cava, Superior / pathology. Vena Cava, Superior / surgery

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  • (PMID = 20446606.001).
  • [ISSN] 0021-5252
  • [Journal-full-title] Kyobu geka. The Japanese journal of thoracic surgery
  • [ISO-abbreviation] Kyobu Geka
  • [Language] jpn
  • [Publication-type] Case Reports; English Abstract; Journal Article
  • [Publication-country] Japan
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12. Muro M, Kubo S, Yoshioka T, Idani H, Ishikawa T, Ishii T, Asami S, Kurose Y, Hirata M, Yamashita T, Kin H: [Thymic carcinoma; report of a case]. Kyobu Geka; 2009 Feb;62(2):169-71
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  • [Title] [Thymic carcinoma; report of a case].
  • Chest computed tomography scan and magnetic resonance imaging demonstrated an anterior mediastinal tumor.
  • The tumor was extirpated completely with combined partial resection of the left lung through a median sternotomy.
  • Microscopically, the tumor was diagnosed thymic cancer, basaloid carcinoma.
  • The patient was treated with combination chemotherapy and radiation, postoperatively.
  • We reported a case of thymic carcinoma.
  • [MeSH-major] Carcinoma, Transitional Cell / surgery. Thymus Neoplasms / surgery
  • [MeSH-minor] Chemotherapy, Adjuvant. Diagnostic Imaging. Female. Humans. Middle Aged. Radiotherapy, Adjuvant. Sternum / surgery. Thymectomy. Treatment Outcome

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  • (PMID = 19202942.001).
  • [ISSN] 0021-5252
  • [Journal-full-title] Kyobu geka. The Japanese journal of thoracic surgery
  • [ISO-abbreviation] Kyobu Geka
  • [Language] jpn
  • [Publication-type] Case Reports; English Abstract; Journal Article
  • [Publication-country] Japan
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13. Ponchel F, Verburg RJ, Bingham SJ, Brown AK, Moore J, Protheroe A, Short K, Lawson CA, Morgan AW, Quinn M, Buch M, Field SL, Maltby SL, Masurel A, Douglas SH, Straszynski L, Fearon U, Veale DJ, Patel P, McGonagle D, Snowden J, Markham AF, Ma D, van Laar JM, Papadaki HA, Emery P, Isaacs JD: Interleukin-7 deficiency in rheumatoid arthritis: consequences for therapy-induced lymphopenia. Arthritis Res Ther; 2005;7(1):R80-92
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  • [Title] Interleukin-7 deficiency in rheumatoid arthritis: consequences for therapy-induced lymphopenia.
  • We previously demonstrated prolonged, profound CD4+ T-lymphopenia in rheumatoid arthritis (RA) patients following lymphocyte-depleting therapy.
  • Poor reconstitution could result either from reduced de novo T-cell production through the thymus or from poor peripheral expansion of residual T-cells.
  • Interleukin-7 (IL-7) is known to stimulate the thymus to produce new T-cells and to allow circulating mature T-cells to expand, thereby playing a critical role in T-cell homeostasis.
  • To investigate whether such an IL-7 deficiency could account for the prolonged lymphopenia observed in RA following therapeutic lymphodepletion, we compared RA patients and patients with solid cancers treated with high-dose chemotherapy and autologous progenitor cell rescue.
  • Chemotherapy rendered all patients similarly lymphopenic, but this was sustained in RA patients at 12 months, as compared with the reconstitution that occurred in cancer patients by 3-4 months.
  • The main distinguishing feature between the groups was a failure to expand peripheral T-cells in RA, particularly memory cells during the first 3 months after treatment.
  • Most importantly, there was no increase in serum IL-7 levels in RA, as compared with a fourfold rise in non-RA control individuals at the time of lymphopenia.
  • Our data therefore suggest that RA patients are relatively IL-7 deficient and that this deficiency is likely to be an important contributing factor to poor early T-cell reconstitution in RA following therapeutic lymphodepletion.
  • Furthermore, in RA patients with stable, well controlled disease, IL-7 levels were positively correlated with the T-cell receptor excision circle content of CD4+ T-cells, demonstrating a direct effect of IL-7 on thymic activity in this cohort.
  • [MeSH-minor] Antibodies, Monoclonal / adverse effects. Antibodies, Monoclonal / therapeutic use. Antibodies, Monoclonal, Humanized. Antibodies, Neoplasm / adverse effects. Antibodies, Neoplasm / therapeutic use. Blood Specimen Collection / instrumentation. Bone Marrow / metabolism. Cells, Cultured / metabolism. Cohort Studies. Combined Modality Therapy. Cytokines / blood. Gene Rearrangement, T-Lymphocyte. Humans. Interleukin-6 / blood. Lymphopoiesis. Neoplasms / drug therapy. Neoplasms / therapy. Oncostatin M. Peripheral Blood Stem Cell Transplantation. Stromal Cells / metabolism. Thymus Gland / pathology. Transforming Growth Factor beta / blood. Tumor Necrosis Factor-alpha / analysis. Tumor Necrosis Factor-alpha / antagonists & inhibitors

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  • (PMID = 15642146.001).
  • [ISSN] 1478-6362
  • [Journal-full-title] Arthritis research & therapy
  • [ISO-abbreviation] Arthritis Res. Ther.
  • [Language] eng
  • [Publication-type] Journal Article; Research Support, Non-U.S. Gov't
  • [Publication-country] England
  • [Chemical-registry-number] 0 / Antibodies, Monoclonal; 0 / Antibodies, Monoclonal, Humanized; 0 / Antibodies, Neoplasm; 0 / Cytokines; 0 / Interleukin-6; 0 / Interleukin-7; 0 / OSM protein, human; 0 / Transforming Growth Factor beta; 0 / Tumor Necrosis Factor-alpha; 106956-32-5 / Oncostatin M; 3A189DH42V / alemtuzumab
  • [Other-IDs] NLM/ PMC1064881
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14. Okada M, Koizumi T, Yasuo M, Tsushima K, Urushihata K, Yamaguchi S, Hanaoka M, Fujimoto K, Kubo K: [Successful treatment of intrapericardial administration of carboplatin following systemic chemotherapy in a case of advanced thymic cancer with cardiac tamponade]. Nihon Kokyuki Gakkai Zasshi; 2006 Dec;44(12):968-72
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  • [Title] [Successful treatment of intrapericardial administration of carboplatin following systemic chemotherapy in a case of advanced thymic cancer with cardiac tamponade].
  • A 72-year-old woman developed cardiac tamponade due to direct invasion of thymic cancer.
  • Carboplatin was administered into the pericardial cavity two times with a total dose of 600 mg.
  • Following four cycles of systemic chemotherapy by carboplatin, doxorubicin, vincristine, cyclophosphamide (ADOC), partial response was obtained.
  • She is alive 10 month after being given a diagnosis of cardiac tamponade.
  • Intrapericardial administration of carboplatin is a useful therapy for control of pericardial effusion and chemosensitive cases should de identified among patients with thymic cancer.
  • [MeSH-major] Antineoplastic Combined Chemotherapy Protocols / therapeutic use. Carboplatin / administration & dosage. Carcinoma, Squamous Cell / drug therapy. Cardiac Tamponade / drug therapy. Thymus Neoplasms / drug therapy
  • [MeSH-minor] Aged. Cisplatin / administration & dosage. Cyclophosphamide / administration & dosage. Doxorubicin / administration & dosage. Drug Administration Schedule. Female. Humans. Liver Neoplasms / secondary. Pleural Effusion, Malignant / drug therapy. Pleural Effusion, Malignant / etiology. Remission Induction. Vincristine / administration & dosage

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  • (PMID = 17233396.001).
  • [ISSN] 1343-3490
  • [Journal-full-title] Nihon Kokyūki Gakkai zasshi = the journal of the Japanese Respiratory Society
  • [ISO-abbreviation] Nihon Kokyuki Gakkai Zasshi
  • [Language] jpn
  • [Publication-type] Case Reports; English Abstract; Journal Article
  • [Publication-country] Japan
  • [Chemical-registry-number] 5J49Q6B70F / Vincristine; 80168379AG / Doxorubicin; 8N3DW7272P / Cyclophosphamide; BG3F62OND5 / Carboplatin; Q20Q21Q62J / Cisplatin; ADOC protocol
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15. Pang X, Chen Z, Gao X, Liu W, Slavin M, Yao W, Yu LL: Potential of a novel polysaccharide preparation (GLPP) from Anhui-grown Ganoderma lucidum in tumor treatment and immunostimulation. J Food Sci; 2007 Aug;72(6):S435-42
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  • [Title] Potential of a novel polysaccharide preparation (GLPP) from Anhui-grown Ganoderma lucidum in tumor treatment and immunostimulation.
  • Growing evidence indicates the potential of developing novel polysaccharide-based adjuvant for tumor therapy from edible mushrooms, including Ganoderma lucidum.
  • GLPP was also investigated and compared with PSP (polysaccharopeptide preparation), a commercial antitumor and immunostimulating agent, for its antitumor and immunostimulation capacity, and potential in reducing the toxic effects induced by cyclophosphamide (Cy) treatment and Cobalt-60 ((60)Co) radiation in mice.
  • GLPP at levels of 100 and 300 mg/kg body weight (BW)/d significantly inhibited the growth of inoculated S(180), Heps, and EAC tumor cells in mice.
  • GLPP at a dose of 300 mg/kg BW/d showed stronger growth inhibition against all 3 tested tumor cells than PSP at 1 g/kg BW/d.
  • GLPP also dose-dependently increased phagocytic index, phagocytic coefficient, and 50% hemolysin value in the EAC tumor-bearing mice, indicating its potential immunostimulating property.
  • In addition, GLPP at 300 mg/kg BW/d was comparable to PSP at 1000 mg/kg BW/d in preventing the decrease of thymus index, spleen index, white blood cells, and bone marrow karyote numbers induced by Cy treatment and (60)Co radiation.
  • These data demonstrated the potential utilization of GLPP as an adjuvant to conventional treatments of cancers and its use for cancer prevention.
  • [MeSH-major] Phagocytosis / drug effects. Polysaccharides / analysis. Polysaccharides / therapeutic use. Reishi / chemistry
  • [MeSH-minor] Analysis of Variance. Angiogenesis Inhibitors. Animals. Antineoplastic Agents, Alkylating / adverse effects. Antineoplastic Agents, Alkylating / therapeutic use. Antineoplastic Agents, Phytogenic / analysis. Antineoplastic Agents, Phytogenic / therapeutic use. Cell Line, Tumor. Chemotherapy, Adjuvant. Cyclophosphamide / adverse effects. Cyclophosphamide / therapeutic use. Disease Models, Animal. Dose-Response Relationship, Drug. Female. Humans. Male. Mice. Mice, Inbred ICR. Molecular Weight. Random Allocation. Treatment Outcome

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  • (PMID = 17995702.001).
  • [ISSN] 1750-3841
  • [Journal-full-title] Journal of food science
  • [ISO-abbreviation] J. Food Sci.
  • [Language] eng
  • [Publication-type] Journal Article; Research Support, Non-U.S. Gov't
  • [Publication-country] United States
  • [Chemical-registry-number] 0 / Angiogenesis Inhibitors; 0 / Antineoplastic Agents, Alkylating; 0 / Antineoplastic Agents, Phytogenic; 0 / Polysaccharides; 8N3DW7272P / Cyclophosphamide
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16. Sehbai AS, Tallaksen RJ, Bennett J, Abraham J: Thymic hyperplasia after adjuvant chemotherapy in breast cancer. J Thorac Imaging; 2006 Mar;21(1):43-6
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  • [Title] Thymic hyperplasia after adjuvant chemotherapy in breast cancer.
  • We report 2 patients with breast cancer who were treated with surgery and adjuvant chemotherapy for stage IIa and stage I breast cancers.
  • Follow-up CT scans showed an anterior mediastinal mass, raising concern for tumor recurrence.
  • Thymectomy performed on the first patient, and close follow-up with radiographic studies on the second patient, revealed benign thymic enlargement.
  • Thymic hyperplasia can occur after cytotoxic chemotherapy and may be due to rebound enlargement after initial atrophy caused by chemotherapy.
  • Thymic hyperplasia after chemotherapy has been reported mostly in young age groups and is described in the literature to be associated with various types of cancers, including lymphomas, leukemias, testicular cancer, and sarcomas, and in the stem cell transplant setting.
  • This is the first case series describing 2 patients with early stage breast cancer who, following adjuvant standard dose chemotherapy, developed thymic hyperplasia.
  • Awareness of this unusual side effect in patients treated with chemotherapy may prevent unnecessary investigation and surgical intervention.
  • [MeSH-major] Breast Neoplasms / drug therapy. Thymus Hyperplasia / chemically induced. Thymus Hyperplasia / diagnosis
  • [MeSH-minor] Adult. Chemotherapy, Adjuvant / adverse effects. Diagnosis, Differential. Female. Follow-Up Studies. Humans. Middle Aged. Thymectomy / methods. Tomography, X-Ray Computed / methods


17. Kaira K, Watanabe R, Takise A, Endou K, Kamiyoshihara M, Mori M: [Thymic cancer effectively treated by combination chemotherapy of carboplatin and etoposide with concurrent radiotherapy]. Gan To Kagaku Ryoho; 2005 Nov;32(12):1989-92
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  • [Title] [Thymic cancer effectively treated by combination chemotherapy of carboplatin and etoposide with concurrent radiotherapy].
  • Percutaneous needle biopsy showed that the mass was an advanced thymic cancer (squamous cell carcinoma).
  • The patient was treated by combination chemotherapy of carboplatin and etoposide with concurrent radiotherapy (44 Gy).
  • After 3 courses of chemotherapy, the mass showed an approximately 81% reduction in tumor size and disappearance of the pericardial effusion.
  • Finally, the thymic cancer and small pulmonary metastatic lesions were all resected.
  • This concurrent chemoradiotherapy can be effective against inoperable squamous cell carcinoma of the thymus.
  • [MeSH-major] Antineoplastic Combined Chemotherapy Protocols / therapeutic use. Carcinoma, Squamous Cell / drug therapy. Carcinoma, Squamous Cell / radiotherapy. Thymus Neoplasms / drug therapy. Thymus Neoplasms / radiotherapy
  • [MeSH-minor] Carboplatin / administration & dosage. Combined Modality Therapy. Drug Administration Schedule. Etoposide / administration & dosage. Humans. Lung Neoplasms / secondary. Lung Neoplasms / surgery. Male. Middle Aged. Thymectomy

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  • (PMID = 16282742.001).
  • [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] 6PLQ3CP4P3 / Etoposide; BG3F62OND5 / Carboplatin
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18. Shintani Y, Ohta M, Hazama K, Miyoshi S, Kagisaki K, Matsuda H: Thymic carcinoma successfully resected with superior vena cava after chemoradiotherapy. Jpn J Thorac Cardiovasc Surg; 2001 Dec;49(12):717-21
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  • [Title] Thymic carcinoma successfully resected with superior vena cava after chemoradiotherapy.
  • A 57-year-old woman hospitalized for thymic cancer invading the superior vena cava and left brachiocephalic vein evidenced both pleural and pericardial effusion.
  • After chemotherapy with cisplatin and docetaxel and concurrent radiotherapy, the entire tumor was successfully resected along with the pericardium, superior vena cava, and left brachiocephalic vein, followed by vascular reconstruction.
  • Pathologically, viable tumor cells were identified only in the center of the tumor as anaplastic cell carcinoma.
  • Induction chemoradiotherapy thus appears useful in enabling complete resection of advanced thymic carcinoma.
  • [MeSH-major] Antineoplastic Combined Chemotherapy Protocols / therapeutic use. Carcinoma / surgery. Paclitaxel / analogs & derivatives. Taxoids. Thymus Neoplasms / surgery. Vena Cava, Superior / surgery
  • [MeSH-minor] Cisplatin / administration & dosage. Combined Modality Therapy. Drug Administration Schedule. Female. Humans. Middle Aged. Pericardial Effusion / etiology. Pleural Effusion, Malignant / etiology

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  • (PMID = 11808095.001).
  • [ISSN] 1344-4964
  • [Journal-full-title] The Japanese journal of thoracic and cardiovascular surgery : official publication of the Japanese Association for Thoracic Surgery = Nihon Kyōbu Geka Gakkai zasshi
  • [ISO-abbreviation] Jpn. J. Thorac. Cardiovasc. Surg.
  • [Language] eng
  • [Publication-type] Case Reports; Journal Article; Review
  • [Publication-country] Japan
  • [Chemical-registry-number] 0 / Taxoids; 15H5577CQD / docetaxel; P88XT4IS4D / Paclitaxel; Q20Q21Q62J / Cisplatin
  • [Number-of-references] 10
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19. Xu L, Chen H, Xu H, Yang X: Anti-tumour and immuno-modulation effects of triptolide-loaded polymeric micelles. Eur J Pharm Biopharm; 2008 Nov;70(3):741-8
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  • [Title] Anti-tumour and immuno-modulation effects of triptolide-loaded polymeric micelles.
  • Triptolide (TP) possesses both anti-tumour and immuno-suppressive activities.
  • Its immuno-suppressive activity may be disadvantageous for the therapy of cancers.
  • The anti-tumour and immuno-modulation effects of TP-PM were evaluated in sarcoma 180-bearing mice and A2780 cells.
  • TP-PM could significantly inhibit tumour growth via intravenous injections at the dose levels of 0.0375, 0.075 and 0.15 mg/kg, and their inhibition rates were 42.5%, 46.0% and 49.9%, respectively; they showed similar cytotoxicity against A2780 cells compared to that of TP.
  • Simultaneously, TP-PM had no effect on the thymus index, spleen index, spleen lymphocyte proliferation and the TNF-alpha and IL-2 levels in serum as compared with TP.
  • Therefore, TP encapsulated in polymeric micelles does not demonstrate immuno-suppressive activity but does not lose its anti-tumour effect.
  • These results show that polymeric micelles are a promising carrier for cancer therapy using TP.
  • [MeSH-major] Antineoplastic Agents, Alkylating / pharmacology. Diterpenes / pharmacology. Drug Carriers. Immunosuppressive Agents / pharmacology. Micelles. Phenanthrenes / pharmacology. Polyesters / chemistry. Polyethylene Glycols / chemistry. Sarcoma 180 / drug therapy
  • [MeSH-minor] Animals. Cell Line, Tumor. Cell Survival / drug effects. Chemistry, Pharmaceutical. Dose-Response Relationship, Drug. Drug Compounding. Drug Stability. Epoxy Compounds / administration & dosage. Epoxy Compounds / chemistry. Epoxy Compounds / pharmacology. Female. Humans. Injections, Intravenous. Male. Mice. Particle Size. Solubility. Technology, Pharmaceutical / methods. Time Factors

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  • (PMID = 18761405.001).
  • [ISSN] 0939-6411
  • [Journal-full-title] European journal of pharmaceutics and biopharmaceutics : official journal of Arbeitsgemeinschaft für Pharmazeutische Verfahrenstechnik e.V
  • [ISO-abbreviation] Eur J Pharm Biopharm
  • [Language] eng
  • [Publication-type] Journal Article; Research Support, Non-U.S. Gov't
  • [Publication-country] Netherlands
  • [Chemical-registry-number] 0 / Antineoplastic Agents, Alkylating; 0 / Diterpenes; 0 / Drug Carriers; 0 / Epoxy Compounds; 0 / Immunosuppressive Agents; 0 / Micelles; 0 / Phenanthrenes; 0 / Polyesters; 0 / methoxy poly(ethylene glycol)-poly(lactide); 19ALD1S53J / triptolide; 30IQX730WE / Polyethylene Glycols
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20. Okereke IC, Kesler KA, Morad MH, Mi D, Rieger KM, Birdas TJ, Badve S, Henley JD, Turrentine MW, Nelson RP, Loehrer PJ: Prognostic indicators after surgery for thymoma. Ann Thorac Surg; 2010 Apr;89(4):1071-7; discussion 1077-9
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  • METHODS: From 1989 to 2009, 83 patients underwent surgical resection of thymoma or thymic carcinoma at our institution.
  • Twelve of these patients were determined to have either World Health Organization type C disease or Masaoka stage IV-B disease and were excluded from analysis.
  • Thirteen of the 28 (46.2%) patients who presented with stage III or IV-A disease received preoperative chemotherapy.
  • Late mortality due to secondary cancers and associated immunologic disorders was more frequent than mortality from thymoma in this series.
  • [MeSH-major] Thymoma / mortality. Thymoma / surgery. Thymus Neoplasms / mortality. Thymus Neoplasms / surgery
  • [MeSH-minor] Adult. Aged. Aged, 80 and over. Female. Humans. Male. Middle Aged. Neoplasm Staging. Prognosis. Retrospective Studies. Survival Rate. Time Factors. Young Adult

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  • [Copyright] Copyright (c) 2010 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.
  • (PMID = 20338309.001).
  • [ISSN] 1552-6259
  • [Journal-full-title] The Annals of thoracic surgery
  • [ISO-abbreviation] Ann. Thorac. Surg.
  • [Language] eng
  • [Publication-type] Journal Article
  • [Publication-country] Netherlands
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21. Le Gall JY, Ardaillou R: [The biology of aging]. Bull Acad Natl Med; 2009 Feb;193(2):365-402; discussion 402-4
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  • [Transliterated title] Biologie du vieillissement.
  • Their accumulation leads to DNA, lipid and protein changes, resulting in cell dysfunction;--the telomeres situated at the ends of each chromosome get shorter with time because of inadequate telomerase activity, and this appears to be associated with diminished longevity;--autophagia within lysosomes destroys altered proteins and thereby maintains cell homeostasis.
  • However, this activity diminishes with time, resulting in the accumulation of toxic metabolites in the cell, dysfunction of the endoplasmic reticulum and mitochondria, and increased apoptosis.
  • The different organs age in different ways: vessel walls become rigid due to protein glycation and develop atheroma; the heart is invaded by fibrosis; the brain suffers from neurofibrillar degeneration and senile plaques (responsible for Alzheimer's disease); the retina undergoes macular degeneration; renal function declines in parallel with the fall in the glomerular filtration rate due to a gradual decrease in the nephron pool; and immune defenses become less effective due to the functional degradation of B and T lymphocytes and thymus involution.
  • The frequency of cancers increases with age, due to the increase in somatic mutations and the decline in immune defenses.
  • Drug therapy must be adapted to age, owing to age-related changes in pharmacology.

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  • (PMID = 19718893.001).
  • [ISSN] 0001-4079
  • [Journal-full-title] Bulletin de l'Académie nationale de médecine
  • [ISO-abbreviation] Bull. Acad. Natl. Med.
  • [Language] fre
  • [Publication-type] English Abstract; Journal Article
  • [Publication-country] Netherlands
  • [Chemical-registry-number] 0 / Insulin; 0 / Reactive Oxygen Species; 67763-96-6 / Insulin-Like Growth Factor I
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22. Vignau J, Karila L, Costisella O, Canva V: [Hepatitis C, interferon a and depression: main physiopathologic hypothesis]. Encephale; 2005 May-Jun;31(3):349-57
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  • Imputability of thymic disorders caused by IFNalpha during the chronic Hepatitis C treatment -- hepatitis C and depression -- the infection by the hepatitis C virus (HCV) is a major public health concern since it affects 1.2% in the French population.
  • In drug-addicted subjects using intravenous route, HCV contamination rate ranges from 74 to 100%.
  • Interferon alpha and depression - Interferons are a variety of cytokines naturally produced by human tissues and have also been synthesized for therapeutic purposes (treatment of a variety of cancers and viral infections).
  • Many psychobehavioural symptoms are observed under IFNalpha treatment.
  • Among them, mood disorders are known to occur early after entry into treatment and to be within the reach of preventive measures.
  • The reported frequency of depression during IFNalpha treatment ranges from 0 to 37%.
  • This variation reflects either methodological biases (eg differences in psychiatric assessment) or the heterogeneity of the population of patients accepted in therapeutic protocols.
  • Note that the adjunction of ribavirine to IFNalpha in therapeutic protocols has not brought any changes in the depression frequency.
  • Miscellaneous pathophysiological hypotheses -- nature of the psychobehavioural symptomatology -- in addition to depressive symptoms, IFNalpha treatment also induces various cognitive impairments and disruptions in EEG patterns.
  • Data resulting from pharmacological trials in humans and in animals are controversial (eg IFNalpha-induced symptoms being alleviated by both immune and antidepressant therapies).
  • However, the debate about the nature of the psychobehavioural disorders observed under IFNalpha treatment might be no longer relevant in the light of recent theories which regard depression as a maladaptive response to a particular form of stress, namely a deep and diffuse feeling of sickness ("malaise").
  • The therapeutic effects of anti-depressive drugs are thus attributed to their analgesic properties, reducing the "malaise" feeling underlying depressive symptoms.
  • IFNalpha treatment is reported to produce:.
  • CONCLUSION: A better understanding of pathophysiologic mechanisms underlying psychiatric side-effects of IFNalpha is essential to extend access to treatment to some categories of patients that remain excluded from the protocols.
  • A better management of those psychiatric side effects should help the clinician not to draw aside patients at risk, ie patients with depression, drug and alcohol addiction.
  • Treating them in a pragmatic and careful way is a major issue, since this population represents a high percentage of the potential candidates for interferon therapy.
  • [MeSH-major] Antiviral Agents / adverse effects. Brain / drug effects. Brain / physiopathology. Depressive Disorder / chemically induced. Hepatitis C, Chronic / drug therapy. Interferon-alpha / adverse effects
  • [MeSH-minor] Cognition Disorders / chemically induced. Humans. Monoamine Oxidase / metabolism. Thymus Gland / drug effects. Thymus Gland / physiopathology

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  • (PMID = 16142050.001).
  • [ISSN] 0013-7006
  • [Journal-full-title] L'Encéphale
  • [ISO-abbreviation] Encephale
  • [Language] fre
  • [Publication-type] English Abstract; Journal Article; Review
  • [Publication-country] France
  • [Chemical-registry-number] 0 / Antiviral Agents; 0 / Interferon-alpha; EC 1.4.3.4 / Monoamine Oxidase
  • [Number-of-references] 95
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23. Tampellini M, Alabiso I, Sculli CM, Barberis M, Giachino D, Berruti A, Dogliotti L: Stage IB malignant thymoma in a Lynch syndrome patient with multiple cancers: response to incidental administration of oxaliplatin and 5-fluorouracil. J Chemother; 2006 Aug;18(4):433-6
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  • [Title] Stage IB malignant thymoma in a Lynch syndrome patient with multiple cancers: response to incidental administration of oxaliplatin and 5-fluorouracil.
  • Chemotherapy is active against malignant thymomas, improving the resectability rate and the outcome of the advanced stages.
  • We report the case of a 55 year-old woman with a history of multiple neoplasms including a mixed malignant thymoma WHO type B2 and three synchronous adenocarcinomas of the colon.
  • However, 8 cycles of chronomodulated oxaliplatin, 5-fluorouracil and leucovorin as adjuvant treatment for her colon cancers resulted in a > 30% decrease in the longest diameter of the mediastinal mass.
  • [MeSH-major] Antineoplastic Combined Chemotherapy Protocols / therapeutic use. Colorectal Neoplasms, Hereditary Nonpolyposis / drug therapy. Neoplasms, Multiple Primary / drug therapy. Thymoma / drug therapy. Thymus Neoplasms / drug therapy
  • [MeSH-minor] Female. Fluorouracil / administration & dosage. Humans. Middle Aged. Organoplatinum Compounds / administration & dosage. Tomography, X-Ray Computed

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  • (PMID = 17024802.001).
  • [ISSN] 1120-009X
  • [Journal-full-title] Journal of chemotherapy (Florence, Italy)
  • [ISO-abbreviation] J Chemother
  • [Language] eng
  • [Publication-type] Case Reports; Journal Article
  • [Publication-country] Italy
  • [Chemical-registry-number] 0 / Organoplatinum Compounds; 04ZR38536J / oxaliplatin; U3P01618RT / Fluorouracil
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