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1. Eberle J, Kurbanov BM, Hossini AM, Trefzer U, Fecker LF: Overcoming apoptosis deficiency of melanoma-hope for new therapeutic approaches. Drug Resist Updat; 2007 Dec;10(6):218-34
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  • [Source] The source of this record is MEDLINE®, a database of the U.S. National Library of Medicine.
  • [Title] Overcoming apoptosis deficiency of melanoma-hope for new therapeutic approaches.
  • The increased incidence of malignant melanoma in the last decades, its high mortality and pronounced therapy resistance pose an enormous challenge.
  • Important therapeutic targets for melanoma are the induction of apoptosis and suppression of survival pathways.
  • Preclinical studies have demonstrated the efficacy of pro-apoptotic Bcl-2 proteins and of death receptor ligands to trigger apoptosis in melanoma cells.
  • In the clinical setting, BH3 domain mimics and death receptor agonists are therefore considered as promising, specific novel treatments to add to the conventional pro-apoptotic strategies such as chemo- or radiotherapy.
  • However, constitutively activated survival pathways, in particular the mitogen-activated protein kinases, protein kinase B/Akt and nuclear factor (NF)-kappaB, all may work in concert to prevent effective therapy.
  • Thus, selective biologicals developed with the aim to inhibit pro-survival signaling are currently tested in melanoma.
  • For highly therapy-resistant tumors such as melanoma, development of novel drug combinations will be essential, and combinations of survival inhibitors and pro-apoptotic mediators appear most promising.
  • The challenge of the near future will be to make a rational choice of the multiple possible combinations and protocols.
  • This review gives a critical overview of proteins involved in melanoma chemoresistance, which are targets for current drug development leading to the best choice for future trials.
  • [MeSH-major] Antineoplastic Agents / therapeutic use. Antineoplastic Combined Chemotherapy Protocols / therapeutic use. Apoptosis / drug effects. Melanoma / drug therapy. Signal Transduction / drug effects
  • [MeSH-minor] Animals. Caspases / metabolism. Cell Survival / drug effects. Cysteine Proteinase Inhibitors / therapeutic use. Drug Resistance, Neoplasm. Gene Expression Regulation, Neoplastic. Humans. Intracellular Signaling Peptides and Proteins / metabolism. Mutation. Protein Kinase Inhibitors / therapeutic use. Proto-Oncogene Proteins c-bcl-2 / antagonists & inhibitors. Proto-Oncogene Proteins c-bcl-2 / metabolism. Receptors, Death Domain / agonists. Receptors, Death Domain / metabolism. Tumor Suppressor Protein p53 / metabolism

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  • (PMID = 18054518.001).
  • [ISSN] 1532-2084
  • [Journal-full-title] Drug resistance updates : reviews and commentaries in antimicrobial and anticancer chemotherapy
  • [ISO-abbreviation] Drug Resist. Updat.
  • [Language] eng
  • [Publication-type] Journal Article; Research Support, Non-U.S. Gov't; Review
  • [Publication-country] Scotland
  • [Chemical-registry-number] 0 / Antineoplastic Agents; 0 / Cysteine Proteinase Inhibitors; 0 / Intracellular Signaling Peptides and Proteins; 0 / Protein Kinase Inhibitors; 0 / Proto-Oncogene Proteins c-bcl-2; 0 / Receptors, Death Domain; 0 / Tumor Suppressor Protein p53; EC 3.4.22.- / Caspases
  • [Number-of-references] 215
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2. Bogenrieder T, Weitzel C, Schölmerich J, Landthaler M, Stolz W: Eruptive multiple lentigo-maligna-like lesions in a patient undergoing chemotherapy with an oral 5-fluorouracil prodrug for metastasizing colorectal carcinoma: a lesson for the pathogenesis of malignant melanoma? Dermatology; 2002;205(2):174-5
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  • [Source] The source of this record is MEDLINE®, a database of the U.S. National Library of Medicine.
  • [Title] Eruptive multiple lentigo-maligna-like lesions in a patient undergoing chemotherapy with an oral 5-fluorouracil prodrug for metastasizing colorectal carcinoma: a lesson for the pathogenesis of malignant melanoma?
  • Induction of multiple eruptive dermal and atypical melanocytic naevi has frequently been reported in children with malignant haematological diseases and chemotherapy-induced immunosuppression.
  • This is the first report of an adult patient to develop multiple eruptive melanocytic skin lesions while undergoing chemotherapy with an oral 5-fluorouracil prodrug for metastasizing cancer.
  • [MeSH-major] Antimetabolites, Antineoplastic / adverse effects. Carcinoma / drug therapy. Carcinoma / secondary. Colorectal Neoplasms / pathology. Deoxycytidine / adverse effects. Deoxycytidine / analogs & derivatives. Drug Eruptions / etiology. Hutchinson's Melanotic Freckle / chemically induced. Prodrugs / adverse effects. Skin Neoplasms / diagnosis
  • [MeSH-minor] Administration, Oral. Capecitabine. Fluorouracil. Humans. Male. Melanoma / physiopathology. Middle Aged. Neoplasms, Second Primary / chemically induced. Neoplasms, Second Primary / pathology. Nevus, Pigmented / chemically induced. Nevus, Pigmented / diagnosis. Nevus, Pigmented / pathology. Skin / pathology

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  • [Copyright] Copyright 2002 S. Karger AG, Basel
  • (PMID = 12218237.001).
  • [ISSN] 1018-8665
  • [Journal-full-title] Dermatology (Basel, Switzerland)
  • [ISO-abbreviation] Dermatology (Basel)
  • [Language] eng
  • [Publication-type] Case Reports; Journal Article
  • [Publication-country] Switzerland
  • [Chemical-registry-number] 0 / Antimetabolites, Antineoplastic; 0 / Prodrugs; 0W860991D6 / Deoxycytidine; 6804DJ8Z9U / Capecitabine; U3P01618RT / Fluorouracil
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3. Coleman A, Augustine CK, Beasley G, Sanders G, Tyler D: Optimizing regional infusion treatment strategies for melanoma of the extremities. Expert Rev Anticancer Ther; 2009 Nov;9(11):1599-609
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  • [Title] Optimizing regional infusion treatment strategies for melanoma of the extremities.
  • The incidence of malignant melanoma is increasing faster than any other cancer.
  • In cases of recurrent melanoma confined to the extremities, hyperthermic isolated limb perfusion and isolated limb infusion provide a way to isolate the extremity and deliver a dose of chemotherapy several orders of magnitude higher than would be tolerated systemically.
  • Currently, new chemotherapy agents and small-molecule inhibitors are being investigated as a means of overcoming chemoresistance and improving response rates.
  • In patients with advanced cutaneous disease confined to the extremities, evaluation of these new therapies can be very informative, as tissue acquisition at multiple treatment time points is easy owing to the superficial and multifocal nature of the disease.
  • Through studying the biomolecular and genetic alterations in tumor tissue in response to these new therapies, genetically customized treatment regimens in which tumor resistance and sensitivity is predicted and treatment strategy is optimized before treatment begins may soon be available.
  • Progress in regional therapy will prove not only beneficial for patients with disease confined to an extremity, but may also provide insight into developing novel treatment strategies for patients with systemic disease for whom current disease management options are poor.

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  • (PMID = 19895244.001).
  • [ISSN] 1744-8328
  • [Journal-full-title] Expert review of anticancer therapy
  • [ISO-abbreviation] Expert Rev Anticancer Ther
  • [Language] ENG
  • [Grant] United States / NCI NIH HHS / CA / CA074241-04; United States / NCRR NIH HHS / RR / TL1 RR024126; United States / NCI NIH HHS / CA / K08 CA074241-04; United States / NCRR NIH HHS / RR / TL1RR024126
  • [Publication-type] Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't; Review
  • [Publication-country] England
  • [Chemical-registry-number] 0 / Antineoplastic Agents
  • [Number-of-references] 65
  • [Other-IDs] NLM/ NIHMS169083; NLM/ PMC2819027
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4. Hayes AJ, Clark MA, Harries M, Thomas JM: Management of in-transit metastases from cutaneous malignant melanoma. Br J Surg; 2004 Jun;91(6):673-82
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  • [Title] Management of in-transit metastases from cutaneous malignant melanoma.
  • BACKGROUND: In-transit metastases from cutaneous malignant melanoma (cutaneous or subcutaneous deposits between the primary melanoma and regional lymph nodes) represent late-stage disease, and their treatment should be tailored accordingly.
  • This article reviews the pathology, clinical significance and treatment options for in-transit disease from melanoma.
  • METHODS: An initial Medline search was undertaken using the keywords 'melanoma and in-transit' and 'melanoma and non-nodal regional recurrence'.
  • The method of treatment should be tailored to the extent of cutaneous disease.
  • The first line of treatment remains complete excision with negative histopathological margins.
  • Carbon dioxide laser therapy is valuable for multiple small cutaneous deposits.
  • Systemic chemotherapy has response rates of about 25 per cent and is reserved for patients for whom surgery is no longer feasible.
  • [MeSH-major] Melanoma / secondary. Melanoma / surgery. Skin Neoplasms / surgery
  • [MeSH-minor] Amputation. Chemotherapy, Cancer, Regional Perfusion. Humans. Laser Therapy / methods. Lymphatic Metastasis. Neoplasm Recurrence, Local / etiology. Risk Factors. Terminology as Topic

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  • [Copyright] Copyright 2004 British Journal of Surgery Society Ltd. Published by John Wiley & Sons, Ltd.
  • (PMID = 15164434.001).
  • [ISSN] 0007-1323
  • [Journal-full-title] The British journal of surgery
  • [ISO-abbreviation] Br J Surg
  • [Language] eng
  • [Publication-type] Journal Article
  • [Publication-country] England
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5. Atallah E, Flaherty L: Treatment of metastatic malignant melanoma. Curr Treat Options Oncol; 2005 May;6(3):185-93
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  • [Title] Treatment of metastatic malignant melanoma.
  • The rapid increase in incidence of malignant melanoma has not been associated with better therapeutic options over the years.
  • Single-agent chemotherapy or immunotherapy remain the treatments of choice when systemic therapy is offered.
  • Dacarbazine (DTIC) is the chemotherapy of choice with a response rate of 16%.
  • However, in randomized phase III trials the two most active chemotherapy combination regimens, cisplatin, vinblastine, and DTIC (CVD) and the Dartmouth regimen (DTIC, cisplatin, bischloroethylnitrosourea , and tamoxifen), did not prove to be superior to single-agent DTIC for overall survival.
  • In patients who achieve a complete response, responses can be of greater durability than those with chemotherapy.
  • However, IL-2 and IFN administration are associated with multiple side effects, and only physicians experienced in the management of such therapies should administer them.
  • The potential benefit of combining chemotherapy with immunotherapy has led to multiple phase II trials of biochemotherapy that appeared to be associated with higher response rates and longer median survivals.
  • However, several phase III trials have been completed that have not consistently demonstrated an improvement in either response rates or overall survival, and these approaches to therapy cannot be routinely recommended outside the context of a clinical trial.
  • In our opinion, if complete metastasectomy is not feasible and in the absence of brain metastases, single-agent IL-2 is a good initial treatment choice in appropriately selected patients.
  • Single-agent chemotherapy with DTIC is the treatment of choice for patients who are not candidates for IL-2.
  • Adoptive immunotherapy combining nonmyeloablative chemotherapy with high-dose IL-2 is a potentially promising therapeutic strategy under investigation.
  • Targeted therapy is also an area of promising development as single agents, in combination, and combined with chemotherapy.
  • [MeSH-major] Melanoma / therapy. Skin Neoplasms / therapy
  • [MeSH-minor] Antineoplastic Agents / therapeutic use. Antineoplastic Combined Chemotherapy Protocols / therapeutic use. Clinical Trials as Topic. Combined Modality Therapy. Humans. Immunotherapy. Neoplasm Metastasis

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  • (PMID = 15869730.001).
  • [ISSN] 1527-2729
  • [Journal-full-title] Current treatment options in oncology
  • [ISO-abbreviation] Curr Treat Options Oncol
  • [Language] eng
  • [Publication-type] Journal Article; Review
  • [Publication-country] United States
  • [Chemical-registry-number] 0 / Antineoplastic Agents
  • [Number-of-references] 31
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6. Schwager SS, Leiter U, Buettner PG, Voit C, Marsch W, Gutzmer R, Näher H, Gollnick H, Bröcker EB, Garbe C: Management of primary and metastasized melanoma in Germany in the time period 1976-2005: an analysis of the Central Malignant Melanoma Registry of the German Dermatological Society. Melanoma Res; 2008 Apr;18(2):112-9
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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 primary and metastasized melanoma in Germany in the time period 1976-2005: an analysis of the Central Malignant Melanoma Registry of the German Dermatological Society.
  • The study also evaluated surgical management in different geographical regions and treatment options for metastasized melanoma.
  • A total of 42 625 patients with invasive primary cutaneous melanoma, recorded by the German Central Malignant Melanoma Registry between 1976 and 2005 were included.
  • Multiple linear regression analysis was used to investigate time trends of excision margins adjusted for tumour thickness.
  • In the case of primary melanoma, one-step surgery dominated until 1985 and was mostly replaced by two-step excisions since the early 1990s.
  • During the last three decades loco-regional metastases were predominantly treated by surgery (up to 80%), whereas systemic therapy decreased.
  • The primary treatment of distant metastases has consistently been systemic chemotherapy.
  • A significant trend towards two-step excisions in primary cutaneous melanoma was observed throughout Germany.
  • Management of metastasized melanoma showed a tendency towards surgical procedures in limited disease and an ongoing trend to systemic treatment in advanced disease.
  • [MeSH-major] Antineoplastic Combined Chemotherapy Protocols / therapeutic use. Melanoma / secondary. Melanoma / therapy. Skin Neoplasms / therapy

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  • (PMID = 18337647.001).
  • [ISSN] 0960-8931
  • [Journal-full-title] Melanoma research
  • [ISO-abbreviation] Melanoma Res.
  • [Language] eng
  • [Publication-type] Evaluation Studies; Journal Article
  • [Publication-country] England
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7. Guenova E, Lichte V, Hoetzenecker W, Woelbing F, Moehrle M, Roecken M, Schaller M: Nodular malignant melanoma and multiple cutaneous neoplasms under immunosuppression with azathioprine. Melanoma Res; 2009 Aug;19(4):271-3
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  • [Title] Nodular malignant melanoma and multiple cutaneous neoplasms under immunosuppression with azathioprine.
  • Immunosuppressed patients are at increased risk of skin cancer.
  • A 67-year-old renal transplant recipient developed a nodular malignant melanoma after 30 years of immunosuppression with azathioprine and prednisolone.
  • Renal transplant recipients are at high risk of developing nonmelanocytic skin tumors when on immunosuppressive therapy with cyclosporine A.
  • Less common is the development of skin cancer during immunosuppression with azathioprine.
  • Latest reports show the increased incidence of malignant melanoma in immunosuppressed patients.
  • Our case illustrates the necessity of close dermatological surveillance of allograft recipients, to assure an early recognition of any malignant skin tumor and to reduce the risk of systemic metastatic disease.
  • [MeSH-major] Azathioprine / adverse effects. Immunosuppressive Agents / adverse effects. Kidney Transplantation. Melanoma / etiology. Neoplasms, Multiple Primary / etiology. Skin Neoplasms / etiology
  • [MeSH-minor] Aged. Antineoplastic Agents, Alkylating / therapeutic use. Carcinoma, Basal Cell / etiology. Carcinoma, Basal Cell / pathology. Carcinoma, Squamous Cell / etiology. Carcinoma, Squamous Cell / pathology. Dacarbazine / analogs & derivatives. Dacarbazine / therapeutic use. Drug Therapy, Combination. Early Detection of Cancer. Humans. Lymphatic Metastasis. Male. Splenic Neoplasms / secondary

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  • (PMID = 19550360.001).
  • [ISSN] 1473-5636
  • [Journal-full-title] Melanoma research
  • [ISO-abbreviation] Melanoma Res.
  • [Language] eng
  • [Publication-type] Case Reports; Journal Article
  • [Publication-country] England
  • [Chemical-registry-number] 0 / Antineoplastic Agents, Alkylating; 0 / Immunosuppressive Agents; 7GR28W0FJI / Dacarbazine; 85622-93-1 / temozolomide; MRK240IY2L / Azathioprine
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8. Oosting SF, Peters FT, Hospers GA, Mulder NH: A patient with metastatic melanoma presenting with gastrointestinal perforation after dacarbazine infusion: a case report. J Med Case Rep; 2010;4:10
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  • [Title] A patient with metastatic melanoma presenting with gastrointestinal perforation after dacarbazine infusion: a case report.
  • INTRODUCTION: We report a rare case of gastrointestinal perforation following dacarbazine infusion for metastatic melanoma.
  • The condition is attributed to a responding malignant melanoma in the gastrointestinal tract.
  • A computed tomography scan showed massive ascites, lymphadenopathy and liver lesions suspect for metastases.
  • An upper gastrointestinal endoscopy was performed and revealed multiple dark lesions of 5 mm to 10 mm in his stomach and duodenum.When his skin was re-examined, an irregular pigmented lesion over the left clavicle measuring 15 mm x 8 mm with partial depigmentation was found.
  • Histological examination of a duodenal lesion was consistent with a diagnosis of metastatic melanoma.
  • The patient was started on systemic treatment with dacarbazine 800 mg/m2 every three weeks and he was discharged one day after the first dose.
  • A laparotomy was discussed with the patient and his family but he decided to go home with symptomatic treatment.
  • CONCLUSION: Melanoma can originate in, as well as metastasize to, the gastrointestinal tract.
  • Gastrointestinal perforations due to responding tumors are a well-known complication of systemic treatment of gastrointestinal lymphomas.
  • However, as the response rate of metastatic melanoma to dacarbazine is only 10% to 20%, and responses are usually only partial, perforation due to treatment response in metastatic melanoma is rare.Medical oncologists should be aware of the risk of bowel perforation after starting cytotoxic chemotherapy on patients with gastrointestinal metastases.

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  • (PMID = 20180962.001).
  • [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/ PMC2829594
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9. Basarab T, Millard TP, McGregor JM, Barker JN: Atypical pigmented lesions following extensive PUVA therapy. Clin Exp Dermatol; 2000 Mar;25(2):135-7
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  • [Title] Atypical pigmented lesions following extensive PUVA therapy.
  • We report a 38-year-old woman with psoriasis who developed multiple atypical lentigines following psoralen photochemotherapy (PUVA).
  • The lentigines first appeared 12 years ago, 3 years after she commenced intermittent PUVA treatment.
  • At present, a link between malignant melanoma and PUVA lentigines has not been established.
  • Instead, limited evidence suggests that PUVA lentigines may be more closely linked with the risk of nonmelanoma skin cancer.
  • [MeSH-major] Lentigo / etiology. PUVA Therapy / adverse effects
  • [MeSH-minor] Adult. Female. Humans. Psoriasis / drug therapy

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  • [CommentIn] Clin Exp Dermatol. 2001 Jul;26(5):459 [11488842.001]
  • (PMID = 10733639.001).
  • [ISSN] 0307-6938
  • [Journal-full-title] Clinical and experimental dermatology
  • [ISO-abbreviation] Clin. Exp. Dermatol.
  • [Language] eng
  • [Publication-type] Case Reports; Journal Article
  • [Publication-country] ENGLAND
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10. Soffietti R, Rudā R, Mutani R: Management of brain metastases. J Neurol; 2002 Oct;249(10):1357-69
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  • Brain metastases occur in 20-40% of patients with cancer and their frequency has increased over time.
  • Lung, breast and skin (melanoma) are the commonest sources of brain metastases, and in up to 15% of patients the primary site remains unknown.
  • After the introduction of MRI, multiple lesions have outnumbered single lesions.
  • There are no pathognomonic features on CT or MRI that distinguish brain metastases from primary malignant brain tumors or nonneoplastic conditions: therefore a tissue diagnosis by biopsy should be always obtained in patients with unknown primary tumor before undergoing radiotherapy and/or chemotherapy.
  • Symptomatic therapy includes corticosteroids to reduce vasogenic cerebral edema and anticonvulsants to control seizures.
  • The combination of surgery and whole-brain radiotherapy (WBRT) is superior to WBRT alone for the treatment of single brain metastasis in patients with limited or absent systemic disease and good neurological condition.
  • WBRT alone is the treatment of choice in patients with single brain metastasis not amenable to surgery or radiosurgery, and with an active systemic disease, and in patients with multiple brain metastases.
  • The response rate of brain metastases to chemotherapy is similar to the response rate of the primary tumor and extracranial metastases, some tumor types being more chemosensitive (small cell lung carcinoma, breast carcinoma, germ cell tumors).
  • New radiosensitizers and cytotoxic or cytostatic agents, and innovative technique of drug delivery are being investigated.
  • [MeSH-major] Brain Neoplasms / diagnosis. Brain Neoplasms / secondary. Brain Neoplasms / therapy
  • [MeSH-minor] Adrenal Cortex Hormones / therapeutic use. Anticonvulsants / therapeutic use. Drug Therapy. Humans. Neurosurgery. Prognosis. Radiosurgery. Radiotherapy. Thromboembolism / therapy. Treatment Outcome

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  • (PMID = 12382150.001).
  • [ISSN] 0340-5354
  • [Journal-full-title] Journal of neurology
  • [ISO-abbreviation] J. Neurol.
  • [Language] eng
  • [Publication-type] Journal Article; Review
  • [Publication-country] Germany
  • [Chemical-registry-number] 0 / Adrenal Cortex Hormones; 0 / Anticonvulsants
  • [Number-of-references] 134
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11. Tsuji M, Nakai N, Ueda E, Takenaka H, Katoh N, Kishimoto S: Double cancer of plantar malignant melanoma and vulvar extramammary Paget's disease. J Dermatol; 2010 May;37(5):484-7
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  • [Title] Double cancer of plantar malignant melanoma and vulvar extramammary Paget's disease.
  • The plantar lesion was a 15-mm ulcerated nodule located at the center of a 25-mm atypical pigmentation region; the nodule was clinically suspected to be a malignant melanoma.
  • There was no evidence of metastasis in the computed tomography (CT) and (18)F-fluorodeoxyglucose positron emission tomography scans.
  • Melanoma cells were identified in the sentinel lymph nodes, and left radical lymph node dissection was performed after a course of neoadjuvant chemotherapy.
  • All the lymph nodes that were resected during the second operation tested negative for melanomas, and the plantar lesion was diagnosed as a stage IIIB malignant melanoma (pT4b, Na2, M0).
  • Thereafter, we administrated four courses of chemotherapy, and 8 months after the operation, there was no evidence of recurrence or metastatic lesions.
  • We present a case report of double cancer: a plantar malignant melanoma and vulvar EMPD, and also discuss the possible genetic mutations responsible for these two tumors.
  • [MeSH-major] Foot Diseases / pathology. Melanoma / pathology. Neoplasms, Multiple Primary / pathology. Paget Disease, Extramammary / pathology. Skin Neoplasms / pathology. Vulvar Neoplasms / pathology


12. Rothfels H, Paschen A, Schadendorf D: Evaluation of combined gene regulatory elements for transcriptional targeting of suicide gene expression to malignant melanoma. Exp Dermatol; 2003 Dec;12(6):799-810
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  • [Title] Evaluation of combined gene regulatory elements for transcriptional targeting of suicide gene expression to malignant melanoma.
  • Selective killing of tumors can be achieved by targeting the transcription of suicide genes via specific DNA control elements to malignant cells.
  • Three different enhancer-promoter systems were constructed and evaluated for their capability to direct gene expression to melanoma.
  • Two tissue-specific (tyrosine and MIA) promoters and one weak viral promoter were fused to multiple tandem copies of a melanocyte-specific enhancer element.
  • Reporter gene assays revealed a maximum increase in transcription by combining each promoter with 3-4 copies of the enhancer and demonstrated that all enhancer-promoter combinations exhibited tissue-specific activity.
  • In contrast, when those combinations were employed to drive the expression of two suicide genes, encoding the diptheria toxin A chain (DT-A) and the prodrug-activating herpes simplex virus thymidine kinase (TK), respectively, only those constructs in which transcription was under control of tissue-specific promoter elements mediated selective killing of melanoma cells.
  • Our data indicate that the enhancer/tyrosinase and enhancer/MIA promoter constructs but not the viral promoter constructs can provide a valuable tool for selective suicide gene expression in melanoma.
  • [MeSH-major] Gene Expression Regulation, Neoplastic. Genes, Regulator. Genetic Therapy / methods. Melanoma / pathology. Transcription, Genetic
  • [MeSH-minor] Animals. Cell Death. Cell Line. Cell Line, Tumor. Chloramphenicol O-Acetyltransferase / genetics. Chloramphenicol O-Acetyltransferase / metabolism. Coloring Agents / pharmacology. Cytomegalovirus / genetics. DNA / genetics. Enhancer Elements, Genetic. Genes, Reporter. HeLa Cells. Humans. Mice. Neoplasm Metastasis. Plasmids / metabolism. Promoter Regions, Genetic. Tetrazolium Salts / pharmacology. Thiazoles / pharmacology. Time Factors. Transfection

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  • (PMID = 14714561.001).
  • [ISSN] 0906-6705
  • [Journal-full-title] Experimental dermatology
  • [ISO-abbreviation] Exp. Dermatol.
  • [Language] eng
  • [Publication-type] Journal Article; Research Support, Non-U.S. Gov't
  • [Publication-country] Denmark
  • [Chemical-registry-number] 0 / Coloring Agents; 0 / Tetrazolium Salts; 0 / Thiazoles; 298-93-1 / thiazolyl blue; 9007-49-2 / DNA; EC 2.3.1.28 / Chloramphenicol O-Acetyltransferase
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13. Sun W, Schuchter LM: Metastatic melanoma. Curr Treat Options Oncol; 2001 Jun;2(3):193-202
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  • [Title] Metastatic melanoma.
  • The overall survival for patients with metastatic melanoma ranges from 4.7 to 11 months, with a median survival of 8.5 months.
  • Standard treatment for patients with metastatic melanoma has not been defined.
  • The range of treatment options includes close observation, surgical resection of isolated metastases, therapy with dacarbazine, combination chemotherapy, and participation in clinical trials.
  • Numerous chemotherapeutic agents have shown activity in the treatment of malignant melanoma.
  • Dacarbazine (DTIC-Dome; Bayer Corporation, West Haven, CT) has a response rate of 15% to 20% and remains the reference agent for the treatment of metastatic disease.
  • Combination chemotherapy with or without tamoxifen has been extensively evaluated in patients with metastatic melanoma.
  • There has been widespread interest in developing immunotherapies against metastatic melanoma.
  • Biochemotherapy, which is a combination of immunotherapy and cytotoxic chemotherapy, has been studied in patients with metastatic melanoma.
  • Multiple phase II studies have demonstrated high response rates but unclear impact on overall survival.
  • Therapy is associated with significant toxicity.
  • Ongoing randomized clinical trials will clarify the role of biochemotherapy in patients with metastatic melanoma.
  • Ongoing new approaches to treatment include the therapeutic use of vaccines alone or in combination with cytokines.
  • [MeSH-major] Melanoma / therapy. Skin Neoplasms / therapy
  • [MeSH-minor] Antineoplastic Agents / therapeutic use. Clinical Trials as Topic. Combined Modality Therapy. Humans. Immunotherapy. Interferon-alpha / therapeutic use. Interleukin-2 / therapeutic use. Radiotherapy. Survival Rate

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  • (PMID = 12057119.001).
  • [ISSN] 1527-2729
  • [Journal-full-title] Current treatment options in oncology
  • [ISO-abbreviation] Curr Treat Options Oncol
  • [Language] eng
  • [Publication-type] Comparative Study; Journal Article; Review
  • [Publication-country] United States
  • [Chemical-registry-number] 0 / Antineoplastic Agents; 0 / Interferon-alpha; 0 / Interleukin-2
  • [Number-of-references] 27
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14. Tas F, Kurul S, Camlica H, Topuz E: Malignant melanoma in Turkey: a single institution's experience on 475 cases. Jpn J Clin Oncol; 2006 Dec;36(12):794-9
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  • [Title] Malignant melanoma in Turkey: a single institution's experience on 475 cases.
  • BACKGROUND: This study was performed to determine the characteristics and the clinical outcomes of patients with cutaneous melanoma in Turkey.
  • METHODS: The medical records of patients between 1991 and 2003 at Institute of Oncology were retrieved from the cancer registry.
  • RESULTS: Of the 475 adult cases with complete staging procedure, the incidence of localized (stages I-II) disease was 301 (63.4%), and followed by node involved (stage III) and metastatic (stage IV) disease with the incidence of 117 (24.6%) and 57 (12.0%), respectively.
  • The superficial spreading type was the commonest histology (52.2%).
  • Unresponsiveness to chemotherapy, visceral metastasis, multiple metastases and not given chemotherapy were the poor prognostic factors for overall survival.
  • [MeSH-major] Melanoma / epidemiology. Skin Neoplasms / epidemiology

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  • (PMID = 17060409.001).
  • [ISSN] 0368-2811
  • [Journal-full-title] Japanese journal of clinical oncology
  • [ISO-abbreviation] Jpn. J. Clin. Oncol.
  • [Language] eng
  • [Publication-type] Journal Article
  • [Publication-country] Japan
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15. Thamm DH, Huelsmeyer MK, Mitzey AM, Qurollo B, Rose BJ, Kurzman ID: RT-PCR-based tyrosine kinase display profiling of canine melanoma: IGF-1 receptor as a potential therapeutic target. Melanoma Res; 2010 Feb;20(1):35-42
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  • [Title] RT-PCR-based tyrosine kinase display profiling of canine melanoma: IGF-1 receptor as a potential therapeutic target.
  • Canine malignant melanoma (CMM) resembles human malignant melanoma in terms of metastatic behavior, refractoriness to standard therapy, and tumor antigen expression but it is largely unknown how CMM resembles human melanoma with regard to molecular pathogenesis and cellular signaling.
  • This study used a reverse transcription-PCR display technique to evaluate the expression of multiple TKs in the 17CM98 CMM cell line.
  • Interestingly, IGF-1R, JAK1, and Axl were detected in human melanoma using similar techniques, supporting the cross-species validity of this assay.
  • Expression of IGF-1R mRNA was detected in five of five additional CMM cell cultures, and IGF-1R protein was detected in five of six primary tumors evaluated, suggesting that IGF-1R expression may be common in CMM and may provide a novel target for future therapy.
  • In conclusion, this study suggests that similar TKs are expressed in human and canine melanoma, and shows potential antitumor effects of IGF-1R inhibition in CMM.
  • [MeSH-major] Dog Diseases / enzymology. Melanoma / enzymology. Melanoma / veterinary. Protein-Tyrosine Kinases / biosynthesis. Receptor, IGF Type 1 / antagonists & inhibitors. Reverse Transcriptase Polymerase Chain Reaction / veterinary. Skin Neoplasms / veterinary
  • [MeSH-minor] Animals. Cell Line, Tumor. Dogs. Humans. Protein Kinase Inhibitors / pharmacology. Pyrimidines / pharmacology. Pyrroles / pharmacology. Signal Transduction / drug effects


16. Sorolla A, Yeramian A, Dolcet X, Pérez de Santos AM, Llobet D, Schoenenberger JA, Casanova JM, Soria X, Egido R, Llombart A, Vilella R, Matias-Guiu X, Marti RM: Effect of proteasome inhibitors on proliferation and apoptosis of human cutaneous melanoma-derived cell lines. Br J Dermatol; 2008 Mar;158(3):496-504
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  • [Title] Effect of proteasome inhibitors on proliferation and apoptosis of human cutaneous melanoma-derived cell lines.
  • BACKGROUND: Cutaneous malignant melanoma is an aggressive type of skin cancer which causes disproportionate mortality in young and middle-aged adults.
  • Once disseminated, melanoma can be considered an incurable disease, highly resistant to standard antineoplastic treatment, such as chemotherapy or radiation therapy.
  • The proteasome represents a novel target for cancer therapy that can potentially be used in melanoma.
  • OBJECTIVES: To assess the effect of four structurally different proteasome inhibitors on human cutaneous melanoma-derived cell lines.
  • METHODS: Sixteen human cutaneous melanoma-derived cell lines which are original were obtained from patients who were treated by two of the authors.
  • RESULTS: Proteasome inhibitors inhibited the in vitro growth of melanoma cells, and this effect was due to a reduction in cell proliferation rate and an induction of both caspase-dependent and caspase-independent cell death.
  • CONCLUSIONS: This study provides information regarding the in vitro effects of proteasome inhibitors on melanoma cell lines, and the molecular mechanisms involved.
  • It also gives support to the future use of such inhibitors in the treatment of patients with melanoma, either administered alone or in combination with other drugs.
  • [MeSH-major] Apoptosis / drug effects. Boronic Acids / pharmacology. Cell Death / drug effects. Melanoma / drug therapy. Protease Inhibitors / pharmacology. Pyrazines / pharmacology. Skin Neoplasms / drug therapy
  • [MeSH-minor] Bortezomib. Cell Line, Tumor. Cell Proliferation / drug effects. Drug Resistance, Multiple. Female. Humans. Male. Treatment Outcome

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  • (PMID = 18205878.001).
  • [ISSN] 0007-0963
  • [Journal-full-title] The British journal of dermatology
  • [ISO-abbreviation] Br. J. Dermatol.
  • [Language] eng
  • [Publication-type] Journal Article; Research Support, Non-U.S. Gov't
  • [Publication-country] England
  • [Chemical-registry-number] 0 / Boronic Acids; 0 / Protease Inhibitors; 0 / Pyrazines; 69G8BD63PP / Bortezomib
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17. Schrofer C, Villiger P, Cathomas R: [Multiple primary neoplasms - coincidence or tumor syndrom?]. Praxis (Bern 1994); 2009 Sep 9;98(18):1027-31
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  • [Title] [Multiple primary neoplasms - coincidence or tumor syndrom?].
  • BACKGROUND: Multiple primary neoplasms occur either by hazard or in the context of hereditary cancer syndromes, after chronic toxic exposition, in immunodeficiency or as secondary malignancies after radio- and/or chemotherapy.
  • CASE REPORT: We present the history of an actually asymptomatic female patient with four different malignancies within 30 years: malignant melanoma (1976), liposarcoma (1983), carcinoma of the appendix (2006) and lymphoma (2006).
  • DISCUSSION: There is not only a remarkable variety of malignant tumors but also an extraordinary long survival without recurrence of the generalised malignomas of the skin and soft tissue (malignant melanoma and liposarcoma).
  • It is difficult to explain the entire restitution with the implemented treatments (several tumor resections, chemotherapy with Ifosfamide).
  • More than 20 years after chemotherapy, the lymphoma can be classified as a secondary malignoma.
  • We discuss the pathogenesis of multiple malignomas in further details.
  • [MeSH-major] Adenocarcinoma, Mucinous / diagnosis. Appendiceal Neoplasms / diagnosis. Ileal Neoplasms / diagnosis. Liposarcoma / diagnosis. Lymphoma, Follicular / diagnosis. Melanoma / diagnosis. Neoplasms, Second Primary / diagnosis. Skin Neoplasms / diagnosis. Soft Tissue Neoplasms / diagnosis
  • [MeSH-minor] Aged. Combined Modality Therapy. Female. Humans. Lymph Nodes / pathology. Neoplasm Staging. Syndrome

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  • (PMID = 19739050.001).
  • [ISSN] 1661-8157
  • [Journal-full-title] Praxis
  • [ISO-abbreviation] Praxis (Bern 1994)
  • [Language] ger
  • [Publication-type] Case Reports; English Abstract; Journal Article
  • [Publication-country] Switzerland
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18. Guzel A, Maciaczyk J, Dohmen-Scheufler H, Senturk S, Volk B, Ostertag CB, Nikkhah G: Multiple intracranial melanoma metastases: case report and review of the literature. J Neurooncol; 2009 Jul;93(3):413-20
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  • [Title] Multiple intracranial melanoma metastases: case report and review of the literature.
  • Although intracerebral metastases of malignant melanoma are common, those located in the sellar region and within the pontocerebellar area are extremely rare.
  • Furthermore, to our knowledge, there is no report about melanoma metastasis to the epiphysis published so far.
  • We report here a 46-year-old patient who had metastatic lesions in the sellar region, cerebellopontine area and epiphysial gland, preceded by a primary melanoma at her left shoulder.
  • The patient received whole-brain irradiation therapy combined with chemotherapy.
  • Autopsy findings confirmed melanoma metastases both in the cerebellopontine angle and additionally in the epiphysial gland.
  • To our knowledge, this is the first case of multiple intracranial melanoma metastases including the suprasellar region, the pontocerebellar and epiphysial area.
  • [MeSH-major] Brain Neoplasms / secondary. Melanoma / secondary. Skin Neoplasms / pathology
  • [MeSH-minor] Antineoplastic Agents, Alkylating / therapeutic use. Combined Modality Therapy. Cranial Irradiation. Dacarbazine / analogs & derivatives. Dacarbazine / therapeutic use. Fatal Outcome. Female. Humans. Magnetic Resonance Imaging. Middle Aged

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  • (PMID = 19184642.001).
  • [ISSN] 1573-7373
  • [Journal-full-title] Journal of neuro-oncology
  • [ISO-abbreviation] J. Neurooncol.
  • [Language] eng
  • [Publication-type] Case Reports; Journal Article; Research Support, Non-U.S. Gov't; Review
  • [Publication-country] United States
  • [Chemical-registry-number] 0 / Antineoplastic Agents, Alkylating; 7GR28W0FJI / Dacarbazine; YF1K15M17Y / temozolomide
  • [Number-of-references] 68
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19. Laffitte E, Revuz J: Thalidomide: an old drug with new clinical applications. Expert Opin Drug Saf; 2004 Jan;3(1):47-56
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  • [Title] Thalidomide: an old drug with new clinical applications.
  • Thalidomide has been used in several cutaneous inflammatory disorders (e.g., erythema nodosum leprosum in lepromatous leprosy, cutaneous lupus erythematosus and severe aphtosis), cancers (e.g., relapsed/refractory multiple myeloma, malignant melanoma and systemic signs in cancer) and inflammatory conditions (e.g., Crohn's disease and rheumatoid arthritis).
  • Somnolence and rash are frequently reported when thalidomide is used at higher doses as an anticarcinogenic agent and can lead to dose reduction or treatment discontinuation depending on severity.
  • [MeSH-major] Adjuvants, Immunologic / therapeutic use. Angiogenesis Inhibitors / therapeutic use. Hypnotics and Sedatives / therapeutic use. Thalidomide / therapeutic use
  • [MeSH-minor] Clinical Trials as Topic. Humans. Inflammation / drug therapy. Neoplasms / blood supply. Neoplasms / drug therapy. Practice Guidelines as Topic. Skin Diseases / drug therapy. Tumor Necrosis Factor-alpha / biosynthesis

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  • (PMID = 14680461.001).
  • [ISSN] 1474-0338
  • [Journal-full-title] Expert opinion on drug safety
  • [ISO-abbreviation] Expert Opin Drug Saf
  • [Language] eng
  • [Publication-type] Journal Article; Review
  • [Publication-country] England
  • [Chemical-registry-number] 0 / Adjuvants, Immunologic; 0 / Angiogenesis Inhibitors; 0 / Hypnotics and Sedatives; 0 / Tumor Necrosis Factor-alpha; 4Z8R6ORS6L / Thalidomide
  • [Number-of-references] 111
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20. Bruno G, Coppola M, Eleuteri E, Barucco M, Molfetta R, Bruno A, Angelini L: An unusual association of malignant melanoma and small cell lung cancer: case report. An eleven-year-follow-up. Clin Ter; 2003 Jul-Aug;154(4):271-5
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  • [Title] An unusual association of malignant melanoma and small cell lung cancer: case report. An eleven-year-follow-up.
  • The authors report the case of a patient affected by malignant melanoma and small cell lung cancer.
  • After having underlined the rareness of this pathological association, reviewing the most recent literature, the description of the clinical case aims at opening a discussion on how the surgical treatment performed, associated to chemotherapy, brought to an unhoped-for success, also helped by an unexpected combination of events that were absolutely out of any protocol.
  • [MeSH-major] Carcinoma, Small Cell. Lung Neoplasms. Melanoma. Skin Neoplasms
  • [MeSH-minor] Adult. Female. Follow-Up Studies. Humans. Neoplasms, Multiple Primary / diagnosis. Neoplasms, Multiple Primary / surgery. Time Factors


21. Chrissos DN, Stougiannos PN, Mytas DZ, Katsaros AA, Andrikopoulos GK, Kallikazaros IE: Multiple cardiac metastases from a malignant melanoma. Eur J Echocardiogr; 2008 May;9(3):391-2
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  • [Title] Multiple cardiac metastases from a malignant melanoma.
  • Metastatic tumors in the pericardium or the heart are more common than primary tumors and their incidence has increased during the last decades due to the prolonged survival of patients with cancer and the increased prevalence of the disease in the general population.
  • He had a history of a malignant skin melanoma surgically removed 4 years ago.
  • The echo study identified multiple metastases in the heart involving the pericardium, the myocardium and the right atrium, where the tumor was mobile creating mechanical tricuspid valve stenosis.
  • Malignant metastasis was confirmed by pericardiocentesis and, although treatment with chemotherapy was promptly initiated, the patient died 4 months later.
  • Despite the difficulty in clinical diagnosis of cardiac melanoma, early detection has important therapeutic and prognostic implications.
  • [MeSH-major] Heart Neoplasms / ultrasonography. Melanoma / ultrasonography. Skin Neoplasms / pathology

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  • (PMID = 17347051.001).
  • [ISSN] 1532-2114
  • [Journal-full-title] European journal of echocardiography : the journal of the Working Group on Echocardiography of the European Society of Cardiology
  • [ISO-abbreviation] Eur J Echocardiogr
  • [Language] eng
  • [Publication-type] Case Reports; Journal Article
  • [Publication-country] England
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22. Adedoyin OT, Johnson AW, Ojuawo AI, Afolayan EA, Adeniji KA: Malignant melanoma in a black child: predisposing precursors and management. J Natl Med Assoc; 2004 Oct;96(10):1368-73
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  • [Title] Malignant melanoma in a black child: predisposing precursors and management.
  • Malignant melanoma (MM) remains a pediatric rarity world-wide, but perhaps more so in black Africans.
  • Primary neoplastic transformation and metastatic spread were suggested by the appearance of multiple swellings over the "garment" precursor nevus at the posterior trunk, multiple ipsilateral axillary nodal enlargement, and fresh occipital swellings postadmission.
  • Chemotherapy was initiated but was truncated shortly after by parent-pressured discharge.
  • Despite the rarity of MM in a tropical African setting where management options are few, the current case underscores the need for a high clinical index of diagnostic suspicion, an early pursuit of investigative confirmation, and prophylactic excision in children with the predisposing skin lesions, like congenital giant hairy nevus.
  • [MeSH-major] African Continental Ancestry Group / genetics. Dysplastic Nevus Syndrome / complications. Melanoma / etiology. Skin Neoplasms / complications
  • [MeSH-minor] Causality. Child, Preschool. Female. Humans. Lymph Nodes / pathology. Nigeria. Risk Factors. Skin Pigmentation / genetics

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  • (PMID = 15540891.001).
  • [ISSN] 1943-4693
  • [Journal-full-title] Journal of the National Medical Association
  • [ISO-abbreviation] J Natl Med Assoc
  • [Language] eng
  • [Publication-type] Case Reports; Journal Article
  • [Publication-country] United States
  • [Other-IDs] NLM/ PMC2568537
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23. Zheng M, Bocangel D, Ramesh R, Ekmekcioglu S, Poindexter N, Grimm EA, Chada S: Interleukin-24 overcomes temozolomide resistance and enhances cell death by down-regulation of O6-methylguanine-DNA methyltransferase in human melanoma cells. Mol Cancer Ther; 2008 Dec;7(12):3842-51
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  • [Title] Interleukin-24 overcomes temozolomide resistance and enhances cell death by down-regulation of O6-methylguanine-DNA methyltransferase in human melanoma cells.
  • Melanoma is the most malignant of skin cancers, highly resistant to chemotherapy and radiotherapy.
  • Temozolomide, a promising new derivative of dacarbazine, is currently being tested for treatment of metastatic melanoma.
  • Interleukin-24 (IL-24; mda-7) is a tumor suppressor cytokine that selectively inhibits tumor cell growth by inducing apoptosis and cell cycle arrest in melanoma cell lines and solid tumors.
  • This tumor-selective activity has been observed in multiple preclinical animal models and in clinical trials.
  • In this study, we analyzed the ability of Ad-IL-24 and its protein product, IL-24, to overcome temozolomide resistance in human melanoma cells.
  • We have shown that Ad-IL-24 via exogenous IL-24 protein induces combinatorial synergy of temozolomide-induced cell killing in temozolomide-resistant melanoma cells by inhibition of MGMT.
  • Neutralizing antibodies against IL-24 or its receptors significantly blocked the apoptotic activity of IL-24 + MGMT treatment.
  • However, MGMT blockade in combination with IL-24 + temozolomide resulted in loss of combinatorial synergy, indicating that MGMT expression is required for the reversal of temozolomide resistance in melanoma cells.

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  • (PMID = 19056673.001).
  • [ISSN] 1535-7163
  • [Journal-full-title] Molecular cancer therapeutics
  • [ISO-abbreviation] Mol. Cancer Ther.
  • [Language] ENG
  • [Grant] United States / NCI NIH HHS / CA / R41 CA088421-01; United States / NCI NIH HHS / CA / R42-CA89778; United States / NCI NIH HHS / CA / R41 CA089778; United States / NCI NIH HHS / CA / CA088421-01; United States / NCI NIH HHS / CA / CA097598; United States / NCI NIH HHS / CA / R42 CA089778-07; United States / NCI NIH HHS / CA / R43 CA097598-01; United States / NCI NIH HHS / CA / R42 CA089778; United States / NCI NIH HHS / CA / CA88421; United States / NCI NIH HHS / CA / CA89778; United States / NCI NIH HHS / CA / P50CA093459; United States / NCI NIH HHS / CA / R41-CA89778; United States / NCI NIH HHS / CA / R41 CA089778-02; United States / NCI NIH HHS / CA / P50 CA093459-01A1; United States / NCI NIH HHS / CA / P50 CA093459; United States / NCI NIH HHS / CA / CA089778-02; United States / NCI NIH HHS / CA / CA097598-01; United States / NCI NIH HHS / CA / CA089778-07
  • [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, Alkylating; 0 / Interleukins; 0 / Tumor Suppressor Protein p53; 0 / interleukin-24; 7GR28W0FJI / Dacarbazine; 85622-93-1 / temozolomide; EC 2.1.1.63 / O(6)-Methylguanine-DNA Methyltransferase
  • [Other-IDs] NLM/ NIHMS84623; NLM/ PMC2653264
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24. Taylor CW, Dorr RT, Fanta P, Hersh EM, Salmon SE: A phase I and pharmacodynamic evaluation of polyethylene glycol-conjugated L-asparaginase in patients with advanced solid tumors. Cancer Chemother Pharmacol; 2001;47(1):83-8
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  • PEG-L-asparaginase was administered by intramuscular injection every 2 weeks to 28 patients with various types of advanced solid tumor malignancies.
  • RESULTS: The in vitro HTCA studies suggested good antitumor activity against malignant melanoma and multiple myeloma.
  • Three patients developed hypersensitivity reactions, but these were not dose related.
  • Two patients developed deep vein thromboses.
  • We saw no partial or complete responses in patients treated in this study, including 11 patients with malignant melanoma.
  • [MeSH-major] Antineoplastic Agents / therapeutic use. Asparaginase / therapeutic use. Glutaminase / therapeutic use. Neoplasms / drug therapy. Polyethylene Glycols / therapeutic use
  • [MeSH-minor] Adult. Asparagine / blood. Carcinoma, Non-Small-Cell Lung / drug therapy. Drug Screening Assays, Antitumor. Humans. Lung Neoplasms / drug therapy. Melanoma / drug therapy. Neoplasm Proteins / blood. Skin Neoplasms / drug therapy

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  • (PMID = 11221967.001).
  • [ISSN] 0344-5704
  • [Journal-full-title] Cancer chemotherapy and pharmacology
  • [ISO-abbreviation] Cancer Chemother. Pharmacol.
  • [Language] eng
  • [Publication-type] Clinical Trial; Clinical Trial, Phase I; Journal Article
  • [Publication-country] Germany
  • [Chemical-registry-number] 0 / Antineoplastic Agents; 0 / Neoplasm Proteins; 30IQX730WE / Polyethylene Glycols; 39335-03-0 / polyethylene glycol-glutaminase-asparaginase; 7006-34-0 / Asparagine; EC 3.5.1.1 / Asparaginase; EC 3.5.1.2 / Glutaminase
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25. Health Quality Ontario: Extracorporeal photophoresis: an evidence-based analysis. Ont Health Technol Assess Ser; 2006;6(6):1-82
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  • OBJECTIVE: To assess the effectiveness, safety and cost-effectiveness of extracorporeal photophoresis (ECP) for the treatment of refractory erythrodermic cutaneous T cell lymphoma (CTCL) and refractory chronic graft versus host disease (cGvHD).
  • BACKGROUND: CUTANEOUS T CELL LYMPHOMA: Cutaneous T cell lymphoma (CTCL) is a general name for a group of skin affecting disorders caused by malignant white blood cells (T lymphocytes).
  • The relative frequency and disease-specific 5-year survival of 1,905 primary cutaneous lymphomas classified according to the World Health Organization-European Organization for Research and Treatment of Cancer (WHO-EORTC) classification (Appendix 1).
  • Cutaneous T cell lymphoma has an annual incidence of approximately 0.4 per 100,000 and it mainly occurs in the 5(th) to 6(th) decade of life, with a male/female ratio of 2:1.
  • Mycosis fungoides is an indolent lymphoma with patients often having several years of eczematous or dermatitic skin lesions before the diagnosis is finally established.
  • Early in the disease biopsies are often difficult to interpret and the diagnosis may only become apparent by observing the patient over time.
  • Most patients will live normal lives and experience skin symptoms without serious complications.
  • A particular syndrome in these patients involves erythroderma (intense and usually widespread reddening of the skin from dilation of blood vessels, often preceding or associated with exfoliation), and circulating tumour cells.
  • CHRONIC GRAFT VERSUS HOST DISEASE: Allogeneic hematopoietic cell transplantation (HCT) is a treatment used for a variety of malignant and nonmalignant disease of the bone marrow and immune system.
  • The procedure is often associated with serious immunological complications, particularly graft versus host disease (GvHD).
  • Of the patients with extensive disease, approximately 60% will respond to treatment and eventually be able to discontinue immunosuppressive therapy.
  • The remaining patients will develop opportunistic infection, or require prolonged treatment with immunosuppressive agents.
  • The extent of involvement varies significantly from mild involvement limited to a few patches of skin to severe involvement of numerous organ systems and profound immunodeficiency.
  • The most commonly involved tissues are the skin, liver, mouth, and eyes.
  • Patients with limited disease have localized skin involvement, evidence of liver dysfunction, or both, whereas those with more involvement of the skin or involvement of other organs have extensive disease.
  • TREATMENT:   CUTANEOUS T CELL LYMPHOMA: The optimal management of MF is undetermined because of its low prevalence, and its highly variable natural history, with frequent spontaneous remissions and exacerbations and often prolonged survival.
  • Nonaggressive approaches to therapy are usually warranted with treatment aimed at improving symptoms and physical appearance while limiting toxicity.
  • Given that multiple skin sites are usually involved, the initial treatment choices are usually topical or intralesional corticosteroids or phototherapy using psoralen (a compound found in plants which make the skin temporarily sensitive to ultraviolet A) (PUVA).
  • Repeated courses are usually required which may lead to an increased risk of both melanoma and nonmelanoma skin cancer.
  • "Second line" therapy for early stage disease is often topical chemotherapy, radiotherapy or total skin electron beam radiation (TSEB).
  • Treatment of advanced stage (IIB-IV) MF usually consists of topical or systemic therapy in refractory or rapidly progressive SS.
  • Bone marrow transplantation and peripheral blood stem cell transplantation have been used to treat many malignant hematologic disorders (e.g., leukemias) that are refractory to conventional treatment.
  • Reports on the use of these procedures for the treatment of CTCL are limited and mostly consist of case reports or small case series.
  • CHRONIC GRAFT VERSUS HOST DISEASE: Patients who develop cGvHD require reinstitution of immunosuppressive medication (if already discontinued) or an increase in dosage and possibly addition of other agents.
  • The current literature regarding cGvHD therapy is less than optimal and many recommendations about therapy are based on common practices that await definitive testing.
  • Numerous salvage therapies have been considered in patients with refractory cGvHD, including ECP.
  • Due to uncertainty around salvage therapies, Bhushan and Collins suggested that ideally, patients with refractory cGvHD should be entered into clinical trials.
  • Two Ontario expert consultants jointly estimated that there may be approximately 30 new erythrodermic treatment resistant CTCL patients and 30 new treatment resistant cGvHD patients per year who are unresponsive to other forms of therapy and may be candidates for ECP.
  • Extracorporeal photopheresis is a procedure that was initially developed as a treatment for CTCL, particularly SS.
  • The lymphocyte layer is treated with methoxsalen (a drug that sensitizes the lymphocytes to light) and exposed to UVA, following which the lymphocytes are returned to the patient.
  • Photosensitization is achieved by administering methoxsalen to the patient orally 2 hours before the procedure, or by injecting methoxsalen directly ino the leucocyte rich fraction.
  • The latter approach avoids potential side effects such as nausea, and provides a more consistent drug level within the machine.
  • In general, from the time the intravenous line is inserted until the white blood cells are returned to the patient takes approximately 2.5-3.5 hours.
  • For CTCL, the treatment schedule is generally 2 consecutive days every 4 weeks for a median of 6 months.
  • For cGvHD, an expert in the field estimated that the treatment schedule would be 3 times a week for the 1(st) month, then 2 consecutive days every 2 weeks after that (i.e., 4 treatments a month) for a median of 6 to 9 months.
  • REGULATORY STATUS: The UVAR XTS Photopheresis System is licensed by Health Canada as a Class 3 medical device (license # 7703) for the "palliative treatment of skin manifestations of CTCL."
  • It is not licensed for the treatment of cGvHD.

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  • (PMID = 23074497.001).
  • [Journal-full-title] Ontario health technology assessment series
  • [ISO-abbreviation] Ont Health Technol Assess Ser
  • [Language] eng
  • [Publication-type] Journal Article
  • [Publication-country] Canada
  • [Other-IDs] NLM/ PMC3379535
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26. Padsis J, Turley R, Tyler D: Pharmacotherapy of regional melanoma therapy. Expert Opin Pharmacother; 2010 Jan;11(1):79-93
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  • [Source] The source of this record is MEDLINE®, a database of the U.S. National Library of Medicine.
  • [Title] Pharmacotherapy of regional melanoma therapy.
  • IMPORTANCE OF THE FIELD: In-transit melanoma metastases develop within regional dermal and subdermal lymphatics before reaching the regional lymph nodes.
  • The prognosis is poor and comparable to multiple nodal metastases.
  • Isolated limb infusion (ILI) or perfusion (ILP) are effective treatments for unresectable, in-transit melanoma, with response rates reaching 95%.
  • Although ILI and ILP are more effective than systemic therapy, most patients will recur, thus highlighting the need for newer strategies to improve durable response rates.
  • AREAS COVERED IN THIS REVIEW: We review historical and current literature from 1958 to 2009 regarding regional therapy for melanoma, with focus on the ILI and ILP techniques, pharmacokinetics and resistance mechanisms of melphalan.
  • Alternative therapies, adjunct strategies and new targeted therapies aimed at improving response rates and long-term remission are also discussed.
  • WHAT THE READER WILL GAIN: The reader will gain a comprehensive review on regional pharmacotherapy for melanoma, including alternative therapies, adjunct strategies and new targeted therapies.
  • TAKE HOME MESSAGE: Regional chemotherapy is a viable, evolving treatment for patients with in-transit melanoma and a springboard for ongoing research aimed at improving therapies for malignant melanoma.
  • [MeSH-major] Antineoplastic Agents, Alkylating / therapeutic use. Extremities / pathology. Lymphatic Metastasis / pathology. Melanoma / pathology. Melphalan / therapeutic use. Neoplasm Recurrence, Local
  • [MeSH-minor] Antineoplastic Combined Chemotherapy Protocols. Chemotherapy, Cancer, Regional Perfusion. Combined Modality Therapy. Humans. Hyperthermia, Induced / methods. Infusions, Intra-Arterial. Skin Neoplasms / drug therapy. Soft Tissue Neoplasms / pathology

  • MedlinePlus Health Information. consumer health - Melanoma.
  • Hazardous Substances Data Bank. MELPHALAN .
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  • (PMID = 20001431.001).
  • [ISSN] 1744-7666
  • [Journal-full-title] Expert opinion on pharmacotherapy
  • [ISO-abbreviation] Expert Opin Pharmacother
  • [Language] eng
  • [Publication-type] Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't
  • [Publication-country] England
  • [Chemical-registry-number] 0 / Antineoplastic Agents, Alkylating; Q41OR9510P / Melphalan
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27. Essner R: Surgical treatment of malignant melanoma. Surg Clin North Am; 2003 Feb;83(1):109-56
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  • [Source] The source of this record is MEDLINE®, a database of the U.S. National Library of Medicine.
  • [Title] Surgical treatment of malignant melanoma.
  • The surgical management of melanoma has evolved over the last 100 years. when early concepts of lymphatic permeation of the tumors and metastases led surgeons to perform radical operative procedures.
  • Wide excision of primary melanoma is now performed with 1- to 2-cm radial margins, significantly reducing the need for complex plastic closures, skin grafts. and hospital admissions.
  • Although elective lymph node dissection remains controversial as a therapeutic procedure, the development of SL has improved the staging of the regional lymph nodes and diminished the morbidity of lymph node dissection.
  • The role of SL for routine care of melanoma patients remains unknown.
  • Metastasectomy, which is the surgical resection of distant metastases with tumor-free surgical margins, has not been popular for AJCC stage IV patients with multiple metastases, because surgery is considered a local therapy and therefore of little value for management of disseminated disease.
  • Nevertheless, the many reports of long-term survival after resection of distant melanoma metastases to diverse soft tissue and organ sites clearly indicate that this form of cytoreductive surgery can be extremely successful in carefully selected patients.
  • Unlike chemotherapy, complete surgical metastasectomy can rapidly render a patient disease-free with only a short period of postoperative morbidity.
  • Most patients fully recover from the surgical procedure within 6 weeks, returning to most or all activities.
  • The ability to select patients for surgery is based on the development of more sophisticated imaging techniques, which allow better preoperative differentiation of patients with single versus multiple metastases and improve the surgeon's ability to identify and resect multiple metastatic sites.
  • We believe that increased understanding of the biology of the primary and metastases, dramatic improvement in the accuracy of staging metastatic disease, and better techniques of surgical resection provide the best chance for long-term palliation or cure of melanoma.
  • The long-term clinical benefit of this therapy depends on the patient's immune response to, the surgical reduction in tumor burden: an immune response that controls subclinical micrometastases should optimize postoperative survival.
  • [MeSH-major] Melanoma / surgery. Skin Neoplasms / surgery

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  • (PMID = 12691453.001).
  • [ISSN] 0039-6109
  • [Journal-full-title] The Surgical clinics of North America
  • [ISO-abbreviation] Surg. Clin. North Am.
  • [Language] eng
  • [Publication-type] Journal Article; Review
  • [Publication-country] United States
  • [Number-of-references] 267
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