Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0025202 (melanoma)
 69,561 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We assessed natural killer (NK) cell activity against cultured melanoma cells using a novel method, with observations on the comparative effects of interferons (IFNs) in NK-stimulating and anti-proliferative assays. Since the tumour cells tested were adherent, a semi-automated colorimetric MTT dye reduction assay was developed to assess NK activity. The three adherent human melanoma cell lines Sk-Mel-28, MM418 and MM96 were shown to be suitable targets for determining NK activity. Also, these were representative of the range of sensitivities of melanoma cells to the anti-proliferative action of type 1 IFNs. The dose-dependent stimulation of NK activity by type 1 IFNs was confirmed in this alternative assay system. IFN-alpha 2b and IFN-beta ser had equivalent stimulatory activities, and IFN-alpha 4 proved less effective, as with assays using the classical K562 system. Augmented NK cytotoxicity did not correlate with anti-proliferative effects of IFN. In anti-proliferative assays, the hierarchy of activity is IFN-beta greater than IFN-alpha 2 greater than IFN-alpha 4, whereas, in the NK augmentation assay IFN-beta and IFN-alpha 2 were of equivalent activity. Interestingly, MM96 was the cell line most resistant to the direct anti-proliferative action of IFN, yet it was the most susceptible of the melanoma cell lines to cytotoxicity by NK cells, whether stimulated or unstimulated by IFN.
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PMID:Natural killer cell activity against cultured melanoma cells: a dye-reduction technique with studies on augmented activity by interferon subtypes. 138 30

The increased incidence of disease, the relative unresponsiveness of advanced tumour to conventional therapies, and high socioeconomic costs make the malignant melanoma an aggressive cancer. During the last decade, several new biological agents have been developed, some of which have shown significant activity in the treatment of disease. However, the impact on the management of melanoma patients is still far from being conclusive. Among biological response modifiers (BRMs), interferons (IFNs) have generated a great deal of interest and have been extensively employed, although incorrectly. IFNs have been used without a specific rationale and at antiproliferative rather than biologically active doses; no extensive laboratory monitoring has been performed. In this paper data available in the current literature are reviewed and the efficacies of the different IFNs, used alone or in combination and in various treatment regimens, are compared in order to understand what is the place of IFNs in the management of patients with metastatic melanoma. Results are encouraging but still disappointing with the most effective treatment, with an overall response rate of 28.5% (10.5% complete responses). However, these results need confirmation. In conclusion, IFN is effective in the therapy of advanced melanoma, but improved response rates are necessary before it may be suitable for general, rather than investigative, use. Alternative biotherapeutical approaches and strategies are suggested.
Melanoma Res
PMID:Role of interferons in the therapy of melanoma. 138 54

Peripheral blood lymphocytes from 146 patients with metastatic melanoma undergoing interleukin 2 (IL-2)-based immunotherapy were characterized for HLA A, B, Cw, DR, DQw, and DRw specificities. Patients had been enrolled into sequential treatment protocols with either IL-2 alone (28) or in combination with tumor-infiltrating lymphocytes (TILs) (86), alpha-interferon (26), lymphokine-activated killer cells (16), radiation therapy (7), cyclophosphamide (3), tumor necrosis factor (1), and interleukin 4 (1) for a total of 168 courses of therapy. HLA phenotype was then correlated with response rate and toxicity to IL-2. We noted: (a) a significant difference in the frequency of A11 (20.5% versus 10.2%; P < 0.05) allele between melanoma patients and the North American Caucasian population; (b) a significantly higher frequency of A11 phenotype among responders (40.5%) than in the melanoma patient population (20.5%; P < 0.01), which was even more obvious among patients responding to TIL therapy (47.4% versus 22.1%; P < 0.05); within TIL patients, responders also had an increased frequency of A19 (42.1% versus 25.6%; P < 0.05); (c) a correlation between the number of TILs received and response rate (P < 0.005); and (d) an association between DR4 haplotype and decreased tolerance to IL-2 among the patients receiving TILs (P = 0.01). These results suggest that, in melanoma patients, some HLA Class I specificities may predict for a greater likelihood of response to IL-2-based therapy, while HLA Class II phenotype correlates with tolerance to the combination of TIL and IL-2 therapy.
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PMID:HLA association with response and toxicity in melanoma patients treated with interleukin 2-based immunotherapy. 142 1

Genetic studies have implicated the early involvement of a gene on chromosome arm 9p in the development of cutaneous melanoma. We have performed loss-of-heterozygosity studies to confirm these original findings and identify the most frequently rearranged or deleted region of 9p. Eight markers were analyzed, including (from 9pter to proximal 9q) D9S33, the beta-interferon (IFNB1) locus, the alpha-interferon (IFNA) gene cluster, D9S126, D9S3, D9S19, the glycoprotein 4 beta-galactosyltransferase (GGTB2) gene, and the argininosuccinate synthetase pseudogene 3 (ASSP3). Two or more of these loci were found to be hemizygously reduced in 12 of 14 (86%) informative metastatic melanoma tumor and cell line DNAs, and homozygous deletions of the marker D9S126 were observed in 2 of 20 (10%) melanoma cell lines. These findings have resulted in the identification of a small critical region of 2-3 megabases on 9p21 in which a putative melanoma tumor-suppressor gene appears likely to reside. Several 9p candidate genes, including IFNB1, the IFNA gene cluster, GGTB2, and the tyrosinase-related protein (TYRP) locus, have all been eliminated as potential targets because they are located outside of the homozygously deleted regions.
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PMID:Homozygous deletions within human chromosome band 9p21 in melanoma. 143 46

Interferon-alpha and dacarbazine combination is a milestone in the treatment of metastatic malignant melanoma. Objective response rate ranged from 3% to 25%. Our phase II study included 34 patients; the overall response was 29.4%. Median time of survival of the responders was significantly longer than that of the nonresponders. Nine of the 34 patients had previously progressed on interleukin-2 (IL-2) and dacarbazine treatment, or had been withdrawn because of unacceptable toxicity. Two patients (22.2%) achieved partial responses. There seemed to be no cross-resistance between the two biologic response modifiers. Successful treatment of melanoma patients by interferon resulted in complete disappearance of all extracerebral lesions, but left the brain vulnerable to involvement by metastases, and was frequently a site of relapse. Brain irradiation is suggested by several investigators to prevent cerebral involvement. Ongoing protocols are an adjuvant treatment for high-risk patients and combination of interferon-alpha, IL-2, dacarbazine and cisplatinum for metastatic melanoma after failure of interferon-dacarbazine regimen.
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PMID:Our experience with interferon alpha: metastatic malignant melanoma. 144 67

Interferon (IFN) has numerous biological properties, and more recently a new role for interferon has emerged, as a modulator of cytotoxic chemotherapeutic agents. This is based upon preclinical data that demonstrate additive and/or synergistic effects of IFN with a number of anticancer drugs including cisplatin against human cancer cell lines. Therefore, we evaluated the outpatient use of recombinant alpha 2a-interferon, 3-15 MU/m2 given on 3 consecutive days, subcutaneously, followed by intravenously administered cisplatin, 25-60 mg/m2, every 21 days. In this phase I clinical study, 23 patients with advanced malignant melanoma were treated. Dose-limiting toxicities included decline in performance status, fatigue, and anorexia. No synergistic or unpredictable toxicities were seen. Of the 20 patients who completed two cycles of therapy, there were three partial responses, for an overall response rate of 15%. Interestingly, responses occurred at the intermediate dose levels.
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PMID:Sequential chemotherapy and immunotherapy for the treatment of metastatic melanoma. 147 78

The aim of this phase I study was to exploit the potential efficacy of an alpha-2a-interferon (alpha-2a-IFN)-subcutaneous interleukin-2 (IL-2) combination, bypassing the toxicity usually associated with bolus or continuous infusion of IL-2. Therefore, nineteen patients with metastatic malignancies (7 melanomas, 6 renal cell carcinomas and 6 soft tissue sarcomas) were treated according to a dose escalating schedule of subcutaneous IL-2 combined with intramuscular alpha-2a-IFN for 5 days/week for 3 consecutive weeks. Cycles were repeated every 2-4 weeks unless disease progressed. Alpha-2a-IFN (3 MU/die) was given continuously, including during the rest weeks. IL-2 doses were started at 2 MIU/day/sqm and the MTD of 6 MIU/day/sqm was progressively reached. The dose of IL-2 was given twice daily every 12 hours. Both of the cytokines were administered in an outpatient setting. The main side effects were fever, chills, fatigue, hypotension, nausea and vomiting. Toxicity was correlated with IL-2 dose level. It was found to be mild at 2 and 4 MIU/day/sqm, while, in contrast, grade III toxicity was observed only at the highest dose of 6 MIU/day/sqm. However, this grade III toxicity was manageable and did not prevent continuation of the treatment as long as the dose was not increased above 6 MIU/day/sqm. Three patients, one with melanoma and two with renal cell carcinomas, obtained clinical partial responses. In eight patients, stable disease, and in the remaining eight, progression, were observed. The data suggest that the combined use of the two BRMs has manageable side effects and would seem to be efficacious. A phase II study at the recommended dose of 6 MIU/day is now necessary.
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PMID:An outpatient phase I study of a subcutaneous interleukin-2 and intramuscular alpha-2a-interferon combination in advanced malignancies. 149 78

Blood-borne metastases to a skeletal muscle are rare and may originate in various primary tumors. Recurrent solitary metastasis of renal cell carcinoma, and metastatic lesion as part of disseminated malignant melanoma in skeletal muscles are reported in two patients. In both cases interferon treatment with or without chemotherapy failed in arresting the disease.
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PMID:Metastases to skeletal muscles and interferon treatment. 151 1

Ninety-three collections of leucocytes by cytapheresis followed by separation of monocytes by centrifugal elutriation were undertaken in twelve metastatic cancer patients (four melanomas, six colon carcinomas, one ovarian carcinoma, and one lung cancer). The leucaphereses were performed aiming to collect a product, ready for introduction into the elutriation chamber, i.e., with low contamination by erythrocytes and granulocytes. The median collection of leucocytes was 7.3 x 10(9). After elutriation, purified monocytes (mean: 0.91 x 10(9)) were cultured with 3-5% autologous serum for 7 days in the presence of 250 IU/ml of recombinant human gamma-interferon (Rh-IFN gamma) for the last 18 h of culture. The median number of activated macrophages (MAK) available for reinfusion was 2.4 x 10(8) for each culture. The phenotypes and the antitumoral potentiality of MAK cells were documented. Reinfusions performed i.v. or i.p. were well tolerated with no major side effects. No complete tumor response was obtained. One partial response and two stabilizations of the disease were observed in one melanoma and two colon carcinomas.
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PMID:Adoptive immunotherapy with activated macrophages grown in vitro from blood monocytes in cancer patients: a pilot study. 151 25

Thirty-one patients, 13 males and 18 females, with metastatic malignant melanoma were treated with human leukocyte interferon (IFN) alpha. The dose was 3 x 10(6) IU daily s.c. for 6 weeks followed by 6 x 10(6) IU/day 3 times a week. Only 1 patient (3%) achieved a partial response (PR) while 14 patients (45%) had disease stabilization for 2-8 months. Three patients experienced mixed responses, where some of the metastases responded, while the others were only stabilized. Interestingly, 1 patient showed regression of lung and disappearance of liver metastases after termination of IFN treatment. Two female patients are still alive without evidence of disease. After IFN they were treated with radiotherapy or surgery. The median survival for all the patients was 48 weeks. Our conclusion is that in IFN therapy long-term follow-up is indicated even in the absence of objective responses. In spite of poor response rate IFN may contribute beneficially to survival in a proportion of patients.
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PMID:Disease stabilization by leukocyte alpha interferon and survival of patients with metastatic melanoma. 154 88


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