Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C1522102 (Melanoma)
 7,698 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Several reports have described an inverse relationship between the frequency of infections and various malignancies. In this paper results of a hospital-based case control study on 139 melanoma patients and 271 suitable selected controls are presented, addressing the question of whether this relationship exists with respect to malignant melanoma while simultaneously controlling for the effects of other risk factors. Data on childhood diseases (group I), febrile diseases of adulthood (group II) and common febrile infections within a 5-year period prior to the diagnosis of melanoma (group III) were collected using a standardized interview. Group I diseases did not show a marked influence on the risk of malignant melanoma. Considering group II diseases, a significant protective effect was determined for chronic infectious diseases (OR = 0.32) and also for wound infections, abscesses and furunculosis (OR = 0.21). In group III, herpes simplex infections (OR = 0.45) and influenza/common cold (OR = 0.32) substantially reduced the melanoma risk. This effect was less pronounced for gastroenteritis (OR = 0.52). Analysis of the cumulative influence of infections pointed to a strong dose-response relationship between the frequency of febrile infections in adulthood and malignant melanoma. In particular, the risk reduction was striking when two or more febrile infections were compared to no febrile infections in group II (OR = 0.09) and group III (OR = 0.20). The study confirms the hypothesis that an inverse relationship exists between febrile infections and malignant melanoma, but these results have to be interpreted cautiously due to the inherent limitations of the case-control design.(ABSTRACT TRUNCATED AT 250 WORDS)
Melanoma Res 1992 Sep
PMID:Febrile infections and malignant melanoma: results of a case-control study. 145 Jun 74

Following extensive phase II trials of the combination of dacarbazine and interferon-alpha 2a we performed a prospective, randomized, controlled trial of this combination versus dacarbazine alone as systemic therapy for symptomatic, measurable metastatic malignant melanoma. The two treatment arms were well matched for age, sex, performance, status, relapse-free survival, prior therapy and sites of disease. Therapy consisted of dacarbazine given in combination in escalating doses of 200 mg/m2, 400 mg/m2 and 800 mg/m2 i.v. every 3 weeks, or alone at 800 mg/m2 i.v. every 3 weeks. Interferon was administered subcutaneously starting at 3 mU daily on days 1-3, 9 mU daily on days 4-70, then 9 mU three times per week. Therapy was continued for at least 6 months unless overt progressive disease was observed. Eighty seven patients were randomized to the combination and 83 patients to dacarbazine alone. Response rates were respectively, complete 7% and 2%, and partial 14% and 15%, for a total response rate of 21% (95% confidence limits 13-31%) and 17% (95% confidence limits 10-27%). Median duration of response was 258 and 286 days, and survival of the whole groups 229 and 269 days respectively. Toxicity was worse in the combination arm, with more patients experiencing fatigue, nausea and anorexia, flu-like symptoms and neutropenia. However quality of life was not significantly different in either group, except that fatigue, as measured at week 12 by LASA scales, and activity, as measured by the functional living index, were both improved in the combination.(ABSTRACT TRUNCATED AT 250 WORDS)
Melanoma Res 1993 Apr
PMID:Interferon-alpha 2a does not improve response or survival when combined with dacarbazine in metastatic malignant melanoma: results of a multi-institutional Australian randomized trial. 851 52

Cellular immune responses to melanoma-associated Ags are the focus of ongoing studies aimed at developing immunotherapies for treatment of malignant melanoma. Melanoma predominantly affects Caucasians, a population in whom expression of HLA-A2 is prevalent. Among HLA-A2 subtypes, HLA-A*0201 is widely expressed, and HLA-A*0201-restricted, tumor-reactive CTL responses are well studied. We have observed in a group of melanoma patients an unexpectedly high frequency (approximately 20%) of non-HLA-A*0201 subtypes (*0202, *0204, and *0205), and little is known regarding antimelanoma response profiles in patients expressing such subtypes. We analyzed non-HLA-A*0201 peptide response profiles using HLA-A*0201-restricted epitopes from melanoma Ags MART-1/Melan A and glycoprotein 100. Most of these peptides bound to the majority of subtypes tested with 50% inhibitory concentrations less than 500 nM. Recognition of cells pulsed with different peptides (MART-1(27-35), G9(154), and G9(280) Flu M1(58-66)) and expressing different subtype molecules by HLA-A*0201-restricted CTL was limited to only a subset of non-HLA-A*0201 molecules, and the peptide/subtype complexes recognized varied among the effector populations tested. CTL responses elicited from PBL of patients and healthy donors expressing subtypes HLA-A*0202 and HLA-A*0205 suggested significant differences among HLA-A2 subtype function in the context of melanoma Ag presentation. These observations imply the necessity of subtyping patients considered for peptide-based protocols and highlight the need for further study of melanoma-directed cellular responses among patients expressing non-HLA-A*0201 subtypes.
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PMID:Binding and presentation of peptides derived from melanoma antigens MART-1 and glycoprotein-100 by HLA-A2 subtypes. Implications for peptide-based immunotherapy. 862 27

Antigenic peptides derived from several differentiation antigens of the melanocyte lineage were recently identified in human melanomas as targets for HLA-A2.1-restricted cytotoxic T lymphocytes (CTLs). To examine their potential role in tumour-directed immune responses in vivo, we determined CTL reactivity against seven antigenic peptides derived from the Melan A/MART-1, tyrosinase and gp100/Pmel17 antigens in the peripheral blood of 10 HLA-A2+ healthy controls and 26 HLA-A2+ melanoma patients. The influenza matrix peptide (GILGFVFTL) presented by HLA-A2.1 was used as a control peptide. CTL reactivity was assessed in a mixed lymphocyte 'peptide' culture assay. Reactivity against Melan A/MART-1-derived peptide antigens was readily detectable in both melanoma patients and controls. Reactivity directed against tyrosinase-derived peptide antigens was also detected in both melanoma patients and healthy individuals, but less frequently. A measurable response against gp100/Pmel17-derived antigens was found in 1/10 controls and in 1/26 of the melanoma patients. Reactivity against the influenza matrix peptide was common in both melanoma patients and controls. Our findings show that precursor CTLs against melanocyte differentiation antigens can be detected in peripheral blood of melanoma patients and healthy individuals. The pattern of CTL reactivity directed against melanoma-associated antigens does not seem to be altered in melanoma patients. Despite antigen-specific CTL reactivity, tumour growth was not prevented in melanoma patients and autoimmune phenomena were not detected in healthy individuals. It remains to be determined whether precursor CTLs recognizing melanocyte differentiation antigens can be activated by immunization and lead to effective tumour rejection in vivo.
Melanoma Res 1996 Dec
PMID:Cytolytic T cell reactivity against melanoma-associated differentiation antigens in peripheral blood of melanoma patients and healthy individuals. 901 79

In order to estimate the therapeutic activity and tolerability of immunochemotherapy with recombinant interferon-alpha 2b (rIFN-alpha 2b) plus dacarbazine (DTIC), a study was carried out in 61 patients with cytologically and/or histologically confirmed metastatic malignant melanoma. The treatment regimen was as follows: rIFN-alpha 2b 2 x 10(6) IU intramuscularly on days 1 to 4, and DTIC 800 mg/m2 intravenously on day 5, repeated at 3-week intervals until the progression of the disease or, in the case of a complete response, for up to 6 months. The overall response rate was 28%-12% complete response (CR) and 16% partial response (PR). The median response duration was 10.9 months (CR 11.5 months, PR 9.3 months; P > 0.05). Responses occurred in soft tissue and lung metastases only. The median times to treatment failure for responding and non-responding patients were 10.9 and 3 months, respectively (P < 0.0001), and the median survival durations were 16.5 and 5.8 months, respectively (P < 0.0001). The stratification of the patients into a low-risk group (World Health Organization performance status [WHO PS] < or = 1 and soft tissue or lung metastases) and a high-risk group (WHO PS = 2 or disease localization other than skin, lymph nodes or lung) showed a significant advantage for the first group with respect to the response rate, median time to treatment failure and survival duration. A flu-like syndrome was recorded in 72% of patients, nausea and vomiting in 34%, haematological toxicity in 26%, hepatic toxicity in 5%, and neurotoxicity in 5%. In view of the results obtained in our study and those reported in the literature, IFN plus DTIC immunochemotherapy represents a reasonable treatment option, particularly for patients with soft tissue and lung metastases.
Melanoma Res 1997 Oct
PMID:Immunochemotherapy with recombinant interferon-alpha 2b plus dacarbazine in the treatment of advanced malignant melanoma. 942 26

The therapy of metastatic melanoma is limited by poor responses to known chemotherapeutic agents. The report of Mulder et al. (Proc ASCO 1992; 11: 347) raised the possibility of the known interaction between 5-fluorouracil and interferon-alpha2a improving response rates in melanoma. This study was designed to examine the effects of 5-fluorouracil plus interferon-alpha2a alone without the confounding effects of dacarbazine. Doses were chosen based on the earlier study rather than the higher doses used in colon cancer. Therapy for metastatic melanoma with 5-fluorouracil and interferon-alpha2a is manageable in terms of toxicity. The major toxicities were lethargy, nausea/anorexia and flu-like symptoms. These were thought to be primarily attributable to interferon-alpha2a. Only one case of severe diarrhoea occurred. The response rate of 14% is similar to the reported results of interferon-alpha2a treatment alone. On these data, there is no evidence of synergy using this dose and schedule.
Melanoma Res 1997 Dec
PMID:Recombinant interferon-alpha2a plus 5-fluorouracil for the treatment of metastatic melanoma. 946 25

The aim of this study was to evaluate the toxicity and efficacy of a monochemotherapy regimen of dacarbazine (DTIC), tamoxifen , interferon-alpha2a and interleukin-2 (IL-2) and two polychemotherapy regimens of cisplatin, DTIC, vindesine, tamoxifen, interferon-alpha2a with or without IL-2 in patients with metastatic melanoma. Consecutive patients with metastatic melanoma were enrolled in this trial and were randomized to arm A, consisting of DTIC 800 mg/m2 every 21 days, IL-2 9 MIU subcutaneously days 1-5 and 8-12, arm B, consisting of cisplatin 30 mg/m2 days 1-3, DTIC 250 mg/m2 days 1-3 and vindesine 2.5 mg/m2 day 1 every 28 days (CVD), or arm C, consisting of CVD plus IL-2 6 MIU days 1-5 and 8-12 every 28 days. In all three arms Interferon 3 MU subcutaneously three times a week and tamoxifen 20 mg orally were given throughout. Ninety-two patients were included in this study. Patient characteristics in the three groups were well balanced. The three regimens were delivered on an outpatient basis without major toxicity. The toxicities that did occur consisted primarily of flu-like symptoms in the IL-2 arms (A and C) and haematological toxicities in the CVD arms (B and C). No grade IV toxicities were encountered and no treatment-related deaths occurred. The total response rate was 13% in arm A, 35% in arm B and 37% in arm C. The median duration of response was 6 months and the median survival was 11 months. According to this phase II randomized trial polychemoimmunotherapy with CVD has an objective response rate of 35-36%, while monochemoimmunotherapy with DTIC has a response rate of 13%.
Melanoma Res 1999 Oct
PMID:Multi-institutional phase II randomized trial of integrated therapy with cisplatin, dacarbazine, vindesine, subcutaneous interleukin-2, interferon alpha2a and tamoxifen in metastatic melanoma. BREMIM (Biological Response Modifiers in Melanoma). 1059 17

Immune function plays a prominent role in the defence against cutaneous malignant melanoma and the increased risk of melanoma development during immunosuppression. Since the immune system is challenged beyond its routine activity by an infection, the effect of previous infectious diseases on the risk of melanoma may also be crucial. In a European Organization for Research and Treatment of Cancer (EORTC) case-control study performed in six European countries and Israel, we compared the history of severe infections in 603 melanoma patients with that in 627 population controls. We calculated adjusted odds ratios (ORs) to estimate the effect of infectious diseases on melanoma risk. The ORs for melanoma risk were below 1 for nearly all types of infections (except two) if body temperature was not taken into consideration, and for all infections with a body temperature above 38.5 degrees C. In the latter category significantly lowered ORs were found for pulmonary tuberculosis (0.16; 95% confidence interval [CI] 0.01-0.98), Staphylococcus aureus infections (0.54; 95% CI 0.31-0.94), sepsis (0.23; 95% CI 0.06-0.70), influenza and related infections (0.65; 95% CI 0.48-0.86) and pneumonia (0.45; 95% CI 0.27-0.73). Analysis of the cumulative influence revealed a consistent pattern of results pointing to a reduction in melanoma risk with increasing numbers of recorded infections and fever height. This apparent dose-response relationship suggests a causal association. Speculations on the underlying mechanism include a Shwartzman-like phenomenon when melanoma formation precedes the infection and/or an infection-related Th1-cell activation preventing the establishment of the tumour.
Melanoma Res 1999 Oct
PMID:Infections and melanoma risk: results of a multicentre EORTC case-control study. European Organization for Research and Treatment of Cancer. 1059 18

A significant correlation between a reduced risk of melanoma and BCG and vaccinia vaccination in early childhood or infectious diseases later in life has already been reported from the FEBrile Infections and Melanoma (FEBIM) multicentre case-control study. This correlation is further evaluated in this study based on 603 incident cases of malignant melanoma and 627 population controls in six European countries and Israel by means of a joint analysis of the influence of vaccinations and infectious diseases. In addition, the previously unconsidered impact of influenza vaccinations is evaluated for the whole study population. The strong effects of the frequently given BCG and vaccinia vaccinations in early childhood, as well as of uncommon previous severe infectious diseases, were apparently not cumulative. With the Odds Ratio (OR) being set at 1 in the absence of vaccinations and infectious diseases, the OR dropped to 0.37 (95% Confidence Interval (CI): 0.10-1.42) when subjects had experienced one or more severe infectious diseases, associated with a fever of > 38.5 degrees C, and had not been vaccinated with BCG or vaccinia. The OR was 0.29 (CI: 0.15-0.57) in those who had had a severe infectious disease and were vaccinated with either BCG or vaccinia and 0.33 (CI: 0.17-0.65) for those with 1 or more severe infectious diseases and who had received both vaccinations. We conclude that both vaccinations as well as previous episodes of having a severe infectious disease induced the same protective mechanism with regards to the risk of melanoma. Because of a 'masking effect' by the vaccinia vaccination, the protective effect of the BCG vaccination and of certain infectious diseases against cancer has remained undetected. The vaccinations contributed more to the protection of the population than a previous episode of having an infectious disease. In view of the termination of vaccinations with vaccinia in all countries and of BCG in many of them, these findings call for a re-evaluation of vaccination strategies.
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PMID:Impact of vaccinations and infectious diseases on the risk of melanoma--evaluation of an EORTC case-control study. 1455 30

Melanoma-specific T cells can occur spontaneously or in response to vaccination or other therapies, but the frequency is much lower than observed in viral infections. The presence of tumor-specific T cells does not necessarily translate into clinical regressions for a variety of reasons such as an insufficient frequency, activation state or homing capacity of the T cells or escape strategies of the tumor. Having screened melanoma patients prior to inclusion in vaccination trials for spontaneous tumor-specific T cells either by Elispot or tetramer-staining, we have identified 3 patients with sufficient numbers of tumor-reactive T cells to more than 1 TAA and at least 1 virus-antigen to perform phenotypic and functional analysis directly ex vivo. These stage IV melanoma patients showed specific CTL against melan-A.A2, tyrosinase.A2 and influenza matrix peptide (IMP).A2 readily detectable in peripheral blood. T-cell receptor (TCR) staining using the tetramer technology was combined with phenotypic characterization and functional assays. In contrast to IMP-specific CTL, melanoma-specific CTL were predominantly terminally differentiated effector cells. However, analysis of melan-A- and tyrosinase-specific T-cell lines showed that only a part of the melanoma-specific CTL were able to lyse peptide-loaded target cells. Interestingly, the described phenotypic and functional differences of melan-A- and tyrosinase-specific CTL appeared not only between patients but were also evident within patients, suggesting that the immune response against various tumor antigens is regulated independently.
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PMID:Differences in phenotype and function between spontaneously occurring melan-A-, tyrosinase- and influenza matrix peptide-specific CTL in HLA-A*0201 melanoma patients. 1568 71


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