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)

Our results with concurrent biochemotherapy in patients with stage IV melanoma have been encouraging. Based on these data, we conducted a phase II study to determine the clinical and histological response rate to neoadjuvant concurrent biochemotherapy in patients with local-regional metastases of cutaneous melanoma (stage III). A total of 65 patients with biopsy-proven, measurable and potentially resectable local-regional disease (nodal, satellite/in-transit metastases and/or local recurrence) were treated with cisplatin 20 mg/m2 intravenously (i.v.) on days 1 to 4, vinblastine 1.5 mg/m2 i.v. on days 1 to 4, dacarbazine 800 mg/m2 i.v. on day 1 only, interleukin-2 9 MIU/m2 per day i.v. by 96 h continuous infusion on days 1 to 4, and interferon-alpha 2a 5 MU/m2 subcutaneously on days 1 to 5, repeated every 3 weeks. Patients underwent surgery after two to four courses of biochemotherapy. Those with tumour regression after two preoperative courses received two additional postoperative courses. Of the 64 patients assessable for clinical response, 28 (44%) had a partial response. Of the 62 patients whose response was assessed histologically, four (6.5%) had no evidence of viable tumour in the surgical specimen (pathological complete remission, pCR) and 27 (43.5%) had a partial response, giving an overall response rate of 50%. Tumour burden did not correlate with response, although patients who achieved a pCR had a significantly lower tumour burden (P = 0.02). Our phase II study indicates that neoadjuvant biochemotherapy is an active treatment for melanoma patients with local-regional metastases. However, it is unclear if biochemotherapy is more active than chemotherapy alone; phase III randomized trials are ongoing to answer this question in patients with stage IV disease.
Melanoma Res 1998 Dec
PMID:Phase II study of neoadjuvant concurrent biochemotherapy in melanoma patients with local-regional metastases. 991 17

The CDKN2A gene encodes the cell cycle inhibitor p16/ INK4A, which is involved in familial cutaneous melanoma. We have studied five Swedish familial melanoma kindreds characterized by germline mutations in CDKN2A and dysplastic naevus syndrome (DNS). We found significant correlations between germline CDKN2A mutations and melanoma and between DNS phenotype and melanoma, respectively. There was also a correlation between mutation status and the presence of DNS. In CDKN2A mutation carriers, all cases of early-onset melanoma occurred in DNS individuals, and the mean age at melanoma diagnosis was significantly lower in individuals with DNS than in those without a confirmed DNS phenotype. In one family where the proband had a P48L mutation in CDKN2A exon 1, the DNS phenotype was studied in detail. In vitro binding experiments established that the P48L mutant protein does not bind to cdk4 or cdk6 and thus is functionally abnormal. Furthermore, we demonstrated loss of heterozygosity at markers on chromosome 9p flanking the CDKN2A locus in a primary melanoma and a metastasis from the proband. Our results are consistent with the hypothesis that germline CDKN2A mutations and DNS both contribute to the predisposition to melanoma and may lead to the development of early-onset melanoma when present in the same individual.
Melanoma Res 1999 Feb
PMID:Melanoma development in relation to non-functional p16/INK4A protein and dysplastic naevus syndrome in Swedish melanoma kindreds. 1033 31

We examined the incidence of primary invasive melanoma in the municipality of Reggio Emilia, northern Italy, in the period from 1986 to 1997. We identified 169 cases, five of which were intraocular. After adjustment for confounders, the risk of having a thick melanoma (Breslow > or = 1 mm) did not decrease over time, except in older females. The age-standardized incidence of cutaneous melanoma during the entire study period was 7.57 in males and 11 in females; from 1986-1991 to 1992-1997, it rose from 5.04 to 10.04 cases/100,000 person-years in males and from 8.96 to 13.09 cases/100,000 person-years in females. In males, the increase in incidence was almost entirely confined to subjects aged 30 or more, suggesting a possible cohort effect. We noted rising age-standardized incidences over time both in males with thin tumours (Breslow < 1 mm) (from 2.05 to 4.38 cases/100,000 person-years) and thick tumours (from 2.73 to 5.51 cases/100,000 person-years), while in females the increase was limited to thin melanomas (from 3.14 to 6.93 cases/100,000 person-years), mainly due to an increase in the older age groups (50 69 years and > or =70 years). The increase in thick melanomas among males and the expected cohort effects suggests antecedent exposure to environmental risk factors.
Melanoma Res 1999 Feb
PMID:Rising melanoma incidence in an Italian community from 1986 to 1997. 1033 40

Excessive sun exposure and family history are strong risk factors for the development of cutaneous melanoma. Inherited susceptibility to this type of skin cancer could therefore result from constitutively impaired capacity to repair ultraviolet (UV)-induced DNA lesions. While a proportion of familial melanoma kindreds exhibit germline mutations in the cell cycle regulatory gene CDKN2A (p16INK4a) or its protein target, cyclin-dependent kinase 4 (CDK4), the biochemical basis of most familial melanoma is unknown. We have examined lymphoblastoid cell lines from melanoma-affected and unaffected individuals from large hereditary melanoma kindreds which are not attributable to CDKN2A or CDK4 gene mutation. These lines were tested for sensitivity of clonogenic growth to UV radiation and for their ability to repair transfected UV-damaged plasmid templates (host cell reactivation). Two of seven affected-unaffected pairs differed in colony survival after exposure to UVB radiation; however, no significant differences were observed in the host-cell reactivation assays. These results indicate that melanoma susceptibility genes other than CDKN2A and CDK4 do not impair net capacity to repair UV-induced DNA damage.
Melanoma Res 1999 Apr
PMID:Normal repair of ultraviolet radiation-induced DNA damage in familial melanoma without CDKN2A or CDK4 gene mutation. 1038 Sep 35

Cutaneous malignant melanoma has an increasing importance all over the world. However very few epidemiological studies have been published from Spain, and Spanish people have not become aware of the problem. This study was designed to examine sun exposure patterns and other related items among 116 consecutive patients with melanoma and 235 controls. Each subject answered a questionnaire covering the place of residence, sun exposure details and other risk factors, and underwent a skin examination. Continuous sun exposure due to residence or occupation was associated with an odds ratio (OR) of 2.0 (95% confidence interval [CI] = 1.2-3.3). People who lived in the city but spent 50% of their time in rural areas for holidays had an OR of 2.2 (95% CI = 1.3-3.8) when compared with those living in urban and rural areas. The OR for people who sunbathed more than 30 times a year was 1.8 (95% CI = 1.2-2.8), and outdoor leisure time was also associated with melanoma appearance when exposure was greater than 60 units in the last 2 years, with an OR of 3.0 (95% CI = 1.6-5.5); 1 unit is equivalent to total body sun exposure for at least 2 h. These OR estimates were adjusted for age, skin type and the number of naevi. Construction workers (OR = 1.6; 95% CI = 0.5-5.6) had increased risk after adjustment for skin type, age and freckle count (OR = 4.3; 95% CI = 1.8 9.9) or mole count (OR = 2.8; 95% CI = 1.4-5.8). Working as a farmer was a protective factor after adjustment (OR = 0.5; 95% CI = 0.3-0.8). The use of sunscreens was a protective factor against melanoma (OR = 2.6; 95% CI = 1.6-3.6 for non-users). Campaigns should focus on advising people to avoid sun exposure in sunny places and to use sunscreens every time they are exposed to the sun.
Melanoma Res 1999 Apr
PMID:Cutaneous malignant melanoma and sun exposure in Spain. 1038 Sep 43

Recent insights in antigen presentation, the identification of human tumor antigens, and the demonstration of MHC class-I-restricted cytotoxic T lymphocyte (CTL) recognition of peptides encoded by tumor antigen have renewed the interest and enthusiasm for the development of cancer vaccines. Melanoma serves as a paradigm of an immunogenic human tumor, and several tumor antigens, including MAGE, MART-1/Melan-A and gp100, recognized by CTLs, have now been isolated. Candidate antigens for novel vaccine trials may include HLA class-I-binding tumor peptides that serve as CTL epitopes, whole tumor protein, or DNA-based vaccines. Requirements for the use of peptides are that the patient's tumor presents the relevant CTL epitopes as used in the vaccine and expresses the appropriate MHC class-I-restricting molecule. Immunological monitoring may be facilitated when using peptide-based vaccines. Because optimal presentation of tumor antigens may depend on provision of appropriate costimulatory signals, it may be more advantageous to administer professional antigen-presenting cells (APCs), such as dendritic cells (DCs) pulsed with tumor peptide or protein, to cancer patients. Developments in molecular genetics have led to a new approach in vaccines consisting of cancer cells genetically engineered to express immunomodulatory molecules. This may result in increased antitumor responses to both gene-modified as well as unmodified tumor cells. The therapeutic approach is extended to vaccination trials with recombinant viruses containing the genes encoding tumor antigens, minigenes containing multiple CTL epitopes, or double recombinant vectors engineered to express both the tumor antigen and immunostimulatory molecules. Clinical peptide, protein and DNA-based vaccine trials have recently been initiated. Thus far, exciting clinical remissions were obtained in melanoma patients following vaccination with HLA-A1-binding MAGE-3 peptide and in B-cell lymphoma patients immunized with autologous DCs pulsed with anti-idiotype protein, i.e., the individual patient's unique tumor antigen. Also, following injection of foreign HLA-B7 DNA into cutaneous melanoma metastases, T-cell migration into treated lesions and enhanced cellular immunity at the site of the tumor were shown in some patients. These encouraging results suggest that effective new vaccines in cancer will be identified.
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PMID:Vaccine Trials for the Clinician: Prospects for Tumor Antigens. 1038 61

Purine nucleotide metabolism was studied in two human cutaneous melanoma cell lines IPC182 and IGR221. IPC182 cells do not differentiate, while IGR221 cells differentiate spontaneously at confluency, with intense melanin production. The activities of 11 enzymes involved in the de novo or salvage synthesis or the catabolic pathway of purine nucleotides were measured at different times (from day 3 to day 18), after subculture, during exponential growth and the stationary phase, with or without differentiation. The results demonstrated remarkable differences in the enzyme activity levels and/or the evolution from exponential growth to the stationary phase for each cell line, as well as between the two cell lines. In the non-differentiating IPC182 cells, the activity of enzymes involved in purine nucleotide synthesis decreased when the growth rate slowed down and remained at a low level with a concomitant increase in catabolic activities. In the differentiating IGR221 cells, the activity of enzymes involved in purine nucleotide salvage synthesis increased during the proliferative phase and was maintained at a high level when the cells reached confluency and differentiated; catabolic activities were always lower than in the IPC182 cells. This suggests that extra purine nucleotides, synthesized preferentially by the salvage pathway, could be required for the differentiation of human melanoma cells. Since the two cell lines were cultured in the absence of any differentiation-inducing agents, these results indicate that various metabolic modifications are associated with the natural processes of cell proliferation and differentiation. This research could help to identify some of the enzymes involved in purine metabolism as the targets for the induction of differentiation.
Melanoma Res 1999 Aug
PMID:Purine metabolism in two human melanoma cell lines: relation to proliferation and differentiation. 1050 53

In order to evaluate the natural history, prognostic parameters and treatment modalities for metastatic uveal melanoma, a review of the clinical data from the current literature was performed based on a Medline database search. Uveal melanoma represents approximately 5% of all melanomas. It is a distinct clinico-pathological entity, differing in many aspects from cutaneous melanoma. The clinical course is unpredictable and metastatic disease can develop very late after a long disease-free interval. Uveal melanoma metastasizes haematogenously, predominantly to the liver. The most Important prognostic parameters for primary uveal melanoma are tumour diameter, the patient's age and gender, histological features and tumour location. Systemic chemotherapy that is effective in cutaneous melanoma has failed to show activity in uveal melanoma. So far only the BOLD chemotherapy regimen (dacarbazine, lomustine, vincristine and bleomycin) combined with interferon-alpha has been shown to produce an objective tumour response in approximately 20% of previously untreated patients. For metastatic disease localized to the liver, intra-arterial application of fotemustine or carboplatin or chemoembolization with cisplatin have shown useful activity, resulting in a response in up to 40% of patients. Selected patients may benefit from palliative surgery. Immunotherapy with interleukin-2 or interferon-alpha has not shown consistent activity in metastatic uveal melanoma. In conclusion, patients with uveal melanoma metastatic to the liver should undergo one of the local treatment options. Carefully selected patients with extrahepatic disease or patients failing local treatment may benefit from systemic therapy using the BOLD regimen combined with interferon.
Melanoma Res 1999 Dec
PMID:Uveal melanoma: natural history and treatment options for metastatic disease. 1066 68

The ABCD (asymmetry, border, colour, dimension) criteria represent a commonly used clinical guide for the diagnosis of early cutaneous melanoma (CM). This guide stipulates that CMs usually are more than 6 mm in diameter. The purpose of this retrospective study was to establish the frequency of occurrence of small (< or =6 mm) melanomas in a clinical context. Our series consisted of 270 consecutive CMs (39 in situ and 231 invasive) in 267 patients. Of these 270 lesions, 47 (17%) were small lesions, ranging from 2 to 6 mm in maximum linear extent, with a median value of 5 mm. Of these small lesions, 14 were in situ and 33 Invasive CMs. The median thickness of the 33 small invasive lesions was 0.31 mm. The clinical features of CMs were sufficiently distinctive to suggest a diagnosis of CM in half of the cases, irrespective of the invasiveness or not of the lesions. Dermatoscopy was performed on 36 of the small lesions and achieved a correct diagnosis in 72% of the cases. The combination of simple visual examination with dermatoscopy allowed a higher rate of recognition (86%) than when the two methods were considered separately. Results of our study show that small CMs represent a considerable clinical subset of all CMs. Clinicians must be aware of this fact in their diagnostic activity.
Melanoma Res 1999 Dec
PMID:Small melanomas: a clinical study on 270 consecutive cases of cutaneous melanoma. 1066 69

The vast majority of healthy individuals have some form of melanocytic lesions with most having several cutaneous melanocytic nevocellular nevi. The incidence of cutaneous melanoma, despite improved prevention and early diagnosis of precursor melanocytic lesions, is on the increase with a projection that one in 75 persons born in the year 2000 will develop cutaneous melanoma in his/her lifetime. With cutaneous melanoma, the number, location and type of nevi, sun exposure and inability to tan, and presence or absence of dysplastic nevi affect transformation to a malignant process. Certain familial factors, syndromes, cytogenetic abnormalities, and mutations in tumor suppressor genes also influence tumor formation. In contrast, mucosal melanoma involving the oral cavity and head and neck regions is not as well understood or characterized. No doubt, this is due to the fact that this subtype of melanoma accounts for less than 1% of all cases. Mucosal melanomas tend to present at a higher stage, are more aggressive, and in a vertical growth phase of disease. A definitive precursor lesion for mucosal melanoma has not been identified; however, atypical melanocytic hyperplasia may represent a proliferative phase before overt tumorigenesis occurs. Melanoma-related antigens, growth factors, and proliferation markers have been identified in cutaneous melanoma, and allow for development of immunotherapy directed against melanoma-associated entities. It is currently possible to evaluate the cytogenetic make-up of precursor melanocytic lesions and frank melanoma, and the constitutional genetic background of individuals at risk for melanoma. No doubt, as concerted investigations of mucosal melanomas of the oral cavity and head and neck evolve, similar factors will be identified which will direct therapy and predict recurrence and survival. In the not too distant future, innovative retroviral transfection, antibodies against specific melanoma-associated factors, vaccination against melanoma, and gene therapy to repair cytogenetic abnormalities and tumor suppressor gene mutations may provide effective therapy and protection against melanomas.
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PMID:Oral mucosal melanoma: epidemiology and pathobiology. 1074 67


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