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

The following review considers epidemiological data published from 1990 onwards on oral contraceptives (OCs) and the risk of cancers of the breast, cervix uteri, endometrium, ovary, liver and skin. In several studies, breast cancer risk was seen to be elevated among women who were current users of an OC, or had recently stopped using an OC, whereas there was no residual risk 5 or more years after stopping OC use. No interaction was observed between type of OC, or with any recognised risk factor for breast cancer, or time-factor, except for some potential excess risk for women who started OC use at a young age. Most studies have confirmed that OCs moderately increase the risk of cervical cancer, particularly in human papilloma virus (HPV)-positive women, thus suggesting that OCs may act as a promoter for HPV-induced carcinogenesis. Recent epidemiological studies have confirmed that combined OCs provide substantial protection against endometrial and ovarian cancers, and results suggest that such protection is long-lasting, and may persist for 15 years or more after stopping OC use. Most case-control studies have shown a relationship between OC use and hepatocellular carcinoma. However, data from cohort studies or analysis of vital statistics indicate that the public health impact of such an association is modest, if not negligible. No association was observed between combined OC use and the incidence of skin melanoma, or any other common skin neoplasm. In terms of clinical and public health implications, the most relevant points regarding OC use are: (i) recent data confirm that OCs confer presistent protection against ovarian cancer; and (ii) any increased risk of breast cancer in OC users is moderate and is restricted to current/recent users. This is reassuring for younger women, whose baseline risk of this disease is extremely low.
 ...
PMID:Oral contraceptives and cancer. A review of the evidence. 871 94

Organ-specific cancer incidence rates can vary dramatically between low- and high-incidence areas. Such differences are due to (1) heritable susceptibility determinants, (2) risk factors associated with the environmental and local living conditions (e.g., viruses, pollution), and (3) personal life-style factors. For organs showing large differences between cancer registries, exogenous factors might be most important, while for organs showing only small differences, endogenous and unavoidable factors are expected to be more important. In this paper, a working hypothesis based on descriptive cancer epidemiology is presented to estimate, in a quantitative manner, the unavoidable contribution to the process of carcinogenesis and to discuss limitations to individual cancer prevention. Cumulative cancer incidence rates for a 75-year period of life (CR74, in percent) were taken from IARC Scientific Publication No. 120 (1992). For each organ, values were ranked in ascending order, and the ratio between high-rate and low-rate registries (90th percentile/10th percentile) was determined. This measure of variability among registries differed strongly between organs. Largest ratios were seen for organs with well-known exogenous risk factors, such as pharynx, lip, tongue, mouth, liver, esophagus, and melanoma in males, and lung, esophagus, gallbladder, liver, and bladder in females. Small ratios were seen for rectum, brain, colon, and Hodgkin's disease in males, and breast, rectum, ovary, brain, and colon in females. It is concluded that the process of carcinogenesis in the latter organs has a stronger endogenous/unavoidable component, for some tissues possibly of hormonal type. A fictitious population was composed where, for each organ, the minimum reported cancer rate was taken. When based on all cancer registries world-wide, CR74 sums over all sites of 2.0% and 2.3% resulted in males and females, respectively. When only Central/Western European countries were included in the analysis in order to reduce differences in risk factors nos. 1 and 2, the sum of the minimum values was 10.4% and 8.7%. After correction of the data for smoking, 'minimum' cancer incidence rates in males and females were estimated to be 7.6% and 6.8%. Based on a median cancer incidence rate for nonsmoking males in Europe of about 21%, therefore, individual preventive measures taken by a nonsmoker can reduce the cancer risk, on average, 'only' by a factor of about 3. A considerable fraction of cases thus appears to be hardly avoidable.
 ...
PMID:Endogenous and exogenous factors in carcinogenesis: limits to cancer prevention. 872 Feb 82

The association between genetic disorders and diverse cancers has provided clues for laboratory research into carcinogenesis. Such an opportunity now arises from studies of cancer in Werner syndrome (WRN). Soft-tissue sarcoma (STS) and benign meningioma have been associated with WRN, an autosomal recessive disorder characterized by premature aging, more commonly reported in Japan than elsewhere, in part because of inbreeding. In the literature we found 124 case-reports of neoplasia and WRN from Japan and 34 from outside Japan, 1939-August, 1995. They reveal a greater diversity of neoplasia in WRN than was previously known. In Japanese, there were 127 cancers, 14 benign meningioma, and 5 myeloid disorders, as compared with 30, 7 and 2 respectively in non-Japanese. The ratio of epithelial to non-epithelial cancers was about 1:1 for Japanese and for non-Japanese instead of the usual 10:1. Both series had excess of STS, osteosarcoma, myeloid disorders, and benign meningioma. In addition, the Japanese had an excess of thyroid cancer (20 versus 2 cases in non-Japanese) and melanoma (21 versus 3 cases), including 5 intranasal and 13 of the feet. STS, osteosarcoma, melanoma, and thyroid carcinoma accounted for 57% of all cancer in WRN as compared with 2% expected based on the Osaka population at 25-64 years of age. Multiple tumors were reported in 19 Japanese and 5 non-Japanese. In Japan, nine first-degree relatives had WRN and cancer, six of whom were concordant as to site and/or cell type. The WRN gene has been mapped to chromosome 8p. The high frequency of thyroid cancer and melanoma in Japanese, not found in Caucasians, may be related to a report of linkage disequilibrium with the WRN gene in Japanese but not in Caucasians and to haplotype differences within and between the two races, suggesting multiple independent mutations.
 ...
PMID:Excess of rare cancers in Werner syndrome (adult progeria). 872 14

Expression of mutant p53 detected by immunohistochemistry has been described in human malignant melanoma, but there are few reports of molecular analyses. To investigate the genetic basis for p53 expression in malignant melanoma, we examined 58 primary tumors and 5 cutaneous metastases. The entire coding sequence of the p53 gene was screened by single-strand conformation polymorphism analysis and direct genomic sequencing of polymerase chain reaction products. p53 and mdm-2 expression were studied by immunohistochemistry. Two p53 gene mutations could be found in 1/63 samples examined, both having occurred in the same specimen from a patient with a nodular melanoma. p53 and mdm-2 expression were found immunohistochemically to increase with tumor progression both in frequency and in the mean proportion of positive cells, with the same cases staining positively for both antibodies. Our results suggest that a) p53 gene mutations are a rare event in human melanoma; b) accumulation and thus immunohistochemically detectable expression of p53 may result from posttranslational mechanisms affecting the p53 gene product; and c) p53 and mdm-2 are more important in late events in melanoma carcinogenesis.
 ...
PMID:Immunohistochemical detection of p53 in melanomas with rare p53 gene mutations is associated with mdm-2 overexpression. 874 96

Microcell transfer of intact normal human chromosomes into immortal mouse and hamster fibroblast cell lines has revealed growth suppressive activity associated with a small sub-set of the human complement. Here, we describe the results of a detailed study aimed at identifying the gene or genes responsible for the rapid growth-arrest response obtained with human chromosome-9. Initially, STS-PCR deletion mapping of segregants arising in monochromosome transfer experiments was used successfully to localize the active sub-chromosomal region to 9p21. Subsequent fine-structure deletion mapping of previously uniformative hybrid segregants, employing additional markers between D9S162 and D9S171, provided strong evidence that the cyclin-dependent kinase (cdk) inhibitor gene CDKN2A (p16INK4A) was solely responsible for the chromosome-9 effect; 9p21 microdeletions in a significant proportion of segregant clones were restricted to a single CDKN2A exon. Transfection experiments with CDKN2A and CDKN2B cDNA expression vectors, using mouse A9 cells and three human malignant melanoma cell lines as recipients, provided further evidence in support of this hypothesis. Collectively, our results indicate that expression of human CDKN2A (controlled either by its natural regulatory elements, or by a cytomegalovirus promoter) is incompatible with in vitro proliferation in immortalized rodent cells and in human melanoma cell lines. The rapidity of the growth inhibitory effects of CDKN2A was inconsistent with a mode of action involving induction of replicative cell senescence via telomerase repression, but was consistent with a mechanism based on cell cycle arrest through cdk inhibition. The study described here has generated a panel of microdeleted monochromosome-9 donor hybrids which may prove valuable in functional investigations aimed at identifying other important tumour suppressor genes located on human chromosome-9.
Carcinogenesis 1996 Aug
PMID:Identification of human tumour suppressor genes by monochromosome transfer: rapid growth-arrest response mapped to 9p21 is mediated solely by the cyclin-D-dependent kinase inhibitor gene, CDKN2A (p16INK4A). 876 11

Cancer is a multi-stage process in which the accumulation of genetic changes allows clonal expansion of abnormal cells that will eventually form a tumor. Skin cancer is the most common malignancy affecting human beings. Mutations of the tumor suppressor gene p53 are often found in non-melanoma skin cancer and pre-invasive lesions, like actinic keratosis. The type of mutations detected in the p53 gene strongly indicate UV light as the initiating and promoting agent in skin cancer development. Chromosome instability is also an early event in skin tumor formation. However, despite the huge amount of information available in the literature on molecular markers of skin cancers, much remains to be uncovered about the progression of genetic events that separate normal sun-exposed epidermis from skin cancer. In this paper the following issue will be addressed: how far are we from being able to define a human model for multistage skin carcinogenesis in humans?
 ...
PMID:Genetic alterations in skin cancer. 880 85

p53, A tumor suppressor gene, has been documented as the most frequently mutated gene in human cancers including non-melanoma skin tumors. It has been controversial whether the p53 gene mutation plays a major role for melanoma genesis. To examine the role of p53 in human malignant melanoma carcinogenesis, we performed immunohistochemical analysis using anti-p53 antibodies (CM-1 and DO-7) in microwaved paraffin sections. When cases having more than 1% reactive cells were regarded as positive, immunohistochemical analysis revealed that in primary melanomas 14 of 51 (27%) were positive with CM-1 or 15 of 51 (29%) were positive with DO-7. Tumor thickness of primary melanomas in p53 positive cases was significantly thicker than that in p53 negative cases. In metastatic melanomas, 35 of 41 (85%) lymph node metastases were positive with either antibody and in skin metastases 16 of 28 (57%) lesions with CM-1 or 18 of 28 (64%) lesions with DO-7 were positive. The mean percentages of reactive cells were 2.3% in primary lesions and 4.9% in metastases. The incidence of positivity was significantly higher in metastases than primary lesions. In 10 cases examined, with both primary and metastatic melanoma, 3 cases were negative in both lesions and 1 case was positive in both lesions, while 6 cases were negative in the primary lesions and positive only in metastatic lesions. Four Spitz nevi, 6 dysplastic nevi and 11 common nevi were all negative. These data suggest that the expression of p53 protein may be a late event in melanoma progression.
 ...
PMID:Expression of p53 protein in melanoma progression. 881 40

Because interleukin-10 (IL-10) has potent immunosuppressive and anti-inflammatory properties and is produced by some cancers, we hypothesized that its production might play a role in carcinogenesis by inhibiting adequate antitumoral immune responses. To test this hypothesis, retroviral vectors containing the IL-10 cDNA were generated and used to infect B16F1 melanoma cells that were injected subcutaneously in syngeneic mice. Surprisingly, IL-10 gene transfer resulted in a loss of tumorigenicity that was proportional to the amount of IL-10 secreted. Histological analysis showed massive area of necrosis of these tumor cells, with infiltration of polymorphic inflammatory cells. Parental cells simultaneously implanted had decreased tumorigenicity only when mixed with IL10-producing cells, but not when injected contralaterally, suggesting that their eradication is mediated mostly by a local phenomenon. Host T lymphocytes and natural killer (NK) cells were involved in this eradication because IL-10-producing cells grew in nude mice and in CD8+ or NK-depleted mice. Finally, mice injected with IL-10-secreting cells developed an antitumoral systemic immune response able to protect them against a subsequent challenge with parental cells. These results demonstrate that, in some settings, IL10 may have in vivo immunostimulating and proinflammatory properties that need to be considered in its therapeutic development.
 ...
PMID:Loss of tumorigenicity and increased immunogenicity induced by interleukin-10 gene transfer in B16 melanoma cells. 882 65

In animal models, isoforms of CD44 (CD44v) containing sequences encoded by one or several of ten different exons (v1-v10) contribute to tumour metastasis. In certain human cancers, CD44v6 expression is associated with poor prognosis. This paper examines CD44v expression in skin carcinogenesis and skin cancer metastasis. CD44v expression was studied in basal cell carcinoma (BCC), squamous cell carcinoma (SCC), primary malignant melanoma (PMM), metastases of MM (MMM), benign melanocytic naevi (BMN) and normal skin (NS) by immunohistochemistry and reverse transcript polymerase chain reaction (RT-PCR). BCC, SCC and NS expressed several CD44v, including v6, albeit in different distributions and intensities. PMM, MMM and BMN expressed isoforms containing v7/8 and v10, but failed to express epitopes encoded by v5 or v6. Thus, different CD44 isoforms are found in human skin cancers and are modulated during carcinogenesis. However, we did not observe a correlation of CD44v6 expression with metastatic potential.
 ...
PMID:Expression of CD44 isoforms in human skin cancer. 886 5

The EVI-1 gene was originally detected as an ectopic viral insertion site and encodes a nuclear zinc finger DNA-binding protein. Previous studies showed restricted EVI-1 RNA or protein expression during ontogeny; in a kidney and an endometrial carcinoma cell line; and in normal murine oocytes and kidney cells. EVI-1 expression was also detected in a subset of acute myeloid leukaemias (AMLs) and myelodysplasia. Because EVI-1 is expressed in the urogenital tract during development, we examined ovarian cancers and normal ovaries for EVI-1 RNA expression using reverse transcription polymerase chain reaction (RT-PCR) and RNAase protection. Chromosome abnormalities were examined using karyotypes and whole chromosome 3 and 3q26 fluorescence in situ hybridisation (FISH). RNA from six primary ovarian tumours, five normal ovaries and 47 tumour cell lines (25 ovarian, seven melanoma, three prostate, seven breast and one each of bladder, endometrial, lung, epidermoid and histiocytic lymphoma) was studied. Five of six primary ovarian tumours, three of five normal ovaries and 22 of 25 ovarian cell lines expressed EVI-1 RNA. A variety of other non-haematological cancers also expressed EVI-1 RNA. Immunostaining of ovarian cancer cell lines revealed nuclear EVI-1 protein. In contrast, normal ovary stained primarily within oocytes and faintly in stroma. Primary ovarian tumours showed nuclear and intense, diffuse cytoplasmic staining. Quantitation of EVI-1 RNA, performed using RNAase protection, showed ovarian carcinoma cells expressed 0 to 40 times the EVI-1 RNA in normal ovary, and 0-6 times the levels in leukaemia cell lines. Southern analyses of ovarian carcinoma cell lines showed no amplification or rearrangements involving EVI-1. In some acute leukaemias, activation of EVI-1 transcription is associated with translocations involving 3q26, the site of the EVI-1 gene. Ovarian carcinoma karyotypes showed one line with quadruplication 3(q24q27), but no other clonal structural rearrangements involving 3q26. However, whole chromsome 3 and 3q26 FISH performed on lines with high EVI-1 expression showed translocations involving chromosome 3q26. EVI-1 is overexpressed in ovarian cancer compared with normal ovaries, suggesting a role for EVI-1 in solid tumour carcinogenesis or progression. Mechanisms underlying EVI-1 overexpression remain unclear, but may include rearrangements involving chromosome 3q26.
 ...
PMID:Expression of the zinc finger gene EVI-1 in ovarian and other cancers. 893 29


<< Previous 1 2 3 4 5 6 7 8 9 10