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)

The CDKN2A gene encodes p16 (CDKN2A), a cell-cycle inhibitor protein which prevents inappropriate cell cycling and, hence, proliferation. Germ-line mutations in CDKN2A predispose to the familial atypical multiple-mole melanoma (FAMMM) syndrome but also have been seen in rare families in which only 1 or 2 individuals are affected by cutaneous malignant melanoma (CMM). We therefore sequenced exons 1alpha and 2 of CDKN2A using lymphocyte DNA isolated from index cases from 67 families with cancers at multiple sites, where the patterns of cancer did not resemble those attributable to known genes such as hMLH1, hMLH2, BRCA1, BRCA2, TP53 or other cancer susceptibility genes. We found one mutation, a mis-sense mutation resulting in a methionine to isoleucine change at codon 53 (M531) of exon 2. The individual tested had developed 2 CMMs but had no dysplastic nevi and lacked a family history of dysplastic nevi or CMM. Other family members had been diagnosed with oral cancer (2 persons), bladder cancer (1 person) and possibly gall-bladder cancer. While this mutation has been reported in Australian and North American melanoma kindreds, we did not observe it in 618 chromosomes from Scottish and Canadian controls. Functional studies revealed that the CDKN2A variant carrying the M531 change was unable to bind effectively to CDK4, showing that this mutation is of pathological significance. Our results have confirmed that CDKN2A mutations are not limited to FAMMM kindreds but also demonstrate that multi-site cancer families without melanoma are very unlikely to contain CDKN2A mutations.
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PMID:CDKN2A mutation in a non-FAMMM kindred with cancers at multiple sites results in a functionally abnormal protein. 938 68

Epidemiologic evidence on the relationship between selected industries and cancer is reviewed. This article will focus on several industries which have not been covered elsewhere in this volume, briefly describe current research on cancer in the agricultural and construction industries, and discuss surveillance data on cancer mortality in relation to industry listed on US death certificates. Employment in the rubber industry has been associated with bladder cancer, leukemia, stomach, and lung cancer and is considered by the International Agency for Research on Cancer (IARC) to have 'sufficient evidence of carcinogenicity in humans.' Studies of workers exposed to polychlorinated biphenyls (PCBs) have reported excess mortality from gastrointestinal neoplasms, hematologic neoplasms, and skin cancer (specifically malignant melanoma); IARC considers that the evidence for carcinogenicity in humans is 'limited.' Employment in the boot and shoe industry has been associated with nasal adenocarcinomas in England and Italy ('sufficient'). Hairdressers and barbers have been found to have excess bladder cancer and less consistent evidence for several other sites ('limited'). Workers exposed to wood dust have excess mortality from cancer of the nasal sinuses and paranasal cavities; there is less consistent evidence for excess laryngeal cancer ('sufficient'). Workers employed in the petroleum industry have limited evidence for excess leukemia and other lymphatic and hematopoietic neoplasms, and skin cancer (particularly malignant melanoma) ('limited').
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PMID:Industries and cancer. 949 99

Secular and cohort trends in mortality from cancer in Scotland during 1953-93, and incidence during 1960-90, were analysed using individual records from the national mortality and registration files. For certain cancer sites, the secular analyses of mortality were extended back to 1911 by use of published data. Mortality from cancer at older ages in Scotland has increased over the last 40 years. In each sex, this trend has been dominated by the effects of smoking: all-cancer rates and rates of lung cancer, now the most common fatal cancer in men and in women in Scotland, reached a peak in the cohort of men born at the turn of the century and the cohort of women born in the 1920s. For much of the period, the Scottish all-age rates of lung cancer were the highest reported in the world; they are now decreasing on a secular basis in men, but are still increasing in women. There have also been large increases at older ages in the incidence and mortality rates for cancer of the prostate in recent years. bladder cancer, nervous system cancer, non-Hodgkin's lymphoma, myeloma and leukaemia; for each there is likely to be a considerable artefactual element to the increase, with differing degrees of possibility that there may in addition be an element of real increase. Substantial decreases in mortality at all ages have occurred for stomach and colorectal cancers and substantial increases at all ages for pleural cancer and melanoma. Rates of mortality from breast cancer, the most common cancer in women in Scotland, have generally increased over the past 80 years; a temporary cessation in this upward trend occurred in the years during and after the Second World War, and recently rates have turned downward, probably at least in part because of better treatment. Mortality from ovarian cancer, the second most common reproductive-related female tumour in Scotland, has also increased at older ages. At younger ages, mortality from cancer in Scotland has decreased, especially in men, whereas incidence has not. This divergence, which has been a consequence of better treatment, has occurred especially for cancers of the testis and ovary, Hodgkin's disease and leukaemia. There have been increases at young adult ages, however, in both mortality from and incidence of oral and pharyngeal, oesophageal and laryngeal cancers in men, and melanoma and non-Hodgkin's lymphoma in each sex. Cervical cancer rates at young ages also increased, but this trend has reversed for incidence in the most recent birth cohorts. Incidence rates have also increased for testicular cancer in young adults and leukaemia in children. With the possible exceptions of non-Hodgkin's lymphoma and childhood leukaemia, the increasing rates are likely largely to reflect real rises in incidence, and they highlight the need for investigation of the causes of these cancers, and, when causes are known, for preventive action.
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PMID:Trends in cancer incidence and mortality in Scotland: description and possible explanations. 966 78

Bisphosphonates are used in oncology as a means of decreasing complications due to bone metastases, in association with anticancer treatment, especially in patients with breast cancer, prostate cancer and myeloma. Little is known about the effects of bisphosphonates on bone metastases from other tumors and in particular from tumors for which no effective treatment is available. We conducted a randomized, double-blind placebo-controlled trial of oral clodronate in patients with bone metastases from tumors poorly responsive to chemotherapy, with the aims of evaluating the effects of this drug on symptoms control and bone metastases evolution. Sixty-six patients with poorly responsive tumors such as non-small cell lung cancer (NSCLC), bladder cancer, gastrointestinal cancers, kidney cancer, melanoma and metastatic carcinoma of unknown origin entered the study. Patients were randomized to receive either clodronate 1,600 mg/day for one year or identical placebo-containing tablets. Various parameters such as Karnofsky performance status, pain score (measured by a visual-analogue scale) and analgesic requirement were recorded at monthly intervals. Of the 66 patients enrolled, 9 were observed for one month or less; 7 were followed for two months; only 50 patients were followed for more than 2 months and could be adequately evaluated. At 3 months both clodronate and placebo-treated patients had a decrease in Karnofsky performance status, with the decrease being more evident in the placebo group. Mean pain scores showed an increase of pain in patients receiving placebo and a decrease of pain in patients receiving clodronate, although the difference failed to be statistically significant. Analgesics requirement increased in both groups, but significantly more in patients receiving placebo (p = 0.042), in whom increase in opioid requirements was particularly evident. Toxicity was low, with occasional gastroenteric discomfort in both groups. The main problem of this study was the difficulty in recruiting an adequate number of patients and following them for a sufficient period of time: general conditions rapidly deteriorated in many patients, and approximately 25% of the 66 enrolled were not considered evaluable; few patients survived for the length of the study, one year. This might partly account for the lack of significance of some of the parameters under study. With these limits, oral clodronate demonstrated some efficacy in symptom control and in reducing the need for analgesics.
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PMID:A double blind randomized study of oral clodronate in the treatment of bone metastases from tumors poorly responsive to chemotherapy. 970 May 83

Cancers seen and recorded between 1983 and 1995 in the Hospital Tumor Registry at the American University of Beirut Medical Center (AUBMC), one of the largest primary and tertiary care hospitals in Lebanon, were retrospectively reviewed and analyzed. There was a total of 10,220 cases, excluding 916 skin cancers other than skin melanoma, averaging 786 cases per year. There were 5086 cancer cases in males with the five most common cancers being: lung cancer (915 cases: 17.9%) followed by bladder cancer (503 cases: 9.8%), larynx (438 cases: 8.6%), lymphoma (393 cases: 7.7%) and leukemia (336 cases: 6.6%). As for female cancer cases, a total of 5134 cases were observed with the five most common cancers being: breast cancer (1821 cases), followed by cervical cancer (535 cases), colo-rectal cancer (256 cases: 4.9%), lymphoma (232 cases: 4.5%), and brain cancer (213 cases: 4.1%). The average age for all cancer cases was 50.5 years with a standard deviation (SD) of 18.8 years. The average age of females (48.8 yrs; SD 17.4) was relatively lower than that of males (52.2 yrs; SD 19.9) and the difference was statistically significant. 40.6% of the patients were under the age of 50 years. 49% of breast cancer patients were below 50 years of age. In children less than 15 years of age, there were 555 cases, with leukemia being the commonest (185 cases: 33.3% of childhood cases) followed by brain cancer (112 cases: 20.1%), lymphoma (63 cases: 11.3%), bone cancer (41 cases: 7.3%), soft tissue sarcoma (35 cases: 6.3%) and kidney cancer (28 cases: 5.0%). Lung cancer in males and breast cancer in females are the most common cancers in Lebanon. These cancers are amenable to prevention (cigarette cessation and anti-smoking campaigns for lung cancer) and early detection (screening, regular breast examination and mammography for breast cancer). Our paper emphasizes the importance of addressing those and other issues including bladder cancer and age at diagnosis of breast cancer. It also presents important epidemiological and historical reference data on cancer in Lebanon during the civil war and immediately after it.
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PMID:Cancer in Lebanon: analysis of 10,220 cases from the American University of Beirut Medical Center. 979 15

Glutathione (GSH) levels were measured in 13 human tumor cell lines derived from carcinomas of the bladder, ovary, and colon and from melanoma and glioblastoma. High levels were found in four of five bladder cell lines. The average GSH concentration in the bladder cell lines was approximately 6-fold higher than in the non-bladder cell lines. Because this difference suggested the possibility of elevation of GSH in urothelial neoplasia, we measured GSH in bladder tumor tissue from patients with transitional cell carcinoma (TCC) of the bladder (Group I, n = 17). GSH was also measured in two types of control tissues: (a) nontumor bladder tissue from patients with TCC or a history of TCC of the bladder (Group II, n = 23); and (b) bladder tissue from patients without bladder cancer (Group III, n = 14). Thirteen sets of paired specimens of tumor and nontumor bladder tissue from the same patient were evaluated. The tissues were flash-frozen, and GSH was measured after histological assessment of the same samples. Free and total GSH (free + mixed disulfides) were measured by a high-performance liquid chromatography assay with fluorescence detection and expressed as nanomoles/mg protein. The mean free GSH (+/- SD) for groups I, II, and III was 32.0 +/-18.7, 17.3 +/- 11.4, and 9.3 +/- 4.0, respectively, and the mean total GSH was 45.9 +/- 32.5, 23.7 +/- 17.1, and 12.2 +/- 6.7. The respective differences between groups (I and II, I and III, and II and III) were statistically significant for both free and total GSH (Ps ranging from <0.0001 to </=0.05). Free and total GSH were higher in tumor than in nontumor tissue in 11 of 13 paired specimens (free, 29.5 +/- 20.4 versus 18.7 +/- 11.7, P = 0.017; total, 41.7 +/- 33.8 versus 24.9 +/- 18.4, P = 0.005). No correlation was found between GSH levels and the proportion of tumor cells in the tissue. Influence of smoking on GSH expression could not be assessed because 81% of the patients with TCC had a smoking history. Similarly, because only 11% had prior cytotoxic chemotherapy, the influence of prior cytotoxic exposure on GSH could not be assessed. The results indicate: (a) significantly higher levels of GSH in TCC compared to tumor-free bladder tissue; and (b) higher GSH levels in nontumor bladder tissue from patients with bladder cancer than from patients without TCC. The clinical implications of this work include the possibility that GSH may play a role in the resistance of bladder cancer to chemotherapy and may be associated with bladder carcinogenesis.
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PMID:Translational studies of glutathione in bladder cancer cell lines and human specimens. 981 51

Since 1990 age-standardized cancer mortality in men has decreased by about 1% per year. This decrease is due to a decrease in the mortality from lung cancer, stomach cancer, pancreatic cancer and bladder cancer. The mortality from melanoma, prostate cancer and oesophageal cancer in men has increased. After a slight increase in age-standardized cancer mortality in women, the rate has remained constant since 1990 in spite of the rapid increase in lung cancer mortality. Mortality due to cancers of the stomach, pancreas, cervix and ovary has decreased. Total cancer incidence in both men and women didn't change much during 1989-1994. In men the incidence of prostate cancer strongly increased. For women both the incidence of lung cancer and breast cancer increased. In the south-east of the Netherlands cancer incidence has been registered since 1973. In this area, the incidence increased before 1989. Therefore, it is likely that the national cancer incidence rates have also increased. Despite this increase, the age-standardized overall cancer mortality in the Netherlands did not increase during recent years.
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PMID:[Trends in cancer incidence and cancer mortality in Netherlands: good and bad news]. 1044 70

Gene amplifications are common in many different tumor types and may confer diagnostic, prognostic, or therapeutic information for patient management. Tedious experiments are often required to determine which tumor types have amplifications of a specific oncogene. To facilitate rapid screening for molecular alterations in many different malignancies, a tissue microarray consisting of samples from 17 different tumor types was generated. Altogether, 397 individual tumors were arrayed in a single paraffin block. To determine whether results from the literature can be reproduced on minute tissue samples (diameter, 0.6 mm), amplification of three extensively studied oncogenes (CCND1, CMYC, and ERBB2) was analyzed in three fluorescence in situ hybridization experiments from consecutive sections cut from the tissue microarray. Amplification of CCND1 was found in breast, lung, head and neck, and bladder cancer, as well as in melanoma. ERBB2 was amplified in bladder, breast, colon, stomach, testis, and lung cancer. CMYC was amplified in breast, colon, kidney, lung, ovary, bladder, head and neck, and endometrial cancer. These results confirm and even extend existing data in the literature on such amplifications. In summary, we applied three fluorescence in situ hybridization experiments to analyze amplifications of three oncogenes in three x 397 tumors within a week. This demonstrates the power of using minute arrayed tissue specimens for tumor screening.
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PMID:Tissue microarrays for gene amplification surveys in many different tumor types. 1047 73

The incidence of non-Hodgkin's lymphoma (NHL) has been increasing rapidly over the last three decades. The reasons for this trend are not known although increasing exposure to sunlight has been postulated. We used data from the New South Wales Central Cancer Registry to analyse second primary neoplasms following NHL diagnosed between 1972 and 1995, to identify possible common causal agents. A total of 12,452 patients contributed 54,308 person-years of follow-up during which time there were 705 second primary neoplasms compared to 592.99 expected (standardized incidence ratio (SIR = 1.19, 95% confidence interval (CI) 1.10-1.28). There were excesses of melanomas of skin (SIR = 2.38, 95% CI 1.92-2.91), lip cancer (SIR = 2.74, 95% CI 1.59-4.38), tongue cancer (SIR = 2.53, 95% CI 1.09-4.99) and bladder cancer (SIR = 1.64, 95% CI 1.19-2.21). There was also over a threefold excess in soft tissue sarcomas (SIR = 3.61, 95% CI 1.80-6.45) and in thyroid cancer (SIR = 3.42, 95% CI 1.56-6.49). The SIR for myeloid leukaemia was 0.78 (95% CI 0.28-1.69). The increases in melanoma of the skin and cancer of the lip and tongue among patients with NHL strongly suggest sunlight exposure as a shared causal agent. The increase in soft tissue sarcomas might be due to shared effects of exposure to chemicals such as phenoxy acid herbicides. The increases in bladder and thyroid cancers are likely to be explained by effects of treatment for NHL. We did not find a chemotherapy related increased risk of myeloid leukaemia among NHL patients.
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PMID:Second primary neoplasms following non-Hodgkin's lymphoma in New South Wales, Australia. 1075 12

The results of studies on antiproliferative activity in vitro of nine new platinum(II) complexes against cells of eight human and six murine neoplastic cell lines are described. New complexes with the anionic rest originating from enantiomeric forms of hydroxydicarboxylic malic acid were synthesized to obtain agents with increased water solubility and decreased toxicity. Three compounds, coded 1-3, with ethylenediamine as a neutral ligand, showed cytotoxic activity against 12 out of 14 target cell lines. Their cytotoxic activity was similar or even slightly higher than that of the reference carboplatin. The remaining six compounds, coded 4-9, with 1-alkylimidazole as a neutral ligand, revealed rather low cytotoxic activity, and only against the cells of the human bladder cancer cell line Hu1703He, ovarian cancer cell line OAW-42 and mouse leukemia P388. Most of them appeared to be negative against all other cell lines. No compounds, including reference carboplatin, showed any cytotoxicity against the cells of the T47D human breast cancer cell line or B16F-10 mouse melanoma cell line. The results obtained are in accordance with common opinion, i.e. that the presence of neutral amine ligands with NH groups is required for the cytotoxic activity of platinum complexes. Compounds with a primary amine (ethylenediamine) showed higher cytotoxic activity in vitro than complexes with a tertiary amine (1alkylimidazole).
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PMID:Antiproliferative activity in vitro of new malatoplatinum(ll) complexes. 1091 52


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