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)

Many cancers have been cured by chemotherapeutic agents. However, other cancers are intrinsically drug resistant, and some acquire resistance following chemotherapy. Cloning of the cDNA for the human MDR1 gene (also known as PGY1), which encodes the multidrug efflux protein P-glycoprotein, has made it possible to measure levels of MDR1 RNA in human cancers. We report the levels of MDR1 RNA in greater than 400 human cancers. MDR1 RNA levels were usually elevated in untreated, intrinsically drug-resistant tumors, including those derived from the colon, kidney, adrenal gland, liver, and pancreas, as well as in carcinoid tumors, chronic myelogenous leukemia in blast crisis, and cell lines of non-small cell carcinoma of the lung (NSCLC) with neuroendocrine properties. MDR1 RNA levels were occasionally elevated in other untreated cancers, including neuroblastoma, acute lymphocytic leukemia (ALL) in adults, acute nonlymphocytic leukemia (ANLL) in adults, and indolent non-Hodgkin's lymphoma. MDR1 RNA levels were also increased in some cancers at relapse after chemotherapy, including ALL, ANLL, breast cancer, neuroblastoma, pheochromocytoma, and nodular, poorly differentiated lymphoma. Many types of drug-sensitive and drug-resistant tumors, including NSCLC and melanoma, contained undetectable or low levels of MDR1 RNA. The consistent association of MDR1 expression with several intrinsically resistant cancers and the increased expression of the MDR1 gene in certain cancers with acquired drug resistance indicate that the MDR1 gene contributes to multidrug resistance in many human cancers. Thus, evaluation of MDR1 gene expression may prove to be a valuable tool in the identification of individuals whose cancers are resistant to specific agents. The information may be useful in designing or altering chemotherapeutic protocols in these patients.
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PMID:Expression of a multidrug resistance gene in human cancers. 256 56

Previous New Zealand case-control studies have found increased risk for leukaemia, non-Hodgkin's lymphoma (NHL) and multiple myeloma in farmers. We report here a further series of New Zealand Cancer Registry based case-control studies of farming and site-specific cancer risks. These involved 19,904 males aged 20 years or more who were registered with cancer between 1980 and 1984. For each cancer site, the registrations for other sites formed the control group. Farmers had elevated risks for malignant melanoma (Odds Ratio [OR] = 1.25, 95% confidence interval [Cl] 1.05-1.50), and for cancer of the lip (OR = 2.43, 95% Cl 1.81-3.27), rectum (OR = 1.19, 95% Cl 1.03-1.38), bone (OR = 1.95, 95% Cl 1.00-3.80), prostate (OR = 1.26, 95% Cl 1.13-1.41) and brain (OR = 1.34, 95% Cl 1.04-1.74). Decreased risks were observed for cancer of the larynx (OR = 0.66, 95% Cl 0.45-0.96), lung (OR = 0.70, 95% Cl 0.63-0.77) and testis (OR = 0.58, 95% Cl 0.39-0.88). Livestock farmers had a relatively high risk for brain cancer, while the risk for cancer of the lip was highest among dairy farmers. Farmers also had increased risks for cancer of the lymphatic and haematopoietic system (International Classification of Disease 9th edn (ICD) 200-208) (OR = 1.24, 95% Cl 1.08-1.42), leukaemia (OR = 1.24, 95% Cl 0.99-1.55) and non-Hodgkin's lymphoma (NHL) (OR = 1.24, 95% Cl 0.99-1.56), as described previously.
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PMID:Cancer risks in New Zealand farmers. 262 Oct 12

To determine the incidence of secondary cancers after bone marrow transplantation, we reviewed the records of all patients at our center who received allogeneic, syngeneic, or autologous transplants for leukemia (n = 1926) or aplastic anemia (n = 320). Thirty-five patients were given a diagnosis of secondary cancer between 1.5 months and 13.9 years (median, 1.0 year) after transplantation. Sixteen patients had non-Hodgkin's lymphomas, 6 had leukemias, and 13 had solid tumors (including 3 each with glioblastoma, melanoma, and squamous-cell carcinoma). There were 1.2 secondary cancers per 100 exposure-years during the first year after transplantation (95 percent confidence interval, 0.7 to 2.0). The rate declined to 0.4 (95 percent confidence interval, 0.2 to 0.7) after one year. The age-adjusted incidence of secondary cancer was 6.69 times higher than that of primary cancer in the general population. In a multivariate model, the predictors (and relative risks) of any type of secondary cancer were acute graft-versus-host disease treated with either antithymocyte globulin (relative risk, 4.2) or an anti-CD3 monoclonal antibody (13.6) and total-body irradiation (3.9). Two additional factors were associated with secondary non-Hodgkin's lymphomas: T-lymphocyte depletion of donor marrow (12.4) and HLA mismatch (3.8). We conclude that recipients of bone marrow transplantation have a low but significant risk of a secondary cancer, particularly non-Hodgkin's lymphoma.
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PMID:Secondary cancers after bone marrow transplantation for leukemia or aplastic anemia. 230 21

We have administered 1039 courses of high-dose interleukin-2 (IL-2) to 652 cancer patients. Five hundred ninety-six patients had metastatic cancer that either had failed standard effective therapies or had disease for which no standard effective therapy existed, and 56 patients were treated in the absence of evaluable disease in the adjuvant setting. IL-2 was administered either alone (155 patients) or in conjunction with activated immune cells such as lymphokine activated killer (LAK) cells (214 patients) or tumor infiltrating lymphocytes (TIL) (66 patients), with other cytokines such as alpha interferon (a-IFN)(128 patients) or tumor necrosis factor (TNF)(38 patients), with monoclonal antibodies (32 patients), or with the chemotherapeutic agent cyclophosphamide (19 patients). Initial results with the treatment of high-dose IL-2 alone or in conjunction with LAK cells have indicated that objective regressions of cancer can be achieved in 20% to 35% of patients with selected advanced metastatic cancers. Although most responses have been seen in patients with metastatic renal cell cancer, melanoma, colorectal cancer, and non-Hodgkin's lymphoma, many histologic types of cancer have not been treated in significant numbers. These regressions can be durable; of 18 patients achieving a complete response, ten have not experienced recurrence at intervals from 18 to 52 months. Although combinations of IL-2 with TNF do not appear to result in increased responses, there is a suggestion in our initial phase I studies that the combination of a-IFN and IL-2 is more effective than the administration of cytokine alone and this combination deserves further study. Similarly the adoptive transfer of TIL in conjunction with IL-2 also appears to be more effective than the use of IL-2 alone. The toxic side effects in patients treated with high-dose IL-2 are presented and include malaise, nausea and vomiting, hypotension, fluid retention, and organ dysfunction. Treatment-related deaths were seen in 1% of all treatment courses and in 1.5% of patients. These studies demonstrate that a purely immunologic manipulation can mediate the regression of advanced cancers in selected patients and may provide a base for the development of practical, effective biologic treatments for some cancer patients.
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PMID:Experience with the use of high-dose interleukin-2 in the treatment of 652 cancer patients. 267 56

Cancer incidence among 8,004 patients hospitalized for epilepsy between 1933 and 1962 in the Filadelfia treatment community in Denmark was compared to that of the general population. Patients received powerful and prolonged treatment with phenobarbital, phenytoin, and other anticonvulsants. This new survey extends the follow-up from 1976 through 1984. Among 7,864 patients with epilepsy not known to have received radioactive Thorotrast, record linkage with national cancer incidence files identified 789 cancers, compared to 664 expected [relative risk (RR) = 1.19; 95% confidence interval = 1.11-1.27]. Significant risks were found for cancers of the brain and central nervous system (RR = 5.7; n = 118) and the lung (RR = 1.4; n = 106). The excess numbers of brain cancer were concentrated within 10 years of hospitalization (RR = 20.7; n = 80) and decreased significantly over time, which suggests that brain tumors account for the seizure disorder and are not due to phenobarbital exposure as suggested by some epidemiologic studies. No overall risk was apparent when brain cancers were excluded (RR = 1.03). Because bladder cancer was significantly decreased (RR = 0.6; n = 18), the excess risk of lung cancer may not have been related to the "anecdotal" heavy smoking reported among confined groups of epileptic patients in the early years of the study period. The incidence of malignant melanoma was also significantly low (RR = 0.5; n = 7), which suggested limited exposure to sunlight among confined patients. The risk of non-Hodgkin's lymphoma was increased, but not significantly (RR = 1.4; n = 16), which is interesting in view of previous reports suggesting an association with phenytoin. Overall, these data provide little evidence that phenobarbital and phenytoin are carcinogenic to humans, but the excess risks of lung cancer and non-Hodgkin's lymphoma among epileptic patients in our study deserve further evaluation.
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PMID:Cancer among epileptic patients exposed to anticonvulsant drugs. 250 19

The purpose of this study was to compare the toxicity, immunomodulatory changes, and antitumor efficacy of interleukin 2 (IL-2) and lymphokine activated killer (LAK) cell therapy with two durations of IL-2 infusion. Patients with progressive melanoma, non-Hodgkin's lymphoma, renal carcinoma, or colon carcinoma received IL-2 at 3 X 10(6) units/m2/day on days 1-5 and 13-17, either by bolus injection every 8 h (q8h) or by continuous i.v. (CIV) administration. Peripheral blood mononuclear cells were harvested by leukapheresis on days 8, 9, and 10, were incubated in vitro for 5 days for generation of LAK cells, and were infused on days 13, 14, and 15. The first 11 patients were treated with IL-2 q8h, and the subsequent 13 patients were treated by CIV infusion. Toxicity consisted primarily of fever, chills, emesis, diarrhea, weight gain, and edema but did not require intensive care unit support and did not differ significantly between treatment groups. IL-2-induced lymphocytosis on day 8 was higher with CIV than with q8h administration with a mean lymphocyte count/microliter of 5610 +/- 700 (SE) versus 3300 +/- 500. Immunomodulatory changes observed on days 8 and 20 were also greater with CIV IL-2 and included an increase in peripheral blood mononuclear cell IL-2 receptor expression as well as a marked rise in the number of Leu-11+ and Leu-19+ peripheral blood mononuclear cells. The total leukapheresis yield per patient and total number of LAK cells infused per patient were higher with CIV than q8h administration, with 49.8 +/- 4.9 X 10(9) versus 39.4 +/- 5.4 X 10(9) and 42.6 +/- 5.0 X 10(9) versus 34.0 +/- 5.4 X 10(9), respectively. The cells infused displayed phenotypic evidence of activation and exhibited marked lytic reactivity to Daudi, Raji, and HT-144 targets. One complete and one minimal response were observed in 2 of 8 patients with metastatic renal cell carcinoma who received CIV IL-2 and LAK cells. The results show that IL-2 is more biologically active by CIV than q8h administration, as demonstrated by greater rebound lymphocytosis, LAK cell yield, and in vivo immunostimulation.
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PMID:Influence of schedule of interleukin 2 administration on therapy with interleukin 2 and lymphokine activated killer cells. 278 43

Adoptive immunotherapy with lymphokine-activated killer (LAK) cells and systemic administration of recombinant Interleukin-2 (RIL-2) was carried out in a case of malignant melanoma with lung metastases. Histological specimens from the lung showed a metastatic melanoma heavily invaded by atypical lymphoid cells with convoluted nuclei of varying size. Immunohistochemistry revealed that these cells had the characteristic exclusively of natural killer cell (Leu-7+). Nodules of these cells mimicked the appearance of non-Hodgkin's lymphoma of pleomorphic type. Molecular cytogenetic analysis, however, showed the absence of rearranged bands for the T-cell receptor beta-chain gene, indicating the absence of T-cell clones. At autopsy, 1 month after the LAK therapy, the heavy invasion of convoluted cells had disappeared. These findings clearly indicate that the LAK cell plus RIL-2 therapy induced Leu-7+ lymphoid cells, phenotypically suggestive of natural killer cell aggregation in the tumours.
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PMID:Histological evidence of natural killer cell aggregation against malignant melanoma induced by adoptive immunotherapy with lymphokine-activated killer cells. 278 98

A series of case-control studies was conducted to investigate cancer risks among farmers. These studies were based on Missouri Cancer Registry data for 15,000 white male patients, including 1720 subjects classified as farmers, registered between 1984 and 1988. For each cancer site, all other cancer registrations formed the control group. The largest risks among farmers were found for lip cancer (odds ratio [OR], 3.07; 95% confidence interval [CI], 1.99 to 4.73) and cancer of the bone (OR, 2.02; 95% CI, 0.66 to 5.81). Elevated risks were observed for several other sites, including the nasal cavity and sinuses (OR, 1.66; 95% CI, 0.54 to 4.70), prostate (OR, 1.33; 95% CI, 1.18 to 1.51), non-Hodgkin's lymphoma (OR, 1.40; 95% CI, 1.04 to 1.85), and multiple myeloma (OR, 1.40; 95% CI, 0.87 to 2.24). Other smaller elevations in risk were noticed for cancer of the rectum (OR, 1.21; 95% CI, 0.95 to 1.53), liver (OR, 1.19; 95% CI, 0.58 to 2.37), malignant melanoma (OR, 1.26; 95% CI, 0.63 to 2.45), kidney (OR, 1.21; 95% CI, 0.89 to 1.65), and leukemia (OR, 1.12; 95% CI, 0.81 to 1.55); however, some of these estimates were imprecise due to small numbers. The overall OR for lymphatic and hematopoietic cancers was 1.28 (95% CI, 1.06 to 1.56). Consistent with previous studies, a decreased risk of lung cancer was observed among farmers (OR, 0.67; 95% CI, 0.60 to 0.76). The current findings are presented in the context of other recent studies, including discussions of possible causes of farming-associated excess cancer risk and possible sources of bias.
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PMID:Cancer risks among Missouri farmers. 280 30

Autologous bone marrow transplantation (ABMT) has been increasingly used in the treatment of malignant diseases. Since myelosuppression is one of the major dose limiting factors in cancer chemotherapy, ABMT is effective for hematologic reconstitution after marrow-lethal intensive therapy, which increases the anti-tumor effect. Diseases for which ABMT is indicated are selected on the basis of sensitivity to escalation of drug and radiation dose. These diseases include non-Hodgkin's lymphoma, leukemia, small cell carcinoma of the lung, melanoma, neuroblastoma, metastatic breast cancer and Ewing's sarcoma. Phase I and phase II studies have demonstrated that dose escalation to several times the conventional dosage may be feasible with the use of ABMT. Clinical trials of intensive therapy plus ABMT have produced encouraging results in terms of response rate and long-term survival for selected patients with poor-prognosis malignant diseases which are resistant or refractory to conventional forms of cancer therapy. When these preliminary results are analysed, it is apparent that the outcome of this treatment modality is affected by several factors such as disease status or tumor burden at the time of ABMT, the anti-tumor effect of the pretransplant intensive therapy and the extent of bone marrow invasion by tumor cells. Since ABMT is not yet well established in comparison with allogeneic bone marrow transplantation, carefully designed clinical trials will be required in order to assess the efficacy of ABMT.
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PMID:[The role of autologous bone marrow transplantation in cancer treatment]. 282 20

Data from the population-based cancer registry for Los Angeles County, an area with high risk of AIDS, were used to evaluate secular trends of Kaposi's sarcoma (KS), non-Hodgkin's lymphoma, and other possibly AIDS-related cancers in men aged 18 to 54. Marital status was used as a surrogate for homosexual behavior to compare the proportional incidence rates for the pre-AIDS era, 1972 to 1979, to those for 1980 to 1982 and 1983 to 1985. Both absolute incidence and proportional incidence of KS continue to increase sharply, although in absolute numbers, KS is making a smaller contribution to the total number of AIDS cases as the Los Angeles County epidemic progresses. For never-married men the proportional incidence rate of KS in 1983 to 1985 was nearly 100-fold greater than that of 1972 to 1979 and 7-fold greater than that of 1980 to 1982. High-grade lymphomas show statistically significant secular increases in both never-married and ever-married men, but only the rates of Burkitt's lymphomas have increased to a greater extent in never-married men. A small but significant increase of central nervous system lymphomas is seen in both marital status groups. There is no evidence of any AIDS-related increases in Hodgkin's disease, leukemia, testicular cancer, anal cancer, liver cancer, oral cancer, multiple myeloma, or malignant melanoma. As of 1985, cancer, as a manifestation of AIDS, is still apparently limited to KS and high-grade lymphomas (particularly Burkitt's) in Los Angeles County.
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PMID:AIDS-related secular trends in cancer in Los Angeles County men: a comparison by marital status. 291 Apr 64


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