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Query: UMLS:C0025202 (melanoma)
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The Connecticut Tumor Registry (CTR) was established in 1941 and is the oldest population-based cancer registry in the world. Since 1935, all malignant tumors have been registered, and cancer patients are followed annually for vital status. Reporting by hospitals of all cancers diagnosed in Connecticut residents became mandatory in 1971. The reporting physician or hospital makes the initial determination as to whether a tumor is an independent primary cancer, recurrent tumor, or metastatic lesion. In addition, the Registry maintains stringent quality control procedures to avoid duplication of cancer reports. The Registry reviews reports of new cancers developing in patients with a previous primary cancer to rule out the possibility of misdiagnosed metastases. Microscopic confirmation of the diagnosis has improved from 49% in 1935-39 to 94% in 1980-82. Cancers reported only from death certificates currently account for only 1% of all registrations. Between 1935 and 1979, cancer rates in Connecticut almost doubled among males and increased by more than one-third among females; notable increases were seen for cancers of the lung and prostate in males and cancers of the lung and breast in females. In recent years, rates for malignant melanoma of the skin have increased dramatically among both sexes. Stomach cancer has decreased over time in both sexes, as has cervical cancer in females. Although the CTR has used several revisions of the International Classification of Diseases to code the primary site of cancers, rules for the coding of multiple primary cancers have remained essentially the same. Among 253,536 individuals diagnosed between 1935 and 1982 with an invasive cancer, 16,727 (6.6%) nonsimultaneous second cancers were evaluated and are discussed in subsequent chapters of this monograph. Simultaneous cancers were diagnosed in 4,107 individuals and accounted for approximately 20% of all multiple cancers reported in Connecticut. The most frequent simultaneous tumors were cancers of the colon, rectum, prostate, lung, breast, and bladder. Some simultaneous cancers (chronic lymphocytic leukemia, testis, prostate, rectum, uterine corpus, and liver and biliary tract) occurred almost as frequently as the number of subsequent nonsimultaneous tumors, which suggests that the patterns of risk over time for certain sites may be distorted when diagnoses are advanced in time and removed from analysis.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Cancer registration in Connecticut and the study of multiple primary cancers, 1935-82. 408 94

A solid phase radioimmunoassay was devised for measuring the value of the carcinoma associated carbohydrate antigen CA 50 in serum based on the use of a specific monoclonal antibody (C 50). Samples of serum from 259 patients with carcinoma, 114 patients with other malignancies or inflammatory diseases, and 150 healthy controls were examined. Serum values of CA 50 exceeding the mean plus three standard deviations for control samples from blood donors were found in a high proportion of patients with colorectal adenocarcinomas (50% of those with early, localised tumours and 75% of advanced cases), other gastrointestinal carcinomas (69%), uterine cancer (75% of those with corporeal and 88% of those with cervical cancer), prostatic cancer (90%), lung cancer (52%), and breast, ovarian, kidney, and urinary bladder carcinoma (26-67%). The CA 50 values in samples from patients with inflammatory diseases, including ulcerative colitis, with rare exceptions (0-7%) were within the normal range, as were those in patients with various sarcomas and malignant melanoma. Measuring serum values of CA 50, which is evidently a generalised carcinoma associated antigen, may be useful in clinical research studies of the diagnosis, management, and prognosis of patients with different types of carcinoma.
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PMID:Detection by monoclonal antibody of carbohydrate antigen CA 50 in serum of patients with carcinoma. 642 10

A phase II trial was conducted to determine the clinical activity of amsacrine (m-AMSA) in patients with heavily pretreated solid tumors, myeloma, and lymphoma at the University of Arizona Cancer Center. Additionally, m-AMSA was evaluated at other Southwest Oncology Group institutions in breast cancer, myeloma, melanoma, and oat cell cancer of the lung. At a dose of 120 mg/m2 given iv every 28 days, 12 partial responses were observed in 221 patients evaluable for response. Some antitumor activity was observed in breast cancer (four responses of 65 patients), non-Hodgkin's lymphoma (three of nine), Hodgkin's disease (two of five), and sarcoma (two of 15). A partial response was also documented in one of two patients with cervical cancer. Among the 135 patients treated at the University of Arizona who were extensively evaluated for toxic effects, only myelosuppression and anemia were seen in a significant number of patients. At this dose and schedule, 29% of patients developed leukopenia of less than 3000 cells/mm3, 16% developed a thrombocytopenia of less than 100,000 cells/mm3, and 29% had an acute fall in hemoglobin of greater than or equal to 2 g/100 ml. In addition, two patients suffered grand mal seizures which were not clearly drug-related. These results suggest that further study of m-AMSA in lymphoma, sarcoma, and cervical cancer is warranted.
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PMID:Phase II evaluation of amsacrine (m-AMSA) in solid tumors, myeloma, and lymphoma: a University of Arizona and Southwest Oncology Group Study. 668 99

Cancer survival in Sweden in 1961-1991 is presented as a comprehensive report from the Swedish Cancer Registry. The report shows both successes and failures, confirms some earlier published results and presents some new findings worth further analysis. Survival has increased for female breast cancer, malignant melanoma, cancers of the testis and thyroid gland, acute leukemia, and Hodgkin's disease. No improvements are found for multiple myeloma or cancers of the liver, gall bladder, and pancreas. Small increases are shown for colorectal cancer and cancers of the stomach, oesophagus, and kidney. Increases in postoperative survival are shown for sites dominated by histologically benign tumors, i.e., intracranial neurinoma, meningioma, and cancers of the endocrine glands such as parathyroid tumors. From 1970-1972 to 1980-1982 the 10-year relative survival rate (RSR) increased from 30% to 38% for males and from 44% to 51% for females. Hence, cancer survival for all cases combined has approached the survival of the general population somewhat. Most of the increases took place in the 1970's. Changes in the distribution of incidence towards cancer sites with better prognoses account for some 10-20% of the observed increases in RSR, whereas the aging of the cancer population reduces the upward trend in RSR for all cases combined by some 1-2%. Cancer patients have poorer survival than the population long after 5 years of follow-up. They reach the survival of the population after about 8-12 years for colorectal cancer, 10 years for cervical cancer, 7-10 years for malignant melanoma, 13-18 years for kidney cancer, and more than 19 years for female breast and prostate cancer. For patients diagnosed in 1970-1972 this occurred 16 years after diagnosis at 29% for males and 43% for females when all cancer cases were combined. The extended time until 'statistical cure' for most cancer forms clearly indicates the need to augment the commonly used 5-year RSR with other outcome measures. If cancers on average are discovered earlier today, the 5-year RSR gives an exaggerated impression of the improvement over time. In this case the change in the 10-year RSR is a less biased criterion.
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PMID:Cancer survival in Sweden during three decades, 1961-1991. 749 76

Modulation of cytoplasmic Ca++ concentration is a mechanism common to signal transduction pathways regulating many cellular phenomena, including the interactions of tumors with the hemostatic system. We have investigated the pro-aggregating and pro-coagulant activities of human tumor cell lines cultured in vitro and the ability of different platelet agonists to induce Ca++ transients in these cells. Cells of a malignant mesothelioma line activated platelets by a thrombin-dependent mechanism; on the contrary, HeLa cells, derived from a uterine cervical cancer, possessed ADP-dependent pro-aggregating activity, and DND-IA melanoma cells did not stimulate platelet aggregation. All cell lines showed a tissue-factor-like procoagulant property, more pronounced in mesothelioma cells. Furthermore, ADP was able to induce a transient increase in cytoplasmic Ca++ concentration in tumor cells from all lines; collagen showed this effect in mesothelioma cells and in HeLa cells, and thrombin was effective only in mesothelioma cells. PAF never induced Ca++ fluxes in any of the cell lines investigated. Finally, the calcium-channel blocker verapamil inhibited agonist-induced Ca++ transients in tumor cells and in vitro tumor-cell growth. These data may help to identify new possible mechanisms of the 2-way interaction of tumors with the hemostatic system.
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PMID:Effect of different platelet agonists on intracellular free Ca++ concentrations in human tumor cells: possible role in tumor growth. 762 70

Using the population-based Connecticut Tumor Registry, cancer incidence was examined for residents of Connecticut's eight counties and 169 towns in 1989-91. Findings included high standardized incidence ratios (SIRs) for: certain smoking-related cancers for women in New London County; several cancers (bladder, kidney, and mesotheliomas) for men in Middlesex County; Kaposi's sarcoma in Fairfield County, and in the towns of Hartford and New Haven; skin melanoma in certain ocean-shoreline towns; and invasive cervical cancer in several larger cities. Cancer surveillance data should be useful for promoting such efforts as smoking prevention and cessation, the collection of data on occupation and smoking by physicians and hospitals, reduction in excessive sun exposure, and increased screening for cervical cancer in large towns.
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PMID:Surveillance of cancer incidence in Connecticut counties and towns, 1989-91. 764 50

We have employed conventional polymerase chain reaction (PCR) and nonpalindromic adaptor PCR (NPA-PCR) for the amplification of the heavy- and light-chain transcripts of the cDNAs of two human monoclonal antibodies (MAb), designated AC6C3 (IgM, lambda) and CR4E8 (IgM, lambda), recognizing two different antigens expressed on the cell surface of human ovarian, cervix, breast, colon, melanoma and other carcinomas. With few exceptions these MAbs do not react with normal tissues. The AC6C3 MAb was developed by fusing regional lymph node lymphocytes from a patient with ovarian carcinoma with cells of the hybrid myeloma line SPAZ4, whereas the CR4E8 MAb was developed by fusing SPAZ4 cells with peripheral blood lymphocytes from a patient with cervical cancer, who was immunized intralymphatically with a viral oncolysate allogeneic tumor vaccine. The AC6C3 MAb immunoprecipitated from lysates of the ovarian tumor cell line SKOV3 a 32 kD polypeptide. The CR4E8 MAb reacted in Western blotting of lysates of the SW756 cervical carcinoma line with a 55 kD band. Cell surface immunofluorescence determinations using the fluorescence activated cell sorter revealed that both MAbs stain ovarian or cervix carcinoma tumor cell lines. We amplified the heavy chain transcripts of these two MAbs by conventional PCR, using mixed 5' end amplification primers, corresponding to the most conserved VH leader sequences and a C mu probe as a 3' end amplification primer. However, the mixed primer approach did not permit the amplification of the lambda-chain transcripts of these two human MAbs. This amplification was successfully carried out using the NPA-PCR that we have previously developed, specifically for the amplification of transcripts with unknown or variable 5' end, such as the T-cell receptors and the immunoglobulins. We have cloned and sequenced the amplified cDNAs. Sequence analysis showed that the V lambda segment of the AC6C3 MAb had 80.29% homology to the human germline Ig lambda-chain V lambda III.1, clone DPL2. The V lambda region of the CR4E8 MAb had 99.28% homology also to the human germline Ig lambda-chain, V lambda III.1, clone DPL23. The AC6C3 MAb lambda-chain employed a J segment with 98% homology to J3. The CR4E8 MAb light chain employed the J(H6-3C4) gene segment. Both MAbs utilized identical VH and JH gene segments and different DH segments. The VH regions of the AC6C3 MAb and of the CR4E8 MAb had, respectively, 98.6% and 98.98% homology to the human Ig germline heavy chain V region DP-7, a member of the VH-1 gene family.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Amplification of immunoglobulin transcripts by the non-palindromic adaptor polymerase chain reaction (NPA-PCR). Nucleotide sequence analysis of two human monoclonal antibodies recognizing two cell surface antigens expressed in ovarian, cervix, breast, colon and other carcinomas. 775 78

Preclinical data indicate that the combination of retinoids and interferons have synergistic antiproliferative and differentiating effects in some hematologic and solid tumor models. These observations have led to clinical trials in which 13-cis-retinoic acid (13cRA) 1 mg/kg/day was combined with interferon alpha-2a (IFN alpha) 3 or 6 x 10(6) U/day. The first two such trials produced exciting results: 50% response rate in patients with previously untreated stages IB-IVA cervix cancer and 68% in patients with advanced squamous cell skin cancer. These data led to a number of additional trials of the combination, but the high response rates seen in the initial cervix and skin trials have not been duplicated in the other squamous tumors tested (head and neck, lung, pretreated cervix). In addition, trials in two nonsquamous histologies were negative (lung and melanoma). However, the regimen was not always studied in an optimal population of previously untreated patients and the negative results in pretreated cervix patients point to the relevance of this consideration. Nevertheless, the observation that the combination of 13cRA and IFN alpha (both of which bind to specific receptors and change gene expression) is able to induce regression in advanced tumors, must be regarded as highly important. Key questions to be addressed include an understanding of the biologic mechanism of specific tumor sensitivity (why some squamous tumors and not others?), and mechanisms of resistance in sensitive tumor types (e.g. cervix). Such data may lead to trials targeted to tumor types with defined biologic features having a high liklihood of clinical benefit. In the meantime, studies integrating this combination with other active treatment modalities such as radiation is warranted in cervix and skin carcinomas.
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PMID:Combination 13-cis-retinoic acid and interferon alpha-2a in the therapy of solid tumors. 780 23

This investigation examined the effects of 6-methylene progesterone (6MP), an irreversible inhibitor of 5-alpha-reductase, on prostatic cancer (PC) cell lines. Dose titration microculture tetrazolium assays were used to evaluate cytotoxicity in cultures treated for 72 hr with 6MP (0-20 micrograms/ml). An androgen-sensitive cell line, LNCaP, was drug-sensitive with a mean 50% lethal dose value (LD50) of 2.632 +/- 0.103. Hormone-resistant PC cell lines 1-LN, DU 145, and PC3 also demonstrated sensitivity with LD50 values between 0.8579-1.110 micrograms/ml with a group average of 1.023 +/- 0.082 micrograms/ml. Increasing dosages of dihydrotestosterone in the growth media did not alter 6MP cytotoxicity in androgen-insensitive prostatic cancer cell lines. No correlation between androgen-responsiveness and 6MP-induced cytotoxicity was observed. In nonprostatic malignancies, 6MP inhibited adenocarcinoma cell lines with a mean group LD50 value of 0.7772 micrograms/ml +/- 0.110. J82, a transitional cell carcinoma cell line of bladder origin, exhibited an average LD50 value of 1.041 +/- 0.260. In an epidermoid cervical cancer cell line, ME180, an LD50 value of 0.5356 micrograms/ml +/- 0.010 was noted. In a melanoma cell line, Du Mel 6, a mean LD50 of 0.7428 +/- 0.023 micrograms/ml was achieved with 6MP. We conclude that 6MP, a novel 5-alpha-reductase inhibitor, has potential as a cytotoxic agent in prostatic carcinoma and additional human malignancies. Further study is justified.
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PMID:6-Methylene progesterone is cytotoxic to human cancer cell lines independent of its 5-alpha-reductase activity. 784 64

Preclinical data indicate that the combination of retinoids and interferons have synergistic antiproliferative and differentiating effects in some hematologic and solid tumor models. These observations have led to clinical trials in which 13-cis-retinoic acid (13cRA) 1 mg/kg/day was combined with interferon alpha-2a (IFN alpha) 3 or 6 x 10(6) U/day. The first two such trials produced exciting results: 50% response rate in patients with previously untreated stages IB-IVA cervix cancer and 68% in patients with advanced squamous cell skin cancer. These data led to a number of additional trials of the combination, but the high response rates seen in the initial cervix and skin trials have not been duplicated in the other squamous tumors tested (head and neck, lung, pretreated cervix). In addition, trials in two non-squamous histologies were negative (lung and melanoma). However, the regimen was not always studied in an optimal population of previously untreated patients and the negative results in pretreated cervix patients point to the relevance of this consideration. Nevertheless, the observation that the combination of 13cRA and IFN alpha (both of which bind to specific receptors and change gene expression) is able to induce regression in advanced tumors, must be regarded as highly important. Key questions to be addressed include an understanding of the biologic mechanism of specific tumor sensitivity (why some squamous tumors and not others?), and mechanisms of resistance in sensitive tumor types (e.g. cervix). Such data may lead to trials targeted to tumor types with defined biologic features having a high likelihood of clinical benefit. In the meantime, studies integrating this combination with other active treatment modalities such as radiation is warranted in cervix and skin carcinomas.
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PMID:Combination 13-cis-retinoic acid and interferon alpha-2a in the therapy of solid tumors. 793 56

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