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)

5'-Methylthioadenosine (MTA) is a naturally occurring nucleoside which is degraded by MTA phosphorylase (MTAase) to adenine and methylthioribose-1-phosphate in all normal mammalian cells. These products of the phosphorylytic cleavage of MTA are recycled to the nucleotide pool and methionine, respectively. Thus, supplemental MTA could theoretically be utilized by MTAase-containing cells as a source of methionine and adenine. In fact, in vitro experiments have shown that MTAase-containing cells proliferate normally in methionine-free medium if MTA is added to the cultures (M. K. Riscoe and A. J. Ferro, J. Biol. Chem., 259: 5465-5471, 1984). In contrast, MTAase-deficient malignant cell lines do not proliferate under these conditions. In light of these observations and the recent demonstration (N. Kamatani et al., Blood, 60: 1387-1391, 1982) that a proportion of acute lymphoblastic leukemias lack MTAase, we wished to determine if this enzyme deficiency occurs in a variety of human neoplasms. Accordingly, malignant cells from eight patients with acute nonlymphocytic leukemia and ten patients with various solid tumors were assayed for MTAase activity. Samples from one of the eight acute nonlymphocytic leukemia patients and three of the 10 solid tumor patients (one with melanoma, one with squamous cell lung cancer, and one with adenocarcinoma of the rectum) had undetectable MTAase activity. In contrast, erythrocytes, neutrophils, and monocytes isolated from normal subjects and from patients with immunodeficiency syndromes or cancer all contained enzyme activity. In addition, the methods of preservation, storage, and cell disruption did not affect MTAase activity. These observations confirm and extend the findings of Kamatani et al. (Blood, 60: 1387-1391, 1982) by demonstrating that MTAase deficiency occurs in a variety of human malignancies including acute nonlymphocytic leukemia and solid tumors. This metabolic difference between normal and malignant cells may be therapeutically exploitable.
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PMID:Methylthioadenosine phosphorylase deficiency in human leukemias and solid tumors. 309 64

The medical records of 973 previously untreated patients diagnosed between January 1960 and December 31, 1978 with childhood cancer were reviewed. Siblings in 13 families were diagnosed with cancer 9/12 to 15 years after the diagnosis of cancer in the index sibling. Previously unreported association of acute lymphoblastic leukemia with Hodgkin's disease, neuroblastoma with malignant hemangiopericytoma, non-Hodgkin's lymphoma with malignant melanoma, Wilms' tumor with non-Hodgkin's lymphoma, Hodgkin's disease with malignant teratoma of the testis and craniopharyngioma with acute myeloblastic leukemia were identified. Two families appeared to transmit a predisposition to childhood tumors. The data from these families extend previous observations regarding multiple cases of cancer in sibships.
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PMID:Childhood cancer in siblings. 315 35

It has been well established that specific alterations in members of the ras gene family, H-ras, K-ras and N-ras, can convert them into active oncogenes. These alterations are either point mutations occurring in either codon 12, 13 or 61 or, alternatively, a 5- to 50-fold amplification of the wild-type gene. Activated ras oncogenes have been found in a significant proportion of all tumors but the incidence varies considerably with the tumor type: it is relatively frequent (20-40%) in colorectal cancer and acute myeloid leukemia, but absent or present only rarely in, for example, breast tumors and stomach cancer. No correlation has been found, yet, between the presence of absence of an activated ras gene and the clinical or biological features of the malignancy. The activation of ras oncogenes is only one step in the multistep process of tumor formation. The presence of mutated ras genes in benign polyps of the colon indicates that activation can be an early event, possibly even the initiating event. However, it can also occur later in the course of carcinogenesis to initiate for instance the transition of a benign polyp of the colon into a malignant carcinoma or to convert a primary melanoma into a metastatic tumor. Apparently, the activation of ras genes is not an obligatory event but when it occurs it can contribute to both early and advanced stages of human carcinogenesis.
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PMID:The ras gene family and human carcinogenesis. 328 42

Immune reconstitution after autologous bone marrow transplantation (ABMT) was studied in peripheral blood by phytohemagglutinin stimulated T-cell colony formation (CFU-TL) and by surface phenotype analysis of T-lymphocytes with monoclonal antibodies. Twenty-six patients (15 small-cell lung cancer, 5 lymphoma, 3 acute myeloid leukemia [AML], 2 germ cell cancer, and 1 melanoma) were conditioned with high-dose multiple drug combinations (plus total body irradiation in AML patients). No maintenance chemotherapy was given following treatment. Despite a rapid return to normal values of peripheral T3+, T11+ lymphocytes, the T4/T8 ratio remained below 1.0 up to 24 months after transplant, regardless of infection by cytomegalovirus (CMV). A high percentage (26% +/- 3%) of lymphocyte cells with immature phenotype (T8+, Ia+) was found during the first 6 months after transplant. Out of 84 cultures, performed in 26 patients, no growth was observed in 47 instances (22 patients) up to 28 months after grafting. Growth occurred in 37 cultures (11 patients, from 1 to 51 months after transplant) although it never reached the colony numbers of normal controls. Recombinant human interleukin-2 (rIL-2) added to lymphocyte culture induced proliferation in 8 (4 CMV-positive and 4 CMV-negative patients) out of 12 instances of no growth. In cases of depressed CFU-TL (20 cultures), rIL-2 induced a 48% and 92% increase in six CMV-positive patients and nine CMV-negative patients, respectively. These observations show that after ABMT and regardless of CMV status, defects in CFU-TL can be partially corrected by rIL-2.
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PMID:Recombinant human interleukin-2 restores in vitro T-cell colony formation by peripheral blood mononuclear cells after autologous bone marrow transplantation. 331 85

TCA (T Cell system A) is a di-allelic system of HLA-like antigens encoded by genes located about 15 cM telomeric to HLA-A. In normal individuals, TCA antigens are only expressed on a subpopulation of T cells, the TG lymphocytes. We now report on the expression of TCA on leukemias and other malignancies. An increased proportion of cells carrying the TCA phenotype was encountered in testing peripheral blood lymphocytes from patients with acute lymphoblastic T-cell leukemia (T-ALL), acute myeloid leukemia (AML), and chronic myeloid leukemia (CML). In contrast, patients with B-cell malignancies such as chronic lymphatic leukemia (CLL) and hairy cell leukemia (HCL) or non-T/non-B common acute lymphoblastic leukemia (common ALL) had normal proportions of TCA-positive lymphocytes. Quantitatively different levels of TCA expression are found on some melanoma cell lines and others are TCA negative. These variations are independent of the expression of HLA Class I antigens by the same cells. The expression of TCA antigens by malignant nonlymphoid cells suggests that this system may code for differentiation markers, important in the biology of neoplastic transformation.
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PMID:TCA: a polymorphic genetic marker in leukemias and melanoma cell lines. 348 57

ANLL followed a brief period of aplastic anemia in a man treated intensively 4 years and 3 months previously with dacarbazine as "adjuvant" therapy for malignant melanoma. This is the first reported instance in which the latency between drug exposure and onset of leukemia strongly implicates dacarbazine as a leukemogenic agent.
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PMID:Acute non-lymphocytic leukemia (ANLL) following treatment with dacarbazine for malignant melanoma. 357 61

We have identified a cDNA whose sequence is preferentially expressed when quiescent fibroblasts are stimulated to proliferate. The steady-state levels of the mRNA corresponding to this clone, called 2A9, are increased by serum, platelet-derived growth factor, and epidermal growth factor, but not by insulin or platelet-poor plasma. mRNA levels of 2A9 are also increased in human acute myeloid leukemia. The 2A9 cDNA has been molecularly cloned from an Okayama-Berg library, and its complete nucleotide sequence has been determined. It has an open reading frame of 270 nucleotides, which has a 55% homology with the coding sequence of the beta-subunit of the S-100 protein, a calcium-binding protein that belongs (like calmodulin and the vitamin D-dependent intestinal calcium-binding protein) to the family of calcium-modulated proteins and is found in abundance in several human tumors, including melanoma. The S-100 protein and the deduced aminoacid sequence of 2A9 are also partially homologous to the small subunit of a protein complex that serves as a cellular substrate to tyrosine kinase. The partial homology of 2A9 (whose RNA is inducible by growth factors and is overexpressed in human acute myeloid leukemias) to the S-100 protein, other calcium-modulated proteins, and the subunit of a substrate for tyrosine kinase, is particularly interesting in view of the role attributed to calcium and tyrosine kinases in the regulation of cell proliferation.
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PMID:Molecular cloning of the cDNA for a growth factor-inducible gene with strong homology to S-100, a calcium-binding protein. 375 24

The risk of second primary cancers developing was evaluated in individuals with 6 rare tumors in Connecticut between 1935 and 1982. Small but significant excesses of all second cancers occurred in patients with cutaneous melanoma (42%), and cancers of the brain (59%), thyroid (49%), connective tissue (23%), bone (66%), and eye (40%). In individuals with cutaneous melanoma, the highest risks were for subsequent cutaneous melanomas [relative risk (RR) = 8.5] that persisted throughout all intervals of observation. The risk for second melanomas was higher in persons under age 40, consistent with a heritable component. Connective tissue tumors and breast cancers also occurred in excess. Among patients with brain cancer, an increase of melanoma was observed that may represent an underlying neural crest abnormality, although no excess of brain cancer was seen after melanoma. Reciprocal increases of bone cancer after connective tissue cancer and connective tissue cancer after bone cancer point to shared risk factors, such as high dose radiotherapy or genetic susceptibility states. An anticipated high risk of osteogenic sarcoma following Ewing's sarcoma was not seen. An excess of breast cancer (RR = 1.9) after thyroid cancer indicates common etiologic factors. Expected excesses of bilateral retinoblastoma and bone cancer after retinoblastoma were seen. Tumors commonly treated with alkylating agents or nitrosoureas (melanoma, brain, connective tissue) showed slightly elevated risks of acute nonlymphocytic leukemia. Prostate cancer was frequently found to be in excess, but this is likely an artifact due to ascertainment bias.
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PMID:Second cancer following cutaneous melanoma and cancers of the brain, thyroid, connective tissue, bone, and eye in Connecticut, 1935-82. 408 97

The risk of a person developing a second primary cancer was evaluated in approximately 55,000 women diagnosed with breast cancer in Denmark between 1943 and 1980. Excluding second cancers of the contralateral breast, 2,480 new cancers were observed compared with 2,398 expected (relative risk = 1.03; 95% CI = 0.99-1.08). Breast cancer patients followed for 10 years or more showed a significant 13% excess of all second primary tumors. Significant excesses of cancers of the lung, bone, and connective tissue were observed. Although some misclassification of metastases may have occurred, the risk of second cancers at these sites (as well as the salivary gland and esophagus) increased significantly with time and was especially high among women followed for 10 years or more. These observations suggest that radiation, as a part of the initial treatment, may have been involved. Radiation or chemotherapy, or both, may also have influenced the risk of acute nonlymphocytic leukemia (51 cases observed vs. 20.7 expected), which remained significantly elevated after the first year of follow-up. Common risk factors, related to reproductive experience and nutrition, may have contributed to the excess risk of cancers of the ovary and colon. On the other hand, an anticipated excess of cancer of the corpus uteri was not found, although cancer of the uterus not otherwise specified was significantly increased. Significant deficits were observed for second cancers of the liver and biliary tract, due perhaps to underreporting or conservative coding practices, or both. A significant excess of malignant melanoma was not easily explained but might indicate a common hormonal etiology with breast cancer.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Second cancer following cancer of the female breast in Denmark, 1943-80. 408 6

Among 41,109 women diagnosed with breast cancer between 1935 and 1982 in Connecticut, 3,984 developed a second cancer, whereas 2,426 were expected [relative risk (RR) = 1.64; 95% CI = 1.6-1.7]. This increased risk persisted for 30 years and was highest in women under 55 years of age at the time of breast cancer diagnosis. Second primary breast cancers (RR = 3.0) accounted for almost one-half of all new neoplasms. However, if subsequent breast cancers were excluded, the risk for all other second cancers was only 1.15 (95% CI = 1.10-1.20), and no excess risk was seen among women over age 55 at initial breast cancer. Significant risks were found for cancers of the ovary (RR = 1.7) and uterine corpus (RR = 1.4), possibly linked with shared reproductive factors such as nulliparity or late age at menopause. Malignant melanoma (RR = 1.5), thyroid cancer (RR = 1.6), and colon cancer (RR = 1.2) were also significantly elevated; possible shared risk factors remain to be elucidated. Significant deficits of multiple myeloma and chronic lymphocytic leukemia were noted. Women who received initial radiotherapy compared with those who did not were at slightly higher risk of developing a second cancer, most notably acute nonlymphocytic leukemia, non-Hodgkin's lymphoma, and cancers of the esophagus, kidney, and connective tissue, although the nature of the associations was not always clear. Some of the soft tissue sarcomas were lymphangiosarcomas of the arm, a consequence of the lymphedema that may complicate radical mastectomy (Stewart-Treves syndrome). Women treated with radiation were at higher risk of developing a second breast neoplasm (RR = 3.9) than nonirradiated women (RR = 2.8). Further investigation should focus on the mechanisms underlying the relationships between breast, genital tract, and colon cancers, and on the effects of treatment modalities on the risk of subsequent neoplasms.
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PMID:Second cancer following cancer of the breast in Connecticut, 1935-82. 408 15


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