Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0023418 (leukemia)
 93,477 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Cytochrome P450 CYP2D6 polymorphism is an autosomal recessive trait associated with impaired debrisoquine metabolism in 5-10% of caucasian populations. This polymorphism has been associated with susceptibility to Parkinson's disease, bladder cancer, various forms of leukemia and possibly melanoma. In many other cancer forms, the data remained contradictory due to the technical limitations for identifying affected individuals (poor metabolizers). A recently developed polymerase chain reaction-based assay allows convenient screening of approximately 80% of known mutations. We have tested brain tumors correlated with chromosome 22 deviations for genetic polymorphism in the cytochrome P450 CYP2D6 locus localized on chromosome 22q13. Thirty-one meningioma samples were analyzed and the observed frequency of heterozygotes and homozygotes for the G to A mutation did not deviate significantly from the distribution in a normal population. These data are comparable to previous observations in for example breast and colon cancer and indicate that the CYP2D6 locus on chromosome 22q13 is not involved in the pathogenesis of meningiomas.
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PMID:Debrisoquine hydroxylase gene polymorphism in meningioma. 784 77

The cDNA sequences of thioredoxin obtained by PCR cloning from human colon cancer cells, human lymphoblastoid cells, and human liver have been found to be identical with the cDNA sequence reported for the autocrine growth factor, human adult T-cell leukemia derived factor (ADF). Recombinant human thioredoxin was 95% reduced by dithiothreitol and was a substrate for reduction by human thioredoxin reductase. Human non-small cell primary lung tumors from subjects who were not cigarette smokers at the time of surgery showed significantly increased levels of thioredoxin mRNA compared to thioredoxin mRNA in paired normal human lung tissue. Subjects who were smokers did not show a significant increase in lung tumor thioredoxin mRNA. The results of the study show that human thioredoxin and ADF are identical species and suggest that there may be increased production of thioredoxin (ADF) by some human cancers.
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PMID:The predicted amino acid sequence of human thioredoxin is identical to that of the autocrine growth factor human adult T-cell derived factor (ADF): thioredoxin mRNA is elevated in some human tumors. 804 54

The mortality profile of female nurses and teachers in British Columbia (BC) was examined using age-standardized proportional mortality ratios (PMRs) calculated for the period 1950-1984. Lowered overall mortality among nurses was seen for degenerative heart disease and for cerebrovascular accidents. Significantly elevated PMR values were observed for cancer of the breast and ovary in nurses of age 20-65 years. PMRs were significantly elevated for cancer of the pancreas and leukemia among those age 20 years and older. Elevated values were also observed for motor vehicle accidents and suicide among nurses in both age groups. Lower than expected mortality from degenerative heart disease and cerebrovascular accidents was seen in working age teachers (age 20-65 years). However, elevated PMRs were detected for carcinoma of the colon, breast, endometrium, brain, and melanoma. Among those 20 years and over, significantly elevated PMRs were also observed for cancers of the ovary and other digestive organs. Elevated PMRs were found for motor vehicle and aircraft accidents. Mortality from cirrhosis of the liver was lower than anticipated in both teachers and nurses. A number of significant PMRs declined when deaths of "homemakers" were withdrawn from the comparison group used to generate PMR values, suggesting that risk of death from various causes among women working outside the home differ from those seen in women who are predominantly in the home.
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PMID:Mortality among female registered nurses and school teachers in British Columbia. 807 20

Levamisole, a widely used antihelminthic drug has been shown to restore cutaneous delayed hypersensitivity in anergic patients with cancer and to amplify the activation of T lymphocytes by in vitro mitogens. Levamisole has been approved for the treatment of colon cancer in combination with 5 Fluorouracil. Herein we report a case of a 5 1/2 y.o. male who presented with a fulminant, disseminated mycobacterial infection of his joints secondary to a deficiency in his cellular mediated immunity in association with chemotherapy for a T cell leukemia. The patient was treated with Levamisole resulting in restoration of his T cell functions and resolution of his mycobacterial infection.
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PMID:Levamisole as an immunopotentiator for T cell deficiency. 807 2

A total of 22 genes have been identified in the carcinoembryonic antigen (CEA) gene family. The protein products of this family are highly homologous and include CEA, biliary glycoprotein, nonspecific cross-reacting antigen 50/90 (NCA 50/90), NCA 95, and pregnancy-specific beta-glycoprotein. We used a monoclonal antibody with high affinity to develop a specific enzyme-linked immunosorbent assay (ELISA) method for NCA 50/90 in serum and plasma. Our calibrators were based on affinity-purified recombinant protein from a baculovirus expression system. No significant reactivity with purified CEA, recombinant NCA 95, or recombinant biliary glycoprotein was found by Western blot analysis or in the ELISA method. Only 1 of 15 sera from pregnant women (chorionic gonadotropin > 1000 ng/ml) was positive in the NCA 50/90 ELISA, suggesting that this method does not detect pregnancy-specific glycoprotein. A cutoff value of 18 ng/ml was established based on the 95% value of serum and plasma from 147 healthy volunteers. Only 3 of 31 serum and plasma samples from patients with clinically inactive breast cancer were elevated above the cutoff value, but 44% of 136 samples from patients with clinically active breast cancer were positive. NCA 50/90 measurements were elevated in 7 of 25 patients with active breast cancer whose CEA and CA 15-3 values were below cutoff, and NCA 50/90 values do not correlate with CEA in breast cancer. In addition, we found sensitivities of 70, 39, and 42% for lung cancer, colon cancer, and leukemia, respectively. The sensitivity for non-small cell lung cancer was 85%, however, compared to 50% for small cell lung cancer. Serum from leukemia patients showed an overall sensitivity of 43%, but 71% (10 of 14) sera from patients with chronic myelogenous leukemia were positive compared to, for example, chronic lymphocytic leukemia where 0 of 7 sera had NCA 50/90 values above the cutoff. These studies suggest that NCA 50/90 may have clinical utility in the management of patients with a variety of cancers.
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PMID:Nonspecific cross-reacting antigen 50/90 is elevated in patients with breast, lung, and colon cancer. 811 11

The search for compounds active against solid tumors has led us to the discovery of a novel sulfonamide, E7010 (N-[2-[(4-hydroxyphenyl)amino]-3-pyridinyl]-4- methoxybenzenesulfonamide), which inhibits tubulin polymerization. When administered orally, E7010 showed good antitumor activity against various rodent tumors and human tumor xenografts. In tests on mouse tumor, E7010, administered in doses of 25-100 mg/kg daily for 8 days, inhibited the growth of colon 38 carcinoma inoculated s.c. in mice by 60-99%. E7010 was active against s.c. inoculated M5076 fibrosarcoma (75% tumor growth inhibition), s.c. inoculated Lewis lung carcinoma (84% increase in life span), and i.p. inoculated P388 leukemia (118% increase in life span). In a test on rat tumor, E7010 inhibited the growth of SST-2 mammary carcinoma inoculated s.c. in rats by 84%. In tests on s.c. inoculated human tumor xenografts, E7010, when administered orally, showed a broad spectrum of activity. E7010 inhibited the growth of: four kinds of gastric cancer, H-81, H-111, SC-2, and SC-6 by 60-78%; three kinds of colon cancer, H-143, COLO320DM, and WiDr by 58-83%; three kinds of lung cancer, LC-376, LC-6, and LX-1 by 63-82%; and two kinds of breast cancer, H-31 and MX-1 by 79-87%. In studies on drug-resistant P388 leukemia, E7010 was effective against vincristine-resistant P388, cisplatin-resistant P388, and 5-fluorouracil-resistant P388 sublines in mice. Because of its good activity against rodent tumors and human tumor xenografts, E7010 is currently undergoing Phase I clinical trials.
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PMID:In vivo tumor growth inhibition produced by a novel sulfonamide, E7010, against rodent and human tumors. 813 85

A new class of antitumor agents, having structural analogy to amonafide, but differing by the addition of a fourth ring in the nucleus, was synthesized conveniently from anthracene. Compounds with a variety of substituents, containing a basic nitrogen atom and located on the imide nitrogen, were prepared. Thirteen of 19 new compounds had greater growth inhibitory potency than amonafide in a panel of cultured murine and human tumor cells using the sulforhodamine B and MTT dye assays. The most active agents were similarly more toxic than amonafide to normal neonatal rat myocytes in vitro, but they had better chemotherapeutic indexes. From these compounds, the one with a 2-(dimethylamino)ethyl side chain (named azonafide) was chosen for further study. It showed high potency against a panel of cultured human colon cancer cells and it was active against ip P388 leukemia and subcutaneous B16 melanoma in mice. Preliminary structure-activity correlations suggest that the basicity of the side-chain nitrogen and the length of side chain are important determinants of antitumor potency in vitro. Steric hindrance and rigidity of the side chains might be other determinants.
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PMID:2-substituted 1,2-dihydro-3H-dibenz[de,h]isoquinoline-1,3-diones. A new class of antitumor agent. 845 3

Protein tyrosine phosphatases (PTPases) play an important role in regulating cell growth and transformation. We report that the antitumor agent gallium nitrate is a potent inhibitor (concentration producing 50% inhibition, 2-6 microM) of detergent-solubilized cellular membrane PTPase from Jurkat human T-cell leukemia cells and HT-29 human colon cancer cells. This is the first report of a selective, small molecule drug inhibitor of PTPase. Gallium nitrate did not inhibit CD45, a PTPase found in the membranes of hemopoietic lineage cells such as Jurkat cells. Studies with gallium nitrate and a series of gallium-containing analogues revealed no correlation between growth-inhibitory activity in Jurkat and HT-29 cells and the ability to inhibit detergent-solubilized PTPase. Gallium nitrate and most of the gallium analogues penetrate poorly into cells. In contrast, a gallium-hydrogen peroxide complex inhibits DNA synthesis in Jurkat cells and induces the accumulation of phosphotyrosines on multiple intracellular proteins in this cell line. Gallium-hydrogen peroxide complex and gallium nitrate have similar inhibitory activity toward detergent-soluble PTPase. This is a new mechanism of action for gallium nitrate but it is not known if the inhibition of PTPase is related to the antitumor activity of gallium nitrate.
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PMID:Inhibition of protein tyrosine phosphatase by the antitumor agent gallium nitrate. 846 6

For more than 50 years, there has been documentation in the medical literature suggesting that regular sun exposure is associated with substantial decreases in death rates from certain cancers and a decrease in overall cancer death rates. Recent research suggests that this is a causal relationship that acts through the body's vitamin D metabolic pathways. The studies reviewed here show that (a) sunlight activation is our most effective source of vitamin D; (b) regular sunlight/vitamin D "intake" inhibits growth of breast and colon cancer cells and is associated with substantial decreases in death rates from these cancers; (c) metabolites of vitamin D have induced leukemia and lymphoma cells to differentiate, prolonged survival of leukemic mice, and produced complete and partial clinical responses in lymphoma patients having high vitamin D metabolite receptor levels in tumor tissue; (d) sunlight has a paradoxical relationship with melanoma, in that severe sunburning initiates melanoma whereas long-term regular sun exposure inhibits melanoma; (e) frequent regular sun exposure acts to cause cancers that have a 0.3% death rate with 2,000 U.S. fatalities per year and acts to prevent cancers that have death rates from 20-65% with 138,000 U.S. fatalities per year; (f) there is support in the medical literature to suggest that the 17% increase in breast cancer incidence during the 1991-1992 year may be the result of the past decade of pervasive anti-sun advisories from respected authorities, coinciding with effective sunscreen availability; and (g) trends in the epidemiological literature suggest that approximately 30,000 U.S. cancer deaths yearly would be averted by the widespread public adoption of regular, moderate sunning.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Beneficial effects of sun exposure on cancer mortality. 847 9

Radiolabeled monoclonal antibodies have been used for radioimmunotherapy studies with human tumor spheroids and murine and human tumor xenografts in experimental animals. This paper reviews the work that has been performed in these models with different types of cancer, and highlights those papers that have presented dosimetry estimates and attempts to correlate the findings. Radioimmunotherapy studies in multicell spheroids, as a model for micrometastases, have been performed in human neuroblastoma, colon cancer, and melanoma cell lines using 131I-, 125I-, 186Re-, and 212Bi-labeled antibodies. The uniform geometry of the spheroid has allowed radiation dose estimates to be made. Up to three logs of cell kill have been achieved with 131I- and 186Re-specific antibody with minimal toxicity from labeled nonspecific antibody, but 212Bi-antibody had little effect because of its short half-life as shown by Langmuir. It appears that the two most important factors for therapeutic efficacy in this model are good penetration of the radiolabeled antibody and an adequate radionuclide half-life to allow penetration of the immunoconjugate prior to significant radionuclide decay. Radioimmunotherapy studies in animals bearing transplants of colon cancer, leukemia, lymphoma, hepatoma, renal cell carcinoma, neuroblastoma, glioma, mammary carcinoma, small cell lung carcinoma, cervical carcinoma, ovarian carcinoma, and bladder cancer have been performed with 131I, 90Y, 186Re, 153Sm, and 177Lu beta emitting, and 212Bi alpha emitting radionuclides conjugated to monoclonal antibodies. A few studies compared different radionuclides in the same model system. The approaches that have been used in these studies to estimate tumor dosimetry include the MIRD approach, thermoluminescent dosimetry, autoradiography, and comparison to external irradiation. The majority of investigators have estimated the dose to tumor and normal organs using MIRD-based calculations (time-activity curve and equilibrium dose constant method). The range of tumor doses has been between 17 and 11 171 mGy/MBq of administered radioactivity. The effectiveness of radiolabeled monoclonal antibody therapy depends on a number of factors relating to the antibody such as specificity, affinity, and immunoreactivity. The density, location, and heterogeneity of expression of tumor-associated antigen within tumors will affect the localization and therapeutic efficacy of radiolabeled antibodies, as will physiological factors such as the tumor vascularity, blood flow, and permeability. These factors are discussed and examples are presented.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Experimental radioimmunotherapy. 849 64


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