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

Activation of the cellular oncogene c-N-ras has been frequently observed in DNA from leukemic cells in acute myeloid leukemia (AML). Ras gene activation sufficient to mediate in vitro transformation and rodent tumorigenesis usually results from point mutations and amino acid substitutions in the 12th or 61st codons. In AML and the related myelodysplastic syndromes, amino acid substitution at the 13th codon has been observed. An activated c-N-ras gene from a 45-year-old patient with AML was isolated by transfection analysis and subjected to molecular cloning and sequence analysis. A point mutation of the 12th codon (GGT to GAT) resulting in aspartic acid substitution for glycine was observed. In other neoplasms such as colon cancer, specific ras mutations occur predominantly (e.g., K-ras, codon 12). This predominance has been of demonstrable value in analyzing large cohorts for ras activation with techniques that are rapid and economical, such as oligonucleotide hybridization. It had previously been thought that such a predominance for activation of c-N-ras at codon 13 existed in AML; however, this study in concert with others underscores the importance of 12th codon c-N-ras mutations, along with 13th and 61st codon mutations in the molecular pathogenesis of AML. Guanylate to adenylate transition mutations are commonly observed in AML and may provide insight into potential environmental leukemogens. Addressing all commonly prevalent ras activating mutations bears impact in the future design of molecular surveys of the role of ras activation in leukemogenesis.
Leukemia 1988 Feb
PMID:12th codon mutation resulting in c-N-ras activation in acute myelogenous leukemia. 327 72

Serum concentration of laminin was measured radioimmunologically in 96 patients suffering from various malignancies. Laminin levels were significantly elevated in patients with carcinomas and leukemias, but not in patients with sarcomas or lymphomas when compared with healthy controls. A good correlation could be found between serum laminin concentration and response to therapy in patients with carcinoma and leukemia. Elevated laminin levels were associated with a progressive course of the tumor condition. Furthermore, a close correlation has been detected between serum concentrations of laminin and carcinoembryonic antigen (CEA) in patients with carcinoma of the colon. The serum laminin level seems to be a valuable parameter for observation of the course of certain malignancies.
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PMID:Serum concentration of laminin, and course of the disease in patients with various malignancies. 362 57

We examined the activity reported in phase II trials for all cytotoxic drugs introduced into clinical trial by the National Cancer Institute (NCI) since 1970. For each drug in each tested tumor type we derived a response rate from the pooled data of all trials reported either in the literature or to the NCI. We rated a drug active if the lower 80% confidence bound of the response rate was greater than 10%. Of the 83 drugs developed and introduced by the NCI, there are 47 which we considered evaluable. Of these drugs, 24 were rated active in at least one cancer type, of which ten were analogs of drugs in wide clinical use. Diseases most commonly responsive include lymphoma (74% of the tested drugs rated active), leukemia (35%), urothelial cancer (29%), small cell lung cancer (29%), ovarian cancer (22%), cervical cancer (22%), and breast cancer (18%). For colon cancer and melanoma, only one of 42 and two of 30 tested drugs rated active, respectively. We also examined the completeness of clinical testing: among the 47 drugs there were 20 tested in greater than or equal to 14 patients with leukemia, 23 tested in patients with lymphoma, and 18 tested in patients with small cell lung cancer; whereas 34 drugs for breast cancer, 42 for colon cancer, and 33 for non-small cell lung cancer were more completely evaluated. Considering the "clinical panel" of seven cancer types (breast, non-small cell lung, small cell lung, colon, melanoma, leukemia, and lymphoma), drugs were tested in greater than or equal to 30 patients in a median of four tumor types. Testing in this panel failed to detect activity in only one drug found active in another tumor, although testing in diseases other than this clinical panel was even less complete. Phase II testing should emphasize completion of minimum accrual goals, testing in patient populations with minimum prior therapy, and evaluation in a minimum set of tumor types.
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PMID:Clinical drug development: an analysis of phase II trials, 1970-1985. 379 Dec 70

Mortality up to 1 January 1983 has been studied in 14,106 patients with ankylosing spondylitis given a single course of X-ray treatment during 1935-54. For neoplasms other than leukaemia or colon cancer, mortality was 28% greater than that of members of the general population of England and Wales, and this increase is likely to have been a direct consequence of the treatment. The proportional increase reached a maximum of 71% between 10.0 and 12.4 years after irradiation and then declined. There was only a 7% increase in mortality from these tumours more than 25.0 years after irradiation and only for cancer of the oesophagus was the relative risk significantly raised in this period. Neither the magnitude of the relative risk, nor its temporal pattern following treatment, were greatly influenced by the age of the patient at first treatment. For leukaemia there was a threefold increase in mortality that is also likely to have been due to the radiotherapy. The relative risk was at its highest between 2.5 and 4.9 years after the treatment and then declined, but the increase did not disappear completely, and the risk was still nearly twice that of the general population more than 25.0 years after treatment. There was some evidence that the risks of acute myeloid, acute lymphatic, and chronic myeloid leukaemia were all increased, but no evidence of any increase in chronic lymphatic leukaemia. The relative risk appeared to be greatest for acute myeloid leukaemia. For colon cancer, which is associated with spondylitis through a common association with ulcerative colitis, mortality was increased by 30%. For non-neoplastic conditions there was a 51% increase in mortality that was likely to be associated with the disease itself rather than its treatment. The increase was apparent for a wide range of diseases and was not confined to diseases that have been associated clinically with ankylosing spondylitis.
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PMID:Long term mortality after a single treatment course with X-rays in patients treated for ankylosing spondylitis. 381 87

The material of the Finnish Cancer Registry from 1953-79 (279,745 cancer patients, 774,518 person-yr at risk) was analyzed for the occurrence of multiple cancer. There were 5,871 new primary cancers in the series (excluding the first 12 mo from diagnosis of the first cancer). A positive association between cancers with similar etiology could be demonstrated, e.g., between cancers of the lip, larynx, and lung (smoking) and between cancers of the breast and endometrium (hormones, reproductive history). Clustering of different risk factors resulted, e.g., in an excess risk of colon cancer among female breast cancer patients (risk factors in both cancers are prevalent particularly in higher-social classes). Differences in the distribution of the risk factors resulted in risk deficits, e.g., low relative risk of lung cancer among male colon cancer patients (the prevalence of smoking was highest in the lower-social classes and the prevalence of risk factors in colon cancer was highest in the higher-social classes). The risk of leukemia was increased among patients with cancers of the breast, endometrium, and thyroid (possibly due to irradiation). There was a high relative risk of salivary gland cancer among patients with skin cancer other than melanoma or basal cell carcinoma in both sexes. The relative risk of a new primary cancer decreased with increasing age at diagnosis of the first cancer. The length of follow-up was positively associated with the relative risk of many cancers, although this finding was not as consistent as that with age.
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PMID:Multiple cancer--an epidemiologic exercise in Finland. 386 Jun 79

A suspicion of an excess cancer risk in automotive model shops prompted the Industrywide Studies Branch, NIOSH, to conduct a proportionate mortality study and an industrial hygiene characterization of operations in these shops. The mortality study showed a statistically significant excess proportion of deaths due to colon cancer and leukemia (for woodshops only). The materials used in the model shops include various natural woods, laminated woods, plastics, resins, varnishes, putties and paints. Personal breathing zone samples were collected for total and respirable dust, amines, various hydrocarbons (including styrene, and toluene), formaldehyde, and nitrosamines. Particle size distribution studies were conducted on the wood dust and bulk airborne samples of dusts were subjected to various mutagenicity test systems. Work practices, ventilation and general housekeeping were checked. Total wood dust samples ranged from 0.03 to 25 mg/m3 with an average around 1.0 mg/m3. The percent respirable dust ranged from 19 to 38% as measured with Andersen impactors. Solvent exposure samples ranged from non-detectable to about 10% of the OSHA Permissible Exposure Levels. Relevant recommendations for improvement of contaminant control were made.
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PMID:Industrial hygiene characterization of automotive wood model shops. 388 Jan 87

The distribution of two monoclonal antibodies with reactivity against human leukemia/lymphoma associated antigens (BA-1 antibody) and carcinoembryonic antigen (202 antibody) when labeled with 131I or 111In was studied in normal Balb/c mice. The BA-1 antibody of the IgM subclass was labeled with 131I by the micro iodine monochloride method at a 12:1 molar ratio and with 111In by the cyclic DTPA anhydride method at a 10:1 molar ratio. In vitro, the 131I-labeled BA-1 antibody bound 35.5% to 10(7) KM-3 leukemic cells while the 111In-labeled BA-1 antibody bound 29.9% to the same number of KM-3 cells. In vivo, the 111In-labeled BA-1 antibody showed a higher accumulation in liver, spleen, and kidney than the 131I-labeled BA-1 antibody. The 202 antibody of the IgG1 subclass was labeled with 131I at a 5:1 molar ratio and with 111In at a 7:1 molar ratio. In vitro, the 131I-labeled 202 antibody bound 30.9%, 27.4%, and 30.0% to 10(7) CO-112, WIDR, and LS-174T colon cancer cells, respectively. The 111In-labeled 202 antibody bound 20.5%, 30.2%, and 33.6%, respectively to the same number of colon cancer cells. In vivo, the 131I-labeled 202 antibody showed a higher tissue to blood ratio in liver, spleen, and kidney than the 111In-labeled 202 antibody. The data indicate that the relative distribution of 131I-labeled versus 111In-labeled monoclonal antibody may depend on the immunoglobulin subclass of the antibody and the molar ratio used in labeling.
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PMID:Comparison of the distribution and binding of monoclonal antibodies labeled with 131-iodine or 111-indium. 400 81

A novel, substituted 4-quinolinecarboxylic acid (NSC 339768) demonstrated antitumor activity against L1210 leukemia and B16 melanoma in the National Cancer Institute's Developmental Therapeutics Program. An extensive analogue synthesis program was initiated; over 200 derivatives were synthesized and tested for anticancer activity. One of these compounds, 6-fluoro-2-(2'-fluoro-1,1'-biphenyl-4-yl)-3-methyl-4-quinolinecarboxylic acid sodium salt, NSC 368390 (DuP-785), was selected for further investigation because of its efficacy against a spectrum of human solid tumors and its water solubility. In initial studies with L1210 leukemia, the compound caused an increase in life span of greater than 80%. The activity was schedule dependent, and the compound was equally efficacious when administered i.p., i.v., s.c., or p.o. In tests against human tumors xenografted under the renal capsule of nude mice, NSC 368390 when injected i.p. in doses of 20-40 mg/kg daily for 9 days inhibited the growth of the MX-1 breast, LX-1 lung, BL/STX-1 stomach, and CX-1 colon carcinomas by greater than 90%. NSC 368390 also inhibited the growth of three distinct human colon carcinomas, the HCT-15, clone A, and DLD-2 tumors, growing s.c. in nude mice. An i.p. dose of 25 mg/kg given daily for 9 days inhibited the growth of the DLD-2 colon cancer by 98%. 1-beta-D-Arabinofuranosylcytosine and Adriamycin were ineffective, and fluorouracil was only moderately effective against these colon tumors. Because of its good activity against human colon tumors and other human carcinomas and its water solubility, NSC 368390 (DuP-785) is being developed as a Phase 1 anticancer agent.
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PMID:Activity of a novel 4-quinolinecarboxylic acid, NSC 368390 [6-fluoro-2-(2'-fluoro-1,1'-biphenyl-4-yl)-3-methyl-4-quinolinecarb oxylic acid sodium salt], against experimental tumors. 405 30

Cisplatin plus 5-FU appears to have significant additive activity in various tumors, such as head and neck carcinoma and esophageal cancer. A partial explanation for this may be drug synergism, which has been noted in the L1210 leukemia model. Based on these data, a prospective trial of weekly bolus 5-FU (15 mg/kg) and cisplatin (60 mg/m2) given every 3 weeks was initiated at Indiana University. Forty-one patients, of whom 38 are fully evaluable for response, were treated with these two drugs. Ten partial and one complete response (complete + partial response rate = 29%) were observed in the 38 evaluable patients. Thirteen additional patients had stable disease for greater than or equal to 3 months. The median durations of remission and survival time were 6 and 10.3 months, respectively. Myelosuppression was unusually severe, with granulocyte counts less than 1000/mm3 in 65% of patients, including four patients with granulocyte count nadirs less than 100/mm3. Three patients developed granulocytopenic fever, with two drug-related deaths (sepsis, hyperosmolar coma). Nearly all patients had nausea and vomiting, but this was not a treatment-limiting toxic effect in any patient. Although this combination suggests a higher response rate than usually seen with bolus iv 5-FU in colon cancer, a trial comparing 5-FU alone or with cisplatin to determine whether true synergy exists is currently underway.
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PMID:Cisplatin plus 5-FU for the treatment of adenocarcinoma of the colon. 407 11

Causes of death among 1598 professional artists were compared with an expected distribution based on the general U.S. population to determine if there were unusual patterns of fatal disease that might be indicative of exposure to hazardous substances in their work environment. Deaths among men and women in the arts were identified from obituaries in Who's Who in American Art published between 1940 and 1969. Among 1253 white male artists, PMRs were significantly elevated for arteriosclerotic heart disease, leukemia and cancers of the bladder, colon, rectum, kidney, and brain. The significant excesses of bladder cancer and leukemia deaths were limited to painters. Proportions of deaths due to colon cancer were significantly elevated among male painters and sculptors. Prostate cancer mortality was slightly higher than expected among painters and significantly elevated among sculptors. Among 345 female artists, painters represented the only specialty category large enough to analyze and excess numbers of deaths due to cancers of the rectum, lung, and breast were noted.
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PMID:Mortality patterns among professional artists: a preliminary report. 407 97


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