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)

Alkylating agents have been the major group of chemotherapeutic agents associated with an increased incidence of secondary leukemias. In ovarian cancer alkylating agents have resulted in a lesser, although still increased, risk of secondary malignancies. This paper reports two cases of ovarian cancer treated with cisplatin and doxorubicin (Adriamycin, Adria Laboratories, Columbus, OH), and the subsequent development of an acute nonlymphocytic leukemia and a preleukemia syndrome. This regimen does not contain alkylating agents, and has not been associated with leukemia in patients with ovarian cancer. In these two cases, abnormalities of chromosomes 5, 7, 11, and 17 are reported which have been shown to occur in therapy-related leukemia.
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PMID:Development of leukemia after doxorubicin and cisplatin treatment for ovarian cancer. 281 55

The lipophilic antitumor alkaloid acronycine (ACRO) was solubilized in the cosolvent system used for etoposide. ACRO in this etoposide diluent (VPD) was found to be cytotoxic (less than or equal to 50% colony formation in soft agar) in fresh human tumors from patients with renal cell cancer, ovarian cancer, uterine cancer, and metastatic tumors of unknown primary. In P-glycoprotein-positive, multidrug-resistant (MDR) cell lines, ACRO in VPD was active in MDR Chinese hamster ovary cells but not against MDR L1210 murine leukemia cells, 8226 human myeloma cells, or human CCRF-CEM lymphoblasts. In mice, ACRO in VPD was active in two solid tumor models and an i.p. MOPC-315 plasmacytoma model. ACRO i.p. in 10% VPD (v/v%) produced significant tumor growth delays in (a) nude mice bearing human MCF-7 breast cancer xenografts and (b) C57BL mice bearing colon 38 tumor. In MOPC-315-bearing mice, a single i.p. ACRO dose of 25 mg/kg was as effective as melphalan (15 mg/kg) at prolonging life span. Finally, ACRO pharmacokinetics was evaluated in mice given single 25-mg/kg doses i.p. or p.o. The oral bioavailability of an ACRO solution in VPD was only 50% but both i.p. and p.o. regimens achieved plasma levels greater than 1.0 micrograms/ml. The plasma half-life was just under 2 h. These results show that parenteral ACRO in VPD comprises a cytotoxic antitumor agent with improved bioavailability over p.o. administration. ACRO is active in vitro against several human solid tumors but is cross-resistant in 3 of 4 MDR tumor cell lines. The prior clinical activity of p.o. ACRO in myeloma and the new results in MOPC-315 plasmacytomas in mice suggest that ACRO in VPD could have activity against human multiple myeloma.
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PMID:Antitumor activity and murine pharmacokinetics of parenteral acronycine. 291 Apr 53

The above methodology has been used to prepare a variety of PE-immunotoxins. These reagents are potent cytotoxic agents for cells in culture that bind the appropriate antibody and nontoxic when cells do not bind the antibody. PE-immunotoxins can be used to select for mutant cultured cells which lack the target of the antibody (see chapter by Gottesman [9] on drug-resistant mutants). Recently, we have also demonstrated in vivo activity when a PE-immunotoxin was used to inhibit the growth of human ovarian cancer cells in a nude mouse model of ovarian cancer. Also PE-immunotoxins are currently being evaluated in Phase 1 clinical trials for the treatment of adult T-cell leukemia.
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PMID:Construction of immunotoxins using Pseudomonas exotoxin A. 312 80

HMFG antigen is a tumour associated glycoprotein that has been immunohistochemically shown to be expressed by malignant cells in breast and ovarian and to a lesser degree in gastro-intestinal carcinomas. We have developed a non-isotopic sandwich ELISA for secretory HMFG antigen utilizing a polyclonal catcher and a tracer monoclonal antibody (MAb). 52/52 of healthy medical students (controls) had a serum value under 400 U/ml whereas 15/30 patients (50%) with evident ovarian cancer and 13/37 (35%) with advanced breast cancer had a value exceeding 400 U/ml. From other patients with malignant tumours 2/14 (14%) with endometrial carcinoma, 0/5 with cervical carcinoma, 0/5 with vulvar carcinoma, 1/33 with gastro-intestinal carcinoma, 0/4 with oesophageal carcinoma and 2/45 of patients with leukemia or lymphoma had an elevated serum HMFG value. Four cases of Crohn disease, 3 cases of ulcerative colitis and 2 cases of pelvic inflammatory disease all showed a serum value below 400 U/ml. Progression of ovarian cancer was accompanied by increasing serum HMFG antigen levels. The antigen detected by our assay is different from CA 125 but may be related with the tumour associated antigen CA 15-3.
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PMID:Elevated serum HMFG antigen levels in breast and ovarian cancer patients measured with a sandwich ELISA. 316 44

The risk of cancer associated with a broad range of organ doses was estimated in an international study of women with cervical cancer. Among 150,000 patients reported to one of 19 population-based cancer registries or treated in any of 20 oncology clinics, 4188 women with second cancers and 6880 matched controls were selected for detailed study. Radiation doses for selected organs were reconstructed for each patient on the basis of her original radiotherapy records. Very high doses, on the order of several hundred gray, were found to increase the risk of cancers of the bladder [relative risk (RR) = 4.0], rectum (RR = 1.8), vagina (RR = 2.7), and possibly bone (RR = 1.3), uterine corpus (RR = 1.3), cecum (RR = 1.5), and non-Hodgkin's lymphoma (RR = 2.5). For all female genital cancers taken together, a sharp dose-response gradient was observed, reaching fivefold for doses more than 150 Gy. Several gray increased the risk of stomach cancer (RR = 2.1) and leukemia (RR = 2.0). Although cancer of the pancreas was elevated, there was no evidence of a dose-dependent risk. Cancer of the kidney was significantly increased among 15-year survivors. A nonsignificant twofold risk of radiogenic thyroid cancer was observed following an average dose of only 0.11 Gy. Breast cancer was not increased overall, despite an average dose of 0.31 Gy and 953 cases available for evaluation (RR = 0.9); there was, however, a weak suggestion of a dose response among women whose ovaries had been surgically removed. Doses greater than 6 Gy to the ovaries reduced breast cancer risk by 44%. A significant deficit of ovarian cancer was observed within 5 years of radiotherapy; in contrast, a dose response was suggested among 10-year survivors. Radiation was not found to increase the overall risk of cancers of the small intestine, colon, ovary, vulva, connective tissue, breast, Hodgkin's disease, multiple myeloma, or chronic lymphocytic leukemia. For most cancers associated with radiation, risks were highest among long-term survivors and appeared concentrated among women irradiated at relatively younger ages.
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PMID:Radiation dose and second cancer risk in patients treated for cancer of the cervix. 318 29

Second malignancies are one of the known complications of cancer treatment. Several recent studies which have quantified the risk of treatment-induced cancers following gynecologic malignancies are reviewed. After cervical cancer, there is a 9% excess risk of second cancers, of which only 5% could be attributed to radiation therapy. Most of the treatment-related malignancies after cervical or endometrial cancer are solid tumors occurring within the radiation field. Following both cervical and endometrial cancer, there is a small increased risk of leukemia associated with radiation therapy. In contrast, after ovarian cancer, there is significantly increased risk of leukemia related to treatment with alkylating agents, which varies by drug type and total dose. The cumulative risk of leukemia and preleukemia following single agent melphalan is 11.2% +/- 2.6% at ten years; the risk after cyclophosphamide is 5.4% +/- 3.2%. Overall, the risk of second malignancies following treatment of gynecologic cancers is small.
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PMID:Treatment-related cancers after gynecologic malignancy. 330 71

The occurrence of various types of cancer have been reviewed and evaluated in 4 religious groups. These patterns have been critically assessed in light of the distinctive life-style features of these groups. All 4 religious groups considered in this paper have reduced overall rates of cancer, suggesting that the life-styles of all 4 groups have merit in terms of reducing the overall risk of cancer. The rate of smoking among these groups is nearly nil, and the lung cancer rate in all 4 of these religious groups is strikingly low. Cancer of the oral structures, pharynx, larynx, and esophagus is also generally quite low. Amish and Hutterites have unusually high rates of breast cancer and juvenile leukemia. Reproductive factors frequently mentioned as risk factors for breast cancer cannot explain the excess breast cancer in the Amish and Hutterite women because they should have had the effect of reducing the rate. None of the numerous risk factors, normally suggested for leukemia, are consistent with this observation. The observations on ovarian cancer tend to confirm low parity and late age at first birth as risk factors, although the evidence is not entirely consistent. Also, contrary to common observations, the pattern of ovarian cancer contrasts greatly with the breast cancer pattern, suggesting dissimilar risk factors. Their low rate of cervical cancer is consistent with promiscuity being a strong risk factor, but other frequently suggested risk factors were generally inconsistent with the observations. Cancers of the stomach, colon, rectum, urinary bladder and prostate, in these 4 religious groups, are not readily explained by the risk factors commonly implicated in cancer of these sites. The patterns of a few types of cancers were consistent with the prevailing opinions of risk factors, but some cancers were poorly explained and, in some cases, the cancer patterns contradicted commonly held opinions concerning risk factors. Religions that provide strong directives for the personal lives of adherents result in distinctive life-style, reflecting multiple disease related factors (risk factors and protective factors). Disease related factors are related to each other in simple or more complex ways (e.g. additive, multiplicative or even more complex). Therefore, when dealing with distinctive life-styles, it may be unwarranted to attempt to isolate individual risk factors.
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PMID:Review of cancer among 4 religious sects: evidence that life-styles are distinctive sets of risk factors. 339 18

Cisplatin and melphalan given ip exert a synergistic therapeutic effect against ascitic P388 leukemia in mice and have different dose-limiting toxic effects as well as favorable pharmacokinetic characteristics in ip phase I studies. We gave a total of 98 courses of cisplatin (escalated from 40 to 120 mg/m2) and melphalan (escalated from 12 to 30 mg/m2) to 30 patients with ip tumors, most of whom had residual ovarian cancer following iv cisplatin-containing regimens. Treatment was delivered in 2 L of 0.9% NaCl through a Tenckhoff catheter with or without a Port-a-Cath system every 28 days for one to nine cycles. Myelosuppression was dose-related and leukopenia was dose-limiting. The maximum tolerated dose was 120 mg of cisplatin/m2 and 20 mg of melphalan/m2. With the exception of treatment-induced nausea and vomiting, nonhematologic toxic effects were mild and no (or very little) local toxicity occurred. Pharmacokinetic analyses showed that the areas under the peritoneal concentration versus time curve averaged 16-fold and 17-fold more than the area under the plasma curve for cisplatin and melphalan, respectively. Objective responses were documented by third-look laparotomy in ovarian cancer patients with minimal (less than 2 cm) residual disease.
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PMID:Intraperitoneal chemotherapy with cisplatin and melphalan. 341 24

Eleven population-based cancer registries tabulated second cancers among 133,411 patients diagnosed with testicular cancer, ovarian cancer or Hodgkin's disease between 1945 and 1984. Overall, 3,157 second cancers were observed, as compared with 2,420 expected at least one year after the first cancer. Survivors of testicular and ovarian cancer experienced 30% and 20% more cancers respectively than the general population comparison group, and patients previously diagnosed with Hodgkin's disease had an 80% excess of cancer. No information was available either on treatment for the first cancer, or other risk factors. However, temporal patterns in the risk of specific second cancers were analysed, with particular reference to the possible role of therapy for the first cancer. Leukaemia of the acute or non-lymphatic type, which has been previously linked to alkylating agent therapy, occurred in excess following all 3 first cancers, as did non-Hodgkin's lymphoma (overall relative risks of 6.1 and 1.8 respectively, with considerably higher relative risks following Hodgkin's disease). Other cancers for which important and plausibly therapy-induced excesses occurred were lung cancer following Hodgkin's disease (relative risk 1.9), breast cancer following Hodgkin's disease (relative risk 1.4) and bladder cancer following ovarian cancer and Hodgkin's disease (relative risks 1.7 and 2.2 in women, respectively). Rarer sites at which striking excesses occurred were the salivary gland, thyroid, bone and connective tissue. There were smaller, but clear excesses for cancers of the rectum and colon following ovarian cancer and testicular cancer, skin cancer following Hodgkin's disease, and kidney cancer following ovarian cancer. Overdiagnosis, misclassification of metastases and confounding by other risk factors were all considered as explanations of observed excesses. Nonetheless, it appeared that there are clear excess risks for cancers other than acute leukaemia which must be ascribed to therapy for the first cancer, especially in view of the possible under-reporting in registry material. Case-control studies are under way to provide information on the role of specific aspects of therapy.
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PMID:Second malignancies following testicular cancer, ovarian cancer and Hodgkin's disease: an international collaborative study among cancer registries. 357 May 50

In recent years, epidemiological methods have been used increasingly to study the carcinogenicity of drugs used in the chemotherapy of cancer. Such studies are useful to clinicians in identifying therapeutic agents with particular long-term risk to patients. They can also provide information on the dose- and time-related risks of cancer in one of the few human populations intentionally exposed to known levels of carcinogens. Aspects of epidemiological studies of second cancer risk are described, including sources of cases, study design, statistical methods, and possible biases. Results from a cohort study of second cancers following ovarian cancer, testicular cancer and Hodgkin's disease and from a case-control study of leukaemia following Hodgkin's disease are also given.
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PMID:Epidemiological studies of anticancer drug carcinogenicity. 358 90


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