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)

Follow-up surveys of patients with ovarian cancer revealed an increased risk of second primary cancers of the uterine corpus, colon, bladder, breast, and hematopoietic system. The excess risk or uterine corpus cancer was independent of therapy. The risk of colon cancer was increased in all treatment groups but was especially high among patients receiving radiation or chemotherapy. The predisposition to other neoplasms was limited to certain treatment groups: bladder cancer to irradiation, leukemia to chemotherapy, and lymphoma to either modality. The pattern of second neoplasms following ovarian cancer appears to be influenced by therapy as well as by common etiologic factors.
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PMID:Second primary neoplasms following ovarian cancer. 28 Jul 6

To estimate the leukemogenic potential of alkylating agents, we surveyed 70 institutions using these drugs for the frequency of second cancers in patients with advanced ovarian cancer. Thirteen cases of acute nonlymphocytic leukemia occurred among 5455 patients, as compared to 0.62 cases expected (relative risk = 21.0). All 13 had received alkylating agents. Nine also received radiotherapy. The relative risk for patients given chemotherapy was 36.1 and rose to 171.4 for those surviving for two years (rate = 13.75 per 1000 patients per year). To evaluate the role of therapy versus underlying disease, a historical control of 13,309 patients with ovarian cancer in the National Cancer Institute's End Results Program was analyzed. No excess of leukemia was noted in this group, even among 6596 women receiving radiation. The excess of acute nonlymphocytic leukemia, therefore, appears attribute to alkylating agents, although the effect may be enhanced by exposure to radiation, as previously suggested for Hodgkin's disease.
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PMID:Acute leukemia after alkylating-agent therapy of ovarian cancer. 40 60

Rapidly fatal acute myelogenous leukemia (AML) occurred in a woman with advanced (Stage III) ovarian carcinoma who was treated with thiotepa for 30 months. This patient was 1 of 10 long term survivors and represented less than 2% of patients with advanced ovarian carcinoma with regional metastases who received long term chemotherapy during the period 1947-1975. Acute leukemia developed 44 months after initial diagnosis and was preceded by a 10 month period of pancytopenia following cessation of thiotepa. The leukemia did not respond to treatment and the patient expired 3 weeks after its onset. At autopsy, leukemic infiltration of organs was seen, but there was no evidence of carcinoma. A review of the literature suggests that the development of AML reported in ovarian cancer patients is related to alkylating agent therapy.
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PMID:Ovarian carcinoma terminating in acute nonlymphocytic leukemia following alkylating agent therapy. 41 94

We compared age-adjusted mortality rates for cancer of selected sites for Chinese, Japanese, and native Indian residents of British Columbia during the years 1964-73 to the corresponding rates for the white population. Mortality from all cancers of the Chinese did not differ significantly from that of whites. Elevated rates are seen for cancer of the nasopharynx in both sexes, of the liver and esophagus in males, and of the lung in females. Chinese males had a lower mortality than whites from stomach, prostate, and bladder cancer and brain tumors, whereas females had a lower mortality from tumors of the colon, breast, and ovary; both sexes had a lower mortality from leukemia. For Japanese males and females, the mortality rates for all cancers combined were similar to those of the white population. The rates for cancer of the stomach and gallbladder were higher in both sexes; males also showed a higher rate of liver cancer. Prostate and breast cancer mortality rates were lower. Native Indian males had a lower mortality rate from all cancers combined; the difference was significant for stomach, colon, lung, and prostate cancers, and for leukemia. Native Indian females showed a lower rate for ovarian cancer and a higher rate of tumors of the gallbladder and uterine cervix, but their overall cancer mortality was similar to that of whites.
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PMID:Cancer mortality among Chinese, Japanese, and Indians in British Columbia, 1964-73. 53 37

L-Asparaginase sensitivity and asparagin-deficiency of 5 tumor cell populations, i.e. mouse lymphoma L-1210, LI0-1, LTL, Berkitt lymphoma and human ovary cancer, line CaOv were studied. Radiometric estimation of 3H-thimidine incorporation into the cells of DNA served a criterion of cytotoxicity. "Krasnitin" (FDR) was used as L-asparaginase. The cells of leukemia L-1210, lymphosarcoma LIO-1 and line CaOv were asparagine-independent and non-sensitive to L-asparaginase. The cells of mouse lympholeukemia LTL and the cultures of Berkitt human lymphoma proved to be asparagin-dependent and highly sensitive to L-asparaginase. In concentration of 50 IU/ml the drug inhibited incorporation of 3H-thimidine in the cells of LTL and Berkitt lymphoma by 97-98 and 75-80 per cent respectively. Inhibition of 3H-thimidine incorporation in the cells of LTL and Berkitt lymphoma was more pronounced after incubation with the drug for 8 and 24 hours respectively. Two out of the 5 tumor cell populations were chosen as a result of the study. One of these 2 populations, i.e. the cells of Berkitt lymphoma was asparagin-dependent and highly sensitive to L-asparaginase, the other, i.e. the cells of line CaOv was asparagin-independent and resistant to the specific antitumor effect of the enzyme. The use of a system of these two cell lines provided estimation of the ratio of the specific cytostatic (antitumor activity) and non-specific cytostatic properties in the preparations with L-asparaginase activity.
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PMID:[Cellular test system for studying the biological properties of preparations with L-asparaginase activity]. 59 48

There are few published reports on cancer incidence in the Puerto Rican-born populations of the northeastern United States. In Connecticut, in the Puerto Rican-born population, which was of low socioeconomic status (i.e., 42% below the poverty level in the 1980 Census), the standardized incidence ratio (SIR) for all invasive cancers diagnosed in 1980-1986 was significantly reduced for female patients (SIR = 0.77) but not for male patients (SIR = 1.16), on the basis of expected numbers derived from incidence rates for the entire state of Connecticut. For female patients, only the SIR for cancers of the stomach, esophagus, and cervix were elevated significantly, whereas those for colorectal, lung, breast, and ovarian cancer were significantly reduced. For male patients, SIR were elevated significantly for cancer of the oral cavity, esophagus, and stomach and for leukemia, whereas none of the sites (including lung) had significantly reduced SIR. When incidence rates for Puerto Rico were used, the SIR for all sites combined was 1.99 (95% confidence interval = 1.78-2.22) for male patients but only 1.39 (95% confidence interval = 1.24-1.56) for female patients. These findings suggest sex differences in acculturation and lifestyle changes relevant to cancer risks in immigrants from Puerto Rico residing in Connecticut. Comparisons were made with cancer incidence and mortality data from other Puerto Rican immigrant populations.
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PMID:Cancer incidence in the Puerto Rican-born population of Connecticut. 151 93

2',2'-Difluorodeoxycytidine (LY 188011, Gemcitabine) is a novel pyrimidine antimetabolite with promising activity in preclinical models for leukemia and solid tumors. Phase I clinical trials with the agent are ongoing. In order to better define types of tumors with clinical sensitivity to Gemcitabine (to help target phase II trials), we have studied the antitumor effects of this agent against a variety of freshly explanted human tumor specimens using an in vitro capillary soft agar cloning system. Final concentrations of 2.0-200 micrograms/ml were used for short-term (1 h) and continuous incubations experiments. Using a short-term incubation, 94/215 (44%) tumor specimens were evaluable for the determination of antitumor activity. The most common tumor types studied included colorectal, breast, non-small cell lung, ovarian cancer, kidney and melanoma. A concentration-dependent increase in the frequency of inhibited tumor specimens was noted (2 micrograms/ml: 6/94 specimens, 20 micrograms/ml: 13/94 specimens, 200 micrograms/ml:33/94 specimens; p less than 0.0001). A similar increase in tumor growth inhibition was found using a continuous incubation (2 micrograms/ml: 0/14 specimens, 20 micrograms/ml: 1/14 specimens, 200 micrograms/ml: 7/14 specimens; p less than 0.001). We conclude that Gemcitabine is an active antitumor agent against tumor colony forming units from a variety of human malignancies if sufficiently high concentrations can be achieved. The agent should be evaluated for Phase II clinical activity against those tumor types.
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PMID:Activity of 2',2'-difluorodeoxycytidine (Gemcitabine) against human tumor colony forming units. 152 92

Since 1983, the National Cancer Institute (NCI) has collected data by means of its Cancer Information Service (CIS), a toll-free telephone helpline for health care professionals and members of the public who have questions about cancer treatment, diagnosis, and prevention. These data reveal information about the characteristics of callers and their questions and about how inquiries reflect mass media promotions and secular trends. A request for a publication is the most common type of inquiry, followed by information about specific cancer sites, smoking prevention and cessation, other types of prevention, cancer treatment, cancer symptoms, referrals to physicians, NCI clinical trials, hospital and clinic-based screening programs, and general counseling or coping. Breast cancer is the most common cancer of interest, followed by respiratory system cancers, colon and prostate cancers, leukemia, melanoma, nonHodgkin's lymphoma, cervical cancer, general or unspecified skin cancer, and ovarian cancer. Responding to these other caller inquiries, CIS counselors may proactively guide callers to a desirable goal, such as screening mammography. Protocols have been developed to assist counselors' proactive efforts, and preliminary results are beginning to support this approach. The findings gathered in this study underscore the health education potential of telephone helplines and point to the need for controlled evaluation research on the effectiveness of proactive counselor advice.
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PMID:Cancer prevention counseling on telephone helplines. 159 37

Chemotherapy cures a minority of adult tumours (e.g. Hodgkin's and non-Hodgkin's lymphoma, acute leukaemia, teratoma) and the majority of childhood tumours. Prolongation of survival by chemotherapy has been shown for small cell lung cancer, ovarian cancer and breast carcinoma (when used as an adjuvant). However, in the majority of solid tumours there is a less than 20% response to chemotherapy and even curable tumours may relapse and become resistant. Resistance may be de novo, acquired as a stable change within the cell, or be rapidly inducible within the cell after drug administration. Several mechanisms have been described including multidrug resistance, glutathione transferases and DNA repair. Understanding these mechanisms may help to improve the therapeutic ratio and develop new approaches.
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PMID:Drug resistance. 165 Jun 21

Resistance to multiple chemotherapeutic agents is a common clinical problem in the treatment of cancer: such resistance may occur in primary therapy or be acquired during treatment. The most commonly used antineoplastic agents in the treatment of disseminated breast cancer are adriamycin, methotrexate and cyclophosphamide. Cell lines selected for resistance to adriamycin often develop cross-resistance to structurally dissimilar antineoplastic drugs with different mechanisms of cytotoxic action; this phenomenon has been called pleiotropic or multidrug resistance (MDR). In vitro models of MDR have shown that this type of resistance is accompanied by a decrease in cellular drug accumulation, mediated by the over-expression of a 170 kD plasma membrane glycoprotein referred to as P170. Glycoprotein P170 is an energy-dependent multidrug efflux pump, whose activity can be inhibited in vitro by a variety of agents including verapamil, quinidine and reserpine. P170 is over-expressed also in some human malignancies, and evidence exists about its role in examples of clinical resistance in vitro. Clinical trials using verapamil, a calcium channel blocker which selectively enhances drug cytotoxicity in MDR cell lines, have been prompted for leukemia and ovarian cancer. In addition other approaches are the subject of current preclinical investigations. Several observations as well the phenomenon of "atypical" MDR in cell lines which do not overexpress P170, suggest that also other factors are involved in multidrug resistance. Qualitative or quantitative changes in the activity of topoisomerases, protein kinase-related systems and glutathione S-transferase, may confer pleiotropic resistance. As the role of these genes and their regulation is clarified, they may also serve as useful targets for pharmacologic intervention in the treatment of drug-resistant human tumors. The mechanisms involved in resistance to methotrexate and cyclophosphamide are less studied, particularly in vivo samples. Methotrexate resistance is probably a complex multifactorial phenomenon; in some cases it is due to an increase in the expression of the drug target dihydrofolate reductase, often as a result of gene amplification, but in other cases a transport defect of the methotrexate or alterations of the activity of different enzymes have been reported. Cyclophosphamide (CP) resistance has been attributed to an increased activity of two different enzymes, glutathione S-transferase, also involved in MDR phenotype, and aldehyde dehydrogenase, which catalyzes inactivation of CP in non cytotoxic metabolites. This paper reviews the current state of our knowledge of chemo-resistance and the utility of available markers to identify potentially resistant tumors in vivo; the strategies that might be used to overcome this phenomenon are also described.
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PMID:Chemoresistance in breast tumors. 168 Jun 89


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