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)

The effects of acute and chronic ethanol administration on tumor progression and metastasis were studied in rat models of leukemia and breast cancer, respectively. Acute administration of 1.5-3.5 g of ethanol/kg body weight significantly reduced survival of rats injected with CRNK-16 leukemia cells in a dose-related manner. Acute administration of 2.5-3.5 g of ethanol/kg body weight, one hour before tumor inoculation, or chronic consumption of liquid diet containing ethanol for two weeks before and three weeks after tumor inoculation, significantly increased the number of lung metastases of MADB106 mammary adenocarcinoma. The ethanol-induced increase in the number of metastases was not correlated with plasma levels of corticosterone and was not altered by the opiate antagonist naltrexone. Incubation of spleen cells in vitro in the presence of ethanol, at concentrations comparable to those measured in the blood of ethanol-treated rats, significantly suppressed natural killer (NK) cell activity against MADB106 cells in a standard chromium-release assay and decreased the binding of effector to MADB106 tumor cells. However, neither acute nor chronic ethanol administration in vivo altered splenic NK activity against this tumor in the same in vitro assay, in which the ethanol would have been washed away. These results suggest that, in the presence of ethanol, tumor progression is facilitated. The possibility that this facilitation is related to ethanol-induced impairment of the normal tumoricidal interaction between NK and tumor cells is discussed.
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PMID:Ethanol increases tumor progression in rats: possible involvement of natural killer cells. 157 4

An important question in the management of patients with cancer is early identification of the individual who following 'curative' primary therapy will develop recurrence. Another question is which of several alternative treatments is most appropriate. If the patient at risk can be identified early more aggressive and appropriate adjuvant chemotherapy can be initiated to insure remission or longer periods of disease free survival. In this review the role of tissue and/or serum enzyme activities in this regard is considered. Enzymes alone or in combination with tumor markers or other factors may be used. Lactic dehydrogenase (LDH) is perhaps the most common clinical enzyme used in cancer patients for prognostic purposes. It has an important role in germ cell tumors and in association with chorionic gonadotropin and can predict response to therapy and the prospects of remission. LDH is a valuable prognostic marker in lymphoma, leukemia and in colon cancer. Patients can be stratified into treatment protocols based on LDH activity. The stage of cellular proliferation can be evaluated by assay of thymidine kinase in the serum of patients with Hodgkins Disease and in Lymphoma. An important new marker, Cathepsin D in breast tissue may be useful in predicting women with breast cancer who are at risk for early recurrence.
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PMID:Enzymes as prognostic markers and therapeutic indicators in patients with cancer. 157 80

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

The occurrence of new primary tumours among postmenopausal patients with primary breast cancer subsequent to adjuvant treatment in Denmark was assessed by linkage to the cancer registry. Following primary surgery, patients in low risk of recurrence (n = 1,828) received no further treatment while patients in high risk randomly received either adjuvant radiotherapy alone (n = 846) or radiotherapy + tamoxifen 30 mg daily for 48 weeks (n = 864). With a median follow-up of 8 years, the incidence of tumours in the contralateral breast was similar among tamoxifen-treated, and non-treated high-risk patients even after adjusting for tumours arising within the first year. The standardized incidence ratio for endometrial cancer was 1.9 (95% confidence interval 0.8-3.9) among tamoxifen treated, the cumulative incidence 1% compared to 0.3% among non-treated patients (p = 0.11). The cumulative risk of non-lymphocytic leukaemia was 0.9% and 0.1% among irradiated and non-irradiated patients respectively (p = 0.4). Prolonged follow-up of tamoxifen-treated patients with regard to new tumours is recommended.
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PMID:Carcinogenic effects of adjuvant tamoxifen treatment and radiotherapy for early breast cancer. 162 43

Between 2/87 and 2/91, 49 women with operable breast cancer involving greater than or equal to 10 axillary nodes were treated following mastectomy, with four cycles of Cyclophosphamide, Adriamycin, 5FU, followed by high doses of Cyclophosphamide, Cisplatin, Carmustine (HDCT) with autologous bone marrow transplant support. Forty patients received local-regional radiotherapy (generally to the chest wall, internal mammary, supraclavicular, +/- axillary nodal areas; minimum 44-50 Gy, 1.8-2 Gy/fraction, +/- 10-15 Gy scar boost; standard radiation techniques). The first nine patients did not receive local-regional radiotherapy. Three developed a local-regional failure (6-12 months after HDCT); six are without evidence of disease. Local-regional radiotherapy (LR XRT) was delivered to the subsequent 40 patients following HDCT+autologous bone marrow transplant. Six received less than 44 Gy of the planned local-regional radiotherapy due to significant toxicity and one of these failed locally. Only one local failure was observed among the 34 patients who received greater than or equal to 44 Gy. Two additional patients developed distant metastases. None of these 40 patients have failed in the axilla despite the fact that the axilla was irradiated in only 18 cases. Overall, 36/40 (90%) of these patients are without evidence of disease 4-30 months following HDCT (approximately 10-36 months after mastectomy, median 22 months). Radiotherapy was interrupted or discontinued because of progressive dyspnea, thrombocytopenia, or neutropenia in nine patients. Further studies to determine the roles of local-regional radiotherapy and HDCT in the development of these toxicities are underway. These encouraging results suggest that HDCT + autologous bone marrow transplant+local-regional radiotherapy may improve the survival rate in these high risk patients. A national randomized study to test the efficacy of this HDCT regimen is currently underway (Cancer and Leukemia Group B#9082 and Southwest Oncology Group #9114).
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PMID:Post-mastectomy radiotherapy following adjuvant chemotherapy and autologous bone marrow transplantation for breast cancer patients with greater than or equal to 10 positive axillary lymph nodes. Cancer and Leukemia Group B. 163 44

The paper discusses the results of an epidemiologic case-control study dealing with the risk of development of acute nonlymphoblastic leukemia in patients treated with radio- or chemotherapy. Out of 165 patients with primary multiple metachronous tumors, primary Hodgkin's disease, lymphosarcoma and breast, ovarian and testicular cancer, 18 developed secondary acute nonlymphoblastic leukemia; in 13, the primary tumor had been Hodgkin's disease, in 4--breast cancer and in one--testicular cancer. Relative risk (RR) of acute nonlymphoblastic leukemia proved higher in patients who had undergone radiation (RR = 6.4) or chemotherapy (RR = 1.9). Combination of those two procedures carried a higher risk, too (RR = 5.9). Relative risk of acute nonlymphoblastic leukemia proved the highest in patients treated with adriamycin (11.3) and nitrogen mustard (9.9) and much lower for cyclophosphamide (RR = 1.5).
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PMID:[The risk of the occurrence of acute nonlymphoblastic leukemia in patients with malignant neoplasms undergoing radio- and chemotherapy]. 166 2

Human lactoferrin has been found to be decreased or absent in most breast cancer and leukemia cells. In order to examine the lactoferrin gene for both structural alterations and the degree of methylation, we isolated a 2117-kilobase complementary DNA from human breast tissue. This complementary DNA was used to probe DNA extracted from normal peripheral blood, leukemia cells from patients, leukemia cell lines, and breast cancer cell lines. Immunocytochemical staining of these cells confirmed the decreased production of lactoferrin in malignancy. MspI restriction enzyme fragment patterns demonstrated genetic polymorphism which occurred in DNA from both normal and malignant cells. Polymorphism was also noted with XbaI. In this case, there were two fragment patterns that were only found in DNA from malignant cells. The degree of DNA methylation was also evaluated. The methylation pattern of DNA extracted from malignant cells was highly variable and generally less methylated than DNA extracted from normal WBCs. It is possible that the decrease in lactoferrin associated with cancer is multifactorial and includes gene structural changes as well as altered regulation. Further study is needed to determine whether the changes found in this study are the result of the malignancy or contribute to its onset or maintenance.
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PMID:Polymorphism and altered methylation of the lactoferrin gene in normal leukocytes, leukemic cells, and breast cancer. 167 48

Efforts to diminish the overall morbidity and mortality of malignancy have required a variety of strategies and a balanced national research agenda. The design of curative regimens against leukemia, lymphomas, testis cancer, and childhood malignancies is a tribute to the interactions between laboratory and clinical scientists. Laboratory models illustrated the importance of dose and the need for combinations to avoid the emergence of drug resistance in heterogeneous tumors. In addressing the incurability of common epithelial cancers in adults once disseminated, again laboratory models suggested that regimens which produced responses in advanced disease might be curative in patients with micro-metastases. Such proved to be the case in adjuvant therapy for breast cancer involving lymph nodes and for osteogenic sarcoma. Recent studies have extended this strategy to less advanced breast cancer and to locally advanced colon cancer. Lung cancer has required a different strategy. A coalition has developed to support the strongest possible public position against smoking. For the first time lung cancer incidence has leveled off in white males. Women and minorities continue to be a major target for smoking cessation programs. While large randomized trials are expensive (and to some scientists, unexciting), they are our most reliable means of detecting treatment differences of 10 to 15%. Because lung, breast, and colon cancer kill almost 250,000 Americans each year, such "small" differences represent thousands of Americans. There are also a number of interesting current studies that may impact in the longer term on the care of patients with cancer. Research of three different groups of investigators has recently converged. Over the past 3 decades several groups of basic laboratory investigators had been studying and cloning hematopoietic growth factors. Large randomized trials now confirm that myelosuppression after intensive chemotherapy can be substantially ameliorated, reducing infections and decreasing hospital days, risks, and costs. Another cohort of clinical pharmacologists and clinicians were studying bone marrow transplantation, developing combinations of agents that can be given at high dose to overcome resistance, albeit with considerable toxicity. Other groups in blood banks and those interested in the regulation of hematopoiesis recognized that early hematopoietic progenitor cells circulate in the peripheral blood. Their number were increased after certain chemotherapy regimens, by growth factors and most remarkably, with growth factors given after chemotherapy. Patients supported with peripheral blood progenitor cells reengraft both platelets and granulocytes more rapidly than those given marrow, in the time frame of recovery after standard doses of chemotherapy (i.e., 21 days).(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:New developments in clinical oncology: the interdependence of bench and bedside. 167 75

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

Mitoxantrone is a dihydroxyanthracenedione derivative which as intravenous mono- and combination therapy has demonstrated therapeutic efficacy similar to that of standard induction and salvage treatment regimens in advanced breast cancer, non-Hodgkin's lymphoma, acute nonlymphoblastic leukaemia and chronic myelogenous leukaemia in blast crisis; it appears to be an effective alternative to the anthracycline component of standard treatment regimens in these indications. Mitoxantrone is also effective as a component of predominantly palliative treatment regimens for hepatic and advanced ovarian carcinoma. Limited studies suggest useful therapeutic activity in multiple myeloma and acute lymphoblastic leukaemia. Regional therapy of malignant effusions, hepatic and ovarian carcinomas has also been very effective, with a reduction in systemic adverse effects. Mitoxantrone inhibits DNA synthesis by intercalating DNA, inducing DNA strand breaks, and causing DNA aggregation and compaction, and delays cell cycle progression, particularly in late S phase. In vitro antitumour activity is concentration- and exposure time-proportional, and synergy with other antineoplastic drugs has been demonstrated in murine tumour models. Leucopenia may be dose-limiting in patients with solid tumours, whereas stomatitis may be dose-limiting in patients with leukaemia. Other adverse effects are usually of mild or moderate severity although cardiac effects, particularly congestive heart failure, may be of concern, especially in patients with a history of anthracycline therapy, mediastinal irradiation or cardiovascular disease. Mitoxantrone displays an improved tolerability profile compared with doxorubicin and other anthracyclines, although myelosuppression may occur more frequently. Thus, mitoxantrone is an effective and better tolerated alternative to the anthracyclines in most haematological malignancies, in breast cancer and in advanced hepatic or ovarian carcinoma. Further studies may consolidate its role in the treatment of these and other malignancies.
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PMID:Mitoxantrone. A review of its pharmacodynamic and pharmacokinetic properties, and therapeutic potential in the chemotherapy of cancer. 171 46


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