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)

Our objective was to define the functional characteristics of chemotactic inhibitors in sera of patients with various neoplastic diseases. Fifty-nine patients were studied: lung cancer (15), breast cancer (11), lymphoma (20), leukemia (13). Chemotaxis and random motility were measured using a modified agarose technique with C5a and a bacterial filtrate of E. coli as the chemoattractants. Two types of inhibitors were found: chemotactic factor inhibitors and cell-directed inhibitors. The type of inhibitor as well as the specificity of the inhibitor for the chemoattractant (C5a or bacterial filtrate) varied depending upon the underlying neoplasm. Cell-directed inhibitors were reversible and none of the inhibitors affected random motility. Contrary to previous reports, the chemotactic factor inhibitors were heat-stable (p less than 0.001). Morphometric analysis of inhibited and non-inhibited cells using scanning electron photomicrographs showed a significant alteration in shape of the inhibited cells (p less than 0.003). The results indicate greater heterogeneity of the chemotactic inhibitors than was previously thought, as well as a tumour-dependent specificity of the inhibitors for the chemoattractants.
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PMID:Chemotactic inhibitors in sera of patients with neoplastic disease. 206 Jan 90

Survival data from eight Cancer and Leukemia Group B (CALGB) protocols were examined for patients with lung cancer (N = 961), multiple myeloma (N = 577), gastric cancer (N = 231), pancreatic cancer (N = 174), breast cancer (N = 87), and Hodgkin's disease (N = 58). After accounting for differences in survival rate attributable to type of cancer, initial performance status, age, and 14 other protocol-specific prognostic indicators, the additional predictive value of socioeconomic status (SES) was evaluated. Race (white v non-white) was not a significant predictor of survival time, but income and education were. People with lower annual incomes (below $5,000 per year in the years 1977 to 1981) and those with lower educational level (grade school only) showed survival times significantly shorter than those with higher income or education, respectively. These survival differences were associated with, but could not be fully explained by, severity of disease at initial presentation. SES continued to exert a small but significant impact on cancer survival, even after controlling for all known prognostic variables. Economically and educationally disadvantaged cancer patients may require treatment programs that include education about treatment and compliance, even after an initial diagnosis is made and treatment is initiated. Because SES is related to survival independent of all known prognostic variables, it should be included in the data bases of clinical trial groups to provide a more accurate test of the effectiveness of new therapies.
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PMID:Socioeconomic status and cancer survival. 207 49

The incidence of new primary cancers was evaluated in 3538 postmenopausal patients who had received surgical treatment for primary breast cancer. Of these patients, 1828 with a low risk of recurrence received no further treatment. High-risk patients were randomly assigned to one of two groups. The first group (n = 846) received postoperative radiotherapy, while the second group (n = 864) received radiotherapy plus tamoxifen at a dose of 30 mg given daily for 48 weeks. The median observation time was 7.9 years. In comparison with the number of new cancers in the general population, the number of new cancers in the three groups was elevated mostly due to a high number of cancers of the contralateral breast and of colorectal cancers in the high-risk groups. The cumulative risk of nonlymphatic leukemia was increased among patients who received postoperative radiotherapy (P = .04). Cancer incidence in the high-risk tamoxifen-treated group relative to that in the high-risk group not treated with tamoxifen was not significant (1.3). No protective effect of tamoxifen on the opposite breast was seen (rate ratio for breast cancer = 1.1), but a tendency to an elevated risk of endometrial cancer was observed (rate ratio = 3.3; 95% confidence interval = 0.6-32.4). Continued and careful follow-up of women treated with tamoxifen is necessary to clarify the potential cancer-suppressive or cancer-promoting effects of this drug.
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PMID:Incidence of new primary cancers after adjuvant tamoxifen therapy and radiotherapy for early breast cancer. 207 7

Mitoxantrone, an anthracenedione derivative, has been used for preclinical and clinical studies from the end of the 1970s. Several working mechanisms are suggested such as intercalation and electrostatic interactions with DNA with or without involvement of topoisomerase II, immunosuppressive effects and inhibition of prostacyclin synthesis. Efficacy of mitoxantrone alone or in combination with other chemotherapeutic drugs has been especially demonstrated in patients with breast cancer, leukemia and lymphoma. Locoregional (but not intrathecal) therapy with this drug is possible because it is not a vesicant. It has an improved tolerability profile compared with doxorubicin. Dose-limiting toxicity is myelotoxicity and mucositis. Therefore this drug has recently also been used in high doses with bone marrow support and in combination with hematopoietic growth factors. Cardiotoxicity is less frequent than after doxorubicin and daunorubicin. However, cardiac function tests are warranted after cumulative doses greater than 160 mg/m2 or earlier if additional risk factors, namely previous mediastinal irradiation, anthracycline therapy or cardiovascular disease, are present.
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PMID:Mitoxantrone: bluebeard for malignancies. 215 49

The ability of a variety of analogues of tamoxifen to inhibit calmodulin dependent cyclic AMP phosphodiesterase has been determined. Effective inhibition requires that the aminoethoxy side chain bears a positive charge at physiological pH and is not too bulky. Amongst 4-substituents, inhibitory potency increases with lipophilicity. The stereochemistry about the olefinic linkage is not important. The most potent agent found (IC50 1.4 microM, compare tamoxifen = 6.75 microM) has a 4-iodine substituent and pyrrolidino in place of dimethylamino. This analogue is also more cytotoxic than tamoxifen against MCF-7 human breast cancer cells as determined in a 24-hr assay, but there was no correlation found between calmodulin inhibition and cytotoxicity against the L1210 murine leukaemia or Walker rat carcinosarcoma cells in culture. The results are consistent with the possibility that calmodulin is important to the functioning of oestrogen receptor mediated growth in MCF-7 cells.
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PMID:Variation of the inhibition of calmodulin dependent cyclic AMP phosphodiesterase amongst analogues of tamoxifen; correlations with cytotoxicity. 216 3

Mitoxantrone, a cytotoxic anthracenedione derivative, has given clinical evidence of beneficial activity in breast cancer, lymphoma and leukaemia. Several different mechanisms of action have been suggested to account for this. In addition to intercalation, biological effects such as electrostatic interactions with DNA, DNA-protein cross-links, immunosuppressive activities, inhibition of topoisomerase II, prostaglandin biosynthesis and calcium release have been described. Various methods of drug monitoring in biological fluids and tissues are available: the highest sensitivity has been achieved with high performance liquid chromatography with electrochemical detection, radioimmunoassay and enzyme linked immunosorbent assay. Early pharmacokinetic studies of mitoxantrone in experimental animals using radioactive material showed an extensive tissue distribution and a long terminal plasma half-life. The best fit for the plasma concentration-time curve in humans is achieved in a 3-compartment model. All studies reported a short absorption half-life of between 4.1 and 10.7 minutes, with the distribution phase being between 0.3 and 3.1 hours. In contrast, the values of the terminal half-life are quite variable, ranging from 8.9 hours to 9 days. Differences might be attributed to assay sensitivity, number and weighting of data points beyond 24 hours and coadministration drugs. Many studies showed a very large volume of distribution with sequestration of mitoxantrone in a deep tissue compartment. In autopsy studies, relatively high tissue concentrations have been measured in liver, bone marrow, heart, lung, spleen and kidney. Bile is the major route for the elimination of mitoxantrone, with lesser amounts excreted in the urine. Several metabolites have been separated, 2 of which were identified as the monocarboxylic and dicarboxylic acid derivatives. Mitoxantrone is usually administered by rapid intravenous infusion at 3-weekly intervals; other regimens include continuous infusion, daily repeated doses or weekly administration. In peritoneal carcinosis, the pharmacological advantage of intraperitoneal administration is clear. The optimal regimen for different disease categories with respect to efficacy and side-effects remains to be determined in future clinical trials.
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PMID:Pharmacokinetics and metabolism of mitoxantrone. A review. 218 7

Cancer mortality in relation to radiation dose was evaluated among 4153 women treated with intrauterine radium (226Ra) capsules for benign gynecologic bleeding disorders between 1925 and 1965. Average follow up was 26.5 years (maximum = 59.9 years). Overall, 2763 deaths were observed versus 2687 expected based on U.S. mortality rates [standardized mortality ratio (SMR) = 1.03]. Deaths due to cancer, however, were increased (SMR = 1.30), especially cancers of organs close to the radiation source. For organs receiving greater than 5 Gy, excess mortality of 100 to 110% was noted for cancers of the uterus and bladder 10 or more years following irradiation, while a deficit was seen for cancer of the cervix, one of the few malignancies not previously shown to be caused by ionizing radiation. Part of the excess of uterine cancer, however, may have been due to the underlying gynecologic disorders being treated. Among cancers of organs receiving average or local doses of 1 to 4 Gy, excesses of 30 to 100% were found for leukemia and cancers of the colon and genital organs other than uterus; no excess was seen for rectal or bone cancer. Among organs typically receiving 0.1 to 0.3 Gy, a deficit was recorded for cancers of the liver, gall bladder, and bile ducts combined, death due to stomach cancer occurred at close to the expected rate, a 30% excess was noted for kidney cancer (based on eight deaths), and there was a 60% excess of pancreatic cancer among 10-year survivors, but little evidence of dose-response. Estimates of the excess relative risk per Gray were 0.006 for uterus, 0.4 for other genital organs, 0.5 for colon, 0.2 for bladder, and 1.9 for leukemia. Contrary to findings for other populations treated by pelvic irradiation, a deficit of breast cancer was not observed (SMR = 1.0). Dose to the ovaries (median, 2.3 Gy) may have been insufficient to protect against breast cancer. For organs receiving greater than 1 Gy, cancer mortality remained elevated for more than 30 years, supporting the notion that radiation damage persists for many years after exposure.
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PMID:Cancer mortality following radium treatment for uterine bleeding. 221 30

Cancer is a disease predominantly seen in the older age group. The most frequent forms are in males: lung, prostatic, stomach, colonic and bladder cancer. In females: breast, colonic, stomach cancer, lymphoma, leukaemia and rectal cancer. In view of the expected demographic figures a dramatic increase in the incidence of cancer is expected. The malignancies seen in the elderly respond generally poor to chemotherapy. Most cytotoxic drugs are excreted by the kidneys. Especially the renal clearance of anticancer drugs will therefore be compromised in the elderly, this should be considered when giving cytostatics. Mucositis, bone marrow toxicity, pulmonary and neurotoxicity are quite often enhanced in the older patient group. The indications for chemotherapy are limited. Chemotherapy should not be withheld from patients with advanced breast cancer and certain haematological malignancies. Further clinical research focussed on the elderly is warranted. Drugs with a mild spectrum of side effects deserve priority. Hormonal treatment is an important modality in breast, prostatic and endometrial carcinoma. The burden for the patients is limited and the advantages are well documented.
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PMID:[Drug treatment of cancer in elderly patients]. 221 38

The enantiomeric [1,2-bis(4-fluorophenyl)ethylenediamine]dichloroplatinum(II) complexes were synthesized and tested on the hormone-sensitive human MCF7 breast cancer cell line and on the P388 leukemia of the mouse. They showed a strong and comparable activity on both tumor models.
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PMID:Tumor-inhibiting [1,2-bis(fluorophenyl)ethylenediamine]platinum(II) complexes. V. Synthesis and evaluation of enantiomeric [1,2-bis-(4-fluorophenyl)ethylenediamine]dichloroplatinum(II) complexes. 222 32

Vitamin D3 (D2 is 22-ene,24-methyl D3) is a prehormone which is hydroxylated by mixed function mono-oxygenase NADPH-cytochrome P-450 ferredoxin/ferredoxin reductase systems in liver parenchyma and renal proximal tubular cells to 25-hydroxy, then 1,25-dihydroxyvitamin D, the active hormone. 1,25-dihydroxyvitamin D binds to a mainly intranuclear receptor in target cells [classically, bone, kidney and gut; now shown to be wider including parathyroid cells, endocrine cells generally and many cells of ectodermal (brain, skin) and mesodermal (blood forming cells, lymphnode cells) origin as well as tumour cells (breast, lymphoma, leukaemia)] and activates transcription for products such as calcium binding proteins, its own receptor protein, 24-hydroxylase and non-specific esterase which are active in calcium homeostasis and cell differentiation. Advanced methods for measuring components of the vitamin D endocrine system have been developed and involve column extractions, liquid chromatographic purifications (also HPLC) and protein and receptor binding assays as well as mass spectrometry. These have facilitated elucidation of vitamin D physiology (also in pregnancy and lactation) and of metabolic defects in classical, vitamin D resistant and renal rickets and osteomalacia, in sarcoidosis and in the possible involvement of the vitamin in cell differentiation, e.g. in myeloid leukaemia, and breast cancer.
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PMID:An emerging view of vitamin D. 224 81


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