Therapeutic activity of medroxyprogesterone acetate in metastatic breast cancer: a correlation between estrogen receptors and various dosages.
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Biomedical subjects
Publications and source records attributed to S Villa.
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Peripheral human blood mononuclear leucocytes (MNL) aggregated in response to arachidonic acid (AA) in vitro. This phenomenon was similar to that already described for polymorphonuclear cells (PMN). The effect of AA was concentration-dependent and was shared only by the structurally related di-homo-gamma-linolenic acid among the other fatty acids tested. A number of agents able to induce platelet aggregation such as ADP, collagen, serotonin and a stable prostaglandin analogue all failed to stimulate MNL or PMN aggregation. Inhibitors of cyclo-oxygenase activity such as acetylsalicylic acid and indomethacin not only did not prevent AA-induced aggregation, but even potentiated it. In contrast, both nordihydroguaiaretic acid and BW 755C, two inhibitors of cyclo-oxygenase and lipoxygenase, strongly prevented MNL aggregation. Thus AA seems to aggregate MNL through the mediation of lipoxygenase products. This is supported by the observation that leukotriene B4 (LTB4) also induced MNL aggregation. When highly purified lymphocyte and monocyte preparations were assessed separately, the latter responded to AA similarly to mixed MNL whereas lymphocyte aggregation was inconsistent, small and reversible even at high concentrations of AA. Although the pathophysiological significance of the MNL aggregation described here is still obscure, assembly of these cells--particularly monocytes--at the site of injury might be a crucial event.
Cefoperazone is a third-generation semisynthetic injectable cephalosporin. It has been reported that cefoperazone has beta-lactamase resistance and quite a broad antimicrobial spectrum against many Gram-positive and Gram-negative microorganisms and most anaerobes. In this study, the pharmacokinetics of cefoperazone were examined in a group of 10 patients suffering from acute exacerbations of chronic bronchitis, with purulent or mucopurulent expectorations. Cefoperazone was administered at the dose of 1 g i.m. every 12 hours. Serum and urinary parameters and the profile of bronchial mucus diffusion were assessed after the first administration and during the whole period of treatment which lasted for 7 days. In a second, third, and fourth group of volunteer patients who had to undergo surgical operations, bone, lung and prostatic penetration of cefoperazone was determined in correlation with serum levels.
The tail bleeding time (BT) in rats definitely varies according to the method applied. Of the various variables that may influence BT, we have evaluated the position (horizontal or vertical) of the tail, the environment (air or saline), the temperature (4 degrees, 23 degrees or 37 degrees C) and the type of anaesthesia. Transection of the tail tip cannot be used to screen drugs active on platelet function since it is sensitive to coagulation defects. Template BT in contrast is not modified by heparin and is sensitive to defects of platelet number and function ("storage pool disease", dipyridamole-like drugs, exogenous prostacyclin). In contrast the test fails to detect aspirin-induced platelet dysfunction. The evidence reported indicates that thromboxane A2-prostacyclin balance is not a factor regulating BT. Aspirin treatment however may be a precipitating factor when associated with other abnormalities of platelet function. Template BT is a valid screening test for platelet disorders and for antiplatelet drugs.
Some tumors are known to produce colony-stimulating factors (CSF). In mice bearing s.c. Ehrlich tumor (ET) we observed that tumor growth is responsible for hemopoietic perturbations in which the increase of granulocytic-macrophagic precursors (CFU-C) in bone marrow and in the spleen represents a remarkable aspect. CFU-C in bone marrow from ET-bearing mice are more sensitive than CFU-C from normal mice to CSF from L-cells (LC-CM), mouse embryo fibroblasts (MEF-CM) and from the same tumor (ET-CM). Macrophages from normal and from ET-bearing mice exert the same effect on the proliferation of normal bone marrow CFU-C. Bone marrow CFU-C from ET-bearing mice show an increased sensitivity to the inhibitory factors produced by macrophages from ET-bearing mice.
The possible role of some soluble factor produced by tumor cells or by tumor-host interaction on homeostatic mechanism of normal bone marrow was investigated. Our data show that the in vitro pretreatment of normal bone marrow cells with Ehrlich acellular ascitic fluid (EAF) produces a severe reduction of the number of colonies either in CFU-s (colony-forming unit-spleen assay for pluripotent stem cell compartment) or in CFU-c (colony-forming unit-culture test for granulocytic committed compartment). The differentiation of CFU-s and CFU-c was also affected in respect to the controls. In fact, when normal bone marrow cells were pretreated with EAF the proportion of erythroid colonies deriving from CFU-s changed in favor of the undifferentiated one, while the proportion of pure granulocytic colonies was increased in the CFU-c assay.
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Itanoxone ((chloro-2'-diphenyl)-4-oxo-4 methylene 2-butyric acid), a newly developed, hypolipidemic and hypouricemic compound with moderate anti-inflammatory activity, showed a short-lived, dose-dependent (20--200 mg/kg, orally), apparently competitive inhibition of platelet malondialdehyde (MDA), stimulated by either thrombin or arachidonic acid. Repeated doses did not result in any cumulative effect. At doses which completely blocked MDA production, itanoxone also inhibited thrombin-stimulated thromboxane B2 production in platelets but had no measurable effect on vascular prostacyclin generation. Pretreatment with itanoxone partially prevented the inhibitory effect of aspirin on both platelet and vascular prostaglandin synthesis. This suggests that itanoxone--like aspirin--acts at the level of cyclo-oxygenase but with greater selectivity on the platelet enzyme. This pharmacological activity is of great theoretical interest for the potential use of this compound as an antithrombic drug.
The developmental profiles of the enzyme acetylcholinesterase, and of some of its quaternary structural forms, characterized by discrete sedimentation coefficients, have been comparatively analyzed in chick retina and optic tectum, between embryonic day 8 and day 10 after hatching. Four molecular species of AChE have been characterized in both retina and tectum during this developmental period: two of them with sedimentation coefficients of 11S and 6S, accounting together for 94-99% of the AChE activity in the initial homogenate, can be easily extracted by homogenization in a buffer containing 1% Triton X-100 and 1 M NaC1, at 4 degrees C. The other two, however, are not extractable by such treatment, but can be released by collagenase from the residue left after the detergent-salt extraction; they have apparent sedimentation coefficients of 21.5S and 16.5S and represent, together, less than 2% of activity in the initial homogenate. All four forms of the enzyme show distinctive patterns of change during the developmental period considered, with significant differences between retina and tectum. These differences are discussed in the context of the specific roles of retina and tectum in the visual process.
Sequential evaluation of lymphocyte blastogenic response (LBR) to PHA was performed in 10 melanoma patients and in 10 gastric cancer patients undergoing radical operations. Preoperative determinations showed a significant depression of LBR in both patient groups as compared to healthy controls. In patients operated for melanoma the average duration of anesthesia was 101 minutes and in patients who underwent gastric resection it was 192 minutes. In both patient groups a further significant depression of LBR was observed in the early postoperative period; however the LBR returned to preoperative levels more promptly in patients who underwent melanoma excision than in those who underwent gastric resection.
Mitomycin C was administered to 22 patients with metastatic breast cancer, refractory to hormonal therapy and conventional chemotherapy. Treatment was given by intravenous bolus injection at 20 mg/m2 of the drug and repeated at 6-week intervals. The overall response rate was 23%. Two complete remissions were seen in soft tissue lesions. Leukopenia occurred in 68% of the patients, thrombocytopenia in 36%, and anemia in 14%. One case of cardiotoxicity after previous treatment with adriamycin was observed. We conclude that mitomycin C is an active agent in disseminated breast cancer resistant to hormone therapy and chemotherapy. Combination of mitomycin C with other chemotherapeutic drugs will be tested.
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About 30-70% of microsomal hydroxylation of aniline, 0-demethylation of 4-NO2-anisole, N-demethylation of aminopyrine, were lost when whole organs were frozen and kept at low temperatures (0 degrees, -20 degrees, -196 degrees C). When 9000 X g or 105000 X g fractions were prepared from fresh liver and subsequently frozen to different temperatures, there was little or no such loss of activity. The kinetics of the decrease in microsomal enzyme activities was followed during storage of frozen or freeze-dried microsomes at various temperatures. N-demethylation of aminopyrine appeared to be the most sensitive marker of microsome denaturation.
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5 healthy volunteers (3 males, 2 females, aged 22-35 years) were given 600 mg ditazole (Ageroplas) every 12 h (9.00 a.m. and 9.00 p.m.) for 10 days. Venous blood was collected from all volunteers at 9.00 and 11.00 a.m. on days 0, 3, 5, 7 and 10. The threshold concentrations of adrenaline inducing two distinct waves of platelet aggregation (Born's method) within 3 min were determined each time. Blood levels of ditazole were measured by a gas-chromatographic technique using a nitrogen-phosphorus selective detector. The average blood levels of the drug ranged between 0.84 and 1.30 microgram/ml at 9.00 a.m., and between 1.93 and 2.85 microgram/ml at 11.00 a.m. Inhibition of platelet aggregation (expressed by a grading system in arbitrary units) ranged between 1.6 and 2.0 at 9.00 a.m. and between 2.0 and 2.4 at 11.00 a.m. The fluctuations of blood levels and platelet aggregation inhibitory activity of ditazole observed during the study period were virtually the same. It is suggested that the treatment schedule used in the present study results in blood levels of ditazole sufficient to reveal any consistent alteration of platelet function in normal subjects.
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