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Biomedical subjects

B Desoize

Publications and source records attributed to B Desoize.

At least 37 records · Page 2Linked to original sources

Comparison of phosphatase isoenzymes PAP and PSA with bone scan in patients with prostate carcinoma.

The aim of this study was to assess the diagnostic value of five biological markers--prostate acid phosphatase (PAP), prostate specific antigen (PSA), tartrate resistant (Tr-ACP), and tartrate labile (TI-ACP) acid phosphatases, and alkaline phosphatase bone isoenzyme (B-ALP)--for the detection of bone metastases in patients with prostate carcinoma. Using the Tc-99m HMDP bone scans of 80 patients scored from 0 (normal) to 2 (diffuse bone involvement) as the "gold standard," a receiver operating characteristic (ROC) analysis was performed. This method allows the determination of different threshold values (corresponding to different couples of sensitivity and specificity) for the assays. An ROC curve comparison was also performed. Results show that B-ALP is the best test for such detection (area under the ROC curve = 0.93; Spearman Rank correlation with bone scan r' = 0.81). Among the other markers, PSA was found to be the best (area under the ROC curve = 0.81; Spearman Rank correlation with bone scan r' = 0.58). In addition to the prostatic tumor markers (PSA and PAP), we suggest the use of the low-cost B-ALP assay in the follow-up of prostate carcinoma patients to determine the optimum moment to perform a bone scan. A normal result of this assay indicates a very low probability of bone metastasis; conversely, raising of B-ALP concentration must lead to a bone scan.

Acid Phosphatase↗

Alterations of growth fraction and DNA content in K562 cells by differentiating agents.

The growth fraction, estimated by the monoclonal antibody Ki-67 labeling, and DNA content, assessed by ethidium bromide staining, were determined simultaneously in K562 leukemic cells by flow cytometry. A multiparametric analysis enabled the fraction of the cell population with G1, S, and G2 + M contents in Ki-67-positive and Ki-67-negative cells to be evaluated. Butyric acid (BUT) was used as positive control. The fraction of Ki-positive cells decreased with the BUT concentration, while the proportion of cells with G1 DNA content increased only in the Ki-negative cells. Adriamycin, aclacinomycin A, and fagaronine induced differentiation, as assessed by benzidine staining and glycophorin A expression. These drugs decreased the fraction of Ki-positive cells by more than 50% for both anthracyclines and by 25% for fagaronine. Following treatment, Ki-negative cells displayed a G1, but also a G2 and a S DNA content in different proportions, indicating that induction of quiescent cells by differentiating agents is not a uniform process and is worthy of interest.

Aclarubicin↗

[Evaluation of two serum isoenzyme phosphatases as bone metastasis markers].

Serum activities of bone alkaline phosphatase (b-ALP) and of tartrate resistant acid phosphatase (tr-ACP) were evaluated in 271 cancer patients; 120 of them had bone metastases (BM) and 151 had none. Correlation coefficients, specificities, sensitivities, negative and positive predicting values were computed. They showed the important contribution that these isoenzymes can bring to the diagnosis of BM in 80 patients with prostate cancer, and to the followup of 191 patients with breast cancer. The assay results were analysed in parallel with bone scan and radiography. They were also compared to those of serum antigens: PSA and PAP for prostate cancer, and CEA and CA15.3 for breast cancer. These results clearly indicate that both isoenzymes are better correlated with BM than antigens, these antigens being markers of the whole tumor burden--primary tumor, metastases, recurrence--whereas b-ALP and tr-ACP are specific markers of bone metabolism.

Acid Phosphatase↗

[Induction of quiescence by differentiating agents].

The growth fraction of cancer cells, estimated by the monoclonal antibody Ki-67 labelling, and DNA content were determined simultaneously en K562 human leukemic cells by flow cytometry. Adriamycin, aclacinomycin A and fagaronine induced differentiation, as assessed by benzidine staining and glycophorin A expression. These drugs decreases the fraction of Ki-67 positive cells, Ki-67 negative cells displayed a G1, but also a G2 and a S DNA content in different proportions, indicating that induction of quiescent cells by differentiating agents is not a uniform process and is worthy of interest.

Aclarubicin↗

Superiority of perfusion over bolus administration in cancer chemotherapy: proposition of a compartmental model.

Recent studies indicate that, for cancer chemotherapy, prolongation of drug injection time yields lower toxicity and better efficacy. We propose a compartmental pharmacological model to explain these observations. The model has been simulated on an analog computer. The curves obtained give a credible explanation for the clinical data. The superiority of perfusion over bolus injection may be attributed to plasma peak suppression.

Antineoplastic Agents↗

Effect of fagaronine on cell cycle progression of human erythroleukemia K562 cells.

Fagaronine (Fine) is a novel antileukemic drug extracted from Fagara xanthoxyloides Lam. (Rutaceae). In an attempt to know more about its mechanism of action we describe here its inhibitory activity on cell division, 3H-thymidine incorporation and on cell cycle progression. Fine inhibits cell proliferation of K562 cells by 50% at a concentration of 3 x 10(-6) mol/l at day 4. It stimulates incorporation of labelled macromolecular thymidine on day 1, but decreases incorporation on days 2, 3 and 4. Fine induces a cell accumulation in G2 and late-S phases. This accumulation (i) increases with Fine concentration, but a complete blockade is not observed, (ii) reaches a plateau after approximately 48 h, (iii) is reversible, whereas we have previously shown that cell growth inhibition and differentiation were not reversible.

Alkaloids↗

The antileukemic alkaloid fagaronine and the human K 562 leukemic cells: effects on growth and induction of erythroid differentiation.

In view of new antitumor compounds which could exert their therapeutic effect through a combination of cell growth inhibition and cell maturation, we describe here the effects of a novel antileukemic alkaloid, fagaronine, on the growth and the induction of hemoglobin synthesis in the K 562 cell line. We found that fagaronine, after 3 days, reduces in a concentration dependent relationship the cell growth rate without lethality and this effect on the cell growth is irreversible. Reducing the cell growth rate by 50% (IC50 = 3 X 10(-6)M) is sufficient to induce an optimal amount of hemoglobin synthesis (75% benzidine-positive cells, 13-15 pg hemoglobin/cell) after 4 days of culture. Considering the variation of the total intracellular protein content during the response, it appears that fagaronine stimulated mainly hemoglobin synthesis, and to a lesser extent non-hemoglobin proteins. These results suggest that the novel antileukemic alkaloid, fagaronine, can be considered as a potent inducer of differentiated-associated properties in the human K 562 leukemic cells.

Alkaloids↗

Growth inhibition and morphological alteration of L 1210 cells by polyglutaraldehyde nanospheres.

The potentials drug vectors, polyglutaraldehyde nanospheres (Ns), are cytotoxic. The neutralization by amine groups of their aldehydic functions lowers their toxicity. When adriamycin is bound to Ns it cannot enter the cells, nevertheless it remains cytotoxic. Cellular morphological alterations induced by different Ns derivatives do not depend on the potency of the toxic element, they are related to nature of the Ns.

Animals↗

[Serum enzymes and triglycerides in mice with a mammary tumor (Ca-755 adenocarcinoma)].

Investigations on mice inoculated with Ca-755 mammary adenocarcinoma have shown that the levels of serum LDH (especially isozymes resulting from the B sub-unit), TGO and TG are higher than those found in normal mice, while PAL (only bone isozyme) and TGP are lower. Comparisons were made with tumour age (exponential and plateau-growth phases), which appeared to be important for LDH and PAL bone isozyme, since LDH increased and PAL decreased with increasing age of the tumour. For the PAL and TG alterations, there could be assumed an effect of cachectin (TNF: tumour necrosis factor).

Adenocarcinoma↗

[Specific precipitation assay of bone and liver isoenzymes of serum alkaline phosphatase].

Wheat Germ Agglutinin (WGA) precipitates bone and biliary isoenzymes of serum alkaline phosphatase, when liver and intestinal isoenzymes remain in the supernatant. Biliary and intestinal isoenzymes--when present--are evaluated with electrophoresis. Isoenzymes content in precipitate and supernatant is studied by electrophoresis and heat-inactivation. The results of WGA technique are compared to those obtained with heat-inactivation. Heat inactivation reproducibility is poor when compared to WGA precipitation. Differences are found when data of 61 sera are studied. Since a reference method is lacking, results are correlated with other biological parameters, specific of hepato-biliary pathology, and with clinical data, such as metastasis localisation. This study shows that lectin precipitation yields more accurate results than heat-inactivation.

Alkaline Phosphatase↗

In-vitro cytotoxic activity of cross-linked protein microcapsules.

Microcapsules (5-100 microns) were prepared through interfacial cross-linking of various proteins (human serum albumin, lysozyme, haemoglobin, casein, pepsin) with glutaraldehyde or terephthaloylchloride. Surprisingly they all showed an inhibitory effect on cultured cells in a concentration range of 100 micrograms ml-1 to 10 mg ml-1. This effect seemed non-specific, reversible and to depend on contact with the cell plasma membrane. The electric charges of microcapsules could be involved in the inhibition phenomenon.

Animals↗

In vivo inhibition of enterocyte metabolism by delta 9-tetrahydrocannabinol.

Mice were given 10 to 100 mg/kg by stomach tube of delta 9-tetrahydrocannabinol (THC) in a single dose or for 4 consecutive days. [3H]Thymidine or [3H]glucosamine was given 3 or 24 hr before sacrifice. Enterocytes were isolated, and the incorporation of radioactivity into the acid insoluble fraction was measured. THC significantly inhibits in a dose-related fashion (from 10 to 90%) in vivo enterocyte metabolism. This inhibition is found in all enterocytes whatever their position in the intestinal tract; it is also independent of the state of differentiation of enterocytes. After a single ingestion of THC, crypt cells which synthesize DNA incorporate 37 to 45% less thymidine, and villus cells, which synthesize important amounts of glycoproteins, incorporate 15 to 39% less glucosamine. After 4 days of THC administration, the inhibition of thymidine incorporation is even more significant (up to 88%).

Analysis of Variance↗

[Cancer of the prostate: prostatic acid phosphatases. Biochemical properties and assay].

The first data on acidic phosphatase were published in the beginning of the 20th century. The applications to prostatic carcinoma were performed by Gutman in 1936. The enzyme is a glycoprotein which action mechanism is similar to a histidine-phosphatase. Acidic phosphatase has been found in numerous tissues and blood-stream cells. Its structure is dimeric and glycans average 10% of the M.W. The enzyme has been assayed in serum, using numerous substrates in the presence of specific inhibitors. The best results were obtained with thymolphthalein phosphate. Improvements were done by assays in bone marrow and by the introduction of immunological technics which lead to a better appreciation of tumoral invasion.

Acid Phosphatase↗

[Effect of methotrexate on oxygen consumption of L1210 cells and their isolated mitochondria].

Methotrexate, at doses inhibiting cell growth without any lethal effect, alters oxygen consumption in L 1210 cells as soon as 3 hrs. after culture. After a 24 hrs. treatment with methotrexate, there is a close relationship between cellular oxygen uptake and growth inhibition. These two effects are reversible. With mitochondria from treated cells, an inhibition of respiration is observed in the presence of glutamate-malate. No effect occurs with succinate. These results in vitro are compatible with concentrations used in patients.

Animals↗