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Biomedical subjects

V Dobre

Publications and source records attributed to V Dobre.

At least 19 recordsLinked to original sources
PubMed1990

Stimulation of transient elevations in cytosolic Ca2+ is related to inhibition of Pi transport in OK cells.

Stimulation of changes in cytosolic free calcium by parathyroid hormone was determined in three opossum kidney (OK) cell types, OK wild-type, OKP clone, and OKH clone. All three types of OK cells express parathyroid hormone (PTH)-sensitive adenylate cyclase and adenosine 3',5'-cyclic monophosphate (cAMP) production. However, only the OK wild-type and the OKP clone respond to PTH with inhibition of sodium-dependent Pi transport and transient increase in cytosolic calcium. Characterization of the increases in cytosolic calcium in the wild-type and OKP clones revealed they were due in part to stimulation of Ca2+ release from intracellular stores, probably by inositol 1,4,5-trisphosphate (IP3), which was stimulated by PTH. PTH-stimulated Ca2+ transients were also inhibited by protein kinase C activation. These data are compatible with PTH receptor-mediated phospholipase C activation and its feedback inhibition by protein kinase C. The OKH cells demonstrated a slow increase in cytosolic calcium when stimulated by cyclic nucleotides but no evidence for PTH stimulation of Ca2+ release from intracellular stores. Thus the absence of an inhibitory response of sodium-dependent Pi transport to PTH in the OKH cells is associated with the absence of the rapid transient elevations of cytosolic Ca2+ such as those produced by IP3 production. These data suggest an important cooperative role for cAMP and the phospholipase C-stimulated Ca2(+)-protein kinase C message system in the regulation of Pi transport.

Adenylate Cyclase Toxin↗
PubMed1982

Potential anticancer agents. XXIII. 1. Qualitative structure--activity relationship in the "classical" antifolates area.

In order to obtain "classical" antifolates with improved therapeutic index, 32 new Methotrexate analogues were synthesized and studied. Their structure--activity relationship analysis led to the following conclusions: a) the replacement of glutamyl moiety with other amino acids led to compounds which are powerful inhibitors of DHFR but were devoid of activity against L1210 leukemia, b) the phenylic nucleus substitution with methoxy groups afforded potent inhibitors of DHFR and also effective derivatives against experimental tumors, c) the insertion of an extra amino acid between the phenylic ring and the terminal moiety proved to be an unfavorable event for the activity of such compounds, d) the MTX-analogues with the peptidic side chain grafted at C7 of the pteridine ring were ineffective against both DHFR and L1210 leukemia. From the investigated derivatives p[2,4-diamino-6-pteridinyl)-methyl-N10-methyl] aminobenzoyl-L-leucine 16 is twofold more potent as MTX by respect to DHFR and could be used in MTX-resistant (by impaired transport) cell lines being more hydrophobic.

Animals↗
PubMed1981

Potential anticancer agents. XXII. Pharmacological properties of some new triazene derivatives.

The pharmacological properties (toxicity and antitumor activity against W256 carcinosarcoma and L1210 leukemia) of thirty five new triazenes derived both from amides and esters of 3-methyl-4-amino-benzoic acid and from aromatic dipeptidic esters were investigated. The new compounds proved to be moderately effective against W256 carcinosarcoma and totally devoid of activity against L1210 leukemia, except for ethyl,4-(3,3-dimethyltriazenophenyl)-N-alpha-(9-fluorenyl)-acetyl-L-alanine ester which exhibited borderline activity against this leukemia. The pharmacological data thus obtained were correlated with the physico-chemical parameters of the new triazenes in a quantitative structure-activity relationship (QSAR approach). The results of the computed equations suggested that the electronic and the lipophilicity factors alone are not sufficient to give a satisfactory picture of the in vivo behavior of such compounds.

Animals↗
PubMed1981

[Repulsion against smoking- a paradoxical subjective clinical symptom in smokers' pulmonary cancer with central localization (author's transl)].

The paper insists on a paradoxical clinical symptom in smokers' pulmonary cancer; the disgust for smoking. A group of 79 smokers (men), of which 68 had smoked an average of over 200,000 cigarettes, among 71 had smoked more than 20 cigarettes per day, presenting a centrally localized pulmonary cancer, was interrogated with the aid of a simple questionnaire, about the changes that had appeared in their smoking habits during the last 24 months. The consultation revealed that 70 patients (88.6%) complained about a repulsion against smoking which had appeared 2-4 months before, making them stop smoking or reduce the number of cigarettes. This repulsion against smoking may be considered as a new sign in the diagnosis of the central pulmonary cancer in men smokers

Aged↗
PubMed1978

Potential anticancer agents. XVII. New developments in the benzoic acid nitrogen mustards area.

In order to obtain aromatic nitrogen mustards with improved therapeutic index against experimental neoplasms, greater than 75 new compounds were synthetized and studied. Their structure-activity relationship analysis led to the following conclusions: (a) the carboxylic group (especially when located in the meta position with respect to the nitrogen mustard group) exerts a favorable effect on the biologic properties of such compounds, probably by improving their transport characteristics; (b) a linear relationship was found between the chemical reactivity (expressed as alkylation rate, log k66) and toxicity (LD50) of 31 investigated compounds; and (c) the ortho effects also seem to be of importance in this area for a more accurate control of the nitrogen mustard activity. Other criteria (ie, log P, nucleophilicity of the target centers) involved in the rational design of aromatic nitrogen mustards are discussed. The design of new derivatives was oriented toward compounds which (a) were able to couple with selected proteins (ie, antibodies) leaving the cytotoxic moiety intact, and (b) were obtained by coupling of the 3-N,N-bis(2-chloroethyl)amino-4-methyl-benzoyl moiety with selected carriers (steroids, chromanones, etc) by way of an esteric bond.

Aminobenzoates↗