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O Chinot

Publications and source records attributed to O Chinot.

26 records · Page 2Linked to original sources
PubMed1995

Prognostic value of cytosolic thymidine kinase activity as a marker of proliferation in breast cancer.

Thymidine kinase (TK) is involved in DNA synthesis by the salvage pathway. In this study, thymidine kinase (TK) was determined in routinely prepared cytosols of primary tumors from 290 breast-cancer patients. Enzyme activity was measured using a radioenzymatic method optimized for detection of the fetal isoenzyme. High levels of TK (> or = 126 mU/mg protein) were positively associated with histological grade in both pre/peri-and post-menopausal patients. In pre/peri-menopausal patients, high concentrations of TK were also found more frequently in progesterone receptor (PgR)-negative tumors than in PgR-positive samples. In post-menopausal patients, high levels of TK were associated with large tumor size, estrogen receptor (ER) negativity and PgR negativity. In univariate analysis, high levels of TK were strongly associated with shorter overall survival in both pre/peri- (p = 0.001) and post-menopausal patients (p = 0.02). Pre/peri-menopausal patients whose tumors had high levels of TK also had an increased risk of relapse (p = 0.001). In multivariate analysis (including treatment protocol, patient age, lymph-node involvement, tumor size, histological grade, ER and PgR status), TK status was found to be an independent prognostic factor for recurrence-free survival in pre/peri-menopausal patients with a weight similar to that of PgR status. In post-menopausal patients, TK was the only factor selected for overall survival.

Adult↗
PubMed1995

[Biological profiles of malignant gliomas].

Specific and recurring chromosomal and genetic alterations have been identified in gliomas and could described a model of tumoral progression from benin glioma to glioblastoma multiforme. However, the heterogeneity of profiles of molecular alterations that have been observed in gliomas seems to reflect the variety of clinical evolutions which characterise those tumors. Loss of genetic material on chromosomes 17, 9 and 19, then of chromosome 10 have been associated to pathogenesis of glioma and a pejorative prognostic value have been attributed to the alteration of chromosome 10. Gliomas also express growth factors and growth factors receptors that may be important in promoting tumor growth, like Epidermal growth factor (EGF), fibroblast growth factors (FGF) and vascular endothelial growth factor (VEGF). Tumoral invasion which characterise also gliomas, may involve proteases like plasminogen activators (PA) and metalloproteases, under the regulation of specific receptors and inhibitors. PA inhibitor type 1 (PAI1), associated to the most aggressive form of gliomas, may also participate to tumoral neoangiogenesis. Description and understanding of these alterations may contribute to develop new treatment modalities in gliomas.

Chromosome Aberrations↗
PubMed1994

Biological heterogeneity of ER-positive breast cancers in the post-menopausal population.

In the natural history of post-menopausal patients with primary breast cancer, high estrogen receptor levels (ER) have been associated with a poor recurrence-free survival. The purpose of this study was to investigate whether there are any biological intratumoral characteristics to support this puzzling clinical observation. In a population of 542 post-menopausal, primary-breast-cancer patients, 3 normal distributions fitted into the frequency distribution curve of the logarithmically transformed ER-EIA values. The biological profiles of the low ER group, and of the intermediate and high ER groups identified in the ER-positive population were compared. Parameters correlated with ER functional aspect (progesterone receptors and PS2), receptors of epidermal growth factor (EGFR), protease cathepsin D and tumor proliferation (deduced from thymidine kinase activity) were analyzed. As previously reported, the levels of progesterone receptors and PS2 increased significantly from the low to the high ER groups. The highest levels of cathepsin D and thymidine kinase which have been previously related to a poor prognosis in breast cancer were found in the low ER group, but high levels were, surprisingly, also found in the high ER group. This study indicates that the ER-positive post-menopausal population is biologically heterogeneous. The high levels of thymidine kinase found in the high ER group suggest that overexpression of ER may be associated with proliferation enhancement, partly explaining the poor spontaneous prognosis related to this subset.

Breast Neoplasms↗
PubMed1994

Technical evaluation of thymidine kinase assay in cytosols from breast cancers. EORTC Receptor Study Group Report.

Pilot retrospective studies have pointed to the prognostic value of thymidine kinase (TK) in breast cancer. We studied the Prolifigen TK-REA assay (Sangtec Medical, Sweden), usually applied to serum, for TK analysis in breast cancer cytosols. Reproducibility was good, provided that small volume pipetting was performed carefully. The TK assay was not influenced by the short-term storage of cytosols in liquid nitrogen or at -80 degrees C. However, some steps appeared critical for good laboratory practice. The TK level was affected by thawing the cytosols more than twice. Tumour storage in liquid nitrogen should be preferred over storage at -80 degrees C. The components of the homogenisation buffer, especially sodium molybdate and KCl can have a marked influence on results. Finally, linearity problems arose with some cytosols. Thus, although assay of TK in cytosols is apparently simple, care must be taken in practice. The TK-REA kit should be standardised before widespread use in breast cancer.

Breast Neoplasms↗
PubMed1994

Prognostic value of cytosolic tyrosine kinase activity in 249 node-positive breast cancer patients.

Tyrosine-specific protein kinase (TPK) has been associated with the cytoplasmic domain of growth factor receptors as well as oncoproteins. Enzymatic activation appears to be a major initial event in these signal transduction pathways. In this study, TPK was determined in the cytosols of 249 node-positive primary breast tumours. Enzyme activity was measured using [32P]ATP and poly(glutamic acid-tyrosine) (4:1) as an artificial substrate. Levels of TPK varied from 0 to 35.9 pmol ATP min-1 mg-1 protein (median 11.4). No correlation was found with tumour size or number of positive lymph nodes. In contrast, levels of TPK were negatively associated with age (P = 0.01) and menopausal status (P < 0.05) of the patients. Higher concentrations of TPK were in addition found in tumours negative for oestradiol (P < 0.01) and progesterone (P < 0.05) receptors. Finally, a positive correlation was found between TPK and urokinase plasminogen activator (UPA) (P < 0.05). Patients whose tumours contained high levels of TPK had reduced disease-free (P = 0.01) and overall survival (P < 0.05). In Cox multivariate analysis, including patient's age, menopausal status, tumour size, number of positive lymph nodes, steroid receptors and UPA, TPK retained its independent prognostic importance.

Adult↗