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Biomedical subjects

J Bonneterre

Publications and source records attributed to J Bonneterre.

At least 145 records · Page 8Linked to original sources

[Low-dose aminoglutethimide (500 mg/day) and hydrocortisone (30 mg/day) in advanced cancer of breast].

One hundred-twenty-seven advanced breast cancer patients who had been -for most of them- heavily pretreated with chemo- and/or hormone therapy received 500 mg aminoglutethimide and 30 mg hydrocortisone/day. The response rate was 20% (58% when stabilizations were included); the best responses were observed in skin and node metastases. The response rate in bone metastasis was 16%. The general condition of the patient (according to the Karnofsky index) was improved in 50% of the responders (including stabilizations) and in 23% of the non-responders. The survival of patients who were only stabilized was close to the survival of responders. The tolerability of this treatment was very good.

Aged↗

Correlation between prolactin receptors (PRL R), estradiol (ER) and progesterone receptors (PgR) in human breast cancer.

Free (n = 432) and total (n = 387) prolactin receptors (PRL R) (after 3 M MgC12 desaturation) as well as estradiol (ER) and progesterone receptors (PgR) were measured in 547 breast cancer patients surgically treated in the Oscar Lambret Centre. Free PRL-R were found in 43% of the cases, total PRL R in 72%, ER in 81% and PgR in 55%. A statistically significant correlation was found by the Spearman test between ER on the one hand free PRL R (P less than 0.02) and total PRL R (P less than 0.001) on the other and between PgR on the one hand, free PRL-R (P less than 0.05) and total PRL R (P less than 0.01) on the other. A linear correlation test could be done on subgroups of values, excluding zero values, of each of the receptor type; a statistically significant correlation could be found between ER and total PRL R (P less than 0.001) and between PgR and total PRL R (P less than 0.05). These results confirm, on a large series, the relation between PRL R, ER and PgR in breast cancer.

Breast Neoplasms↗

[Aminoglutethimide and cancer of the prostate].

Aminoglutethimide (AG) is a drug that inhibits several steps of steroidogenesis; it is used in post-menopausal advanced breast cancer. More recently it has been proposed as a hormone therapy in prostatic cancer. Clinical studies involving patients resistant to orchidectomy and estrogens have generally given poor objective results and a frequent subjective response. It is too early to predict the interest of AG in the hormone therapy of prostate cancer since the studies are too few and since it has been used very late in the evolution of cancer.

Adrenal Glands↗

Platinum concentration in human tumors of head and neck, uterine cervix, and breast following treatment with cisplatin.

Intratumoral platinum concentrations were measured in three tumor sites (head and neck, uterine cervix, and breast) 48 h after cisplatin administration according to the same protocol. The platinum levels were in the same order of magnitude in all tumors, but the concentration in breast tumors was found to be higher than that in tumors of the head and neck and of the uterine cervix.

Breast Neoplasms↗

Transferrin receptors in cultured breast cancer cells.

Transferrin receptors were demonstrated on the cell membrane of breast cancer epithelial cells in primary or long-term culture. Diferric transferrin binding was saturable, specific and was not related to DNA content or clinical and histological features of the tumour. However a good correlation (p less than 0.01) was found between transferrin binding and thymidine incorporation. These results suggest the possibility of transferrin receptor measurement as a reflection of the proliferative activity of cultured breast tumour cells.

Breast Neoplasms↗

Estradiol and progesterone receptors in breast cancer: prognostic value after relapse.

The prognostic significance of estradiol (ER) and progesterone receptors (PgR) for survival from relapse has been studied in two groups of breast cancer patients: group 1, 35 patients in whom receptor levels were measured at the time of mastectomy; group II, 49 patients in whom receptor levels were measured at the time of recurrence. ER+ (greater than 10 fmoles/mg) patients had a better survival from relapse than ER- patients. High levels of PgR (greater than 50 fmoles/mg) had a prognostic significance only in group II patients.

Adult↗

Catecholestrogen binding sites in breast cancer.

The binding of 2-hydroxyestrone (2OH E1), a catecholestrogen which is the main end product of the 2-hydroxylation of estrogen, was investigated in breast cancers. 2OH E1-specific bindings were found in the cytosol (Kd = 0.54 +/- 0.10 nM) and in the endoplasmic reticulum (Kd = 3.36 +/- 1.32 nM). The dissociation rate constants of complexes between [3H]2OH E1 and cytosol or membrane binding sites were 3.30 h-1 and 8.30 h-1 respectively. Qualitative analysis of [3H]2OH E1 cytosolic complexes demonstrated a specific binding component with a mol. wt of 330,000 Daltons. Specificity experiments showed that nonestrogenic hormones were unable to compete with 2OH E1 for its binding sites, whereas triphenylethylene derivatives and catecholamines were potent 2OH E1 competitors. The presence of 2OH E1 specific bindings suggests a potential role of catecholestrogen in breast cancer.

Binding Sites↗

Aminoglutethimide in advanced breast cancer: clinical results of a French multicenter randomized trial comparing 500 mg and 1 g/day.

We have conducted a multicenter randomized clinical trial comparing in advanced post-menopausal breast cancer patients 500 mg vs 1 g AG/day. The hydrocortisone dose was 40 mg/day in both groups. One hundred and seventy patients have been randomized; 161 were evaluable for tolerability, 149 for effectiveness. Response rates were similar in both groups, 19 and 24% respectively for the 500 mg and 1 g groups. No difference was observed according to tumor site. Duration of response was the same in both groups (14 months), as was mean time to response (about 3 months). Survival (studies in 125 patients) was similar in both groups (responders and non-responders). No response could be obtained with 1 g after relapse or failure with 500 mg (n = 17). Tolerability was good in 91% of the 500 mg group patients and 78% of the 1 g group patients (P less than 0.03). It was poor in 4 and 15% respectively (P less than 0.03). Side-effects were the same in both groups but less frequent and less severe in the 500 mg group; however, these patients more frequently had 'moon face'.

Aged↗

[Aminoglutethimide-induced dyslipemia. Clinical study].

Plasma levels of cholesterol, HDL cholesterol (HDL chol), LDL cholesterol (LDL chol), triglycerides, Al apoprotein and B apoprotein were studied in 73 patients receiving 500 mg aminoglutethimide (AG)/day and 40 mg hydrocortisone/day for advanced breast cancer. These dosages were done before treatment and then repeated during AG therapy. When all patients were considered together, a significant increase of cholesterol, HDL chol, LDL chol and Al apoprotein was noted. If one considers two groups of patients: group A (where cholesterol and triglycerides plasma levels were normal before treatment) and group B (where cholesterol and/or triglycerides plasma levels were high before treatment), it appears that variations differ in both groups. In group A patients we found an increase in cholesterol, chol LDL, B apoprotein and to a lesser extent Al apoprotein plasma levels. In group B patients there was an increase in cholesterol, HDL chol and Al apoprotein plasma levels.

Aminoglutethimide↗

Time dependency in plasmatic protein binding of cisplatin.

The rate of cisplatin binding on proteins was measured in plasma collected from the same patients at several different times of the day. Statistical analysis showed that binding on plasma followed a circadian rhythm with the acrophase occurring around 4 PM. The amplitude of the apparent circadian variation of the binding depends on each patient (mean value, 11%). The binding capacity of plasma was also found to be time-dependent when the patients were prehydrated. The existence of a circadian rhythm in total protein concentration of the plasma could explain the observed results. Since cisplatin is bound more quickly on proteins in the afternoon, the circulating levels of free cisplatin must be lower when the injection is given at this time of day and this may partly explain the reduction in nephrotoxicity for some patients when cisplatin is injected in the afternoon.

Blood Proteins↗

[Aminoglutethimide-induced dyslipidemia. Experimental study].

Aminoglutethimide (AG) is a drug that inhibits steroid synthesis; it is used in advanced breast cancer. After the observation of abnormalities in lipid metabolism in patients, we realized an experimental study to try to look for a pathogenetic hypothesis. Three groups of rats received respectively AG, Hydrocortisone (HC) or both (AG + HC) and were compared to controls. Animals treated with AG (with or without HC) had a greater liver content of triglycerides, cholesterol and phospholipids than controls. Cholesterol plasma level was higher in animals treated with AG + HC. The bile flow was higher in rats receiving AG and AG + HC whereas biliary salt concentrations were lower. These variations could be the consequence of both an enzymatic induction and an inhibition of some cytochrome P450 dependent hydroxylases.

Aminoglutethimide↗

Characterization of prolactin receptors in human breast cancer.

In order to perform measurement of PRL binding and to improve the knowledge of pathophysiological variations in human mammary cancers, we have investigated in detail the binding characteristics of PRL in membranes prepared from these tumors. The optimization of the assay requires the selection of membranous components of light density (less than 1.17); the tracer could be either 125I-PRL after affinity purification on PRL receptors or 125I-hGH without a purification step. It is favorable to utilize a high amount of protein and 200 000 cpm (2 ng) of tracer. Demonstration of the presence of receptors for PRL with a high affinity (Kd= 3 X 10(-10) M) in breast cancer is presented. The hormonal specificity of these receptors is studied: only lactogenic hormones (hGH, oPRL, hPRL, and hPL) are able to compete for binding of 125I-hPRL whereas bGH or insulin are without effect. Considering the known effect of PRL on cell multiplication, it is tempting to suggest that this hormone could have a crucial role in the development of breast tumor in humans and that therapies which would suppress secretion of PRL and GH could be beneficial.

Breast Neoplasms↗

Effect of bromocriptin treatment on prolactin and steroid receptor levels in human breast cancer.

We have investigated the effect of bromocriptin, a prolactin-lowering drug, on prolactin, estradiol and progesterone receptors in breast cancers. Doses of 2.5 mg per os of bromocriptin were given twice daily for 4 days before surgery. The efficiency of the treatment was evaluated by assaying the plasma prolactin level. The results obtained for the treated population (n = 30) was compared to those obtained for an untreated one (n = 120) during the same period. Bromocriptin does not increase the available prolactin receptors in breast cancer specimens. Unmasking in vitro receptors with MgCl2 3 M leads in both cases to an increase in prolactin receptors. The number of positive estradiol receptor tumors was increased after bromocriptin treatment. Neither the rate of positivity nor the level of progesterone receptors is changed by the treatment. This study demonstrates clearly the inefficiency of bromocriptin in unmasking in vivo prolactin receptors in breast cancer.

Breast Neoplasms↗

[EGF receptors in human breast cancer. Relation to hormonal receptors].

EGF membrane receptors (R-EGF) were assayed in 65 human breast cancer biopsies. The Scatchard analysis of the binding of 125I-EGF indicated a single class of sites with an apparent dissociation constant of 1 nM. Fourty-eight percent of the tumors are R-EGF positive (specific binding greater than 1% of total radioactivity), the level of receptors reaching 14%. We have not observed any relationship between R-EGF and hormone receptors (estradiol, progesterone and prolactin) or clinical and histological characteristics of the tumor. Taking into account the role of EGF in growth of some human breast cancer epithelial cells culture and the possible production of R-EGF by oncogenes, these results suggest that R-EGF could be an uindependent biochemical marker of human breast cancer.

Breast Neoplasms↗