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Biomedical subjects

M Francoual

Publications and source records attributed to M Francoual.

At least 19 recordsLinked to original sources
PubMed1994

Determination of oestrogen receptors by enzyme immunoassay. Technical differences between laboratories and their consequences.

When multicentre breast cancer trials are performed, receptor analyses must be comparable both over time and in the participating laboratories. However, we show for the first time a high variability for the distribution of oestradiol receptor (ER) values measured by enzyme immunoassay (EIA) from 1987 to 1991. This variability could be explained by calibration changes in the immunoassay kits. We have also analysed the influence on ER-EIA levels of technical differences between laboratories apart from the assay itself. Many steps emerged as being critical, i.e. homogenisation buffer, homogenisation procedure and cytosol dilution. Finally, we show that addition of 4-monohydroxytamoxifen increases the apparent ER content measured by EIA in 92% of cytosols. Thus, many factors must be controlled to ensure high precision with ER-EIA assays. We have to be particularly cautious with the conformational changes that could occur during cytosol preparation and that could also pre-exist in the tumour samples. Quality controls of cytosol preparation are essential.

Breast Neoplasms↗
PubMed1994

[EGF receptor, a prognostic factor in epidermoid cancers of the upper aerodigestive tracts].

EGFR was determined, before treatment; in tumors biopsies obtained from 109 consecutive patients with head and neck cancer (100 men and nine women), using iodine labelled recombinant EGF. The median age of the study population was 60 years. EGFR levels varied from 2 to 2302 fmol/mg membrane protein (median 71). There was a significant difference of distribution for EGFR levels between stages I and II tumors and stages III and IV tumors (P = 0.03). The EGFR cut-off value for overall survival was 120 fmol/mg protein and the median follow-up was 18 months (3-35) EGFR overexpression was associated with shorter relapse-free (P = 0.0125) and overall survival (P = 0.028). By multivariate analysis the only significant variables were EGFR for relapse-free survival and tumor staging and EGFR for overall survival. Analyzed in 60 patients treated by first-line chemotherapy CDDP-5FU, the longest survival was achieved for patients who had a complete response to chemotherapy and the lowest EGFR levels (P = 0.018). EGFR expression in the primary tumor allows survival among first line chemotherapy responder categories to be discriminated.

Adult↗
PubMed1993

Expression of epidermal growth factor receptor and survival in upper aerodigestive tract cancer.

PURPOSE: To determine the expression of epidermal growth factor receptor (EGFR) in head and neck squamous cell carcinoma and to evaluate its prognostic value. MATERIALS AND METHODS: EGFR was determined in tumor biopsies obtained from 109 consecutive patients with head and neck cancer (100 men, nine women). Control biopsies were obtained from 94 patients in a symetric nontumoral area of the same anatomic site. EGFR was measured by a binding assay using human recombinant iodine 125-EGF. RESULTS: The presence of detectable EGFR levels was found in all explored tumors with highly marked differences between patients (median, 71 fmol/mg protein; range, 2 to 2,302). In 93 of 94 cases, EGFR levels were higher in tumor samples as compared with healthy control zones. There was no significant difference in EGFR expression according to the various anatomic sites explored or tumoral differentiation status. There was a significant difference of distribution for EGFR levels between stages I and II tumors and stages III and IV tumors. The tumor EGFR levels were not linked to the response to first-line chemotherapy by cisplatin (CDDP) and fluorouracil (5FU). Survival was assessable for 103 patients for overall survival and for 81 patients for recurrence. EGFR overexpression was associated with shorter relapse-free (P = .0125) and overall survival (P = .028) rates. By multivariate analysis, the only significant variable was EGFR for relapse-free survival and tumor staging for overall survival. The association of EGFR to tumor staging markedly improves the significance for overall survival predictability (P = .002). CONCLUSION: EGFR determination deserves particular attention in head and neck cancer, since it independently carries a strong prognostic value.

Adult↗
PubMed1993

[Demonstration and characterization of EGF receptors in cancer of the uterine cervix].

Epidermal Growth Factor in a polypeptide growth factor of which receptor EGFR has a prognosis value for some malignant tumours. Data are limited concerning the EGFR value in cervix tumours. EGFR was measured in biopsies obtained in cervix cancer patients before any treatment. Twenty-two patients (18 squamous carcinomas, 4 adenocarcinomas) were studied. EGF binding was characterized in seven tumour samples. Scatchard representation identified a single family of binding sites. Kd value revealed high affinity for EGF binding: 0.645 +/- 0.769 nmol/l. EGFR values were determined by a simplified competition method using a radiolabeled ligand. EGFR was found to be more elevated in tumours (n = 20) than in normal tissue (n = 4): (59.5 vs 10.5 fmol/mg proteins). There was a tendency for higher EGFR values in squamous tumours (m = 83.5 fmol/mg proteins) as compared to adenocarcinomas (m = 35.5 fmol/mg proteins), P = 0.09. There was no difference in the distribution of EGFR values according to tumour differentiation and staging. This work confirms the presence of EGFR in cervix tumours. Interestingly, we found that tumours with high EGFR values were more radiosensitive than tumours with low values.

Adenocarcinoma↗
PubMed1991

Oestrogen and progesterone receptor status in bone biopsy specimens from patients with breast cancer.

Of 16 breast cancer patients with histologically proven, tumour-infiltrating biopsy specimens most had low ER and PR values; the ER and PR contents varied between 0 and 135 and 0 and 44 fmol/mg protein, respectively. With the conventional clinical threshold of 10 fmol/mg protein, 8 specimens (50%) were ER-PR-, 4 (25%) ER-PR+, 3 (19%) ER+PR+ and 1 (6%) ER+PR-. ER levels were significantly lower in the tumoral bone lesion compared with the primary tumour. For 15 patients with negative biopsies and without endocrine treatment, ER and PR concentrations were quantifiable (2 fmol/mg protein or more) in 9 (60%) and 11 cases (73%), respectively. 8 of 9 patients over 55 (89%) were ER+ (2 fmol/mg protein or more). Conversely, for patients under 55, 1 of 6 (17%) was ER+ (P less than 0.001). Results for PR were similar. These data strongly suggest that steroid receptors are present in healthy bone tissue.

Adult↗
PubMed1990

Steroid receptors in human osteoblast-like cells.

The presence and functions of steroid receptors were evaluated in three human osteosarcoma cell lines (OS1 = SA OS; OS2 = HOS TE 85, and OS3 = MNNG HOS TE 85). The human breast cancer cell line MCF-7 was used as internal control for oestrogen receptors (E2R). High and low affinity sites were characterised. The high affinity sites had a similar dissociation constant in all four cell lines. In contrast, the number of sites per cell was higher in MCF-7 cells. E2 did not significantly modify the number of progesterone receptors (PgR) per cell in any of the osteosarcoma lines. As expected, E2 increased the number of PgR sites per MCF-7 cell. 4-hydroxytamoxifen decreased the growth of MCF-7 cells only. OS1 and OS2 were sensitive only to the highest concentration tested, which produces only non-specific cytotoxic effects. Thus E2R and PgR were found in osteoblast-like cells, but the function of E2R in such cells remains unknown.

Breast Neoplasms↗
PubMed1990

[Percutaneous occlusion by a detachable balloon of a fistula between the left coronary and the pulmonary artery].

A large fistula between the left circumflex coronary artery and the distal branches of the right pulmonary artery resulting in myocardial ischemia in a 52 year old woman with no angiographic atheromatous coronary lesions, was occluded by a detachable balloon introduced percutaneously and positioned at the origin of the fistula. A control angiogram performed one month later showed the balloon in position and the disappearance of the fistula. The Thallium myocardial scintigraphic abnormalities regressed after occlusion of the fistula. This is the second case (the first one in France) of radical non-surgical treatment of a congenital coronary fistula.

Angiocardiography↗
PubMed1987

HPLC micromethod for simultaneous measurement of estradiol, progesterone, androgen and glucocorticoid receptor levels. Application to breast cancer biopsies.

Estradiol (ER), progesterone (PR), androgen (AR) and glucocorticoid receptor (GR) levels were assayed in 25 breast cancer tumors. The tissue was pulverized and homogenized in buffer, then divided into two parts: one was assayed by the standard dextran-coated charcoal method (DCC), with Scatchard plot analysis, the other was assayed by a micromethod developed in our laboratory, as described below: --incubation of the cytosol with several ligands (labelled and unlabelled) selected to avoid unwanted cross-reactions --DCC separation, followed by extraction of all receptor-bound steroids by precipitation of proteins with methanol/TCA --separation of these steroids on a high pressure liquid chromatography (HPLC) column using a methanol/water solvent --collection of the fractions of the column outlet and counting. Use of three labelled ligands and appropriate unlabelled ligands allowed assays of the four receptors. This micromethod was highly correlated with the standard method: ER = 0.985 (P less than 0.001); PR = 0.999 (P greater than 0.001); AR = 0.989 (P less than 0.001); GR = 0.867 (P less than 0.001). Thresholds of positivity were not modified. This micromethod allowed simultaneous measurement of several receptors in 40 mg biopsy specimens and can be applied to other hormone-dependent tissues.

Breast Neoplasms↗
PubMed1987

Optimised analysis of tamoxifen and its main metabolites in the plasma and cytosol of mammary tumours.

Recent biochemical and pharmacological findings concerning tamoxifen (TMX) have proven that both the unchanged drug and the main metabolites, N-desmethyltamoxifen (NDT) and 4-hydroxytamoxifen (4OHT) are biologically active. An HPLC method based on on-line post-column UV irradiation with fluorescence detection is described. Optimized conditions allowed complete and rapid separation of TMX 4OHT, NDT and two other recently reported metabolites, Y and Z. This method was applied to plasma and cytosol drug and metabolite analyses. In plasma, from the moment of initial drug administration until the steady state (after 1 month or more of continuous oral TMX treatment), the values of NDT to TMX ratios were completely reversed: 22 to 215 in mean %, P less than 0.01. The presence of metabolites Y and Z is significant. 4OHT, hardly detectable at the first dose, was measured at the steady state with high interpatient variability. It is hypothesized that metabolite evolution with time may be due to auto-induction of drug metabolism. In cytosols, which were all obtained during continuous TMX treatment, the ratios between TMX and metabolites were comparable to those observed in plasma, but with greater interpatient variability. Metabolite Y was not detectable in cytosols. This variability was not linked to the levels of cytosolic oestradiol receptors before initiation of treatment.

Breast Neoplasms↗
PubMed1984

[Median-term results of the Ionescu-Shiley valve bioprosthesis (98 patients)].

Between April 1979 and September 1981, 98 patients have undergone valve replacement with an Ionescu-Shiley bovine pericardium xenograft (54 men and 44 women, average age 53 years, range 13 to 76 years). Fifty-three patients underwent aortic valve replacement (AVR); 28 had a mitral valve replacement (MVR) and 17 had double valve replacement (MAVR). Nine patients (9%) were operated as an emergency for endocarditis or for acute malfunction of a previously implanted prosthesis. The hospital mortality was 9% (AVR: 7%, MVR: 7%, MAVR: 17%). The eighty nine survivors were followed up for 6 to 37 months (average: 21 months). All patients were examined or contacted directly (as were the treating cardiologists) during the 2nd trimester of 1982. Eight patients were lost to follow-up. Six patients died during follow-up (6,7%) 3 to 22 months after surgery. The valvular prosthesis was the cause of death in 2 cases. Although only 37 patients (41%) were maintained on long-term anticoagulant therapy, there were no cases of thrombosis of the valve and the incidence of embolic complications was 0,9% per patient year in AVR and 2,6% per patient year in MVR. Four patients (2,6% per patient year) developed endocarditis on their prosthesis and 3 were cured by medical treatment alone. One patient was reoperated 1 year after the initial operation. One case (0,7% per patient year or 0,5% per valve year) of premature calcification was observed (18th month) in a 16 year old boy who was reoperated as an emergency without any success.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1983

Simultaneous micro measurement of steroid receptors in breast cancer.

The oestradiol (RE) and progesterone (RP) receptor levels were analyzed in 26 tumour fragments (200-500 mg) from breast cancer patients. After pulverization of tissue, one part was analyzed by the routine dextran-coated charcoal (DCC) method and the other by a micromethod as follows: (i) cytosol incubation using the DCC method but in the simultaneous presence of [3H]oestradiol and [3H]R5020 (ii) extraction of the steroids bound to the receptor by precipitation with ethanol/TCA (iii) high pressure liquid chromatography (HPLC) on a modular system, with a C185 microns column and an elution by gradient mixture methanol/water. The fractions were collected and the radioactivity counted. The separation of oestradiol from R 5020 was rapid and complete. In addition dexamethasone was separated by this system making possible triple measures of RE, RP and glucocorticoid receptors. A highly significant correlation was obtained between the 2 methods: RE = 0.996, P less than 0.001; RP r = 0.975, P less than 0.001, implying that the thresholds of positivity, i.e. for therapeutic decisions, remain unchanged. Simultaneous measurement of RE and RP in a single needle biopsy is possible with this micromethod.

Breast Neoplasms↗
PubMed1982

[Rupture of post-infarction left ventricular aneurysm. Apropos of 2 cases treated surgically successfully].

Two cases of post-infarction anterior left ventricular aneurysm complicated by localised rupture into the pericardium are reported. The clinical features of these cases were severe cardiac failure, 10 days or more after initial necrosis posing the problem of myocardial failure due to extension of the infarct. The surgical indications were brought by left ventricular angiography performed under intra-aortic balloon pumping: in the first case the diagnosis had already been suggested by the detection of a hemopericardium on echocardiography. In both cases, the surgical procedure comprised aneurysmectomy with reinforcement of the ventricular wall with bands of Teflon. The postoperative period was complicated due to the very precarious hemodynamics at the time of surgery. The functional status of both patients is now very satisfactory.

Echocardiography↗