Biomedical subjects

M Francoual

Publications and source records attributed to M Francoual.

At least 19 recordsLinked to original sources

PubMed2003

Molecular mechanisms underlying the interaction between ZD1839 ('Iressa') and cisplatin/5-fluorouracil.

ZD1839 ('Iressa'), an orally active, selective epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor, is currently being investigated in clinical trials as a treatment for cancer. 'Iressa' is a trademark of the AstraZeneca group of companies. We have previously demonstrated a synergistic interaction between ZD1839 and cisplatin/5-fluorouracil (5FU) in CAL33, a human head and neck cancer cell line that markedly expresses EGFR. This study examined the effects of this drug combination on the cell cycle, cell cycle regulators, apoptosis-related factors, EGFR-related signalling and DNA repair in CAL33 cells. The cells were incubated with ZD1839 alone for 48 h, then cisplatin and 5FU were added. Exposure to the drug combination continued for a further 48 h. ZD1839 alone induced accumulation of cells in the G0/G1 phase of the cell cycle at 24 h accompanied by a concomitant increase in p21, p27 and Bax, a significant decrease in Bcl2 and a decrease in Akt phosphorylation. A decrease in DNA-PK was observed at 48 h. ZD1839 alone had no effect on caspase-3 activity, but addition of ZD1839 to cisplatin-5FU led to a significant increase in caspase-3 activity at 96 h. Thus, ZD1839 affects key cellular pathways controlling cell proliferation, apoptosis and DNA repair. These data provide a rationale to support clinical trials combining ZD1839 and cisplatin-5FU and other protocols that combine EGFR-targeting agents with chemotherapy or radiotherapy.

Antineoplastic Agents↗

PubMed2003

Dihydropyrimidine dehydrogenase circadian rhythm in mouse liver: comparison between enzyme activity and gene expression.

Dihydropyrimidine dehydrogenase (DPD) is the rate-limiting enzyme of 5-fluorouracil (FU) catabolism. The relevance of the measurement of DPD activity for identifying DPD-deficient patients is lessened by circadian variability in DPD activity. Our purpose was to determine whether or not DPD mRNA is sustained by a circadian rhythm. Synchronised mice (male B6D2F1) were sacrificed at 3, 7, 11, 15, 19 or 23 Hours After Light Onset (HALO; eight mice per time-point). Liver DPD activity was determined by a radio-enzymatic assay and liver DPD expression by a reverse transcriptase-polymerase chain reaction (RT-PCR) enzyme-linked immunosorbent assay (ELISA) method. Mice synchronisation was controlled by leucocyte and neutrophil counts. Individual DPD activity ranged from 555 to 1575 pmol/min/mg prot; mean DPD activity was highest at 3 HALO (mean+/-standard error of the mean (S.E.M.); 1105+/-70) and lowest at 15 HALO (889+/-71). Individual liver DPD expression varied from 761 to 3481 units (DPD/beta actin ratio); the mean was lowest at 3 HALO (1406+/-112) and highest at 15 HALO (2067+/-214). Cosinor analysis indicated that respective double amplitudes of DPD activity and expression were 21 and 30% of the 24-h mean. The acrophases for activity and expression were 6:40 and 14:10 HALO, respectively, meaning that maximum activity occurred 16 h after the maximum observed expression. These results, revealing the existence of a circadian rhythm in DPD expression, should stimulate further studies to enhance our understanding of the molecular mechanisms involved in the circadian regulation of the DPD enzyme.

Animals↗

PubMed2003

[A platypnea-orthodeoxia syndrome].

We report the case of a 68 years old patient with platypnea orthodeoxia syndrome who has been clinically suspected on cutaneous saturation position's variation. It has been confirmed by transthoracic and transesophageal echocardiography (TEE). TEE showed the size of patent foramen ovale (PFO), visualised the right to left shunt. A right heart angiography confirmed echocardiographic data and allowed successful closure by a Cardioseal percutaneous transcatheter button device implantation. Symptom's disappearance and a TEE control after 2 months confirmed the success of the procedure.

Aged↗

PubMed2001

The relationship of epidermal growth factor receptor levels to the prognosis of unresectable pharyngeal cancer patients treated by chemo-radiotherapy.

The aim of this study was to analyse prognostic factors for time to treatment failure (TTF) and overall survival (OS) in patients with unresectable cancer of the pharynx. A twice daily (b.i.d.) radiotherapy with concomitant cisplatin-5-fluorouracil chemotherapy was administered to 77 consecutive patients (68 males, 9 females; median age: 56 years). The studied factors were: age, gender, tumour differentiation, tumour volume, initial hemoglobin level, karnofsky index (KI), primary tumour location, T, N, epidermal growth factor receptor (EGFR) level in the tumour (fmol/mg protein). KI and EGFR level were significant predictors in a multivariate analysis for TTF (P=0.004 and P=0.0001) and OS (P=0.004 and P=0.0001). In order to select subgroups with different outcomes, a stratification of patients was performed based on the EGFR value: patients with tumour EGFR levels <35 fmol/mg protein, between 35 and 275 fmol/mg protein and >275 fmol/mg protein had 95%, 51% and 16% 3 year OS rates, respectively (log rank test; P=0.0001). Interestingly, for patients exhibiting a complete response (CR) after concomitant b.i.d. chemo-radiotherapy, patients with EGFR levels <35 fmol/mg protein were all alive at 3 years; in contrast, there was only 70 and 13% 3 year survival rates for patients with EGFR tumour levels between 35 and 275 fmol/mg protein and above 275 fmol/mg protein, respectively. EGFR determination appears to be a powerful prognostic parameter in unresectable pharyngeal cancer patients treated by concomitant chemo-radiotherapy.

Adult↗

PubMed2001

Epidermal growth factor receptor expression in 780 breast cancer patients: a reappraisal of the prognostic value based on an eight-year median follow-up.

PURPOSE: Because new therapeutic approaches target tumors expressing epidermal growth factor receptor (EGFR), the aim was to undertake a thorough analysis of the expression profile of EGFR in breast cancer and to reassess its prognostic value. PATIENTS AND METHODS: Tumor EGFR levels were determined by a specific ligand binding assay in 780 consecutive breast cancer patients followed in our institute between 1980 and 1993. Mean age was 61 years (25-85 years). All patients had undergone tumor resection with axillary lymph node dissection: 373 patients (47.8%) underwent mastectomy, 37 (5%) subcutaneous mastectomy and 370 (47.2%) tumorectomy. RESULTS: EGFR levels ranged between non-detectable up to 789 fmol/mg protein. EGFR median value was 9 fmol/mg protein and only a small proportion of patients exhibited a relatively marked EGFR expression. There was no link between tumor size, grade, node status and EGFR tumoral levels. There was a constant and significant decrease in EGFR tumoral levels according to patient age. A significant inverse relationship was found between estradiol receptors (ER) and EGFR. Median follow-up was 97 months with a minimum at 4 months and a maximum at 228 months. From univariate analysis it was found that histological grade, tumor size, node status and ER status were all significant predictors of survival, considering metastasis-free as well as overall survival. Using multivariable analysis, only histological grade, tumor size and node status remained independent predictors of survival. CONCLUSION: EGFR determination is of limited value as a prognostic indicator in breast cancer.

Adult↗

PubMed2000

P53 determination alongside classical prognostic factors in node-negative breast cancer: an evaluation at more than 10-year follow-up.

BACKGROUND: There is heterogeneity of methods and conflicting results concerning the prognostic value of p53 in node-negative breast cancer. The clinical value of a quantitative method for measuring tumoralp53 content still needs to be evaluated. PATIENTS AND METHODS: A long-term retrospective study was conducted on 297 node-negative patients with a median follow-up greater than 10 years (11 years, 101-172 months). Classic prognostic factors were considered including age, tumor size, histoprognostic grade and estradiol (ER) and progesterone receptors (PR). In addition, the value of p53 determination (immunoluminometric assay in tumor cytosol) was assessed for this long follow-up period. RESULTS: p53 concentrations were significantly linked to the histological grade (P = 0.001), to tumor size (P = 0.02) and ER status (P = 0.01). Higher p53 tumoral concentrations were found in tumors with large size, pejorative histological grade and negative ER status. In contrast, p53 tumoral concentrations were not influenced by menopausal or PR status. Multivariate Cox analysis demonstrates that tumor size was the only significant predictor of disease-free survival (P = 0.049) with a risk factor at 1.38. As regards specific survival, univariate Cox analysis indicates that p53 taken as a continuous variable is a significant predictor (P = 0.024) together with histological grade, tumor size and ER status. In a multivariate Cox analysis there were two significant and independent variables for predicting overall survival: tumor size (P = 0.031) and, ER status (P = 0.015) with the highest risk factor (RR = 2.14). CONCLUSIONS: The present investigation points out that the prognostic power of p53 tumor determination evaluated at more than 10 years median survival is not higher than the well-recognized classic prognostic factors in node-negative breast cancer. The present data highlight the need to assess the prognostic value of potentially new biological factors in node-negative breast cancer on cohorts of patients followed over periods in excess of 10 years.

Adult↗

PubMed2000

Application of an original RT-PCR-ELISA multiplex assay for MDR1 and MRP, along with p53 determination in node-positive breast cancer patients.

The long-term prognostic value of tumoural MDR1 and MRP, along with p53 and other classical parameters, was analysed on 85 node-positive breast cancer patients receiving anthracycline-based adjuvant therapy. All patients underwent tumour resection plus irradiation and adjuvant chemotherapy (the majority receiving fluorouracil-epirubicin-cyclophosphamide). Median follow-up for the 54 alive patients was 7.8 years. Mean age was 53.7 years (range 28-79) and 54 patients were post-menopausal. MDR1 and MRP expression were quantified according to an original reverse transcription polymerase chain reaction multiplex assay with colourimetric enzyme-linked immunosorbent assay detection (beta2-microglobulin as control). P53 protein was analysed using an immunoluminometric assay (Sangtec). MDR1 expression varied within an 11-fold range (mean 94, median 83), MRP within a 45-fold range (mean 315, median 242) and p53 protein from the limit of detection (0.002 ng mg(-1)) up to 35.71 ng mg(-1) (mean 1.18, median 0.13 ng mg(-1)). P53 protein was significantly higher in oestrogen receptor (ER)-negative than in ER-positive tumours (P = 0.039). The higher the p53, the lower the MDR1 expression (P = 0.015, r= -0.27). P53 was not linked to progesterone receptor (PR) status, S phase fraction, or MRP Significantly greater MDR1 expression was observed in grade I tumours (P = 0.029). No relationship was observed between MDR1 and MRP. Neither MDR1 nor MRP was linked to ER or PR status. Unlike MDR1, MRP was correlated with the S phase: the greater the MRP, the lower the S phase (P = 0.006, r = -0.42). Univariate Cox analyses revealed that MDR1, MRP, p53 and S phase had no significant influence on progression-free or specific survival. A tendency suggested that the greater the p53, the shorter the progression-free survival (P = 0.076 as continuous and 0.069 as dichotomous).

ATP Binding Cassette Transporter, Subfamily B, Mem↗

PubMed1999

A multifactorial approach including tumoural epidermal growth factor receptor, p53, thymidylate synthase and dihydropyrimidine dehydrogenase to predict treatment outcome in head and neck cancer patients receiving 5-fluorouracil.

The prognostic value of tumoural epidermal growth factor receptor (EGFR), p53, thymidylate synthase (TS) and dihydropyrimidine dehydrogenase (DPD) was analysed on 82 advanced head and neck cancer patients (71 men, 11 women; mean age 59). Induction treatment was cisplatin-5-FU +/- folinic acid (61 patients, Chem group) or concomitant cisplatin-5-FU-radiotherapy (21 patients, RChem group). EGFR (binding assay), p53 protein (Sangtec immunoluminometric assay), TS and DPD activities (radioenzymatic assays) were measured on biopsies obtained at time of diagnosis. Significant positive correlation was demonstrated between p53 and EGFR. In the RChem group, p53 was higher in non-complete responders (median 1.03 ng mg(-1)) than in complete responders (median 0.08 ng mg(-1)) (P = 0.057). Univariate Cox analyses stratified on treatment group showed that specific survival (33 events) was significantly related to T staging, p53 taken as continuous or categorial (below vs over 0.80 ng mg(-1)) variable, and EGFR (below vs over 220 fmol mg(-1)); survival increased when EGFR and p53 were below thresholds. Multivariate stepwise analysis including T staging, EGFR and p53 revealed that T staging and EGFR were independent predictors of survival; relative risks were 3.68 for T staging and 2.65 for EGFR. Overall, EGFR remained an independent prognostic factor when response to treatment and T staging were considered in the multivariate analysis.

Adult↗

PubMed1998

Combination of irinotecan (CPT11) and 5-fluorouracil with an analysis of cellular determinants of drug activity.

We evaluated the combination SN38 (7-ethyl-10-hydroxycamptothecin) -5fluorouracil (5FU) +/- folinic acid (FA) on six human colon cancer cell lines expressing spontaneous sensitivity to both drugs. Tumoral parameters potentially related to drug sensitivity were investigated: topoisomerase I (topo I) cleavable complexes formed with SN38, thymidylate synthase (TS) activity, folylpolyglutamate synthetase activity and dihydropyrimidine dehydrogenase activity. Drugs (SN38 and/or 5FU +/- FA) were applied for 72 hr, either sequentially or together. The concentration ratio between SN38 and 5FU was 100. Cytotoxicity (MTT [3-(4,5-dimethylthiazol-2-yl)-2,5 diphenyltetrazolium bromide] test), DNA flow cytometry and isobologram analysis (Chou and Talatay) were performed. Based on 5FU IC50 values and isobologram analyses, the most cytotoxic schedule was SN38 followed by 5FU - FA, with high synergistic effects. Flow cytometry indicated that SN38 induced a more or less marked S-G2 block in all cell lines. Sensitivity to SN38, 5FU +/- FA, or combinations were not linked to the potential above-cited tumoral parameters. Interestingly, an inverse correlation was demonstrated between TS activity and topo I cleavable complexes (r2 = 0.78, P = 0.019). These data emphasize the critical importance of the irinotecan-5FU schedule and strongly support this association for the treatment of potentially 5FU-sensitive tumors.

Antineoplastic Combined Chemotherapy Protocols↗

PubMed1998

A clinically applicable assay for tumoral thymidylate synthase combining reverse transcriptase-PCR and high-performance liquid chromatography.

The main clinically relevant cellular target of 5-fluorouracil (5-FU) is the enzyme thymidylate synthase (TS). Both preclinical data and clinical data in digestive tract cancer indicate that an increased amount of TS in tumours can predict for 5-FU resistance. We developed an automated method combining the principle of RT-PCR coupled with HPLC separation and quantification. The RT-PCR HPLC method was applied to TS determination in tumoral biopsies from patients with colorectal cancer. The PCR samples were separated and quantified using a polystyrene divinylbenzene C 18 column. Within 22 min, it was possible to elute 18 peaks representing DNA sizes ranging from 34 to 622 bp. Both separation and quantification of beta 2 microglobulin (beta 2m, internal standard) and TS PCR products were achieved in approximately 10 min per sample. Validation of the RT-PCR HPLC method was established by comparing RT-PCR quantification of TS after electrophoresis and HPLC and by comparing the RT-PCR quantification of TS after HPLC with the classical biochemical method. The proposed HPLC method offers a 10-50 fold sensitivity advantage over electrophoresis. In addition, this RT-PCR HPLC procedure allows not only the quantification of TS expression but also the direct collection of unaltered amplified DNA sequence which could be useful for sequencing analysis, since TS mutations have been described. The present RT-PCR HPLC method for determining TS expression in tumoral biopsies is a valuable analytical approach as it is specific, sensitive and clinically applicable.

Adult↗

PubMed1998

[A prospective comparative study of coronary angiography and endocoronary ultrasonography in the detection of coronary lesions after cardiac transplantation].

Coronary angiography is the reference method for the detection of coronary disease of the cardiac grafts which threatens the long-term prognosis of cardiac transplantation. The primary results of treatment for slowing, stabilising or even improving coronary transplant disease are encouraging and make necessary the development and evaluation of reliable diagnostic methods. The authors undertook a prospective study of 48 asymptomatic patients with normal graft wall motion between January 1995 and March 1997 to compare the results of coronary angiography and endocoronary ultrasonography. The patients had been transplanted in the 10 years preceding the study. The results of the two methods were concordant in 33 cases (69%) (NS), for the confirmation (9 cases) or the information of coronary transplant disease (24 cases). The results were contradictory in 15 cases (31%): in 12 cases, endocoronary ultrasonography showed signs of coronary disease whereas the coronary angiography was estimated to be normal: in the remaining 3 cases, coronary angiography was abnormal but no signs of coronary disease were found on endocoronary ultrasonography. The specificity of coronary angiographic detection was 89% and therefore very satisfactory, but its sensitivity (43%) was poor. In addition, endocoronary ultrasonography allows analysis of the extension of coronary lesions to unstenosed segments, the quantification of intimal thickening. Therefore, endocoronary ultrasonography should become the reference investigation for coronary disease of cardiac transplants.

Adult↗

PubMed1998

Epidermal growth factor receptor and labeling index are independent prognostic factors in glial tumor outcome.

The aim of this study was to perform a multivariate analysis including clinical and biological prognostic factors on glial tumor outcome. Seventy-nine patients were analyzed (48 men and 31 women; mean age = 56 years, range = 16-77 years): 7 had a benign glial tumor (grades 1 and 2), 21 had an anaplastic glial tumor (grade 3), and 51 had a glioblastoma (grade 4). Median follow-up was 17.9 months for patients who survived (50 patients died). Biopsies were obtained at time of diagnosis (complete tumor resection in 62 patients and stereotaxic biopsies in 17 patients). Epidermal growth factor receptor (EGFR) was measured by a binding assay, and labeling index (LI) was measured by tritiated thymidine incorporation. EGFR varied from 4 to 73,110 fmol/mg protein (mean = 3912 fmol/mg protein; median = 374 fmol/mg protein; n = 79). LI varied between 0.1 and 16.5% (mean = 6.2%; median = 5.2%; n = 40). Log10 EGFR was significantly and positively correlated with patient age. LI was significantly different according to tumor histology. Univariate Cox analysis (end point was cancer death) showed that age (P = 0.027), log10 EGFR (P = 0.025), and LI (P = 0.0019) were significant continuous variables, the survival being shortened when the covariable increased; tumor resection (P = 0.015, relative risk = 0.45) and histology (P = 0.0009) were significant categorical factors. A multivariate Cox analysis (forward selection) including age, histology, tumor resection, log10 EGFR, and LI revealed that log10 EGFR, LI, and tumor resection were the only independent significant predictors of survival. This multivariate approach reveals that the clinical prognostic factors of glial tumors, namely age and tumor histology, disappear, to the benefit of intrinsic characteristics of the tumor, i.e., EGFR expression and LI, suggesting that coupled EGFR and LI determination could be a useful tool for better evaluation of glial tumor outcome.

Adolescent↗

PubMed1997

Decreased folylpolyglutamate synthetase activity in tumors resistant to fluorouracil-folinic acid treatment: clinical data.

Thymidylate synthase (TS) is the main target for fluorouracil (FU). Optimal cellular concentrations of reduced folates in polyglutamated forms [via folylpolyglutamate synthetase (FPGS)] are necessary for achieving maximal TS inhibition. The aim of this multicentric prospective study was to analyze the link between clinical response to FU therapy for liver metastases of colorectal carcinoma and tumoral TS and FPGS activities. Forty-four advanced colorectal cancer patients (15 women and 29 men; median age 63, range, 27-78 years) receiving a standard FU-folinic acid protocol were included. A single hepatic tumoral biopsy was obtained systematically at the time of diagnosis. For 24 patients, a biopsy in the primary colon tumor was available. TS and FPGS activities were measured by radioenzymatic assays. Clinical response on hepatic metastases was 1 complete response, 12 partial responses, 14 stabilizations, and 17 progressions. In hepatic biopsies, TS activity (median, 185; range, <10-3111 fmol/min/mg protein) and FPGS activity (median, 1270; range, <400-3730 fmol/min/mg protein) exhibited a wide variability. TS activity in primary tumors (median, 461; range, 35-2565 fmol/min/mg protein) was significantly higher than in hepatic metastases. No difference was observed between primaries and metastases for FPGS. FPGS activity expressed in liver metastases was significantly correlated to that expressed in primaries. The distribution of TS activity in liver metastases was not significantly different between responsive and nonresponsive patients. However, FPGS activity measured in liver metastases was significantly higher in responsive patients (median, 1550 fmol/min/mg protein) than in nonresponsive patients (median, 1100 fmol/min/mg protein). A discriminant analysis revealed that 24 of the 25 patients exhibiting a liver FPGS activity </=1100 fmol/min/mg protein and/or a liver TS >320 fmol/min/mg protein were nonresponding patients. These data establish for the first time the potential importance of tumoral FPGS activity for assessing FU-folinic acid responsiveness in the clinical setting.

Adult↗

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↗