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Biomedical subjects

M F Pichon

Publications and source records attributed to M F Pichon.

At least 19 recordsLinked to original sources
PubMed2000

Serum sICAM-1 (soluble intercellular adhesion molecule-1) and M-CSF (macrophage colony-stimulating growth factor) throughout monitoring of 34 non-serous ovarian cancers.

PURPOSE: Evaluation of serum ICAM-1 (soluble intercellular adhesion molecule-1) and M-CSF (macrophage colony-stimulating growth factor) determinations for monitoring patients with non-serous ovarian cancers. METHODS: ELISA assay of sICAM-1 (cut-off 235 ng/ml) and M-CSF (cut-off 450 pg/ml) in 190 blood samples from 34 patients. RESULTS: In pre-treatment sera (n=17), sICAM-1 was over the cut-off in 12/17 (70.6%), M-CSF in 14/17 (82.4%) and CA 125 in 12/16 (75%). sICAM-1 was related only to age at diagnosis (p=0.0008). M-CSF was positively correlated to FIGO stage (p=0.04) CA 125 was elevated in 90.9% of adenocarcinomas (p=0.033 vs other). None of the 3 biological markers were related to other clinico-pathological criteria. Among disease-free patients, higher median concentrations of sICAM-1 and M-CSF were recorded under adjuvant treatment than without (p=0.014, and p=0.08, respectively). After relapse, the highest levels of sICAM-1, M-CSF and CA 125 were observed in progressive disease (46/53, 86.8% (p=0.014), 51/53 96.2% (p=0.008) and 46/52 88.5% (p>0.05), respectively). CONCLUSION: In non-serous ovarian cancers, sICAM-1 although elevated in most cases, is not useful for monitoring. Serum M-CSF is a valuable marker when ovarian tumours do not express CA 125.

Adenocarcinoma↗
PubMed2000

[Standards, Options and Recommendations (SOR) for tumor markers in breast cancer. SOR Working Group].

CONTEXT: The "Standards, Options and Recommendations" (SOR) project, started in 1993, is a collaboration between the Federation of the French Cancer Centres (FNCLCC), the 20 French Cancer Centres and specialists from French Public Universities, General Hospitals and Private Clinics. The main objective is the development of clinical practice guidelines to improve the quality of health care and outcome for cancer patients. The methodology is based on literature review and critical appraisal by a multidisciplinary group of experts, with feedback from specialists in cancer care delivery. OBJECTIVES: To define, according to the definitions of the Standards, Options and Recommendations project, the characteristics of various tumour markers in breast cancer and the potential role of these markers in the management of patients with this malignancy. METHODS: Data were identified by searching Medline and the personal reference lists of members of the expert groups. Once the guidelines were defined, the document was submitted for review to 43 independent reviewers, and to the medical committees of the 20 French Cancer Centres. RESULTS: The main recommendations are: 1) CA 15.3 and CEA are the serum tumour markers most often used in breast cancer (standard). 2) If the CA 15.3 is raised at presentation, there is no place for the measurement of other tumour markers (standard, expert agreement). 3) All analyses for each patient must be performed in the same laboratory, using the same technique (standard, expert agreement). 4) CA 15.3 should not be used for screening or diagnosis. 5) The level of CA 15.3 before treatment is a recognised prognostic factor, the independent value of which has not been proven (standard, level of evidence C). 6) If the initial value of CA 15.3 is greater than 50 kU.L(-1), disseminated disease should be actively sought before any treatment decisions are made (standard, expert agreement). 7) An initial elevation of CA 15.3 that does not return to normal, reflects a lack of response to treatment and is a strong adverse prognostic factor (standard, level of evidence C). 8) The accuracy of tumours markers (especially CA 15.3) as early indicators of metastatic disease is well recognised (standard) but the clinical benefit has not been established. 9) There is a correlation between tumour markers and clinical response in the treatment of metastatic disease (level of evidence C). The level of CA 15.3 in metastatic disease does not predict response to treatment.

Biomarkers, Tumor↗
PubMed2000

[1959-1999: from serum markers to 18-FDG in oncology. The experience of the René-Huguenin Center].

Blood tumour markers are widely used in the follow up of patients treated for a malignant tumour. In many cases where the tumour associated marker is increasing the clinical and radiological evaluations remain normal. PET and CDET-scan with 18-FDG have been demonstrated as powerful tools in oncology and their use in such situations may give a new appraisal on the development of the disease. Seventy patients with an isolated increasing of a tumour associated marker (CEA or CA19.9, CA15.3, CA125) were tested. Accuracy and sensitivity of the method were 82.8 and 96.5%, specificity 25%, and positive and negative predictive values 50% and 87%. Focusing on breast carcinomas and CA15.3 as well as ovarian cancers and CA125, the sensitivity and the predictive value are reaching 100%. Patients exhibiting a tumor target associated to an increasing in blood tumour marker may be treated earlier with dedicated protocols.

Adult↗
PubMed1998

Cancer of the uterine cervix: sensitivity and specificity of serum Cyfra 21.1 determinations.

PURPOSE: The purpose was to evaluate the usefulness of serum Cyfra 21.1 assay for the monitoring of patients with uterine cervix cancer. METHODS: Pre-treatment sera and complete follow-up of the patients were available for SCC and Cyfra 21.1 for 79 patients Another group of 50 patients was studied to evaluate the specificity, sensitivity, negative or positive predictive values of the markers. The cut-off value for Cyfra 21.1 (1.1 ng/ml) was established by ROC curve analysis. RESULTS: A positive or negative concordance between SCC and Cyfra 21.1 was observed in 65.8% of the cases. Positive SCC and negative Cyfra 21.1 were found in 22.8% of the sera, while the inverse was observed in 11.4% of the cases. The mean concentrations of SCC and Cyfra 21.1 were correlated to FIGO stages, with Cyfra 21.1 being elevated in 100% of stages III and IV. Cyfra 21.1 was also correlated with the extension of the cancer, and to the presence of metastases. The mean concentrations of both markers were significantly higher in the sera of patients with constant progression (P < or = 0.0019). Analysis of 186 results from 91 patients followed-up with a median of 3.29 years showed a sensitivity of 89.5% for Cyfra 21.1, 75.0% for SCC, and a specificity of 86.4% and 99.1%, respectively. The positive predictive values were 91.9% for Cyfra 21.1 and 98.3% for SCC, and the negative predictive values 92.7% and 85.2%, respectively. Median lead times, calculated from the records of 18 selected patients with complete resection of the tumour, were found to be 60 days for Cyfra 21.1 and 50 days for SCC (P > 0.05). CONCLUSION: In cervical cancer Cyfra 21.1 is very well-correlated to the tumour burden and the extent of the disease. In the case of recurrence, this marker rises more often than SCC. We therefore propose the use of Cyfra 21.1 for the monitoring of cervical cancer.

Adult↗
PubMed1998

[Long-term prognostic role of steroid receptors in cancer of the breast].

We screened for the prognostic value of estrogen receptor (ER) and progesterone receptor (PR) through a multicentric study of 2,257 operable breast cancer patients who did not received adjuvant therapy. Three hundred and seven local-regional recurrences, 105 metachronous contralateral breast cancer, 589 metastases and 537 deaths from cancer had been diagnosed with a median follow-up of 8.5 years. A total of 69% of the tumors were ER positive and 54% PR positive. For statistical analysis, 1,665 patients were studied because of complete clinical and biological data. In univariate analysis, ER and PR status were of prognostic value for the metastases-free interval (MFI) and the overall survival (OS). In multivariate analysis (Cox proportional hazard model), only the ER status showed a significant difference between positive and negative groups regarding the MFI and OS. By using Cox regression model with time-dependent covariates, we show that the predictive value of ER status of the primary tumor decreases by approximately 20% per year, losing its significance after 8 years of follow-up. These results show that ER and PR status have a relatively limited predictive value and their major interest remain in the domain of therapeutic decision.

Adult↗
PubMed1997

[Follow-up of treated cancers of the ovary].

The main goal of the follow up in ovarian cancer is to achieve an early detection of recurrence after a complete remission or to assess the antitumoral efficiency of the treatment used. When the tumoral antigen CA125 is expressed by the primary tumor, the most sensitive test is the sequentially evaluation of the CA125 in the blood. An increasing slope of the serous CA125 is related to disease progression which must be confirmed by imaging techniques including immunoscintigraphy.

CA-125 Antigen↗
PubMed1996

Prognostic value of steroid receptors after long-term follow-up of 2257 operable breast cancers.

The prognostic value of oestrogen receptor (ER) and progesterone receptor (PR) was estimated through a multicentric study of 2257 operable breast cancer patients followed up for a median of 8.5 years. None of the patients had received adjuvant therapy. The series included 33.3% stage I patients, 57.1% stage II, 5.7% stage IIIa and 2.4% stage IIIb. At the end point of the study 589 metastases and 537 deaths from cancer were recorded. Receptor measurements were performed by radiolgand assay according to a uniform protocol. A total of 68.8% of the tumous were ER positive and 54.0% PR positive ( > or = 10 fmol mg-1 cytosol protein). In univariate analysis, ER and PR status (positive/negative) were of prognostic value (P < 0.001) for the disease-free interval (DFI), the metastases-free interval (MFI) and the overall survival (OS). The OS of the patients after a first metastasis was also significantly different between ER-positive and -negative tumours (P < 0.001). In multivariate analysis (Cox proportional hazard model, 1665 patients), only the ER status showed a significant difference (P < 0.01) between positive and negative groups regarding the DFI, MFI and OS. By using Cox non-proportional, time-dependent models, we show that the predictive value of ER status of the primary tumour decreases by approximately 20% per year, losing its significance after 8 years of follow-up. Overall, when compared with TNM and histological grading, ER and PR status have a low prognostic value, their major interest remaining solely in the domain of therapeutic decision.

Adult↗
PubMed1993

Clinical significance of the estrogen regulated pS2 protein in mammary tumors.

A third of breast cancers are estrogen dependent and respond to endocrine therapy. The estrogen receptor (ER) was the first marker used to predict the responses to treatment, and two-thirds of ER positive tumors show a favourable response. Several estrogen-regulated proteins were further studied in a search to enhance the prediction accuracy of ER status: progesterone receptors, 24-K heat shock protein, cathepsin D, and recently pS2 protein. The pS2 gene, also named BCEI, pNR-2 [4], Md2, was first identified by two groups using differential screening of a complementary DNA library derived from a human breast carcinoma cell line (MCF-7) grown with and without estrogens. Later on two independent English groups and a Japanese group identified a gene similar to pS2. The pS2 mRNA, relatively abundant (0.8%) in the MCF-7 cell line when stimulated by estrogens, encodes a cystein-rich, 84 aminoacids peptide which is secreted by breast cancer cells. The expression of the pS2 gene, pS2 protein assays in tumor cytosols and more recently pS2 detection by immunocytochemistry, have been described in several series of breast cancers.

Aromatase Inhibitors↗
PubMed1993

Immunohistochemistry of pS2 in normal human breast and in various histological forms of breast tumours.

Expression of pS2 was studied by immunocytochemistry in normal breast tissue (n = 20), benign tumours (n = 9) and 145 breast cancers representative of the different histological types. pS2 immunostaining was scored as negative (D1 = 0-5% stained cells), positive (D2 = 5-75% stained cells) or highly positive (D3 > 75% stained cells). pS2 protein was evident in all normal breast samples examined. Six of nine benign lesions showed pS2 staining. In both cases, immunostaining was weaker than in breast cancers. Of breast cancers, 77/145 (53.1%) were pS2 positive, including 33.1% with intense staining. The presence of pS2 was not correlated with the age of patients, the size of the primary tumour, or lymph node status, but was correlated with histological grading and nuclear grading. pS2 expression was also correlated with menopausal status and oestrogen receptor status (59% of receptor-positive tumours were pS2 positive), but not to progesterone receptor status. pS2 expression in breast carcinomas is not a characteristic of specific histological types. Although this protein is predominantly expressed in oestrogen receptor-positive and differentiated tumours, it shows oestrogen-independent expression in about 30% of cases.

Aged↗
PubMed1992

Prognostic value of progesterone receptor after long-term follow-up in primary breast cancer.

In a previous study of a series of 105 patients with primary breast cancer we found that the progesterone receptor (PgR) status was an important prognostic factor for early recurrences. 95 patients from the same series were followed-up for a median of 9.5 years and reassessed for the prognostic value of PgR status by univariate and multivariate statistical methods. In univariate analysis, the disease-free interval was only related to the lymph-node status. For overall survival, PgR and combined PgR-ER (oestradiol receptor) status had a prognostic value (P = 0.035 and 0.05, respectively). Moreover, PgR status was found to be discriminant for the survival of the node-negative patients (P = 0.017). In multivariate analysis, ER and PgR status were not significant, indicating that receptor status is not a powerful predictor of the course of breast cancer.

Adult↗
PubMed1992

Oestrogen receptor negative-progesterone receptor positive phenotype in 1,211 breast tumours.

From 1,211 breast cancers, 15 oestrogen receptor (ER) negative-progesterone receptor (PgR) positive breast cancers by conventional dextran coated charcoal steroid binding assays in cytosol were reassessed using Elisa techniques with monoclonal antireceptors antibodies in the cytosolic and nuclear fractions, and immunocytochemistry on cryostat sections. Three categories of results were found in this series. Two tumours were false negative ER due to receptor sites occupancy by hormonal contraceptive treatment. A second group of ten tumours, with high PgR concentrations and immunoreactive ER, corresponds to non ER-binding forms of receptors. One PgR positive tumour was found to be devoid of PgR by using monoclonal antiPgR antibodies might contain a progesterone binding cyst protein. Only two tumours were found to be true ER negative-PgR positive by all methods. This rare phenotype deserves further study of the regulation of the PgR gene.

Adult↗
PubMed1990

Monoclonal antibodies against native ant denatured forms of estrogen-induced breast cancer protein (BCEI/pS2) obtained by expression in Escherichia coli.

Several vectors were used to express the complementary DNA for breast cancer estrogen-induced protein BCEI (also called pS2) in Escherichia coli. The best results were obtained by using the pUR 290 expression vector after deletion of the sequence encoding the signal peptide of the protein. In these conditions, beta-galactosidase-BCEI/pS2 fusion protein accounted for approximately 20% of total proteins in bacterial extracts. It was purified by chromatography on DEAE-Trisacryl or by gel electrophoresis and electroelution. Polyclonal antibodies were obtained by immunization of rabbits and goats, and monoclonal antibodies were raised in mice. Two types of monoclonal antibodies were obtained: one class recognized the native protein and was very efficient for the immunoprecipitation and immunopurification of the protein from breast cancer cells; a second class recognized the denatured protein and was especially effective for immunoblot studies. BCEI/pS2 could be detected by immunocytochemistry in breast cancer biopsies using monoclonal antibodies on frozen or paraffin-embedded sections. One of the antibodies (mBCEI11) exhibited high affinity for the protein and could be used at 1.9 micrograms/ml concentration for immunolabeling of histological sections. The mBCEI11 antibody was used in immunoaffinity chromatography to purify the peptide in a single step from culture media of estrogen-treated MCF-7 cells.

Antibodies↗
PubMed1989

Lymphocytic progesterone receptors in normal and pathological human pregnancy.

The progesterone receptor-specific monoclonal antibody (MoAb) mPRI was tested for its reactivity towards peripheral blood lymphocytes (PBL) of 49 healthy pregnant women, nine pregnant women with clinical symptoms of threatened preterm delivery, seven women with recurrent spontaneous abortion, ten women in labour and ten women with spontaneous abortion. Lymphocytes of 12 healthy age-matched non-pregnant volunteers were used as controls. Lymphocytes of nine healthy pregnant women at the 1st trimester of pregnancy and those of two non-pregnant donors were tested for the presence of estrogen and progesterone receptors by enzyme immunoassay. PBL of healthy pregnant women contained significantly more positive cells than those of non-pregnant controls. Furthermore, the number of receptor-containing cells increased in parallel with gestational age. In blood samples drawn during labour, as well as in those obtained from women with spontaneous abortion or clinical symptoms of threatened pre-term delivery, the percentage of positively stained lymphocytes was significantly lower than normal pregnancy values. This was also the case in peripheral blood of pregnant women with a history of recurrent spontaneous abortions.

Abortion, Habitual↗
PubMed1988

Modulation of estrogen receptors by phorbol diesters in human breast MCF-7 cell line.

Treatment of MCF-7 cells with 12-O-tetradecanoylphorbol 13-acetate (TPA) results in an inhibition of cell proliferation and a reduction in the number of estrogen receptors (ER), shown by binding studies and immunoassay. The decrease in ER concentration induced by phorbol ester derivatives parallels their growth inhibitory effect. Moreover, the estrogen receptor of TPA-resistant RPh4 cells (which are insensitive to the antiproliferative and morphological effects of TPA) is not affected by TPA treatment. The reduction in ER concentration appear to be a specific phenomenon since it contrasted with the 2-fold increase in total cell protein content which included an increase in progesterone receptor (PgR). We also found that addition of TPA does not affect estrogen induction of PgR.

Binding, Competitive↗
PubMed1986

Abbott monoclonal enzyme immunoassay measurement of estrogen receptors in human breast cancer: a European multicenter study.

A new enzyme immunoassay (Abbott ER-EIA Monoclonal) for the determination of estrogen receptor in cytosols from breast tumor specimens has been developed by Abbott Laboratories. To establish the correlation of the results from this new technique with currently existing steroid binding methods, a multicenter study was conducted in eight European laboratories. All participants followed the same protocol consisting of a familiarization phase, a proficiency evaluation, and a comparison of existing steroid binding methods with the new immunoassay using panel samples and clinical specimens. ER-EIA was compared with the multipoint dextran coated charcoal assay in six laboratories, four of which followed the EORTC protocol; of the remaining two laboratories, one used a single saturating dose assay, the other an isoelectric focusing assay. The results show no significant difference between reducing agents when used in the ER-EIA. Reproducibility for the immunoassay (interassay coefficient of variation, 6%, interlaboratory coefficient of variation, 11-19%) was somewhat better than that for the steroid binding methods (interlaboratory coefficient of variation, 12-32%). The correlation between the methods was dependent on the origin of the lyophilized specimens. In breast tumor samples, an excellent correlation, (not statistically different from 1) was found between the ER-EIA and the steroid binding method in six laboratories. One laboratory showed a slope of 1.1 for the correlation line; the laboratory using isoelectric focusing showed a slope of 1.9. The mean value determined by the enzyme immunoassay in premenopausal women was 74 fmol/mg cytosol protein, and in postmenopausal women it was 187 fmol/mg cytosol protein with no significant difference in the slope of the correlation line. Results suggest the usefulness of the new standardized enzyme immunoassay for routine use in the clinical laboratory.

Antibodies, Monoclonal↗
PubMed1985

Cloning of a gene expressed in human breast cancer and regulated by estrogen in MCF-7 cells.

Messenger RNAs (mRNAs) were prepared from MCF-7 breast cancer cells grown in the presence of estradiol. Complementary DNAs (cDNAs) were inserted into pBR322 plasmid and a library of 4400 recombinant bacterial clones was prepared. The clones were screened by in situ differential hybridization with cDNAs prepared from RNAs of MCF-7 cells grown either in the presence or absence of estradiol. Several estrogen-induced or estrogen-repressed clones were identified. One of them corresponded to a relatively frequent mRNA (0.8% of recombinant plasmids) of 650 nucleotides. The concentration of this mRNA was increased by estradiol (half maximal induction approximately 0.05 nM) but not by progesterone, dexamethasone, or dihydrotestosterone. Tamoxifen inhibited the effect of estradiol but was devoid of any agonistic activity when administered separately. This messenger was present in biopsies of breast cancer, but not in endometrium or liver. The cloned cDNA was sequenced. An open reading frame was found corresponding to a protein of less than 100 amino acids. A search of data banks showed no identity or marked similarity to previously published DNA or protein sequences, particularly to those of growth factors evoked by some characteristics of the coded polypeptide. The cloned cDNA probe was used to screen a library of Charon 4A phage containing human genomic fragments. Screening of 300,000 phages yielded two different recombinants hybridizing to the cDNA. Southern blot experiments using DNA from recombinant phage, MCF-7 cells, and placenta showed the presence of a unique gene exhibiting a similar restriction pattern in DNAs from malignant and nonmalignant tissues.

Amino Acid Sequence↗