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S Fabre

Publications and source records attributed to S Fabre.

At least 19 recordsLinked to original sources
PubMed2005

BMP-4 inhibits follicle-stimulating hormone secretion in ewe pituitary.

Activins and inhibins, members of the transforming growth factor-beta family are able to stimulate and inhibit, respectively, FSH synthesis and release. Other members of this superfamily, the bone morphogenetic proteins (BMPs), may also affect FSH synthesis in the mouse. The aim of this work was to determine whether BMPs are expressed in the ovine pituitary and whether they play a role in the regulation of FSH release. The mRNAs encoding BMP-2, BMP-4, BMP-7 and the oocyte-derived growth factor, growth differentiation factor (GDF)-9 were detected in the pituitaries of cyclic ewes by reverse-transcriptase PCR, as well as the mRNAs encoding the BMP type I receptors, BMPR-IA (activin-receptor-like kinase (ALK)-3) and BMPR-IB (ALK-6), and type II receptors (BMPR-II). Immunolabeling of pituitary sections revealed the presence of BMPR-IA (ALK-3) and BMPR-II in gonadotrope cells. To investigate the potential effects of BMPs on FSH secretion, ewe pituitary cell cultures were treated with BMP-4 (10(-11) M to 10(-9) M) for 48 h. Interestingly, FSH release was decreased in a dose-dependent manner. At 10(-9) M BMP-4 both FSH concentration and FSHbeta mRNA expression were reduced by 40% of control values. In contrast, there was no inhibitory effect on either LH or LHbeta mRNA expression. A similar result was found with BMP-6. BMP-4 triggered the phosphorylation of Smad1, suggesting that the effect of BMP-4 on FSH secretion is due to the activation of the BMPs signaling pathway. Furthermore, BMP-4 blocked the stimulatory effect of activin on both FSH release and FSHbeta mRNA and amplified the suppression of FSH release and FSHbeta mRNA levels induced by 17beta-estradiol. These results indicate that a functional BMP system operates within the sheep pituitary, at least in vitro, to decrease FSH release and to modulate the effect of activin.

Animals↗
PubMed2004

Molecular basis of bone morphogenetic protein-4 inhibitory action on progesterone secretion by ovine granulosa cells.

We have recently reported that bone morphogenetic protein-4 (BMP-4) can inhibit progesterone production by ovine granulosa cells (GCs). Here, we have investigated the underlying mechanisms of this effect in basal as well as in FSH-induced conditions. We have confirmed that treatment with BMP-4 decreased basal GC progesterone secretion and totally abolished FSH-stimulating action. This inhibitory action was associated with a decrease in the expression of cAMP-regulated genes, steroidogenic acute regulatory protein (StAR) and P450 side-chain cleavage (P450 scc) at mRNA and protein levels. However, BMP-4 did not alter basal cAMP production by GCs. In contrast, BMP-4 decreased by half the FSH-induced cAMP production and strongly inhibited cAMP-induced progesterone production. Thus, the inhibitory effect of BMP-4 was exerted both upstream and downstream of cAMP signalling. We next examined the downstream effect, focusing on cAMP-dependent transcription factors, steroidogenic factor-1 (SF-1) and CREB, through the BMP factor signalling intermediary, Smad1. As expected, BMP-4 induced phosphorylation and transcriptional activity of Smad1 in ovine GCs. BMP-4-activated Smad1 did not affect CREB activity but inhibited the transcriptional activity of SF-1 on the canonical SF-1 responsive element. Interestingly, this transcriptional inhibitory mechanism occurred on transfected StAR and P450 scc promoter. Based on these results, we propose that SF-1 is a key target in the inhibitory mechanism exerted by BMP-4 on progesterone synthesis by ovine GCs in culture. Because SF-1 plays an essential role in the differentiation of GCs, our findings could have new implications in understanding the role of BMP family members in the control of ovarian folliculogenesis.

Animals↗
PubMed2003

[Patients surviving 5 years after curative oesophagectomy for oesophageal cancer].

AIM OF THE STUDY: To analyse the clinical and pathological parameters of 5-year survival patients after curative oesophageal resection for cancer and to identify factors predictive of long-term survival. METHODS: The data of 370 patients who underwent oesophagectomy with curative intent from January 1982 for oesophageal squamous cell carcinoma (n = 320) or adenocarcinoma (n = 50) were reviewed. After excluding postoperative deaths (n = 20), these patients were surviving (S group, n = 113) or dead (NS group, n = 237) with a 60-month follow-up. Uni- and multivariate analysis allowed comparison between the two groups. RESULTS: Postoperative mortality and morbidity rates were 4.0% and 37.6%, respectively. Parameters related to 5-year survival were: absence of preoperative malnutrition or dysphagia, transhiatal resection, no reoperation, limited tumour, histological response to neoadjuvant treatment, absence of lymph node capsular invasion, number of invaded lymph nodes < or = 4, invaded lymph node ratio < or = 0.1, absence of tumour recurrence or metachronous primary cancer. On multivariate analysis, factors predictive of 5-year survival were: absence of preoperative dysphagia (P < 0.001), stage 0-I-IIA tumour (P<0.001) and absence of metachronous cancer (P = 0.016). CONCLUSION: Complete surgical resection allows 5-year survival. Factors predictive of long-term survival assessed in preoperative evaluation, dysphagia and tumour stage, should be useful to select patients for neoadjuvant treatment.

Adenocarcinoma↗
PubMed2003

Surgery after induction chemoradiotherapy for oesophageal cancer.

AIM: We discuss the role of surgery after induction chemoradiotherapy, when a complete response is apparent. METHODS: We enrolled 247 consecutive patients who underwent chemoradiotherapy and oesophagectomy for cancer. Patients were classified in two groups as to whether they had chemoradiotherapy (n = 60) or not (n = 187) before surgery. RESULTS: The 5-year survival rate of patients with complete response was 54% and was significantly higher than that of the other group (P = 0.018). Of the 60 patients responding, 34 (56.7%) were found to have a complete pathological tumour response (pT0). The overall sensitivity and specificity of the post-chemoradiotherapy restaging were 60.7% and 86.4%. CONCLUSIONS: Complete response after induction chemoradiotherapy is not a reliable tool in the management of oesophageal cancer. We need to improve postchemoradiotherapy restaging to be sure that chemoradiotherapy will provide the same long-term survival rates as surgery.

Adult↗
PubMed2003

The Booroola mutation in sheep is associated with an alteration of the bone morphogenetic protein receptor-IB functionality.

The hyperprolificacy phenotype of Booroola ewes is due to the presence of the FecB(B) allele at the FecB locus, recently identified as a single amino acid substitution (Q249R) in the bone morphogenetic protein (BMP) type-IB receptor (BMPR1B), and is associated with a more precocious differentiation of ovarian granulosa cells (GCs). To evaluate the consequences of the Booroola mutation on BMPR1B functions, the action of ligands of the transforming growth factor-beta (TGFbeta)/BMP family that act through (growth and differentiation factor-5, BMP-4) or independently of (activin A, TGFbeta-1) BMPR1B were studied on primary cultures of GCs from homozygous FecB(+) and FecB(B) ewes. All the tested TGFbeta/BMP family ligands inhibited progesterone secretion by FecB(+) GCs. Those inhibitory effects were lower for GCs from preovulatory (5-7 mm diameter) than from small antral follicles (1-3 mm diameter). The presence of the Booroola mutation was associated with a 3- to 4-fold (P<0.001) decreased responsiveness of GCs from FecB(B) compared with FecB(+) small follicles to the action of BMPR1B ligands. In contrast, TGFbeta-1 and activin A had similar inhibitory effects on progesterone secretion by GCs from FecB(+) and FecB(B) small follicles. No difference between genotypes was observed with GCs from preovulatory follicles. In transfection experiments with HEK-293 cells, co-expression of FecB(+) BMPR1B and BMPR2 resulted in a 2.6-fold (P<0.01) induction of the activity of a BMP-specific luciferase reporter construct by BMP-4. Interestingly, no response to BMP-4 was observed when cells were transfected with the FecB(B) form of the BMPR1B receptor. Overall, these data strongly suggest that the Q249R mutation is associated with a specific alteration of BMPR1B signaling in hyperprolific Booroola ewes.

Activins↗
PubMed2003

Prolificacy genes in sheep: the French genetic programmes.

It has been demonstrated that variations in litter size or ovulation rate in different breeds of sheep can be associated with the segregation of several major genes. This set of natural mutants constitutes a valuable resource to determine key points in the biochemical pathways controlling the development of ovarian follicles. The French genetic programmes were devised to identify two of these genes: the Booroola (FecB) and Lacaune genes. The FecB prolific mutation corresponds to a non-conservative mutation (Q249R) in the intracellular kinase-signalling domain of the bone morphogenetic protein receptor type IB (BMPR-IB) gene. The Lacaune gene is situated on ovine chromosome 11. Positional cloning is currently in progress to identify the relevant gene and mutation. A similar approach, limited to linkage testing of candidate genes, is proposed to classify the different prolificacy genes in sheep.

Animals↗
PubMed2002

[Reconstruction after total circular pharyngolaryngectomy: comparison between gastric interposition and free jejunal flap].

AIM OF THE STUDY: To elucidate hospital mortality, morbidity and actuarial survival rates of patients with carcinoma of the hypopharynx and cervical oesophagus and to identify the technique of choice for reconstruction after pharyngolaryngectomy. PATIENTS AND METHODS: We reviewed the records of 209 patients who underwent total pharyngolaryngectomy between May 1982 and January 2000. The majority of patients had advanced cancer: hypopharyngeal in 131 cases and cervical oesophageal in 78 cases. Follow-up was complete for all patients. Chi 2 and log rank tests were used, with a limit of significance of 5%. RESULTS: The postoperative mortality and morbidity rates were 4.8% and 38.3%, respectively. Alimentary continuity was achieved using the stomach (127 patients), colon (5 patients), or free jejunal autograft (77 patients). The 1-year and 5-year survival rates were 62% and 24%, respectively. There was no significant difference with regard to the survival between gastric transposition and free jejunal autograft, but there were fewer complications in the gastric pull-up group with regard to the respiratory complications (33% vs 47.0%, p < 0.05), local recurrences (15.8% vs 33.8%, p = 0.004) and survival without dysphagia (76% vs 89%, p < 10(-5)). CONCLUSION: Surgical ablation is a viable option for advanced hypopharyngeal and cervical oesophageal neoplasms, and stomach interposition is the preferred method of reconstruction.

Actuarial Analysis↗
PubMed2002

[Oesophageal cancer in patients with head and neck cancers: therapeutic implications].

AIM OF THE STUDY: To determine therapeutic and prognostic implications of an associated head and neck primary cancer in patients undergoing oesophagectomy for squamous cell carcinoma of the oesophagus. PATIENTS AND METHODS: Between 1982 and 2000, 868 patients with oesophageal cancer were operated in our institution, including 78 (9%) who underwent oesophagectomy for associated oesophageal and head and neck cancers; the latter was synchronous (n = 52) or anterior metachronous (n = 26). Influence of head and neck cancer on the treatment of oesophageal carcinoma was analysed retrospectively in terms of surgical therapeutic strategy and survival. RESULTS: Oesophageal resection consisted of oeso-pharyngolaryngectomy (n = 14, 17.9%), subtotal oesophagectomy (n = 62, 79.5%) and cervical oesophagectomy (n = 2, 2.6%). Radical resection (R0) was obtained in 85% of cases. Postoperative mortality rate was 5 % (4/78). Main complications were pulmonary (18% = 14/78) and anastomotic leaks (14% = 11/78), all of them cervical. Follow-up (mean = 25 +/- 27 months) was complete for all 78 patients. Five-year survival after R0 resection was 25%. Survival pronostic factors were denutrition, complete resection, and pT status of oesophageal tumor. CONCLUSION: In patients with associated carcinomas of oesophagus and head and neck, agressive treatment -including an oesophagectomy- allowed a 5-year survival rate more than 25% without increased mortality or morbidity rates, compared with patients operated on for isolated oesophageal carcinoma.

Carcinoma, Squamous Cell↗
PubMed2002

Surgical management of and long-term survival after adenocarcinoma of the cardia.

BACKGROUND: The choice of surgical strategy for patients with adenocarcinoma of the oesophagogastric junction is controversial. This study was performed to analyse the surgical results of a 20-year experience with these lesions. METHODS: From January 1981 to January 2001, 126 patients with adenocarcinoma of the cardia underwent resection in the authors' institution. The treatment of choice was oesophagectomy for type I tumours, and extended gastrectomy for type II and III lesions. Morbidity, mortality and survival were determined retrospectively. RESULTS: Fifty-six patients (44.4 per cent) had type I tumours, 44 (34.9 per cent) type II and 26 (20.6 per cent) type III. Primary resection was performed in 113 patients (89.7 per cent). Oesophagectomy with resection of the proximal stomach was carried out in 65 patients (51.6 per cent) and extended total gastrectomy with transhiatal resection of the distal oesophagus in 61 (48.4 per cent). In-hospital mortality and morbidity rates were 4.8 and 34.1 per cent respectively. The overall 3- and 5-year survival rates were 40.9 and 25.1 per cent respectively, and were not affected by the surgical approach. Survival was significantly associated with R0 resection, pathological node-positive category, postoperative complications and tumour differentiation. CONCLUSION: Postoperative mortality, morbidity and long-term survival did not appear to be affected by surgical approach. Further prospective studies are needed to confirm the equivalence between transthoracic and transabdominal approaches.

Adenocarcinoma↗
PubMed2002

Retrospective clinical comparison of Celsior solution to modified blood Wallwork solution in lung transplantation for cystic fibrosis.

OBJECTIVE: To compare the preservative effects of Celsior solution and modified blood Wallwork solution in lung transplantation. METHODS: From 1989 to 2000, 44 lung transplantations for cystic fibrosis were performed: 26 grafts were preserved with modified blood Wallwork solution and 18 with Celsior solution. RESULTS: Preoperative status of the 2 groups was similar. The ratio of arterial oxygen to fraction of inspired oxygen and the pulmonary vascular resistance on the first postoperative day did not differ significantly between the 2 groups. Early death was 4% (SD, 20%) in the Wallwork group versus 11% (SD, 32%) in the Celsior group (not significant). No death was related to graft failure. The forced expiratory volume in 1 second during the first month after transplantation was 63% (SD, 19%) in the Wallwork group versus 63% (SD, 16%) in the Celsior group (not significant). CONCLUSION: Because the solution does not need to be prepared on site and does not require blood from the donor, Celsior seems better than Wallwork solution for preserving lung grafts.

Albumins↗
PubMed2001

Nectin4/PRR4, a new afadin-associated member of the nectin family that trans-interacts with nectin1/PRR1 through V domain interaction.

Nectins are adhesion molecules that participate in the organization of epithelial and endothelial junctions and serve as receptors for herpes simplex virus entry. They belong to the immunoglobulin superfamily, are homologues of the poliovirus receptor (PVR/CD155), and were also named poliovirus receptor-related (PRR) proteins. We identify a new member of the nectin family named nectin4. Peptide sequences of human and murine nectin4 share 92% identity, and as for other members, the ectodomain is made of three immunoglobulin-like domains of V, C, C types. In contrast to other nectin molecules, detection of nectin4 transcripts is mainly restricted to placenta in human tissues. Expression is broader in mouse, and interestingly nectin4 is detected at days 11, 15, and 17 during murine embryogenesis. Nectin4 interacts with afadin, a F-actin-associated molecule, via its carboxyl-terminal cytoplasmic sequence. Both molecules co-localize at cadherin-based adherens junctions in the MDCKII epithelial cell line. Nectins are homophilic adhesion molecules, and recently heterophilic interactions have been described between nectin3/nectin1 and nectin3/nectin2. We confirmed these trans-interactions and also described nectin3 as the PVR/CD155 ligand. By means of several approaches, we report on the identification of nectin4 as a new ligand for nectin1. First, a soluble chimeric recombinant nectin4 ectodomain (nectin4-Fc) trans-interacts with cells expressing nectin1 but not with cells expressing nectin2, nectin3, or PVR/CD155. Conversely, nectin1-Fc binds to cells expressing nectin4. Second, nectin1-Fc precipitates nectin4 expressed in COS cells. Third, reciprocal in vitro physical interactions were detected between nectin4-Fc and nectin1-Fc. The nectin4-Fc/nectin4-Fc interaction was detected suggesting that nectin4 exhibits both homophilic and heterophilic properties. Using the same approaches we demonstrate, for the first time, that the V domain of nectin1 acts as a major functional region involved in trans-heterointeraction with nectin4 and also nectin3.

Actins↗
PubMed2001

Mutation in bone morphogenetic protein receptor-IB is associated with increased ovulation rate in Booroola Mérino ewes.

Ewes from the Booroola strain of Australian Mérino sheep are characterized by high ovulation rate and litter size. This phenotype is due to the action of the FecB(B) allele of a major gene named FecB, as determined by statistical analysis of phenotypic data. By genetic analysis of 31 informative half-sib families from heterozygous sires, we showed that the FecB locus is situated in the region of ovine chromosome 6 corresponding to the human chromosome 4q22-23 that contains the bone morphogenetic protein receptor IB (BMPR-IB) gene encoding a member of the transforming growth factor-beta (TGF-beta) receptor family. A nonconservative substitution (Q249R) in the BMPR-IB coding sequence was found to be associated fully with the hyperprolificacy phenotype of Booroola ewes. In vitro, ovarian granulosa cells from FecB(B)/FecB(B) ewes were less responsive than granulosa cells from FecB(+)/FecB(+) ewes to the inhibitory effect on steroidogenesis of GDF-5 and BMP-4, natural ligands of BMPR-IB. It is suggested that in FecB(B)/FecB(B) ewes, BMPR-IB would be inactivated partially, leading to an advanced differentiation of granulosa cells and an advanced maturation of ovulatory follicles.

Amino Acid Sequence↗
PubMed2001

[Preoperative prognostic factors for squamous cell carcinomas of the thoracic esophagus].

AIM OF THE STUDY: To identify preoperative survival prognostic factors in patients with resectable squamous cell carcinoma of the thoracic esophagus. POPULATION: From January 1982 to September 1999, 868 patients underwent surgery for esophageal carcinoma in our department, including 493 for squamous cell carcinoma of the thoracic esophagus. The following parameters were retrospectively included in univariate and multivariate analysis: age, sex, undernutrition, dysphagia, tumor diameter and nodal involvement on the CT-scan, preoperative treatment, surgical technique, curative resection, pTNM classification, histologic type and postoperative complications. The actuarial survival was determined. RESULTS: Survival prognostic factors were dysphagia, nodal involvement on CT-scan and depth of tumor invasion at pathological examination. Three groups of patients were identified on the two preoperative variables: group 1: patients without dysphagia (n=102), group 2: patients with dysphagia but without nodal involvement on the CT- scan (n=244), group 3: patients with dysphagia and with nodal involvement on the CT- scan (n=147). The median survivals were 62.4, 19.1 and 14.4 months in groups 1, 2 and 3, respectively, and 5-year actuarial survivals were 50%, 21% and 11% (P<0.009). CONCLUSION: Our study confirms that dysphagia and nodal involvement on the CT-scan are simple preoperative prognostic factors in patients with resectable squamous cell carcinoma of the thoracic esophagus.

Aged↗
PubMed2001

[Adenocarcinomas of the distal esophagus and cardia: surgical management].

Adenocarcinoma of the esogastric junction is increasing more rapidly than any other cancer in western country. Patients with carcinoma of the cardia often present at an advanced stage of disease. Accurate preoperative staging of cancer of the cardia need computed tomography, endoscopic ultrasound: laparoscopy is useful for advanced cancer to detect liver and peritoneal metastatis, preventing an unnecessary laparotomy in up to 20% of patients. The Siewert's classification of the cancer of the esogastric junction is accepted internationally: type I: tumor center within the late 5 cm of the distal esophagus, treated with subtotal esophagectomy; type II: located at the esogastric junction, treated with distal esophagectomy and, either proximal or total gastrectomy; and type III: subcardial cancer, treated by extended total gastrectomy. The dominating independent prognostic factors are a complete resection (R0) and the lymph node status (pN0) Expected 5 year survival rate is 30% in patients undergoing surgery with curative intent (R0) and less than 1% in patients undergoing palliative surgery.

Adenocarcinoma↗
PubMed2000

The PDZ protein TIP-1 interacts with the Rho effector rhotekin and is involved in Rho signaling to the serum response element.

The human T-cell lymphotrophic virus, type 1 Tax protein can interact via its C terminus with various proteins including a PDZ domain. In this work, one of them, TIP-1, is characterized as a cytoplasmic 14-kDa protein mainly corresponding to one PDZ domain. A two-hybrid screen performed with TIP-1 as bait showed that it interacts with the human homologue of rhotekin that was previously identified in mice as a Rho effector. Both human and mouse rhotekins exhibit at their C termini the sequence QSPV-COOH that matches the X(S/T)XV-COOH consensus known for proteins recognizing PDZ domains. Mutation of the serine and valine residues to alanine impairs interaction of rhotekin with TIP-1. Transient expression experiments with a reporter construct including the c-Fos serum response element (SRE) showed that coexpression of TIP-1 with the constitutively active RhoA.V14 mutant and human rhotekin caused a strong activation of the SRE. A negative mutant of Rho, RhoA.N19, was unable to cooperate with TIP-1 and rhotekin. The positive effect of TIP-1 was also lost when the C terminus of rhotekin was mutated. These data show that the complex of active Rho with its effector rhotekin bound to TIP-1 produces in the cytoplasm a signal that triggers strong activation of the SRE.

Amino Acid Sequence↗
PubMed2000

Cooperative reactivity of early-late heterodinuclear transition metal complexes with polar organic substrates

A comprehensive investigation into the cooperative reactivity of two chemically complementary metal-complex fragments in early-late heterodinuclear complexes has been carried out. Reaction of the partially fluorinated tripodal amidozirconium complexes [HC-(SiMe2NR)3Zr(mu-Cl)2Li(OEt2)2] (R = 2-FC6H4: 2a, 2,3,4-F3C6H4: 2b) with K[CpM(CO)2] (M=Fe, Ru) afforded the stable metal-metal bonded heterodinuclear complexes [HC[SiMe2NR]3-Zr-MCp(CO)2] (3-6). Reaction of the dinuclear complexes with methyl isonitrile as well as the heteroallenes CO2, CS2, RNCO and RNCS led to insertion into the polar metal-metal bond. Two of these complexes, [HC[SiMe2N(2-FC6-H4)]3Zr(S2C)Fe(CO)2Cp] (9a) and [HC-[SiMe2N(2-FC2H4)]3Zr-(SCNPh)Fe(CO)2-Cp] (12), have been structurally characterized by a single crystal X-ray structure analysis, proving the structural situation of the inserted substrate as a bridging ligand between the early and late transition metal centre. The reactivity towards organic carbonyl derivatives proved to be varied. Reaction of the heterobimetallic complexes with benzyl and ethylbenzoate led to the cleavage of the ester generating the respective alkoxozirconium complexes [HC[SiMe2N(2-FC6H4)]3ZrOR] (R = Ph-CH2: 13a, Et: 13b) along with [CpFe-[C(O)Ph](CO)2], whereas the analogous reaction with ethyl formate gave 13b along with [CpFeH(CO)2]; this latter complex results from the instability of the formyliron species initially formed. Aryl aldehydes were found to react with the Zr-M complexes according to a Cannizzaro disproportionation pattern yielding the aroyliron and ruthenium complexes along with the respective benzoxyzirconium species. The transfer of the aldehyde hydrogen atom in the course of the reaction was established in a deuteriation experiment. [HC[SiMe2-N(2-FC6H4)]3Zr-M(CO)2Cp] reacted with lactones to give the ring-opened species containing an alkoxozirconium and an acyliron or acylruthenium fragment; the latter binds to the early transition metal centre through the acyl oxygen atom, as evidenced from the unusuallly low-field shifted 13C NMR resonances of the RC(O)M units. Ketones containing a-CH units react with the Zr-Fe complexes cooperatively to yield the aldol coupling products coordinated to the zirconium complex fragment along with the hydridoiron compound [CpFeH(CO)2], whereas 1,2-diphenylcyclopropenone underwent an oxygen transfer from the keto group to a CO ligand to give a linking CO2 unit and a cyclopropenylidene ligand coordinated to the iron fragment in [HC-[Si(CH3)2N(2,3,4-F3C6H2)]3Zr(mu-O2C)-Fe(CO)[C3Ph2)Cp] (19). The atom transfer was established by 17O and 13C labelling studies. Similar oxygen-transfer processes were observed in the reactions with pyridine N-oxide, dimethylsulfoxide and methylphenylsulfoxide.

Journal Article↗