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Le Havre, France

Radu A.,Mount Sinai School of Medicine | Pichon C.,French Institute of Health and Medical Research | Camparo P.,Val de Grace Hospital | Antoine M.,Tenon Hospital | And 5 more authors.
New England Journal of Medicine | Year: 2010

BACKGROUND: In adult humans, the follicle-stimulating hormone (FSH) receptor is expressed only in the granulosa cells of the ovary and the Sertoli cells of the testis. It is minimally expressed by the endothelial cells of gonadal blood vessels. METHODS: We used immunohistochemical and immunoblotting techniques involving four separate FSH-receptor-specific monoclonal antibodies that recognize different FSH receptor epitopes and in situ hybridization to detect FSH receptor in tissue samples from patients with a wide range of tumors. Immunoelectron microscopy was used to detect FSH receptor in mouse tumors. RESULTS: In all 1336 patients examined, FSH receptor was expressed by endothelial cells in tumors of all grades, including early T1 tumors. The tumors were located in the prostate, breast, colon, pancreas, urinary bladder, kidney, lung, liver, stomach, testis, and ovary. In specimens obtained during surgery performed to remove tumors, the FSH receptor was not expressed in the normal tissues located more than 10 mm from the tumors. The tumor lymphatic vessels did not express FSH receptor. The endothelial cells that expressed FSH receptor were located at the periphery of the tumors in a layer that was approximately 10 mm thick; this layer extended both into and outside of the tumor. Immunoelectron microscopy in mice with xenograft tumors, after perfusion with anti-FSH-receptor antibodies coupled to colloidal gold, showed that the FSH receptor is exposed on the luminal endothelial surface and can bind and internalize circulating ligands. CONCLUSIONS: FSH receptor is selectively expressed on the surface of the blood vessels of a wide range of tumors. (Funded by INSERM.) Copyright © 2010 Massachusetts Medical Society. Source

Levy A.,Institut Universitaire de France | Saiag P.,University of Versailles | Chargari C.,Val de Grace Hospital | Assouline A.,Porte Of Saint Cloud Clinical Center
Melanoma Research | Year: 2012

The optimal management of patients with few brain metastases is complex. On one hand, stereotactic radiation therapy is a keystone of treatment but is only applicable to highly selected patients fulfilling specific criteria who have access to an adequate radiation unit. On the other, whole-brain radiation therapy may improve survival, but deleterious effects on neurocognitive functions are well known. It has, however, been reported that selected subgroups of patients may benefit from focal dose escalation to brain metastases to prolong survival and the time to intracranial disease progression. Here, we discuss a clinical case to consider the interest of a focal high-dose hypofractionated radiation delivered through a conventional linear accelerator on a large brain metastasis for a patient with metastatic melanoma excluded for stereotactic radiotherapy. © 2012 Wolters Kluwer Health | Lippincott Williams & Wilkins. Source

Vincendeau S.,University of Rennes 1 | Bellissant E.,University of Rennes 1 | Houlgatte A.,Val de Grace Hospital | Dore B.,University of Poitiers | And 5 more authors.
Archives of Internal Medicine | Year: 2010

Background: α-Blockers induce selective relaxation of ureteral smooth muscle with subsequent inhibition of ureteral spasms and dilatation of the ureteral lumen. The aim of the study was to evaluate the efficacy and safety of the α-blocker tamsulosin hydrochloride in patients with ureteral colic owing to a distal ureteral stone. Methods: This was a multicenter, placebo-controlled, randomized, double-blind study. Patients with emergency admission for ureteral colic with a 2- to 7-mmdiameter radio-opaque distal ureteral stone were included in the study. They received tamsulosin (0.4 mg/d) or matching placebo until stone expulsion or day 42, whichever came first. The main end point was time to stone expulsion between inclusion and day 42. Sequential statistical analysis was performed using the triangular test. Results: A total of 129 patients with acute renal colic were recruited from emergency wards between February 1, 2002, and December 8, 2006, in 6 French hospitals. Of these 129 randomized patients (placebo, 63; tamsulosin, 66), 7 were excluded from analyses: 5 for major deviations from inclusion criteria, 1 for stone expulsion before the first treatment administration, and 1 for consent withdrawal. At inclusion, mean (SD) stone diameters were 3.2 (1.2) and 2.9 (1.0)mmin the placebo and tamsulosin groups, respectively (P=.23). Expulsion delay distributions during 42 days did not show any difference (P=.30). The numbers of patients who spontaneously expelled their stone within 42 days were 43 of 61 (70.5%) and 47 of 61 (77.0%) in the placebo and tamsulosin groups, respectively (P=.41). Corresponding delays were 10.1 (10.0) and 9.6 (9.8) days (P=.82). Other secondary end points and tolerance were not different between groups. Conclusion: Although well tolerated, a daily administration of 0.4 mg of tamsulosin did not accelerate the expulsion of distal ureteral stones in patients with ureteral colic. Trial Registration: clinicaltrials.gov Identifier: NCT00151567. ©2010 American Medical Association. All rights reserved. Source

Al Nakouzi N.,University of British Columbia | Le Moulec S.,Val de Grace Hospital | Albiges L.,University Paris - Sud | Wang C.,University of British Columbia | And 9 more authors.
European Urology | Year: 2015

Background Cabazitaxel, abiraterone acetate (AA), and enzalutamide have been approved for the treatment of patients with metastatic castration-resistant prostate cancer (mCRPC) following docetaxel chemotherapy. Whether taxanes and next-generation androgen receptor (AR) axis inhibitors are cross-resistant or not is a subject of debate. Objective To evaluate the antitumour activity of cabazitaxel in mCRPC pretreated with abiraterone or enzalutamide. Design, setting, and participants The antitumour activity of cabazitaxel was assessed in patients with mCRPC and progressive disease after treatment with docetaxel and AA. In parallel, cabazitaxel antitumour activity was studied in enzalutamide-resistant models. Outcome measurements and statistical analysis Changes in prostate-specific antigen (PSA) levels and progression-free survival were used to determine the activity of cabazitaxel treatment. Cell proliferation, immunofluorescence, and AR transactivation assay were used in enzalutamide-resistant models. Results and limitations A total of 79 patients who had progressive mCRPC after docetaxel (median: 8 cycles; range: 4-12 mo), and AA (median: 4.8 mo; range:1-55 mo) received cabazitaxel 25 mg/m2 every 3 weeks (median: 6 cycles; range:1-15 cycles). A PSA decline ≥30% was achieved in 48 patients (62%; 95% confidence interval [CI], 51-73), and a decline ≥50% was achieved in 28 patients (35%; 95% CI, 25-47). The median progression-free survival and overall survival were 4.4 and 10.9 mo, respectively. In vitro, cabazitaxel decreased cell viability in both enzalutamide-sensitive and enzalutamide-resistant prostate cancer cells within the same range of concentrations. PC3, an AR-negative cell line, exhibited similar sensitivity to cabazitaxel. Conclusions Cabazitaxel and AR-pathway inhibitors are not cross-resistant. Preclinical data suggest that cabazitaxel activity does not act mainly through AR axis inhibition. Patient summary The antitumour activity of cabazitaxel, a chemotherapy agent, was studied in prostate cancer resistant to conventional hormonal therapy and to more recent endocrine therapies (abiraterone or enzalutamide). Cabazitaxel retained anticancer activity in more than half of the cases. © 2014 European Association of Urology. Source

Chargari C.,Val de Grace Hospital | Comperat E.,Pitie Salpetriere Hospital | Vedrine L.,Val de Grace Hospital | Houlgatte A.,Val de Grace Hospital | And 2 more authors.
Pathology Research and Practice | Year: 2011

This study aimed at determining whether virtual microscopy improves the accuracy in the pathological examination of prostate needle biopsies regarding maximum tumor length, percentage of positive cores, and Gleason grading.We assessed a series of 816 prostate needle biopsy cores in 68 consecutive patients with prostate adenocarcinoma. Biopsy specimens were reviewed using conventional examination. Then, slides were converted to whole slide imaging (Olympus BX51). Tumor was measured, and Gleason score was assigned using the OlyVia software. Optically evaluated pathological features were compared with digital findings to determine whether one of these two methods for the assignment of a preoperative Gleason score is appropriate for predicting the definitive Gleason score of radical prostatectomy.When comparing optical and digital measurements, maximum tumor length in biopsy cores and percent prostate needle biopsy with cancer showed no significant difference. The mean variation in the measurement of tumor length was 2.65. mm per biopsy. Among 240 biopsy cores involved with cancer, the concordance rate for Gleason score assignment was 75.8% (κ=0.49, good agreement). When considering the higher Gleason score assignment as the score for the entire case (ISUP 2005), the concordance rate was 69.1% (κ=0.46, good agreement). When comparing the biopsy scores with the definitive score of radical prostatectomy, the concordance rate was significantly increased from 54.4% for conventional examination (κ=0.23, marginal agreement) to 66.2% for virtual slide examination (κ=0.42, good agreement).Virtual microscopy does not compromise, but might improve, the accuracy of grading in prostate needle biopsies. This requires further assessment. © 2011 Elsevier GmbH. Source

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