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F Faure

Publications and source records attributed to F Faure.

At least 19 recordsLinked to original sources

Imatinib enhances human melanoma cell susceptibility to TRAIL-induced cell death: Relationship to Bcl-2 family and caspase activation.

In order to define genetic determinants of primary and metastatic melanoma cell susceptibility to tumor necrosis factor-related apoptosis-inducing ligand (TRAIL), we have applied oligonucleotide microarrays to TRAIL-sensitive primary T1 cells and TRAIL-resistant metastatic G1 cells treated or not with TRAIL. T1 and G1 cells are isogenic melanoma cell subclones. We examined 22 000 spots, 4.2% of which displayed differential expression in G1 and T1 cells. Cell susceptibility to TRAIL-mediated apoptosis was found to be correlated with gene expression signatures in this model. Some of the differentially expressed genes were identified as involved in ATP-binding and signaling pathways, based on previously published data. Further analysis provided evidences that c-kit was overexpressed in G1 cells while it was absent in T1 cells. The c-kit inhibitor, imatinib, did not restore TRAIL sensitivity, excluding a role for c-kit in TRAIL resistance in G1 cells. Surprisingly, imatinib inhibited cell proliferation and TRAIL-mediated apoptosis in melanoma cells. We investigated the possible involvement of several molecules, including c-ABL, platelet-derived growth factor receptor (PDGFR), cellular FADD-like interleukin-1 alpha-converting enzyme-like inhibitory protein (c-FLIP)(L/S), Fas-associated DD kinase, p53, p21(WAF1), proteins of B-cell leukemia/lymphoma 2 (Bcl-2) family and cytochrome c. Imatinib did not modulate the expression or activation of its own targets, such as c-ABL, PDGFRalpha and PDGFRbeta, but it did affect the expression of c-FLIP(L), BCL2-associated X protein (Bax) and Bcl-2. Moreover, c-FLIP(L) knockdown sensitized T1 cells to TRAIL-mediated apoptosis, with a sensitivity similar to that of cells previously treated with imatinib. More notably, we found that the resistance to TRAIL in G1 cells was correlated with constitutive c-FLIP(L) recruitment to the DISC and the inhibition of caspase 8, 3 and 9 processing. Moreover, c-FLIP(L) knockdown partly restored TRAIL sensitivity in G1 cells, indicating that the expression level of c-FLIP(L) and its interaction with TRAIL receptor2 play a crucial role in determining TRAIL resistance in metastatic melanoma cells. Our results also show that imatinib enhances TRAIL-induced cell death independently of BH3-interacting domain death agonist translocation, in a process involving the Bax:Bcl-X(L) ratio, Bax:Bcl-X(L)/Bcl-2 translocation, cytochrome c release and caspase activation. Our data indicate that imatinib sensitizes T1 cells by directly downregulating c-FLIP(L), with the use of an alternative pathway for antitumor activity, because PDGFRalpha is not activated in T1 cells and these cells do not express c-kit, c-ABL or PDGFRbeta. Caspase cascade activation and mitochondria also play a key role in the imatinib-mediated sensitization of melanoma cells to the proapoptotic action of TRAIL.

Antineoplastic Agents↗

[Treatments of hereditary hemorrhagic telangiectasia of the nasal mucosa].

UNLABELLED: Hereditary Hemorrhagic Telangiectasia is a systemic autosomal dominant disorder involving blood vessels. The most common symptom is recurrent epistaxis. The treatments of these epistaxis are numerous but such treatments are often symptomatic and their effects are often not sustained. Some of these treatments may be complicated by visceral vascular malformations. The aim of this study is to propose a treatment plan for these patients with hierarchical organisation of therapeutic options taking into account of their previous therapy. METHOD: H. Plauchu organized in Paris, december 2002 a meeting with any medical specialists of this disease. They have analysed variety of therapies that have been proposed for epistaxis control in Hereditary Haemorrhagic Télangiectasia. RESULTS: Most common use packing of nasal fossa and then hyperselective embolization of the internal maxillary and facial arteries for severe epistaxis. For chronic epistaxis, best treatment use sclerotics products (Ethibloc) and laser. After discussion, primary embolization could be useful to reduce vascularization of nasal fossa. CONCLUSION: Treatment of epistaxis in Hereditary Haemorrhagic Telangiectasia could increase in few years. Use of an index card of for epistaxis in the disease of Rendu-Osler could help to find treatment of choice.

Acute Disease↗

A layered model of a virtual human intestine for surgery simulation.

In this paper, we propose a new approach to simulate the small intestine in a context of laparoscopic surgery. The ultimate aim of this work is to simulate the training of a basic surgical gesture in real-time: moving aside the intestine to reach hidden areas of the abdomen. The main problem posed by this kind of simulation is animating the intestine. The problem comes from the nature of the intestine: a very long tube which is not isotropically elastic, and is contained in a volume that is small when compared to the intestine's length. It coils extensively and collides with itself in many places. To do this, we use a layered model to animate the intestine. The intestine's axis is animated as a linear mechanical component. A specific sphere-based model handles contacts and self-collisions. A skinning model is used to create the intestine's volume around the axis. This paper discusses and compares three different representations for skinning the intestine: a parametric surface model and two implicit surface models. The first implicit surface model uses point skeletons while the second uses local convolution surfaces. Using these models, we obtained good-looking results in real-time. Some videos of this work can be found in the online version at doi: 10.1016/j.media.2004.11.006 and at www-imagis.imag.fr/Publications/2004/FLAMCFC04.

Algorithms↗

Tumor-derived exosomes are a source of shared tumor rejection antigens for CTL cross-priming.

The initiation of T-cell-mediated antitumor immune responses requires the uptake and processing of tumor antigens by dendritic cells and their presentation on MHC-I molecules. Here we show in a human in vitro model system that exosomes, a population of small membrane vesicles secreted by living tumor cells, contain and transfer tumor antigens to dendritic cells. After mouse tumor exosome uptake, dendritic cells induce potent CD8+ T-cell-dependent antitumor effects on syngeneic and allogeneic established mouse tumors. Therefore, exosomes represent a novel source of tumor-rejection antigens for T-cell cross priming, relevant for immunointerventions.

Animals↗

Topological chern indices in molecular spectra

Topological Chern indices are related to the number of rotational states in each molecular vibrational band. Modification of the indices is associated to the appearance of "band degeneracies," and exchange of rotational states between two consecutive bands. The topological dynamical origin of these indices is demonstrated through a semiclassical approach, and their values are computed in two examples. The relation with the integer quantum Hall effect is briefly discussed.

Journal Article↗

Natural history of residual renal stone fragments after ESWL.

OBJECTIVE: After extracorporeal shock wave lithotripsy (ESWL), residual fragments (RF) 4 mm or less are usually considered as clinically insignificant. We retrospectively reviewed the natural history and clinical significance of 97 noninfected and isolated RF (4 mm or less) observed 3 months after the last ESWL session on renal tomography. PATIENTS AND METHODS: They represented 83 among 1, 216 patients treated by ESWL over a 9-year period (1989-1997). These RF were mostly localized in the inferior calyx (62%). Median follow-up was 40.6 months (range: 7-96 months). Renal tomography was always performed at the end of follow-up. RESULTS: Stone-free status, or a decreased, stable or increased amount of residual stone occurred in 27 (33%), 1 (1%), 24 (29%) and 31 (37%) of the 83 patients, respectively. During this study, 18 patients (22%) were proposed for a complementary treatment related to a size increase of the residual fragments (13 ESWL, 1 retrograde endoscopy, 3 percutaneous nephrolithotomy, and 1 polar inferior nephrectomy). CONCLUSION: The term clinically insignificant should not be employed to describe RF after ESWL. Efforts should be performed to obtain true stone-free status after ESWL.

Follow-Up Studies↗

Microscopic venous invasion: a prognostic factor in renal cell carcinoma.

OBJECTIVE: Microscopic venous invasion (MVI) is characterized by local destruction of the endothelium by a tumor. The prognostic value of MVI in renal cell carcinoma (RCC) is not well established. MATERIALS AND METHODS: From 1980 until 1990, 255 patients (169 men and 86 women), aged 16-87 (mean 60) years were treated by radical nephrectomy for N0M0 RCC. There were 9 pT1, 163 pT2, 30 pT3a, 34 pT3b, and 19 pT3ab (TNM 1992). The median follow-up time was 74 months. MVI was determined by a double-blind histological study with immunohistochemical staining. RESULTS: MVI was noted in 74 patients (29%). MVI significantly increased metastatic progression (p = 0.003). Only stage and Fuhrman's grade were significant factors for metastatic progression in a multivariate analysis. MVI decreased the actuarial survival rates at 1 year (p = 0.01), but not significantly at 5 and 10 years. MVI and non-MVI survival curves were statistically different with the Peto/Wilcoxon (p = 0.04) and Gehan/Wilcoxon (p = 0.03) tests, but not with the log rank test (p = 0.06). MVI decreased survival in cases with a tumor size of 10 cm or more, capsular invasion, macroscopic venous invasion, stage pT3ab, sarcomatoid cell carcinoma and Fuhrman's grade IV. Only the stage was a significant factor for survival in a multivariate analysis. CONCLUSION: In RCC, MVI is related to cancer progression and survival, but probably not as an independent prognostic factor.

Adolescent↗

[Respiratory failure caused by megaesophagus and tracheomalacia].

We report a case of acute respiratory failure in an 83-year-old woman suffering from a megaoesophagus compressing the posterior tracheal wall. Naso-oesophageal aspiration did not allow tracheal extubation because of associated tracheomalacia. Treatment included tracheostomy and decrease of cardial tonus by administration of botulinic toxin, after weaning from mechanical ventilation.

Aged↗

[Is ultrasonographic evaluation the the length of the kidney possible in children? Apropos of a prospective study in Madagascar children less than 1 year of age].

Renal US was prospectively performed in 124 madagascan children less than 1 year of age. Patients were examined in the prone position and maximum kidney length was measured in the longitudinal plane. These measurements and the height and weight of our patient population were compared to published tables. Kidney length and height and weight of our patient population were inferior to the previously published reference data and the growth curve of kidneys steeper than normative standards (p < 0.001). Because of the important variability in US measurement of kidney length it is not possible to definitely conclude that length and growth curve of kidneys in madagascan children are statistically different from those of the published normative standards.

Age Factors↗

Physiopathogenic investigations in a case of familial stiff-skin syndrome.

BACKGROUND: Stiff-skin syndrome (SSS) is a rare cutaneous syndrome characterized by stony-hard skin and limitation of joint mobility. Its cause is still unknown. OBJECTIVE: Biological investigations were performed in a new case of SSS. METHODS: Collagen production and DNA biosynthesis were studied from fibroblast culture. Proinflammatory cytokines (TNF-alpha, IL-6 and TGF-beta2) were measured in the patient's serum. Results were compared with pathological findings. RESULTS: Collagen production and DNA biosynthesis were normal whereas the level of circulating cytokines was high. Histological examination of the skin showed mild fibrosis in the dermis whereas the fascia was not thickened. CONCLUSION: Our clinical and biological findings suggest that in this case, cutaneous changes may be related to an inflammatory process rather than to a primary fibroblast defect or a fascial abnormality as previously hypothesized.

Collagen↗

Single stones of the lower pole of the kidney. Comparative results of extracorporeal shock wave lithotripsy and percutaneous nephrolithotomy.

OBJECTIVE: To assess the effectiveness of extracorporeal shock wave lithotripsy (ESWL) and percutaneous nephrolithotomy (PCN) as a treatment for stones of the lower pole of the kidney and to compare their morbidity according to the stone size. METHODS: We retrospectively studied 739 patients treated for a single stone of the lower pole. Group I consisted of 666 patients treated by ESWL and group II consisted of 73 patients treated by PCN. RESULTS: These were assessed at 3 months for 587 ESWL patients (88%) and at day 1 for all PCN patients on renal tomography or ultrasonography. Respectively in groups I and II, 335 patients (57%) and 53 patients (72.6%) were stone-free (p = 0.01). For medium-size (10-20 mm) stone patients, stone-free represented 102 patients (44%) and 29 patients (72.5%) in groups I and II respectively (p = 0.001). For smaller stones (< 10 mm), stone-free represented 231 patients (69%) and 21 patients (84%) in groups I and II respectively (p = 0.12). Morbidity rate was less with ESWL than with PCN. CONCLUSIONS: PCN achieves better results than ESWL for single stone of the lower pole with statistical significance for middle-size stones but with higher morbidity.

Adolescent↗

Tumor-specific immune response: current in vitro analyses may not reflect the in vivo immune status.

Although our knowledge and understanding of tumor-specific cytotoxic T lymphocytes (CTL) have expanded considerably, the long-term work needed to assay CTL has precluded their analysis in large numbers of patients. Moreover, in vitro culture steps may introduce major biases. New approaches to identify tumor-specific CTL clones would be helpful. As a means to describe the in situ immune status by T-cell repertoire analysis, we developed the Immunoscope approach, a PCR-based method that allows us to determine the spectra of CDR3 lengths of the TCR chains displayed by complex populations of T cells. We review here some of our data about melanoma. Tumor-infiltrating lymphocytes of a melanoma patient were analyzed by different means and melanoma-specific T-cell clones were derived. Two categories of tumor-specific CD8+ CTL clones were derived from the infiltrate of a tumor-proximal invaded lymph node. The majority of T-cell clones specifically lyse the autologous tumor cell lines and predominantly recognize the HLA-A2/MART-1(27-35) peptide complex. The in vivo representativity of such CTL was assessed by the immunoscope technology. Among three MART-1-specific clones, none was detectable in situ. The other kind of tumor-specific CD8+ CTL did not lyse autologous melanoma cell lines but lysed the "fresh" autologous tumor cells in a MHC class I dependent manner. The immunoscope approach revealed that one of the latter was detectable in situ among tumor-infiltrating lymphocytes although not among PBMC. These data indicate that melanoma-specific lymphocytes that could not have been selected through conventional screening procedures may be important in tumor rejection. Our results suggest that a better characterization of tumor-specific immune responses will be important for the optimization of specific immunotherapy strategies and the long-term follow-up of patients.

Animals↗

In situ T-cell responses in a primary regressive melanoma and subsequent metastases: a comparative analysis.

In an earlier study of the immune response in a patient with a cutaneous primary regressive melanoma, a T-cell-receptor diversity analysis demonstrated in situ amplification of certain lymphocytes. Two of them could be cloned and characterized as CD8+ HLA-class-l-restricted CTL with strong selective anti-tumor activity. Following a disease-free period of 3 years, the patient developed a gastric metastasis and subsequently (after an additional year) a metastasis in one axillary lymph node. Melanoma cell lines derived from the 2 secondary lesions have been established here. It was found that these metastatic cells have maintained expression of both HLA-class-I molecules and the peptidic antigen(s) recognized by the 2 clones amplified at the primary site. However, the corresponding T lymphocytes were either undetectable or poorly represented both in the gastric and in the axillary lesions. These results suggest that substantial alterations in the quality of T-cell infiltrates occurred during melanoma progression, despite an apparent stability in presentation of tumor-associated antigen(s) which initially triggered a positive rejection response.

Aged↗

Diversity of the cytotoxic melanoma-specific immune response: some CTL clones recognize autologous fresh tumor cells and not tumor cell lines.

In the present work, to analyze the heterogeneity of the tumor-specific cytotoxic immune response, a large number of T cell clones were generated from the infiltrate of a tumor-proximal invaded lymph node, and two kinds of melanoma-specific CD8+ CTL clones were derived. The majority of T cell clones (about a hundred) are characterized by a specific lysis of the autologous tumor cell lines. Among 34 of the latter clones, HLA-A2 molecule and MART-1(27-35) peptide have been shown to play a predominant role in tumor recognition. However, no significant amplification at the tumor site was observed for 3 of these CTL. The other kind of tumor-specific CTL (1 oligoclonal and 2 clonal cell lines) did not lyse the autologous melanoma cell lines but lysed the "fresh" autologous tumor cells in a MHC class I-dependent manner. Functional analysis of the two different CTL clones have shown that they did not lyse NK targets, autologous peripheral monocytes, activated T cells, and transformed B cells or any of the few allogeneic cultured and uncultured melanoma cells we tested. TCR repertoire analysis has shown that one of these CTL clones was significantly detectable "in situ" among tumor-infiltrating lymphocytes, while not detectable among PBMC. Such melanoma-specific lymphocytes, which could not have been picked out through conventional screening procedures using tumor cell lines, could potentially play a role in tumor rejection. These results suggest that the immune response analyzed toward melanoma cell lines does not totally reflect the in situ immune status.

Aged↗

[Acute pancreatitis and ectopic pancreas].

We report the case of a 28-year-old woman with a pancreatic heterotopia presenting with a history of acute pancreatitis. Symptoms were epigastric pains. Abdomino-pelvic CT Scan revealed a tumor located in gastro-duodenal area. Exploratory surgery was performed, and the segment containing the mass was resected. Histopathologic examination of the lesion revealed heterotopic pancreatic tissue without malignancy.

Acute Disease↗