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Biblio - Bibliographie IAL
Bibliographie IAL

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Recherche bibliographique scientifique

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Accueil > Références bibliographiques

biblio

2011


  • Ples, R, Mechai, F, Champiat, B, Droupy, S, Huerre, M, Guettier, C & Ferlicot, S 2011, « [Pseudotumoral toxoplasmic cystitis revealing acquired immunodeficiency syndrome] », Ann Pathol, vol. 31, no. 1, p. 46-9, viewed sans date, .
    Résumé : A case of bladder toxoplasmosis in a 57-year-old male Caucasian patient was diagnosed with difficulty due to misleading clinical presentation. The patient presented with pollakiuria and urination burning. Imagery showed pseudotumoral thickening of the vesicle wall. Previously unknown status of HIV infection was found positive through the diagnosis of bladder toxoplasmosis. The patient died rapidly from neurological complications. This is the second published case in which bladder toxoplasmosis reveals an HIV infection.
    Mots-clés : Cerebral/diagnosis/etiology.
  • Proust, A, Rince, P, Creidy, R, Lazure, T, Joab, I, Garcon, L, Fabre, M, Guettier, C & Raphael, M 2011, « p52 Activation in monomorphic B-cell posttransplant lymphoproliferative disorder/diffuse large B-cell lymphoma without BAFF-R expression », Am J Pathol, vol. 179, no. 4, p. 1630-7.
    Résumé : Posttransplantation lymphoproliferative disorders (PTLD) are associated with Epstein-Barr virus (EBV) and activate the NF-kappaB pathway. B-cell activating factor (BAFF) modulates cell growth and survival in non-Hodgkin's lymphomas. However, there are few studies of EBV, BAFF/BAFF-R signaling, and NF-kappaB1 and NF-kappaB2 pathway activation in PTLD. Diffuse large B-cell lymphomas (DLBCL) in two different clinical contexts, immunocompetent patients (DLBCL/IC; n = 30) or posttransplantation solid-organ recipients (DLBCL/PTLD; n = 21), were characterized histogenically as germinal center (GC) or non-germinal center (NGC). Expression of BAFF, BAFF-R, and NF-kappaB proteins p50 and p52 and the presence or absence of EBV were compared in these clinical contexts. Regardless of the GC or NGC pattern of DLBCL, BAFF-R was expressed in 37% of DLBCL/IC but in only 4.8% of DLBCL/PTLD. p52 was expressed in DLBCL/PTLD/NGC (12 of 19 cases) as compared with DLBCL/IC/NGC (0 of 18 cases). This pattern might be related to the presence of EBV and latent membrane protein 1 because p52 expression was observed primarily in EBV-positive DLBCL/PTLD cases expressing latent membrane protein 1. Thus, the activation profile or NGC pattern of DLBCL/PTLD was not associated with BAFF/BAFF-R expression, whereas nuclear p52 related to NF-kappaB2 pathway activation might be linked to EBV.
    Mots-clés : 80 and over B-Cell Activating Factor/metabolism B-Cell Activation Factor Receptor/ metabolism Child, Adolescent Adult Aged Aged, Diffuse/ etiology/ metabolism/pathology/virology Lymphoproliferative Disorders/ etiology/ metabolism/pathology/virology Male Middle Aged NF-kappa B p52 Subunit/ metabolism Signal Transduction Transplantation/ adverse effects, Human/isolation & purification Humans Immunohistochemistry Infant Lymphoma, Large B-Cell, Preschool Female Herpesvirus 4.
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  • Reyal, F, Valet, F, de Cremoux, P, Mathiot, C, Decraene, C, Asselain, B, Brain, E, Delaloge, S, Giacchetti, S, Marty, M, Pierga, JY & Bidard, FC 2011, « Circulating tumor cell detection and transcriptomic profiles in early breast cancer patients », Ann Oncol, vol. 22, no. 6, p. 1458-9, viewed sans date, .
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  • Roche, B & Samuel, D 2011, « Is early antiviral therapy for recurrent hepatitis C after liver transplantation superior to later treatment? The answer is no », Liver Transpl, vol. 17, no. 5, p. 488-91.
    Résumé : Roche, Bruno; Samuel, Didier; Comment; Editorial; United States; Liver Transpl. 2011 May;17(5):488-91. doi: 10.1002/lt.22297.
    Mots-clés : Antiviral Agents/ therapeutic use Clinical Trials as Topic End Stage Liver Disease/complications/ therapy Fibrosis Genotype Hepatitis C/ drug therapy Humans Liver Diseases/ therapy Liver Transplantation/ methods RNA, Viral/genetics Recurrence Time Factors Treatment Outcome.
  • Roche, B & Samuel, D 2011, « The difficulties of managing severe hepatitis B virus reactivation », Liver Int, vol. 31 Suppl 1, p. 104-10.
    Résumé : Reactivation of hepatitis B is characterized by a sudden increase in hepatitis B virus (HBV) replication in a patient with prior evidence of resolved or inactive HBV infection. Although HBV reactivation can occur spontaneously, it usually occurs after chemotherapy, immunosuppression (organ transplantation) or an alteration in immune function (therapy for autoimmune disease, human immunodeficiency virus infection). The clinical presentation cases can vary, ranging from a subclinical, asymptomatic course to severe acute hepatitis and even death. Although reactivation of HBV is mainly found in HBsAg-positive patients, it can be observed in serologically recovered anti-hepatitis B core antibody (HBc)-positive, HBsAg-negative patients. Serum HBV DNA typically increases during immune suppression, followed by a disease flare and HBV DNA clearance following immune restoration after immune suppression is stopped. In organ transplant recipients, without immune reconstitution, high HBV DNA levels can lead to fibrosing cholestatic hepatitis related to the direct cytopathic effect of HBV. Several randomized, controlled trials and meta-analyses have shown that reactivation can be prevented by lamivudine prophylaxis. Screening for HBsAg and anti-HBc should be performed before beginning immunosuppressive treatment and routine prophylaxis is recommended in HBsAg-positive patients. The optimal duration of prophylaxis remains to be determined. In anti-HBc-positive patients with or without anti-hepatitis B surface antigen, alanine transaminase and HBV DNA levels should be closely monitored and antiviral therapy should be started when HBV reactivation is confirmed. The use of new more potent nucleos(t)ides analogues with lower resistance rates would seem to be logical; however, experience with these drugs in the prophylaxis and treatment of severe HBV reactivation is limited.
    Mots-clés : Antiviral Agents/pharmacology/ therapeutic use DNA.

  • Roupret, M, Drouin, SJ, Larre, S, Neuzillet, Y, Botto, H, Hitier, M, Rigaud, J, Crew, J, Xylinas, E, Salomon, L, Cornu, JN, Iborra, F, Champetier, D, Rozet, F, Flamand, V, Bastide, C, Cormier, L, Durand, X, Lunardi, P, Rischmann, P, Nouhaud, FX, Ferlicot, S, Patard, JJ, Floch, AP, Irani, J, Peyronnet, B, Bensalah, K, Poissonnier, L, Gres, P, Droupy, S, Casenave, J, Wallerand, H, Soulie, M, Pfister, C & Bladder Cancer Committee of the French National Association of, U 2011, « Oncologic outcomes and survival in pT0 tumors after radical cystectomy in patients without neoadjuvant chemotherapy: results from a large multicentre collaborative study », Ann Surg Oncol, vol. 18, no. 13, p. 3833-8, viewed sans date, .
    Résumé : PURPOSE: To assess the postsurgical survival of patients with urothelial carcinoma of the bladder with pT0 tumor at pathologic examination of cystectomy specimens. METHODS: A multi-institutional, retrospective database was analyzed with data from 4758 radical cystectomy (RC) patients who underwent RC without neoadjuvant chemotherapy and who were diagnosed with pT0 on the basis of the pathologic specimen. Survival curves were estimated. A multivariate Cox model was used to evaluate the association between prognosis factors and disease recurrence or survival. RESULTS: Overall, 258 patients (5.4%) were included in the study. The median age was 64 years. At last resection, 171 tumors were invasive (at least pT2), and 87 were not. Median follow-up was 51 months. At multivariate analysis, initial location of the tumor and absence of lymphadenectomy were associated with tumor recurrence (P = 0.03 and P = 0.005, respectively) and specific mortality (P = 0.005 and 0.001, respectively). The main limitation of the study is its retrospective design, which is due to the rarity of this situation. Cancer-specific and recurrence-free survival rates were 89 and 85%, respectively, at 5 years and 82 and 80%, respectively, at 10 years. CONCLUSIONS: Despite acceptable oncological outcomes, patients with a pT0 tumor at the time of RC are still at risk of recurrence and progression and should not be considered to be entirely cured. In this population, stringent follow-up according to current recommendations should be effective.
    Mots-clés : 80 and over Carcinoma, Adult Aged Aged, Local/mortality/pathology/surgery Neoplasm Staging Prognosis Retrospective Studies Survival Rate Urinary Bladder Neoplasms/*mortality/pathology/*surgery, Transitional Cell/*mortality/pathology/*surgery Cystectomy/*mortality Female Follow-Up Studies Humans Male Middle Aged Neoadjuvant Therapy Neoplasm Recurrence.


  • Rubinstein, E 2011, « The complexity of tetraspanins », Biochem Soc Trans, vol. 39, no. 2, p. 501-5, viewed sans date, .
    Résumé : Tetraspanins compose a family of structurally related molecules with four transmembrane domains. A total of 33 tetraspanins are present in the human genome, and tetraspanins are also found in plants and certain fungi. A well-known property of tetraspanins is their ability to interact with one another and many other surface proteins, which led to the suggestion that they organize a network of molecular interaction referred to as the 'tetraspanin web', and that they play a role in membrane compartmentalization. Recent studies of the dynamics of these molecules provided important new information that helped refining the models of this 'web'. Several genetic studies in mammals and invertebrates have demonstrated key physiological roles for some of the tetraspanins, in particular in immune response, sperm-egg fusion, photoreceptor function and the normal function of certain epitheliums or vascular development. However, in several examples, the phenotypes of tetraspanin-knockout mice are relatively mild or restricted to a particular organ, despite a wide tissue distribution.
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  • Sakai, K, Barnitz, RA, Chaigne-Delalande, B, Bidere, N & Lenardo, MJ 2011, « Human immunodeficiency virus type 1 Vif causes dysfunction of Cdk1 and CyclinB1: implications for cell cycle arrest », Virol J, vol. 8, p. 219, viewed sans date, .
    Résumé : The two major cytopathic factors in human immunodeficiency virus type 1 (HIV-1), the accessory proteins viral infectivity factor (Vif) and viral protein R (Vpr), inhibit cell-cycle progression at the G2 phase of the cell cycle. Although Vpr-induced blockade and the associated T-cell death have been well studied, the molecular mechanism of G2 arrest by Vif remains undefined. To elucidate how Vif induces arrest, we infected synchronized Jurkat T-cells and examined the effect of Vif on the activation of Cdk1 and CyclinB1, the chief cell-cycle factors for the G2 to M phase transition. We found that the characteristic dephosphorylation of an inhibitory phosphate on Cdk1 did not occur in infected cells expressing Vif. In addition, the nuclear translocation of Cdk1 and CyclinB1 was disregulated. Finally, Vif-induced cell cycle arrest was correlated with proviral expression of Vif. Taken together, our results suggest that Vif impairs mitotic entry by interfering with Cdk1-CyclinB1 activation.
    Mots-clés : CDC2 Protein Kinase/antagonists & inhibitors/*metabolism *Cell Cycle Cyclin B1/antagonists & inhibitors/*metabolism Hiv-1 Humans Jurkat Cells T-Lymphocytes/physiology/virology Virulence Factors/*metabolism vif Gene Products, Human Immunodeficiency Virus/*metabolism.
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  • Saliba, F 2011, « Systematic review and meta-analysis of survival following extracorporeal liver support (Br J Surg 2011; 98: 623-631) », British Journal of Surgery, vol. 98, no. 5, p. 632, viewed sans date, .
  • Saliba, F, Dharancy, S, Lorho, R, Conti, F, Radenne, S, Neau-Cransac, M, Hurtova, M, Hardwigsen, J, Calmus, Y & Dumortier, J 2011, « Conversion to everolimus in maintenance liver transplant patients: a multicenter, retrospective analysis », Liver Transpl, vol. 17, no. 8, p. 905-13.
    Résumé : Data on the conversion of patients to everolimus after liver transplantation are sparse. A multicenter, retrospective study followed 240 maintenance liver transplant patients to analyze the current indications for everolimus conversion, the employed regimens and exposure levels, and the impact on efficacy and safety. The mean time from transplantation to the introduction of everolimus was 4.9 +/- 5.2 years. The mean everolimus trough level was 7.3 +/- 4.1 ng/mL at month 1 and 8.1 +/- 4.7 ng/mL at month 12. At 12 months, 61.6% of the patients were no longer receiving calcineurin inhibitor (CNI) therapy. The mean estimated glomerular filtration rate (eGFR) according to the Cockcroft-Gault formula was 64.2 +/- 30.0 mL/minute on day 0 and 68.4 +/- 32.5 mL/minute at month 12 (P = 0.007). Among patients with baseline serum creatinine levels >/= 130 mumol/L, the eGFR values were 44.3 +/- 15.7 mL/minute on day 0 and 53.7 +/- 26.0 mL/minute at month 12 (P = 0.003). Four patients (1.6%) developed mild or moderate biopsy-proven acute rejection. Adverse events led to everolimus discontinuation in 12.9% of the patients. After the initiation of everolimus, the mean white blood cell count decreased significantly, and the total cholesterol and triglyceride levels increased significantly. In this retrospective analysis of the largest cohort of maintenance liver transplant patients analyzed after their conversion to everolimus, more than 60% of the patients were kept free of CNIs with a very low risk of acute rejection and with an acceptable safety profile. Randomized trials in which maintenance liver transplant patients are switched to everolimus in response to clinical indications or preemptively are warranted.
    Mots-clés : &, Adult, Aged, Agents/therapeutic, analogs, Biopsy, Calcineurin/antagonists, derivatives/therapeutic, Factors, Female, Filtration, Glomerular, Graft, Humans, Immunosuppressive, inhibitors, Liver, Male, methods, Middle, Outcome, Rate, Rejection, Retrospective, Risk, Sirolimus/, Studies, Time, Transplantation/, Treatment, Triglycerides/metabolism, use.
  • Samuel, D 2011, « First year and beyond », J Hepatol, vol. 54, no. 1, p. 3.
    Résumé : Samuel, Didier; Editorial; England; J Hepatol. 2011 Jan;54(1):3. doi: 10.1016/j.jhep.2010.10.001.
  • Samuel, D, Colombo, M, El-Serag, H, Sobesky, R & Heaton, N 2011, « Toward optimizing the indications for orthotopic liver transplantation in hepatocellular carcinoma », Liver Transpl, vol. 17 Suppl 2, p. S6-13.
    Résumé : KEY POINTS: 1. Liver transplantation is currently an effective therapy for patients with HCC who meet the Milan criteria. 2. The proportion of patients on waiting lists for liver transplantation who have HCC has increased substantially in recent years. HCC is currently one of the major indications for liver transplantation; it is the indication for approximately one-third of liver transplants. 3. If the Milan criteria are not met, the survival rates after liver transplantation for HCC tend to decrease, mainly because of the catastrophic consequences of HCC recurrence. 4. A few studies have supported liver transplantation when the Milan criteria are exceeded, but extensions beyond the Milan criteria remain controversial. Even if an individual patient with HCC who does not meet the Milan criteria might benefit from liver transplantation, the limited number of currently available donor organs limits the indications for liver transplantation to those patients with HCC who have the greatest likelihood of survival after the procedure. 5. To patients with early-stage HCC, surgical resection can be offered if the hepatocellular function is well maintained and severe portal hypertension is not present. 6. To enable patients with HCC to have access to liver transplantation that is similar to the access for other patients without HCC in the MELD allocation system, additional points based on the number and size of HCC lesions are assigned to patients on the waiting list. However, this system requires further refinement to ensure that it is as fair as possible. 7. Liver transplantation for HCC should be restricted to those patients who are expected to have the same posttransplant survival as that of patients with nonneoplastic end-stage chronic liver disease. 8. On the basis of these considerations, a 5-year survival rate of 50% after liver transplantation for HCC seems too low.
    Mots-clés : Carcinoma.

  • Sarmast, AH, Parray, FQ, Showkat, HI, Lone, YA & Bhat, NA 2011, « Duodenal perforation with an unusual presentation: a case report », Case Rep Infect Dis, vol. 2011, p. 512607, viewed sans date, .
    Résumé : A young female presented with classical complaints suggestive of peptic ulcer disease leading to signs of peritonitis. The said patient after being subjected to baseline workup was subjected to laparotomy which proved to be a surgical surprise. A live ascaris lumbricoides worm was seen pouting out of a duodenal perforation.
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  • Scully, CG, Karaboué, A, Liu, W-M, Meyer, J, Innominato, PF, Chon, KH, Gorbach, AM & Lévi, F 2011, « Skin surface temperature rhythms as potential circadian biomarkers for personalized chronotherapeutics in cancer patients », Interface Focus, vol. 1, p. 48-60, viewed sans date, .
    Résumé : Chronotherapeutics involve the administration of treatments according to circadian rhythms. Circadian timing of anti-cancer medications has been shown to improve treatment tolerability up to fivefold and double efficacy in experimental and clinical studies. However, the physiological and the molecular components of the circadian timing system (CTS), as well as gender, critically affect the success of a standardized chronotherapeutic schedule. In addition, a wrongly timed therapy or an excessive drug dose disrupts the CTS. Therefore, a non-invasive approach to accurately detect and monitor circadian rhythms is needed for a dynamic assessment of the CTS in order to personalize chronomodulated drug delivery schedule in cancer patients. Since core body temperature is a robust circadian biomarker, we recorded temperature at multiple locations on the skin of the upper chest and back of controls and cancer patients continuously. Variability in the circadian phase existed among patch locations in individual subjects over the course of 2-6 days, demonstrating the need to monitor multiple skin temperature locations to determine the precise circadian phase. Additionally, we observed that locations identified by infrared imaging as relatively cool had the largest 24 h temperature variations. Disruptions in skin temperature rhythms during treatment were found, pointing to the need to continually assess circadian timing and personalize chronotherapeutic schedules.
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  • Sebagh, M, Azoulay, D, Roche, B, Hoti, E, Karam, V, Teicher, E, Bonhomme-Faivre, L, Saliba, F, Duclos-Vallée, J-C & Samuel, D 2011, « Significance of isolated hepatic veno-occlusive disease/sinusoidal obstruction syndrome after liver transplantation », Liver Transpl, vol. 17, no. 7, p. 798-808, viewed sans date, .
    Résumé : After liver transplantation (LT), hepatic veno-occlusive disease (VOD), which is also known as sinusoidal obstruction syndrome (SOS), has been reported initially in relation to azathioprine use and subsequently in relation to acute rejection (AR). Isolated veno-occlusive disease (iVOD)/SOS raises some questions about its significance and especially its treatment. From the post-LT biopsy samples of 1364 patients (2000-2008), 31 patients with index biopsy samples showing VOD/SOS (2.3%) were identified. After a review of the index biopsy samples and previous biopsy samples, those patients not exposed to azathioprine therapy were subdivided into 2 groups according to the absence or presence of AR. Fifteen of the 31 patients had no previous evidence of AR, whereas 16 experienced episodes of AR (before or concurrently with VOD). The 2 groups were similar in terms of demographic and clinical data and the range of histological centrilobular changes. AR episodes were characterized by an endothelial predilection. iVOD/SOS occurred later than acute rejection-related veno-occlusive disease (AR-VOD)/SOS (mean times of 65 and 4.4 months, respectively, P = 0.0098). There was a tendency for iVOD/SOS to progress less frequently to chronic rejection in comparison with AR-VOD/SOS (3/15 versus 9/15, P = 0.06). The histological resolution of iVOD/SOS was significantly more frequent in patients who benefited from increased immunosuppression in comparison with those who did not (5/7 versus 2/8, P = 0.05). When the groups were considered together, the same result was obtained (14/18 versus 4/12, P = 0.024). In conclusion, despite a constant overall prevalence of VOD/SOS, the proportion of iVOD/SOS has increased. The histological resolution of iVOD/SOS after increase in immunosuppression suggests an immune-mediated origin. Better optimization of immunosuppression may be a curative treatment.
    Mots-clés : Adolescent, Adult, Aged, Agents/therapeutic, Biopsy, Disease/complications/, Failure/complications/, Female, Graft, Hepatic, Humans, Immunosuppressive, Liver, Male, methods, Middle, Prevalence, Prognosis, Rejection, Retrospective, Studies, surgery, Transplantation/, use, Veno-Occlusive.
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  • Sideri, A, Neokleous, N, Brunet De La Grange, P, Guerton, B, Le Bousse Kerdilles, M-C, Uzan, G, Peste-Tsilimidos, C & Gluckman, E 2011, « An overview of the progress on double umbilical cord blood transplantation », Haematologica, vol. 96, no. 8, p. 1213-20, viewed sans date, .
    Résumé : Umbilical cord blood transplantation has been increasingly used over the past years for both malignant and non-malignant hematologic and other diseases as an alternative to mismatched-related or matched-unrelated bone marrow or peripheral blood hematopoietic stem cell transplantation. A disadvantage of cord blood is its low cell content which limits cord blood transplantation to generally low weight recipients, such as children. Various alternatives have been used to overcome this limitation, including co-infusion of two partially HLA-matched cord blood units. According to Eurocord Registry data, this strategy has been applied in approximately 993 adult patients with hematologic diseases since the first double umbilical cord blood transplantation in 1999. In fact, since 2005, the number of adult patients receiving double umbilical cord blood transplantation has surpassed the number of adults transplanted with single cord blood units. The engraftment rate is comparable for both single and double umbilical cord blood transplantation, although the latter is accompanied by a higher incidence of grade II acute graft-versus-host disease and lower leukemia relapse for patients in first complete remission. In the majority of patients undergoing double umbilical cord blood transplantation, transient chimerism, due to the presence of cells from both donor units early post transplant, is replaced by sustained dominance of one unit from which long-term hematopoiesis is derived. Although the biology and the factors that determine unit dominance have not been clarified, the implication of immune-mediated mechanisms has been reported. Preliminary data have demonstrated the safety of double umbilical cord blood transplantation. Ongoing clinical trials and prolonged follow up of the patients will clarify the immunology and determine the efficacy of this approach. We present here a brief overview of the clinical experience on double umbilical cord blood transplantation and its underlying biology.
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  • Sloma, I, Beer, P, Raghuram, K, Bennaceur-Griscelli, A, Turhan, A & Eaves, C 2011, « FORCED EXPRESSION OF NUP98-HOXA9 IN PRIMARY HUMAN CHRONIC PHASE CML CELLS LEADS TO AN ACCELERATED PHASE WITHOUT PROGRESSION TO FULL BLOWN BLAST CRISIS », Experimental Hematology, vol. 39, no. 8, p. S16-S17, viewed sans date, <<Go to ISI>://WOS:000293801700036>.
    Résumé : Sloma, I. Beer, P. Raghuram, K. Bennaceur-Griscelli, A. Turhan, A. Eaves, C. 1
  • Tabaries, S, Dong, Z, Annis, MG, Omeroglu, A, Pepin, F, Ouellet, V, Russo, C, Hassanain, M, Metrakos, P, Diaz, Z, Basik, M, Bertos, N, Park, M, Guettier, C, Adam, R, Hallett, M & Siegel, PM 2011, « Claudin-2 is selectively enriched in and promotes the formation of breast cancer liver metastases through engagement of integrin complexes », Oncogene, vol. 30, no. 11, p. 1318-28.
    Résumé : The liver represents the third most frequent site of metastasis in patients with breast cancer. We performed in vivo selection using 4T1 breast cancer cells to identify genes associated with the liver metastatic phenotype. Coincident with the loss of numerous tight-junctional proteins, we observe claudin-2 overexpression, specifically in liver-aggressive breast cancer cells. We further demonstrate that claudin-2 is both necessary and sufficient for the ability of 4T1 breast cancer cells to colonize and grow in the liver. The liver-aggressive breast cancer cells display a claudin-2-mediated increase in their ability to adhere to extracellular matrix (ECM) components, such as fibronectin and type IV collagen. Claudin-2 facilitates these cell/matrix interactions by increasing the cell surface expression of alpha(2)beta(1)- and alpha(5)beta(1)-integrin complexes in breast cancer cells. Indeed, claudin-2-mediated adhesion to fibronectin and type IV collagen can be blocked with neutralizing antibodies that target alpha(5)beta(1) and alpha(2)beta(1) complexes, respectively. Immunohistochemical analyses reveal that claudin-2, although weakly expressed in primary human breast cancers, is readily detected in all liver metastasis samples examined to date. Together, these results uncover novel roles for claudin-2 in promoting breast cancer adhesion to the ECM and define its importance during breast cancer metastasis to the liver.
    Mots-clés : Breast Neoplasms/ genetics/metabolism/ pathology Cell Adhesion Cell Line.


  • Tincani, G, Hoti, E, Andreani, P, Ricca, L, Pittau, G, Vitale, V, Blandin, F, Adam, R, Castaing, D & Azoulay, D 2011, « Operative risks of domino liver transplantation for the familial amyloid polyneuropathy liver donor and recipient: a double analysis », Am J Transplant, vol. 11, no. 4, p. 759-66, viewed sans date, .
    Résumé : Although domino liver transplantation (LT) is an established procedure, data about the operative risks are limited. This study aimed at evaluating the operative risks of domino LT. Two retrospective analyses were conducted (comparison of familial amyloid polyneuropathy [FAP] liver donors [61 patients] vs. FAP nondonors [39 patients] and FAP liver recipients [61 patients] vs. deceased donor liver recipients [61 patients]). First analysis showed a 60-day mortality of 6.6% for FAP donors and 7.7% for FAP nondonors (p = 1.0). No patient developed primary graft nonfunction. Acute rejection was higher in FAP nondonors compared to FAP donors (38.5% vs. 13.1%). Both groups had similar vascular and biliary complication rates. ICU stay was similar, whereas total hospitalization was longer for FAP nondonors. Both groups had similar 1- and 5-year patient and graft survival rates (83.4% vs. 87.2%, and 79.8% vs. 71.8%, p = 0.7) and (83.3% vs. 87.2%, and 79.1% vs.71.8%, p = 0.7). The second analysis showed a 1.6% mortality for FAP liver recipients vs. 3.2% of the control group (p = 1). Both groups had similar morbidity and technical complication rates (18.0% vs. 13.1%, p = 0.45) and (0.18 vs. 0.15, p = 0.65). The domino procedure does not add any risk to FAP donor or recipient. It increases the organ pool allowing transplantation of marginal recipients who otherwise are denied deceased donor liver transplantation.
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  • Tosca, L, Brisset, S, Petit, FM, Metay, C, Latour, S, Lautier, B, Lebas, A, Druart, L, Picone, O, Mas, AE, Prevot, S, Tardieu, M, Goossens, M & Tachdjian, G 2011, « Genotype-phenotype correlation in 13q13.3-q21.3 deletion », European Journal of Medical Genetics, vol. 54, no. 5, p. E489-E494, viewed sans date, <<Go to ISI>://WOS:000293745400004>.
    Résumé : Pure interstitial deletions of the long arm of chromosome 13 are correlated with variable phenotypes according to the size and the location of the deleted region. Deletions involving the 13q13q21 region are rare. In order to establish interstitial 13q genotype-phenotype correlation, we used high resolution 244K oligonucleotide array in addition to conventional karyotype and molecular (fluorescent in situ hybridization, microsatellite markers analysis) techniques in two independent probands carrying a deletion 13q13 to 13q21. First patient was a 3-year-old girl with mental retardation and dysmorphy carrying a 13q13.3q21.31 de novo deletion diagnosed post-natally. The second one was a fetus with de novo del(13)(q14q21.2) associated with first trimester increased nuchal translucency. We showed that specific dysmorphic features (macrocephaly, high forehead, hypertelorism, large nose, large and malformed ears and retrognathia) were correlated to the common 13q14q21 chromosomal segment. Physical examination revealed overgrowth with global measurement up to the 95th percentile in both probands. This is the second description of overgrowth in patients carrying a 13q deletion. Haploinsufficiency of common candidates genes such as CKAP2, SUGT1, LECT1, DCLK1 and SMAD9, involved in cell division and bone development, is a possible mechanism that could explain overgrowth in both patients. This study underlines also that cytogenetic analysis could be performed in patients with overgrowth. (C) 2011 Elsevier Masson SAS. All rights reserved.

  • Tosca, L, Courtot, AM, Bennaceur-Griscelli, A & Tachdjian, G 2011, « In vitro production of murine and human germinal cells in pluripotent stem cells », M S-Medecine Sciences, vol. 27, no. 10, p. 866-874, viewed sans date, <<Go to ISI>://WOS:000296617000025>.
    Résumé : Tosca, Lucie Courtot, Anne-Marie Bennaceur-Griscelli, Annelise Tachdjian, Gerard

  • Tosca, L, Courtot, A-M, Bennaceur-Griscelli, A & Tachdjian, G 2011, « In vitro strategies for human gametes production from stem cells », Med Sci (Paris), vol. 27, no. 10, p. 866-74, viewed sans date, .
    Résumé : Embryonic stem cells (ESC) are self-renewal and pluripotent cells that are able to differentiate in vitro into several cell types in favourable conditions. Technical protocols for in vitro gametes production have been developed in mice and human species. The functionality of such differentiated cells is not always analysed and an early meiotic arrest is a current observation. These kinds of experimentations have also been tested from human induced pluripotent stem cells (IPSC). However, differentiation ends shortly at the primordial germ cell stage.
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  • Turhan, AG 2011, « STAT5 as a CML target: STATinib therapies? », Blood, vol. 117, no. 12, p. 3252-3253, viewed sans date, <<Go to ISI>://WOS:000288848500005>.
  • van Keimpema, L, Nevens, F, Adam, R, Porte, RJ, Fikatas, P, Becker, T, Kirkegaard, P, Metselaar, HJ & Drenth, JP 2011, « Excellent survival after liver transplantation for isolated polycystic liver disease: an European Liver Transplant Registry study », Transpl Int, vol. 24, no. 12, p. 1239-45.
    Résumé : Patients with end-stage isolated polycystic liver disease (PCLD) suffer from incapacitating symptoms because of very large liver volumes. Liver transplantation (LT) is the only curative option. This study assesses the feasibility of LT in PCLD. We used the European Liver Transplant Registry (ELTR) database to extract demographics and outcomes of 58 PCLD patients. We used Kaplan-Meier survival analysis for survival rates. Severe abdominal pain (75%) was the most prominent symptom, while portal hypertension (35%) was the most common complication in PCLD. The explantation of the polycystic liver was extremely difficult in 38% of patients, because of presence of adhesions from prior therapy (17%). Karnofsky score following LT was 90%. The 1- and 5-year graft survival rate was 94.3% and 87.5%, while patient survival rate was 94.8% and 92.3%, respectively. Survival rates after LT for PCLD are good.
    Mots-clés : Adult, Aged, Cysts/diagnosis/surgery, Diseases/diagnosis/surgery, Estimate, Europe/epidemiology, Female, Graft, Humans, Kaplan-Meier, Liver, Male, Middle, mortality/physiology, Outcome, Registries, Survival, Transplantation/, Treatment.


  • van Niel, G, Charrin, S, Simoes, S, Romao, M, Rochin, L, Saftig, P, Marks, MS, Rubinstein, E & Raposo, G 2011, « The tetraspanin CD63 regulates ESCRT-independent and -dependent endosomal sorting during melanogenesis », Dev Cell, vol. 21, no. 4, p. 708-21, viewed sans date, .
    Résumé : Cargo sorting to intraluminal vesicles (ILVs) of multivesicular endosomes is required for lysosome-related organelle (LRO) biogenesis. PMEL-a component of melanocyte LROs (melanosomes)-is sorted to ILVs in an ESCRT-independent manner, where it is proteolytically processed and assembled into functional amyloid fibrils during melanosome maturation. Here we show that the tetraspanin CD63 directly participates in ESCRT-independent sorting of the PMEL luminal domain, but not of traditional ESCRT-dependent cargoes, to ILVs. Inactivating CD63 in cell culture or in mice impairs amyloidogenesis and downstream melanosome morphogenesis. Whereas CD63 is required for normal PMEL luminal domain sorting, the disposal of the remaining PMEL transmembrane fragment requires functional ESCRTs but not CD63. In the absence of CD63, the PMEL luminal domain follows this fragment and is targeted for ESCRT-dependent degradation. Our data thus reveal a tight interplay regulated by CD63 between two distinct endosomal ILV sorting processes for a single cargo during LRO biogenesis.
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  • Vanrenterghem, Y, Bresnahan, B, Campistol, J, Durrbach, A, Grinyo, J, Neumayer, HH, Lang, P, Larsen, CP, Mancilla-Urrea, E, Pestana, JM, Block, A, Duan, T, Glicklich, A, Gujrathi, S & Vincenti, F 2011, « Belatacept-based regimens are associated with improved cardiovascular and metabolic risk factors compared with cyclosporine in kidney transplant recipients (BENEFIT and BENEFIT-EXT studies) », Transplantation, vol. 91, no. 9, p. 976-83, viewed sans date, .
    Résumé : BACKGROUND: Cardiovascular disease, the most common cause of death with a functioning graft among kidney transplant recipients, can be exacerbated by immunosuppressive drugs, particularly the calcineurin inhibitors. Belatacept, a selective co-stimulation blocker, may provide a better cardiovascular/metabolic risk profile than current immunosuppressants. METHODS: Cardiovascular and metabolic endpoints from two Phase III studies (BENEFIT and BENEFIT-EXT) of belatacept-based regimens in kidney transplant recipients were assessed at month 12. Each study assessed belatacept in more intensive (MI) and less intensive (LI) regimens versus cyclosporine A (CsA). These secondary endpoints included changes in blood pressure, changes in serum lipids, and the incidence of new-onset diabetes after transplant (NODAT). RESULTS: A total of 1209 patients were randomized and transplanted across the two studies. Mean systolic blood pressure was 6 to 9 mm Hg lower and mean diastolic blood pressure was 3 to 4 mm Hg lower in the MI and LI groups versus CsA (P </= 0.002) across both studies at month 12. Non-HDL cholesterol was lower in the belatacept groups versus CsA (P<0.01 MI or LI vs. CsA in each study). Serum triglycerides were lower in the belatacept groups versus CsA (P<0.02 MI or LI vs. CsA in each study). NODAT occurred less often in the belatacept groups versus CsA in a prespecified pooled analysis (P<0.05 MI or LI vs. CsA). CONCLUSIONS: At month 12, belatacept regimens were associated with better cardiovascular and metabolic risk profiles, with lower blood pressure and serum lipids and less NODAT versus CsA. The overall profile of belatacept will continue to be assessed over the 3-year trials.
    Mots-clés : &, *Kidney, Adult, Aged, Agents/*adverse, Blood, Cardiovascular, control, Cyclosporine/*adverse, Diabetes, Diseases/*etiology/physiopathology/prevention, effects, effects/*therapeutic, Factors, Female, Glucose/metabolism, Humans, Immunoconjugates/*adverse, Immunosuppressive, Lipids/blood, Male, Mellitus/blood/*etiology/prevention, Middle, Pressure/drug, Risk, Transplantation/adverse, use.

  • Vibert, E, Duclos-Vallée, J-C, Ghigna, M-R, Hoti, E, Salloum, C, Guettier, C, Castaing, D, Samuel, D & Adam, R 2011, « Liver transplantation for hepatocellular carcinoma: the impact of human immunodeficiency virus infection », Hepatology, vol. 53, no. 2, p. 475-82, viewed sans date, .
    Résumé : UNLABELLED: Liver transplantation (LT) has become an accepted therapy for end-stage liver disease in human immunodeficiency virus-positive (HIV+) patients, but the specific results of LT for hepatocellular carcinoma (HCC) are unknown. Between 2003 and 2008, 21 HIV+ patients and 65 HIV- patients with HCC were listed for LT at a single institution. Patient characteristics and pathological features were analyzed. Univariate analysis for overall survival (OS) and recurrence-free survival (RFS) after LT was applied to identify the impact of HIV infection. HIV+ patients were younger than HIV- patients [median age: 48 (range = 41-63 years) versus 57 years (range = 37-72 years), P < 0.001] and had a higher alpha-fetoprotein (AFP) level [median AFP level: 16 (range = 3-7154 μg/L] versus 13 μg/L (range = 1-552 μg/L), P = 0.04]. There was a trend toward a higher dropout rate among HIV+ patients (5/21, 23%) versus HIV- patients (7/65, 10%, P = 0.08). Sixteen HIV+ patients and 58 HIV- patients underwent transplantation after median waiting times of 3.5 (range = 0.5-26 months) and 2.0 months (range = 0.5-24 months, P = 0.18), respectively. No significant difference was observed in the pathological features of HCC. With median follow-up times of 27 (range = 5-74 months) and 36 months (range = 3-82 months, P = 0.40), OS after LT at 1 and 3 years reached 81% and 74% in HIV+ patients and 93% and 85% in HIV- patients, respectively (P = 0.08). RFS rates at 1 and 3 years were 69% and 69% in HIV+ patients and 89% and 84% in HIV- patients, respectively (P = 0.09). In univariate analysis, HIV status did not emerge as a prognostic factor for OS or RFS. CONCLUSION: Because of a higher dropout rate among HIV+ patients, HIV infection impaired the results of LT for HCC on an intent-to-treat basis but had no significant impact on OS and RFS after LT.
    Mots-clés : Adult Aged Carcinoma, Local Prognosis Retrospective Studies Survival Rate Treatment Outcome.
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  • Villalva, C, Martin-Lannerée, S, Cortes, U, Dkhissi, F, Wager, M, Le Corf, A, Tourani, J-M, Dusanter-Fourt, I, Turhan, AG & Karayan-Tapon, L 2011, « STAT3 is essential for the maintenance of neurosphere-initiating tumor cells in patients with glioblastomas: a potential for targeted therapy? », Int J Cancer, vol. 128, no. 4, p. 826-38, viewed sans date, .
    Résumé : Glioblastoma (GBM), the highest-grade form of gliomas, is the most frequent and the most aggressive. Recently, a subpopulation of cells with stem cells characteristics, commonly named "tumor-initiating stem cells" (TISCs) or "cancer stem cells" (CSCs) were identified in GBM. These cells were shown to be highly resistant to chemotherapeutic drugs and to ionizing radiations. Consequently, the knowledge of the signals that regulate the functions and survival of TISCs is crucial. In our work, we describe a neurosphere-initiating cell (NS-IC) assay to quantify TISC/CSCs from patients with GBM and show that these cells are tumorigenic in vivo. We demonstrate that the intracellular signal transducer and activator of transcription STAT3 is constitutively activated by phosphorylation preferentially on serine 727 in these cells. Moreover, we demonstrate that the selective inhibition of STAT3 by the chemical compound Stattic or by siRNA STAT3 abrogates TISC/CSC proliferation and NS-IC suggesting that self-renewal of GBM "stem-like" cells depends on the presence of STAT3 for their maintenance. Finally, we show that inhibition of STAT3 by Stattic sensitizes TISC/CSCs to the inhibitory action of Temozolomide with a strong synergistic effect of both drugs. Overall, these results suggest that strategies focused on STAT3 inhibition are efficient at the level of "stem-like" cells and could be of interest for therapeutic purposes in patients with malignant GBM.
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  • Wicherts, DA, de Haas, RJ, Sebagh, M, Saenz Corrales, E, Gorden, DL, Lévi, F, Paule, B, Azoulay, D, Castaing, D & Adam, R 2011, « Impact of bevacizumab on functional recovery and histology of the liver after resection of colorectal metastases », Br J Surg, vol. 98, no. 3, p. 399-407, viewed sans date, .
    Résumé : BACKGROUND: The impact of bevacizumab on functional recovery and histology of the liver was evaluated in patients undergoing hepatic resection for colorectal liver metastases (CLM) following bevacizumab treatment. METHODS: Consecutive patients who had resection of CLM between July 2005 and July 2009 following preoperative chemotherapy were identified retrospectively from a prospectively collected database. Patients who had received bevacizumab before the last chemotherapy line were excluded. Postoperative liver function and histology were compared between patients with and without bevacizumab treatment. Recorded parameters included serum prothrombin time, total bilirubin concentration, and levels of aspartate and alanine aminotransferase and γ-glutamyltransferase. RESULTS: Of 208 patients identified, 67 had received last-line bevacizumab, 44 were excluded and 97 had not received bevacizumab. Most patients in the bevacizumab group (66 per cent) received a single line of chemotherapy. Bevacizumab was most often combined with 5-flurouracil/leucovorin and irinotecan (68 per cent). The median number of bevacizumab cycles was 8·6 (range 1-34). Bevacizumab administration was stopped a median of 8 (range 3-19) weeks before surgery. There were no deaths. Postoperative morbidity occurred in 43 and 36 per cent of patients in the bevacizumab and no-bevacizumab groups respectively (P = 0·353). The mean(s.d.) degree of tumour necrosis was significantly higher in the bevacizumab group (55(27) versus 32(29) per cent; P = 0·001). Complete pathological response rates were comparable (3 versus 8 per cent; P = 0·307). Postoperative changes in functional parameters and objective signs of hepatic toxicity were similar in both groups. CONCLUSION: Preoperative administration of bevacizumab does not seem to affect functional recovery of the liver after resection of CLM. Tumour necrosis is increased following bevacizumab treatment.
    Mots-clés : 80 and over Angiogenesis Inhibitors/ therapeutic use Antibodies, Adult Aged Aged, Monoclonal, Monoclonal/ therapeutic use Antibodies.
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  • Wicherts, DA, de Haas, RJ, Andreani, P, Ariche, A, Salloum, C, Pascal, G, Castaing, D, Adam, R & Azoulay, D 2011, « Short- and long-term results of extended left hepatectomy for colorectal metastases », HPB (Oxford), vol. 13, no. 8, p. 536-43.
    Résumé : BACKGROUND: An extended left hepatectomy is a complex hepatic resection often performed for large tumours in close relationship to major hilar structures. Operative outcomes of this resection for colorectal liver metastases (CLM) remain unclear. The aim of the present study was to assess short- and long-term outcome for patients with CLM after an extended left hepatectomy. METHODS: A retrospective analysis of consecutive patients undergoing an extended left hepatectomy for CLM in a large, single-centre cohort between January 1990 and January 2006 was performed. RESULTS: Thirty-one patients (3.9%) from a consecutive series of 802 patients who had undergone hepatic resection were identified as having met the definition of an extended left hepatectomy and were included for further analysis. Maximum tumour size was more than 60 mm in 15 patients, with a median size of 67.5 mm for the total group (range: 20 to 160 mm). Twenty-six patients presented with initially unresectable metastases, related to large tumour size in 11 patients and to a close relation with major vascular structures in six patients. Preoperative chemotherapy was administered to 29 patients. Combined vascular resection was performed in five patients. The mortality rate at 90 days was zero and post-operative morbidity occurred in 17 patients. R0 and R1 resections were performed in 17 and 11 patients, respectively. Three- and 5-year overall survival was 38% and 27%, respectively. Disease-free survival was 9% and 4% at 3 and 5 years. Morbidity did not differ between patients with and without a caudate lobectomy (9 of 17 patients vs. 8 of 14 patients, respectively) (P= 0.815). CONCLUSIONS: An extended left hepatectomy for CLM can provide significant long-term survival. However, morbidity is increased in this complex procedure. A caudate lobectomy does not impact surgical outcome.
    Mots-clés : Adult Aged Chemotherapy.
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    <p>3163275</p>


  • Wicherts, DA, de Haas, RJ, Sebagh, M, Ciacio, O, Lévi, F, Paule, B, Giacchetti, S, Guettier, C, Azoulay, D, Castaing, D & Adam, R 2011, « Regenerative nodular hyperplasia of the liver related to chemotherapy: impact on outcome of liver surgery for colorectal metastases », Ann Surg Oncol, vol. 18, no. 3, p. 659-69, viewed sans date, .
    Résumé : BACKGROUND: Regenerative nodular hyperplasia (RNH) represents the end-stage of vascular lesions of the liver induced by chemotherapy. The goal was to evaluate its incidence and impact on the outcome of patients resected for colorectal liver metastases (CLM). METHODS: Patients who underwent hepatectomy for CLM after six cycles or more of first-line chemotherapy, between January 1990 and November 2006, were included. Detailed histopathologic analysis of the nontumoral liver was performed according to a standard format. RESULTS: From a cohort of 856 resected patients at our institution, 771 (90%) received preoperative chemotherapy. Of these, 146 fulfilled the selection criteria and were included: 24 (16%) received 5-fluorouracil (5-FU) and leucovorin (LV) alone, 92 (63%) had 5-FU/LV and oxaliplatin, 18 (12%) had 5-FU/LV and irinotecan, and 12 (8%) were treated by 5-FU/LV, oxaliplatin, and irinotecan. RNH occurred in 22 of 146 patients (15%). Twenty of these patients (91%) received oxaliplatin, of whom six (30%) had chronomodulated therapy. Patients treated by oxaliplatin more often had RNH compared with oxaliplatin-naïve patients (22 vs. 4%). Although operative mortality was nil, the presence of RNH was associated with increased postoperative hepatic morbidity (50 vs. 29%). Elevated preoperative gamma-glutamyltransferase (GGT) (>80 U/L; >1N) and total bilirubin levels (>15 μmol/L; >1N) were independent predictors of RNH. CONCLUSIONS: Patients with CLM who receive preoperative oxaliplatin have an increased risk of RNH and associated postoperative morbidity. Increased serum GGT and bilirubin are useful markers to predict the presence of RNH.
    Mots-clés : &, Adult, adverse, Aged, Antineoplastic, Camptothecin/administration, chemically, Chemotherapy, Colorectal, Combined, Compounds/administration, derivatives, dosage, dosage/analogs, effects, Female, Fluorouracil/administration, Focal, Humans, Hyperplasia/, induced/, Leucovorin/administration, Liver, Male, Middle, Modality, Neoplasms/drug, Nodular, Organoplatinum, Outcome, pathology, Protocols/, Rate, surgery, Survival, Therapy, therapy/pathology/, therapy/secondary/, Treatment.
    Note Note
    <p>3044234</p>
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    <p>20976564</p>
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    <p>3044234</p>
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    <p>20976564</p>
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    <p>3044234</p>
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    <p>20976564</p>
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    <p>20976564</p>
  • Yousef, I, Breard, J, SidAhmed-Adrar, N, Maamer-Azzabi, A, Marchal, C, Dumas, P & Le Naour, F 2011, « Infrared spectral signatures of CDCP1-induced effects in colon carcinoma cells », Analyst, vol. 136, no. 24, p. 5162-8.
    Résumé : Metastasis is the major cause of death by cancer. Indeed, metastatic colonies can reactivate and become life threatening, sometimes months or years after the initial diagnosis and surgery of the primary tumor. Therefore, there is a crucial need to develop methods for diagnosis of tumor cells that exhibit high metastatic potential. Here, we addressed the capability of vibrational spectroscopy for investigating the effects induced by CDCP1 expression in colon carcinoma cells. This transmembrane protein has been suggested to play a key role in metastasis by its pleiotropic function. We focused on a cellular model constituted by the cell lines SW480 and SW620 derived respectively from the primary tumor and a lymph node metastasis of the same patient. Induced CDCP1 expression in SW480 led to marked changes in cell morphology. Whereas SW480 form a cell layer, the SW480/CDCP1 cells exhibited reduced cell-to-cell contact. On collagen I, SW480 was more spread and filopodia were observed. In contrast, SW480/CDCP1 cells exhibited lower spreading with no formation of filopodia. Synchrotron Fourier transform infrared microspectroscopy experiments were performed on this cellular model. High quality spectroscopic information at sub-cellular resolution, provided by the use of the synchrotron source in infrared microspectroscopy, was recorded on numerous individual cells. Multivariate analysis of spectra recorded using principal component analysis indicated a highest intensity increase of the 970 and 1080 cm(-1) bands, and a modest intensity increase of the 1240 cm(-1) band in the SW480/CDCP1 cells. These bands were correlated with an increased content of phosphorylated proteins as confirmed by in situ labelling using a monoclonal antibody directed against phosphorylated tyrosines. Altogether, these results demonstrate that the vibrational technique used in this study exhibits the capability to characterize spectral signatures of CDCP1-induced effects in colon carcinoma cells. This study may open new avenues for rapid diagnosis of cells with a metastatic potential.
    Mots-clés : Antibodies, CD/ metabolism Blotting, Confocal Neoplasm Proteins/ metabolism Phosphorylation Principal Component Analysis Spectroscopy, Fourier Transform Infrared, Monoclonal/immunology Antigens, Tumor Collagen Type I/metabolism Colonic Neoplasms Humans Microscopy, Western Cell Adhesion Molecules/ metabolism Cell Line.

  • Zalinski, S, Mariette, C & Farges, O 2011, « Management of patients with synchronous liver metastases of colorectal cancer. Clinical practice guidelines. Guidelines of the French society of gastrointestinal surgery (SFCD) and of the association of hepatobiliary surgery and liver transplantation (ACHBT). Short version », J Visc Surg, vol. 148, no. 3, p. e171-82, viewed sans date, .
    Résumé : Zalinski, S; Mariette, C; Farges, O; SFCD-ACHBT evaluation committee : A. Alves, I. Baum-gaertner, C. Cabral, J. Carles, C. Diana, O. Dubreuil, D. Fuks, D. Goere, M. Karoui, J. Lefevre, P. Pessaux, G. Schmidt, O. Turrini, E. Vibert, J-C. Weber; French Society of Gastrointestinal Surgery (SFCD); Association of Hepatobiliary Surgery and Liver Transplantation (ACHBT); France; J Visc Surg. 2011 Jun;148(3):e171-82. doi: 10.1016/j.jviscsurg.2011.05.015. Epub 2011 Jun 24.
  • Zhang, X, Ryu, SH, Xu, Y, Elbaz, T, Zekri, AR, Abdelaziz, AO, Abdel-Hamid, M, Thiers, V, Elena, SF, Fan, X & Di Bisceglie, AM 2011, « The Core/E1 domain of hepatitis C virus genotype 4a in Egypt does not contain viral mutations or strains specific for hepatocellular carcinoma », J Clin Virol, vol. 52, no. 4, p. 333-8.
    Résumé : BACKGROUND: Hepatitis C virus (HCV) infection is a well-documented etiological factor for hepatocellular carcinoma (HCC). As HCV shows remarkable genetic diversity, an interesting and important issue is whether such a high viral genetic diversity plays a role in the incidence of HCC. Prior data on this subject are conflicting. OBJECTIVES: Potential association between HCV genetic mutations or strain variability and HCC incidence has been examined through a comparative genetic analysis merely focused on a single HCV subtype (genotype 4a) in a single country (Egypt). STUDY DESIGN: The study focused on three HCV sequence datasets with explicit sampling dates and disease patterns. An overlapping HCV Core/E1 domain from three datasets was used as the target for comparative analysis through genetic and phylogenetic approaches. RESULTS: Based on partial Core/E1 domain (387 bp), genetic and phylogenetic analysis did not identify any HCC-specific viral mutations and strains, respectively. CONCLUSIONS: The Core/E1 domain of HCV genotype 4a in Egypt does not contain HCC-specific mutations or strains. Additionally, sequence errors resulting from the polymerase chain reaction, together with a strong evolutionary pressure on HCV in patients with end-stage liver disease, have significant potential to bias data generation and interpretation.
    Mots-clés : Carcinoma, DNA Viral Core Proteins/ genetics Viral Envelope Proteins/ genetics, Hepatocellular/ epidemiology/ virology Egypt/epidemiology Genetic Variation Genotype Hepacivirus/classification/ genetics/isolation & purification/pathogenicity Humans Molecular Sequence Data Mutation RNA, Viral/genetics Sequence Analysis.
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    <p>3217131</p>

2010


  • Adam, R, Frilling, A, Elias, D, Laurent, C, Ramos, E, Capussotti, L, Poston, GJ, Wicherts, DA, de Haas, RJ & Centres, LMS 2010, « Liver resection of colorectal metastases in elderly patients », Br J Surg, vol. 97, no. 3, p. 366-76, viewed sans date, .
    Résumé : BACKGROUND: This study evaluated the outcome of liver surgery for colorectal metastases (CLM) in patients over 70 years old in a large international multicentre cohort. METHODS: Among 7764 patients who had resection of CLM, 999 (12.9 per cent) were aged 70-75 years, 468 (6.0 per cent) were aged 75-80 years and 157 (2.0 per cent) were at least 80 years old. Elderly patients were compared with the younger population. RESULTS: Multinodular and bilateral metastases were less common in elderly than in younger patients (P < 0.001). Preoperative chemotherapy was used less frequently and more limited surgery was performed (P < 0.001). Sixty-day postoperative mortality and morbidity rates were 3.8 and 32.3 per cent respectively, compared with 1.6 and 28.7 per cent in younger patients (both P < 0.001). Three-year overall survival was 57.1 per cent in elderly and 60.2 per cent in younger patients (P < 0.001), and was similar among patients aged 70-75, 75-80 or at least 80 years (57.8, 55.3 and 54.1 per cent respectively; P = 0.160). Independent predictors of survival were more than three metastases, bilateral metastases, concomitant extrahepatic disease and no postoperative chemotherapy. CONCLUSION: Liver resection for CLM in elderly patients can achieve a reasonable 3-year survival rate, with an acceptable morbidity rate. There should be no upper age limit but risk factors may help predict potential benefit.
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  • Adam, R, Haller, DG, Poston, G, Raoul, J-L, Spano, J-P, Tabernero, J & Van Cutsem, E 2010, « Toward optimized front-line therapeutic strategies in patients with metastatic colorectal cancer–an expert review from the International Congress on Anti-Cancer Treatment (ICACT) 2009 », Ann Oncol, vol. 21, no. 8, p. 1579-84, viewed sans date, .
    Résumé : Metastatic colorectal cancer is a particularly frequent and severe cancer. Patients die mainly from metastatic disease; however, the survival of these patients has dramatically improved with the progress in chemotherapeutic regimens as new routes of administration and introduction of more potent cytotoxic agents administered in sequential 5-FU-folinic acid-irinotecan/5-FU-folinic acid-oxaliplatine strategies. Biologic therapies have been also developed targeting two different pathways, angiogenesis and the epidermal growth factor receptor. Their combination with chemotherapy leads to improved progression-free survival and overall survival in some cases as the addition of cetuximab in wild-type K-Ras tumors. The objectives of this expert conference were to review the different options, the available prognostic or predictive factors to optimally guide the treatment.
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    <p>20219759</p>
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  • Adam, R, Bhangui, P, Poston, G, Mirza, D, Nuzzo, G, Barroso, E, Ijzermans, J, Hubert, C, Ruers, T, Capussotti, L, Ouellet, J-F, Laurent, C, Cugat, E, Colombo, PE & Milicevic, M 2010, « Is perioperative chemotherapy useful for solitary, metachronous, colorectal liver metastases? », Ann Surg, vol. 252, no. 5, p. 774-87, viewed sans date, .
    Résumé : BACKGROUND: Chemotherapy is increasingly used in colorectal liver metastases (CRLMs) even when they are initially resectable. The aim of our study was to address the still pending question of whether perioperative chemotherapy is really beneficial in patients developing solitary metastases at a distance from surgery of the primary. METHODS: We analyzed a multicentric cohort of 1471 patients resected for solitary, metachronous, primarily resectable CRLMs without extrahepatic disease in the LiverMetSurvey International Registry over a 15-year period. Patients who received at least 3 cycles of oxaliplatin- or irinotecan-based chemotherapy before liver surgery (group CS, n = 169) were compared with those who were resected upfront (group S, n = 1302). RESULTS: Patients of group CS were more frequently females (49% vs 36%, P = 0.001) and had larger metastases (≥5 cm, 33% vs 23%, P = 0.007); no difference was observed with regard to age, site of the primary tumour, time delay to occurrence of metastases, and carcinoembryonic antigen (CEA) levels at the time of diagnosis in the 2 groups. The rate of postoperative complications was significantly higher in group CS (37.2% vs 24% in group S, P = 0.006). At univariate analysis, preoperative chemotherapy did not impact the overall survival (OS) (60% at 5 years in both groups); however, postoperative chemotherapy was associated with better OS (65% vs 55% at 5 years, P < 0.01). At multivariate analysis, age 70 years or older (P = 0.05), lymph node positivity in the primary tumor (P = 0.02), a primary-to-metastases time delay of less than 12 months (P = 0.04), raised CEA levels of more than 5 ng/mL at diagnosis (P < 0.01), a tumor diameter of 5 cm or more (P < 0.01), noncurative liver resection (P < 0.01), and the absence of postoperative chemotherapy (P < 0.01) were independent prognostic factors of survival. The disease-free survival (DFS) was negatively influenced by CEA level of more than 5 ng/mL (P < 0.01), size of the metastases 5 cm or more (P = 0.05), and the absence of postoperative chemotherapy (P < 0.01). When patients with metastases of less than 5 cm in size were compared to those with metastases of size 5 cm or more, preoperative chemotherapy did not influence the OS or DFS in either group. Postoperative chemotherapy, on the other hand, improved OS and DFS in patients with metastases of size 5 cm or more but not in patients with metastases of less than 5 cm in size. CONCLUSIONS: Although preoperative chemotherapy does not seem to benefit the outcome of patients with solitary, metachronous CRLM, postoperative chemotherapy is associated with better OS and DFS, mainly when the tumor diameter exceeds 5 cm.
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  • Adam, R, Hoti, E & Bredt, LC 2010, « Evolution of neoadjuvant therapy for extended hepatic metastases–have we reached our (non-resectable) limit? », J Surg Oncol, vol. 102, no. 8, p. 922-31, viewed sans date, .
    Résumé : Surgical resection offers the best chance for cure in patients with colorectal liver metastases; however, only 15-25% of them can benefit from surgery. To increase resectability a number of strategies have been developed in different fields including chemotherapy, surgery, and radiology. Bringing them together into an integrated framework has expanded the number of patients that can be treated with curative intent. This review focuses on recent oncosurgical changes, their impact, and future directions.
    Note Note
    <p>21165994</p>
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    <p>21165994</p>
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    <p>21165994</p>
  • Adams, D, Slama, M & Samuel, D 2010, « [Liver transplantation for familial amyloid polyneuropathy] », Presse Med, vol. 39, no. 1, p. 17-25.
    Résumé : Familial amyloid polyneuropathy (FAP) is the most serious of the hereditary neuropathies in adults and is due to endoneurial amyloid deposits. These sensorimotor and autonomic diseases are very progressive and disabling. A "typical" patient with FAP is 30-years-old, of Portuguese origin, and has insidiously developed pains or sensory loss in the feet and digestive disorders, such as diarrhea, and has lost weight. Clinical examination shows sensory polyneuropathy of the distal small fibers (with sensory loss prevailing over sensations of temperature and pain). Cardiac disorders are frequent. One parent will have died prematurely from this disease. FAP are fatal 10.8 years after the first symptoms, on average. Neuropathy is usually associated with cardiac manifestations, weight loss, and more rarely renal or eye complications. FAP are secondary to a point mutation of the transthyretin (TTR) or prealbumin gene (18q11.2-q12.1), of which there are 40 variants. In France, the variant TTRMet30 is present in half of all cases and one third of FAP patients present with sporadic disease. Liver transplantation has been proposed as a treatment for FAP because the liver is the main source of variant amyloidogenic TTR. Transplantation makes it possible to eliminate 98% of the variant TTR in the serum, doubles median survival for variant TTRMet30 carriers, and halts the progress of the sensorimotor neuropathy over the long term in 62% of cases. No regression or recurrence has been observed. Poor prognostic factors after liver transplantation are a mutation other than the TTRMet30 variant, severe neuropathy, and late onset. Liver transplantation must be proposed to the symptomatic patients as early as possible. It should be performed in a center specialized in FAP. After LT, periodic follow-up in such a center is essential.
    Mots-clés : Adult Amyloid Neuropathies, Familial/complications/diagnosis/genetics/ surgery Disease Progression Heart Diseases/etiology Humans Liver Transplantation/contraindications Point Mutation Prealbumin/genetics Preoperative Care Prognosis.

  • Aggoune, D, Bertrand, A, Bonnet, ML, Le Corf, A, Girerd, S, Dkhissi, F, Sorel, N, Chomel, JC, Bennaceur-Griscelli, A & Turhan, AG 2010, « T315I Mutation INCREASES the GENOMIC Instability and the Mutator Phenotype IN BCR-ABL-Expressing LEUKEMIC CELLS », Blood, vol. 116, no. 21, p. 1378-1378, viewed sans date, <<Go to ISI>://WOS:000289662203696>.
    Résumé : Aggoune, Djamel Bertrand, Angelina Bonnet, Marie Laure Le Corf, Amelie Girerd, Sandrine Dkhissi, Fatima Sorel, Nathalie Chomel, Jean-Claude Bennaceur-Griscelli, Annelise Turhan, Ali G. 52nd Annual Meeting of the American-Society-of-Hematology (ASH) Dec 04-07, 2010 Orlando, FL Amer Soc Hematol

  • Ahowesso, C, Piccolo, E, Li, XM, Dulong, S, Hossard, V, La Sorda, R, Filipski, E, Tinari, N, Delaunay, F, Iacobelli, S & Lévi, F 2010, « Relations between strain and gender dependencies of irinotecan toxicity and UGT1A1, CES2 and TOP1 expressions in mice », Toxicol Lett, vol. 192, no. 3, p. 395-401, viewed sans date, .
    Résumé : Irinotecan hydrochloride (CPT-11) can display severe toxicities in individual cancer patients. CPT-11 is bio-activated through CES, detoxified through UGT1A1 and inhibits TOP1. CPT-11 toxicity and UGT1A1, CES2 and TOP1 mRNAs and UGT1A1 protein were determined in male and female C57BL/6, B6D2F1 and B6CBAF1, as potential models for tailoring CPT-11 delivery. CPT-11 was administered intravenously (40-90 mg/kg/day for 4 days at 7h after light onset). The relations between dose and lethal toxicity or body weight loss were steep and similar in C57BL/6 (lethality, p=0.001; weight loss, p=0.002) and B6D2F1 (p=0.01; p=0.03, respectively), but weak in B6CBAF1. Females displayed less toxicity than males (p<0.001). Mean mRNA expression of UGT1A1 was highest in B6CBAF1 (p=0.039) and in females (p<0.001). Both CES2 and TOP1 varied according to strain and gender (p<0.001). The three gene expression data explained the most severe toxicity of CPT-11 in male B6D2F1, but displayed inconsistent relations with toxicity in the other groups. Mean UGT1A1 protein expression was highest in males as compared to females, and so by approximately 8-fold in C57BL/6 as compared to B6D2F1 (p<0.0001). Genetic background and gender significantly altered the molecular prediction of irinotecan toxicity by UGT1A1, CES2 and TOP1 mRNA expressions.
    Note Note
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  • Andreani, P, Hoti, E, de la Serna, S, degli Esposti, D, Sebagh, M, Lemoine, A, Ichai, P, Saliba, F, Castaing, D & Azoulay, D 2010, « Ischaemic preconditioning of the graft in adult living related right lobe liver transplantation: impact on ischaemia-reperfusion injury and clinical relevance », HPB (Oxford), vol. 12, no. 7, p. 439-46, viewed sans date, .
    Résumé : BACKGROUND: Ischaemic preconditioning (IPC) of the right liver graft in the donor has not been studied in adult-to-adult living related liver transplantation (LRLT). OBJECTIVE: To assess the IPC effect of the graft on ischaemia reperfusion injury in the recipient and compare recipient and donor outcomes with and without preconditioned grafts. PATIENTS AND METHODS: Alternate patients were transplanted with right lobe grafts that were (n = 22; Group (Precond)) or were not (n = 22; Group (Control)) subjected to IPC in the living donor. Liver ischaemia-reperfusion injury, liver/kidney function, morbidity/mortality rates and outcomes were compared. Univariate and multivariate analyses were performed to identify factors predictive of the aspartate aminotransferase (AST) peak and minimum prothrombin time. RESULTS: Both groups had similar length of hospital stay, morbidity/mortality, primary non-function and acute rejection rates. Post-operative AST (P = 0.8) and alanine aminotransferase (ALT) peaks (P = 0.6) were similar in both groups (307 +/- 189 and 437 +/- 302 vs. 290 +/- 146 and 496 +/- 343, respectively). In univariate analysis, only pre-operative AST and warm ischemia time (WIT) were significantly associated with post-operative AST peak (in recipients). In multivariate analysis, the graft/recipient weight ratio (P = 0.003) and pre-operative bilirubin concentration (P = 0.004) were significantly predictive of minimum prothrombin time post-transplantation. CONCLUSIONS: Graft IPC in the living related donor is not associated with any benefit for the recipient or the donor and its clinical value remains uncertain.
    Mots-clés : &, *Ischemic, *Liver, *Living, *Warm, Adult, Aged, Aminotransferases/blood, Aspartate, Assessment, Biological, Biopsy, Blood, Coagulation, control, Donors, effects, effects/mortality, Estimate, Factors, Female, France, Humans, Injury/blood/etiology/mortality/*prevention, Ischemia/adverse, Kaplan-Meier, Length, Male, Markers/blood, Middle, of, Outcome, Preconditioning/adverse, Prospective, Prothrombin, Rate, Reperfusion, Risk, Stay, Studies, Survival, Time, Transplantation/adverse, Treatment.
    Note Note
    <p>3030752</p>
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  • Ayouaz, A, Schertzer, M, Oudhrihi, N, Yates, F, Magniez, A, Feraud, O, Vallejo, JAL & Bennaceur-Griscelli, AL 2010, « Following Telomeres After Cell Reprogramming and Differentiation of iPS Cells », Human Gene Therapy, vol. 21, no. 6, p. 775-775, viewed sans date, <<Go to ISI>://WOS:000278472300046>.
    Résumé : Ayouaz, Ali Schertzer, M. Oudhrihi, N. Yates, F. Magniez, A. Feraud, O. Vallejo, Londono J. A. Bennaceur-Griscelli, A. L. 9th Annual Congress of the French-Society-of-Cell-and-Gene-Therapy Jun 13-15, 2010 Paris, FRANCE French Soc Cell & Gene Therapy

  • Azzi, S, Parissi, V, Maroun, RG, Eid, P, Mauffret, O & Fermandjian, S 2010, « The HIV-1 integrase alpha4-helix involved in LTR-DNA recognition is also a highly antigenic peptide element », PLoS One, vol. 5, no. 12, p. e16001, viewed sans date, .
    Résumé : Monoclonal antibodies (MAbas) constitute remarkable tools to analyze the relationship between the structure and the function of a protein. By immunizing a mouse with a 29mer peptide (K159) formed by residues 147 to 175 of the HIV-1 integrase (IN), we obtained a monoclonal antibody (MAba4) recognizing an epitope lying in the N-terminal portion of K159 (residues 147-166 of IN). The boundaries of the epitope were determined in ELISA assays using peptide truncation and amino acid substitutions. The epitope in K159 or as a free peptide (pep-a4) was mostly a random coil in solution, while in the CCD (catalytic core domain) crystal, the homologous segment displayed an amphipathic helix structure (alpha4-helix) at the protein surface. Despite this conformational difference, a strong antigenic crossreactivity was observed between pep-a4 and the protein segment, as well as K156, a stabilized analogue of pep-a4 constrained into helix by seven helicogenic mutations, most of them involving hydrophobic residues. We concluded that the epitope is freely accessible to the antibody inside the protein and that its recognition by the antibody is not influenced by the conformation of its backbone and the chemistry of amino acids submitted to helicogenic mutations. In contrast, the AA –>Glu mutations of the hydrophilic residues Gln148, Lys156 and Lys159, known for their interactions with LTRs (long terminal repeats) and inhibitors (5CITEP, for instance), significantly impaired the binding of K156 to the antibody. Moreover, we found that in competition ELISAs, the processed and unprocessed LTR oligonucleotides interfered with the binding of MAba4 to IN and K156, confirming that the IN alpha4-helix uses common residues to interact with the DNA target and the MAba4 antibody. This also explains why, in our standard in vitro concerted integration assays, MAba4 strongly impaired the IN enzymatic activity.
    Mots-clés : Antibodies/chemistry Antibodies.
    Note Note
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  • Baran-Marszak, F, Magdoud, H, Desterke, C, Alvarado, A, Roger, C, Harel, S, Mazoyer, E, Cassinat, B, Chevret, S, Tonetti, C, Giraudier, S, Fenaux, P, Cymbalista, F, Varin-Blank, N, Le Bousse-Kerdilès, M-C, Kiladjian, J-J & Velazquez, L 2010, « Expression level and differential JAK2-V617F-binding of the adaptor protein Lnk regulates JAK2-mediated signals in myeloproliferative neoplasms », Blood, vol. 116, no. 26, p. 5961-71, viewed sans date, .
    Résumé : Activating mutations in signaling molecules, such as JAK2-V617F, have been associated with myeloproliferative neoplasms (MPNs). Mice lacking the inhibitory adaptor protein Lnk display deregulation of thrombopoietin/thrombopoietin receptor signaling pathways and exhibit similar myeloproliferative characteristics to those found in MPN patients, suggesting a role for Lnk in the molecular pathogenesis of these diseases. Here, we showed that LNK levels are up-regulated and correlate with an increase in the JAK2-V617F mutant allele burden in MPN patients. Using megakaryocytic cells, we demonstrated that Lnk expression is regulated by the TPO-signaling pathway, thus indicating an important negative control loop in these cells. Analysis of platelets derived from MPN patients and megakaryocytic cell lines showed that Lnk can interact with JAK2-WT and V617F through its SH2 domain, but also through an unrevealed JAK2-binding site within its N-terminal region. In addition, the presence of the V617F mutation causes a tighter association with Lnk. Finally, we found that the expression level of the Lnk protein can modulate JAK2-V617F-dependent cell proliferation and that its different domains contribute to the inhibition of multilineage and megakaryocytic progenitor cell growth in vitro. Together, our results indicate that changes in Lnk expression and JAK2-V617F-binding regulate JAK2-mediated signals in MPNs.
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  • Bayard, F, Malmassari, S, Deng, Q, Lone, YC & Michel, ML 2010, « Hepatitis B virus (HBV)-derived DRB1*0101-restricted CD4 T-cell epitopes help in the development of HBV-specific CD8+ T cells in vivo », Vaccine, vol. 28, no. 22, p. 3818-26, viewed sans date, .
    Résumé : We previously identified two HLA-DRB1*0101-restricted epitopes in hepatitis B virus (HBV) X protein (HBx) and in HBV envelope proteins (preS2). To evaluated their help in the development of CD8+ T-cell responses, mice transgenic for human class I and class II HLA molecules were immunized with HBV-T helper constructs. The preS2 epitope favored a well-balanced response with CD4+ and CD8+ T cells producing IFN-gamma, IL-2 and TNF-alpha. The response was focused on CD8+ T cells with the HBx epitope. Fine characterization of helper activities may meet clinical needs in terms of enhancing the potency of preventive or therapeutic polyepitope vaccines.
    Mots-clés : Animals CD4-Positive T-Lymphocytes/immunology CD8-Positive T-Lymphocytes/*immunology Epitopes, Transgenic Protein Precursors/immunology Tumor Necrosis Factor-alpha/immunology.


  • Beck, L, Leroy, C, Beck-Cormier, S, Forand, A, Salaun, C, Paris, N, Bernier, A, Urena-Torres, P, Prie, D, Ollero, M, Coulombel, L & Friedlander, G 2010, « The Phosphate Transporter PiT1 (Slc20a1) Revealed As a New Essential Gene for Mouse Liver Development », Plos One, vol. 5, no. 2, viewed sans date, <<Go to ISI>://WOS:000274442700012>.
    Résumé : Background: PiT1 (or SLC20a1) encodes a widely expressed plasma membrane protein functioning as a high-affinity Na(+)-phosphate (Pi) cotransporter. As such, PiT1 is often considered as a ubiquitous supplier of Pi for cellular needs regardless of the lack of experimental data. Although the importance of PiT1 in mineralizing processes have been demonstrated in vitro in osteoblasts, chondrocytes and vascular smooth muscle cells, in vivo evidence is missing. Methodology/Principal Findings: To determine the in vivo function of PiT1, we generated an allelic series of PiT1 mutations in mice by combination of wild-type, hypomorphic and null PiT1 alleles expressing from 100% to 0% of PiT1. In this report we show that complete deletion of PiT1 results in embryonic lethality at E12.5. PiT1-deficient embryos display severely hypoplastic fetal livers and subsequent reduced hematopoiesis resulting in embryonic death from anemia. We show that the anemia is not due to placental, yolk sac or vascular defects and that hematopoietic progenitors have no cell-autonomous defects in proliferation and differentiation. In contrast, mutant fetal livers display decreased proliferation and massive apoptosis. Animals carrying two copies of hypomorphic PiT1 alleles (resulting in 15% PiT1 expression comparing to wild-type animals) survive at birth but are growth-retarded and anemic. The combination of both hypomorphic and null alleles in heterozygous compounds results in late embryonic lethality (E14.5-E16.5) with phenotypic features intermediate between null and hypomorphic mice. In the three mouse lines generated we could not evidence defects in early skeleton formation. Conclusion/Significance: This work is the first to illustrate a specific in vivo role for PiT1 by uncovering it as being a critical gene for normal developmental liver growth.

  • Benderitter, M, Gourmelon, P, Bey, E, Chapel, A, Clairand, I, Prat, M & Lataillade, JJ 2010, « New emerging concepts in the medical management of local radiation injury », Health Phys, vol. 98, no. 6, p. 851-7, viewed sans date, .
    Résumé : Treatment of severe radiation burns remains a difficult medical challenge. The response of the skin to ionizing radiation results in a range of clinical manifestations. The most severe manifestations are highly invalidating. Although several therapeutic strategies (excision, skin grafting, skin or muscle flaps) have been used with some success, none have proven entirely satisfying. The concept that stem cell injections could be used for reducing normal tissue injury has been discussed for a number of years. Mesenchymal stem cells therapy may be a promising therapeutic approach for improving radiation-induced skin and muscle damages. Pre-clinical and clinical benefit of mesenchymal stem cell injection for ulcerated skin and muscle restoration after high dose radiation exposure has been successfully demonstrated. Three first patients suffering from severe radiological syndrome were successfully treated in France based on autologous human grade mesenchymal stem cell injection combined to plastic surgery or skin graft. Stem cell therapy has to be improved to the point that hospitals can put safe, efficient, and reliable clinical protocols into practice.
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  • Bey, E, Doucet, C, Duhamel, P, Brachet, M, Prat, M, Bargues, L, Amabile, J-C, Gourmelon, P & Lataillade, J-J 2010, « [Radiation burn "innovating therapeutic approach"] », Ann Chir Plast Esthet, vol. 55, no. 5, p. 354-62, viewed sans date, .
    Résumé : Radiation burn is a determinist effect of localized irradiation. The lesion is in good correlation with absorbed dose. Radiation burn is different from thermal burn. The evolution is spatiotemporal unpredictable with successive inflammatory waves and recurrence of necrosis. The conventional surgical treatment is rarely efficient because each surgical operative act seems to stimulate the inflammatory waves and fibro-necrosis process. The lesion can escape to this conventional surgical treatment. The new therapeutic approach combines surgery and cellular therapy with local administration of autologous mesenchymal stem cells. From 5 years, cell therapy have been an adjuvant treatment of surgery. This association is a therapeutic innovation, it's now the recommendation for conservative surgery of this very serious radiation burn.
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  • Bey, E, Prat, M, Duhamel, P, Benderitter, M, Brachet, M, Trompier, F, Battaglini, P, Ernou, I, Boutin, L, Gourven, M, Tissedre, F, Créa, S, Mansour, CA, de Revel, T, Carsin, H, Gourmelon, P & Lataillade, J-J 2010, « Emerging therapy for improving wound repair of severe radiation burns using local bone marrow-derived stem cell administrations », Wound Repair Regen, vol. 18, no. 1, p. 50-8, viewed sans date, .
    Résumé : The therapeutic management of severe radiation burns remains a challenging issue today. Conventional surgical treatment including excision, skin autograft, or flap often fails to prevent unpredictable and uncontrolled extension of the radiation-induced necrotic process. In a recent very severe accidental radiation burn, we demonstrated the efficiency of a new therapeutic approach combining surgery and local cellular therapy using autologous mesenchymal stem cells (MSC), and we confirmed the crucial place of the dose assessment in this medical management. The patient presented a very significant radiation lesion located on the arm, which was first treated by several surgical procedures: iterative excisions, skin graft, latissimus muscle dorsi flap, and forearm radial flap. This conventional surgical therapy was unfortunately inefficient, leading to the use of an innovative cell therapy strategy. Autologous MSC were obtained from three bone marrow collections and were expanded according to a clinical-grade protocol using platelet-derived growth factors. A total of five local MSC administrations were performed in combination with skin autograft. After iterative local MSC administrations, the clinical evolution was favorable and no recurrence of radiation inflammatory waves occurred during the patient's 8-month follow-up. The benefit of this local cell therapy could be linked to the "drug cell" activity of MSC by modulating the radiation inflammatory processes, as suggested by the decrease in the C-reactive protein level observed after each MSC administration. The success of this combined treatment leads to new prospects in the medical management of severe radiation burns and more widely in the improvement of wound repair.
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