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Bonnardot L.,University of Nantes | Bardet E.,Center Regional Of Lutte Contre Le Cancer | Steichen O.,University Pierre and Marie Curie | Cassagnau E.,University of Nantes | And 7 more authors.
Head and Neck | Year: 2011

Background The aim of this study was to identify factors predicting poor prognosis at the time of early oral tongue carcinoma diagnosis. Methods A retrospective cohort study was carried out on 70 patients with T1 or T2 squamous cell carcinoma of the mobile tongue treated with primary surgical treatment. Results In all, 47% of patients received adjuvant treatment. Local recurrence was observed in 29% and regional recurrence in 26%. With a median follow-up of 7.3 years for living patients, 5-year actuarial overall, disease-specific, and disease-free survival rates were 48%, 61%, and 42%, respectively. The presence of poor histological differentiation increased the overall risk of death. Tumor thickness and posterior lingual location independently increased overall and disease-specific risk of death. Concurrent or previous diagnosis of oral lichen significantly increased the risk of disease-specific death and disease recurrence. Conclusions This study corroborates several known prognostic factors and indicates that diagnosis of oral lichen planus may be a risk factor for disease recurrence. © 2010 Wiley Periodicals, Inc.

Sulpice L.,French Institute of Health and Medical Research | Sulpice L.,University of Rennes 1 | Sulpice L.,Rennes University Hospital Center | Rayar M.,University of Rennes 1 | And 22 more authors.
Hepatology | Year: 2013

Intrahepatic cholangiocarcinoma (ICC) is the second most common type of primary cancer in the liver. ICC is an aggressive cancer with poor prognosis and limited therapeutic strategies. The identification of new drug targets and prognostic biomarkers is an important clinical challenge for ICC. The presence of an abundant stroma is a histological hallmark of ICC. Given the well-established role of the stromal compartment in the progression of cancer diseases, we hypothesized that relevant biomarkers could be identified by analyzing the stroma of ICC. By combining laser capture microdissection and gene expression profiling, we demonstrate that ICC stromal cells exhibit dramatic genomic changes. We identified a signature of 1,073 nonredundant genes that significantly discriminate the tumor stroma from nontumor fibrous tissue. Functional analysis of differentially expressed genes demonstrated that up-regulated genes in the stroma of ICC were related to cell cycle, extracellular matrix, and transforming growth factor beta (TGFβ) pathways. Tissue microarray analysis using an independent cohort of 40 ICC patients validated at a protein level the increased expression of collagen 4A1/COL4A1, laminin gamma 2/LAMC2, osteopontin/SPP1, KIAA0101, and TGFβ2 genes in the stroma of ICC. Statistical analysis of clinical and pathological features demonstrated that the expression of osteopontin, TGFβ2, and laminin in the stroma of ICC was significantly correlated with overall patient survival. More important, multivariate analysis demonstrated that the stromal expression of osteopontin was an independent prognostic marker for overall and disease-free survival. Conclusion: The study identifies clinically relevant genomic alterations in the stroma of ICC, including candidate biomarkers for prognosis, supporting the idea that tumor stroma is an important factor for ICC onset and progression. © 2013 by the American Association for the Study of Liver Diseases.

Vinchon-Petit S.,French Institute of Health and Medical Research | Jarnet D.,Center Regional Of Lutte Contre Le Cancer | Paillard A.,French Institute of Health and Medical Research | Benoit J.-P.,French Institute of Health and Medical Research | And 3 more authors.
Journal of Neuro-Oncology | Year: 2010

The objective of the present study was to investigate the interest of convection-enhanced delivery (CED) for the administration of a nanocarrier-based radiosensitizing chemotherapy in the rat brain. Pursuing on newly developed lipid nanocapsules (LNC) that can be internalised within brain tumour cells, we studied their intracerebral distribution when labelled with fluorescent Nile red (NR). As paclitaxel (Px) represents an interesting radiosensitiser, we also evaluated the potential radiosensitising effects of Px-loaded LNC administered through CED in the 9L intracranial rat glioblastoma model. The distribution study demonstrated that CED injection of NR-loaded LNC (NR-LNC) improved significantly the volume of distribution of NR when matched with simple injection (by about 150 fold). It also reveals that the LNC perfusion of a whole tumour forming area inside the CNS (6 days after implantation of 103 9L cells) is achievable through CED injection, whilst preserving the ability of LNC to reach the intracellular space of encountered tumour cells. Having established an animal model of encephalic irradiation close to the clinic (18 Gray in three fractions of six Gray at days 8, 11 and 14 after 9L cell implantation) we proved the feasibility of the combination of CED for the administration of drug-loaded LNC with external beam therapy. Although a single CED injection of Px-LNC at low Px dose (375 lg/kg of bodyweight) gave the best median survival (twice that of untreated controls), it underlines the need for optimisation. Hence, the possibility of grafting recognition moieties onto the LNC surface combined to their biocompatibility must be beneficial. © 2009 Springer Science+Business Media, LLC.

Sarrabayrouse G.,French Institute of Health and Medical Research | Corvaisier M.,French Institute of Health and Medical Research | Ouisse L.-H.,French Institute of Health and Medical Research | Bossard C.,French Institute of Health and Medical Research | And 8 more authors.
International Journal of Cancer | Year: 2011

High level of T-cell infiltration in colorectal carcinomas (CRCs) is a good prognostic indicator, but the tumor reactivity of this infiltrate (tumor infiltrating lymphocytes [TIL]) is poorly documented. This study examined the presence, phenotype and functional features of tumor-reactive lymphocytes in human CRC. Freshly dissociated TIL and T cell lines were isolated from CRC samples and from some paired normal colonic mucosa. Four tumor cell lines were obtained. Autologous tumor reactivity of CRC TIL and tumor-reactive cell features were analyzed. We demonstrate the presence among CRC TIL of variable fractions (up to 18%) of double positive CD4+CD8αβ + (DP) αβ T cells. Interestingly, a high proportion (16-20%) of this TIL subset displayed tumor reactivity, whilst this was the case for no or few single positive TIL. Low levels of DP TIL were found in most CRC samples and in normal colonic mucosa, but these cells were higher in metastatic CRC. Furthermore, we showed that DP TIL were polyclonal, restricted by HLA class-I, proliferated poorly and secreted higher amounts of IL-4 and IL-13 than single positive T cells, on cognate or CD3 stimulation. DP CRC TIL also expressed CD103, confirming their mucosal origin. Increased frequencies of tumor-reactive DP TIL in metastatic CRC suggest that these cells play a role in the metastatic process of this cancer. Based on their high secretion of IL-4 and IL-13 and on previously described roles of these cytokines in cancers, we postulate that DP TIL could favor CRC growth or metastasis and/or downmodulate immune responses to these tumors. © 2010 UICC.

Perol M.,Center Regional Of Lutte Contre Le Cancer
Revue des Maladies Respiratoires Actualites | Year: 2011

First-line treatment of advanced non-small cell lung cancer has considerably evolved during the last decade. Most of new therapeutic options are built around the third generation platin-based chemotherapy, with the introduction of pemetrexed in this first-fline setting or the addition of an antiangiogenic antibody as bevacizumab to chemotherapy for eligible patients. Maintenance treatment strategies for patients with controlled disease after induction platin-based chemotherapy provide significant survival benefit with pemetrexed for non-squamous carcinoma or erlotinib for patients with stabilized disease after induction chemotherapy. Personalized treatments are already available with the introduction of EGFR tyrosine kinase inhibitors as first-line therapy for patients with EGFR mutations. Further progress will probably come from a more personalized therapeutic approach with the discovery of new oncogenic molecular abnormalities as ALK gene rearrangement. © 2011 Société de Pneumologie de Langue Française (SPLF).

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