Somatic mutational spectrum analysis in a prospective series of 104 gastrointestinal stromal tumors.

Gastrointestinal stromal tumors (GISTs) are mesenchymal tumors distinguished by driver mutations in proto-oncogenes KIT or PDGFRA in 85-90% of cases. These mutations have been linked to the response to imatinib, a multikinase inhibitor, and have independent prognostic impact. Here, we describe the prospective study of the molecular characteristics of 104 GISTs from French adult patients analyzed routinely through the National Hospital Program of Molecular Cancer Diagnosis.

DNA damage response defect in Williams-Beuren syndrome.

Williams-Beuren syndrome (WBS, no. OMIM 194050) is a rare multisystem genetic disorder caused by a microdeletion on chromosome 7q11.23 and characterized by cardiovascular malformations, mental retardation, and a specific facial dysmorphism.

Bariatric Surgery, Polycystic Ovary Syndrome, and Infertility.

Polycystic ovary syndrome (PCOS) is the commonest cause of female infertility. Visceral obesity and insulin resistance are key pathophysiological mechanisms behind PCOS. Women suffering from this syndrome and infertility often seek bariatric surgery hoping that they would be able to conceive postoperatively.

WITHDRAWN: Root canal posts for the restoration of root filled teeth.

Background: The foundation for the reconstruction of endodontically-treated teeth can be provided by a metal or a non-metal post and core system but no guidelines exist for choosing one or the other in particular clinical cases.

Objectives: To assess the effectiveness of different post and core systems for the restoration of endodontically-treated teeth. The primary objective of this review was to compare the clinical failure rates of the different types of posts.

Fungal peptides from pneumonitis hypersensitivity etiologic agents are able to induce specific cellular immune response.

Purpose: Hypersensitivity pneumonitis (HP) is an immunoallergic disease due to chronic exposure to high quantities of different microorganisms such as Mycobacterium immunogenum (Mi), a mycobacterium, and Lichtheimia corymbifera (Lc), a filamentous fungus. It has recently been demonstrated that the protein DLDH (dihydrolipoyl dehydrogenase), is common to these microorganisms. This study aimed to investigate the immune potential of overlapping peptide pools covering the MiDLDH and LcDLDH.

Additive value of pre-operative and one-month post-operative lymphocyte count for death-risk stratification in patients with resectable pancreatic cancer: a multicentric study.

Background: Pancreatic adenocarcinoma (PDAC) incidence is increasing worldwide. Several studies have shown that lymphopenia was correlated with a poor prognosis but the potential interest to measure lymphopenia in the pre and post-operative setting as well as its added value among conventional prognostic factors was never investigated.

Methods: Data from two independent cohorts in whom patients underwent resection for pancreatic carcinoma were retrospectively recorded.

Bevacizumab Pharmacokinetics Influence Overall and Progression-Free Survival in Metastatic Colorectal Cancer Patients.

Objective: Clinical response to bevacizumab varies between patients treated for metastatic colorectal cancer (mCRC). The aim of this study was to quantify individual factors affecting bevacizumab pharmacokinetic variability and assess the relationship between bevacizumab concentrations and clinical outcomes.

Methods: Bevacizumab pharmacokinetics were assessed in 130 mCRC patients using a two-compartment pharmacokinetic population model.

Docetaxel, Cisplatin, and 5-Fluorouracil as perioperative chemotherapy compared with surgery alone for resectable gastroesophageal adenocarcinoma.

Docetaxel, cisplatin, and 5-fluorouracil (DCF) significantly improved overall survival in metastatic gastroesophageal adenocarcinoma (GEA). The aim of this study was to assess efficacy of DCF regimen as perioperative chemotherapy compared with surgery alone in patients with resectable GEA. We identified 789 patients who underwent surgery alone and 62 patients who received at least one cycle of DCF regimen consisting of docetaxel (75 mg/m on day 1), cisplatin (75 mg/m on day 1), and 5-fluorouracil (750 mg/m /day on continuous perfusion on days 1 to 5), every 3 weeks.

Criteria for Inclusion of Newer Bariatric and Metabolic Procedures into the Mainstream: a Survey of 396 Bariatric Surgeons.

Background: There is currently no consensus on the criteria for inclusion of new bariatric procedures into routine clinical practice. This study canvasses bariatric surgeons in an attempt to define these criteria.

Methods: Bariatric Surgeons from around the world were invited to participate in a questionnaire-based survey on SurveyMonkey ®.

Cost-Effectiveness Analysis of Tyrosine Kinase Inhibitors for Patients with Advanced Gastrointestinal Stromal Tumors.

Introduction: The management of advanced gastrointestinal stromal tumors (GISTs) has been modified considerably by the availability of costly tyrosine kinase inhibitors (TKIs); however, the best therapeutic sequence in terms of cost and effectiveness remains unknown.

Objective: The aim of this study was to compare four potential strategies (reflecting the potential daily practice), each including imatinib 400 mg/day, as first-line treatment: S1 (imatinib/best supportive care [BSC]); S2 (imatinib/imatinib/BSC); S3 (imatinib/sunitinib/BSC); and S4 (imatinib/imatinib/sunitinib/BSC).

Methods: A Markov model was developed with a hypothetical cohort of patients and a lifetime horizon.

Best evidence topic: Should ventral hernia repair be performed at the same time as bariatric surgery?

A best evidence topic has been constructed using a described protocol. The three-part question addressed was: In morbidly obese patients undergoing bariatric surgery, when a ventral hernia is picked up in clinic or intraoperatively is concurrent repair of the hernia better than delayed repair after weight loss with regards to complication rates? Using the reported search, 179 papers were found. 5 studies were deemed to be suitable to answer the question.

Tumor control by human cytomegalovirus in a murine model of hepatocellular carcinoma.

Although viruses can cause cancer, other studies reported the regression of human tumors upon viral infections. We investigated the cytoreductive potential of human cytomegalovirus (HCMV) in a murine model of human hepatocellular carcinoma (HCC) in severe-immunodeficient mice. Infection of HepG2 cells with HCMV resulted in the absence of tumor or in a limited tumor growth following injection of cells subcutaneously.

Heparan Sulfate Proteoglycans Promote Telomerase Internalization and MHC Class II Presentation on Dendritic Cells.

Telomerase is a prototype-shared tumor Ag and represents an attractive target for anticancer immunotherapy. We have previously described promiscuous and immunogenic HLA-DR-restricted peptides derived from human telomerase reverse transcriptase (hTERT) and referred as universal cancer peptide (UCP). In nonsmall cell lung cancer, the presence of spontaneous UCP-specific CD4 T cell responses increases the survival of chemotherapy-responding patients.

Selective Inhibition of STAT3 with Respect to STAT1: Insights from Molecular Dynamics and Ensemble Docking Simulations.

STAT3 protein, which is known to be involved in cancer development, is a promising target for anticancer therapy. Successful inhibitors of STAT3 should not affect an activity of closely related protein STAT1, which makes their development challenging. The mechanisms of selectivity of several existing STAT3 inhibitors are not clear.

Prognostic value of baseline seric Syndecan-1 in initially unresectable metastatic colorectal cancer patients: a simple biological score.

In first-line metastatic colorectal cancer (mCRC), baseline prognostic factors allowing death risk and treatment strategy stratification are lacking. Syndecan-1 (CD138) soluble form was never described as a prognostic biomarker in mCRC. We investigated its additional prognostic value for overall survival (OS).

Immunoprevalence and magnitude of HLA-DP4 versus HLA-DR-restricted spontaneous CD4(+) Th1 responses against telomerase in cancer patients.

Cumulative evidence supports that CD4(+) Th1 cells play a key role in antitumor immunity. We previously reported the presence of spontaneous HLA-DR-restricted CD4(+) Th1 responses against telomerase reverse transcriptase (TERT) in various cancers by using promiscuous HLA-DR epitopes. Here, we described novel highly immunogenic HLA-DP4-binding epitopes from TERT named TERT541-555, TERT573-587, TERT613-627 and TERT911-925 and addressed the question about the immunoprevalence and magnitude of the naturally occurring antitumor CD4(+) T cell responses restricted by HLA-DP4 or HLA-DR, the two most common HLA class II.

Melanoma and immunotherapy bridge 2015 : Naples, Italy. 1-5 December 2015.

MELANOMA BRIDGE 2015 KEYNOTE SPEAKER PRESENTATIONS Molecular and immuno-advances K1 Immunologic and metabolic consequences of PI3K/AKT/mTOR activation in melanoma Vashisht G. Y. Nanda, Weiyi Peng, Patrick Hwu, Michael A.

Perioperative docetaxel, cisplatin, and 5-fluorouracil compared to standard chemotherapy for resectable gastroesophageal adenocarcinoma.

Background: Even though the perioperative chemotherapy improves the overall survival (OS) compared to surgery alone in patients with a resectable gastroesophageal adenocarcinoma (GEA), prognosis of these patients remains poor. Docetaxel (D), cisplatin (C), and 5-fluorouracil (F) regimen improves OS compared to CF among patients with advanced GEA. We evaluated the potential interest of a perioperative DCF regimen, compared to standard (S) regimens, in resectable GEA patients.

Metronomic cyclophosphamide therapy in hormone-naive patients with non-metastatic biochemical recurrent prostate cancer: a phase II trial.

After curative local therapy, biochemical recurrence is a mode of relapse among patient with prostate cancer (PC). Deferring androgen deprivation therapy (ADT) or offering non-hormonal therapies may be an appropriate option for these non-symptomatic patients with no proven metastases. Metronomic cyclophosphamide (MC) has shown activity in metastatic PC setting and was chosen to be assessed in biochemical relapse.

Efficacy, Safety and Cost of Regorafenib in Patients with Metastatic Colorectal Cancer in French Clinical Practice.

Background: Regorafenib is an orally administered multikinase inhibitor that has been approved for patients with chemotherapy-refractory metastatic colorectal cancer (mCRC). Even though regorafenib significantly improved survival in two international phase 3 trials (CORRECT and CONCUR), a high rate of treatment-related toxic effects and dose modifications were observed with a modest benefit. The aim of this study was to provide information concerning the efficacy, safety, and cost of regorafenib in patients with mCRC in clinical practice.

Reassessment of T Lymphocytes Crossmatches Results Prediction With Luminex Class I Single Antigen Flow Beads Assay.

Background: In virtual crossmatch (XM) strategies, a correct anticipation of XM results is required for appropriately allocating organs. We reassessed the ability to predict T lymphocyte flow cytometry and complement dependent cytotoxicity XM results with the mean fluorescence intensity (MFI) in Luminex class I single antigen flow beads (SAFB) assay, after correction of complement interference and exclusion of antidenatured HLA antibodies.

Methods: Among 432 XM with T lymphocytes (T-XM), 407 were analyzed after exclusion of antidenatured HLA antibodies.

IL-21-Induced MHC Class II+ NK Cells Promote the Expansion of Human Uncommitted CD4+ Central Memory T Cells in a Macrophage Migration Inhibitory Factor-Dependent Manner.

NK cells are critical for innate immunity-mediated protection. The main roles of NK cells rely on their cytotoxic functions or depend on the tuning of Th1 adaptive immunity by IFN-γ. However, the precise influence of inflammatory cytokines on NK cell and CD4 T lymphocyte interactions was never investigated.