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Grant
Agency: Cordis | Branch: FP7 | Program: CP-FP | Phase: HEALTH.2013.2.4.1-3 | Award Amount: 7.82M | Year: 2013

Long-term side-effects of radiotherapy impact on the quality-of-life (QoL) of cancer survivors. These side-effects could be reduced if predicted in advance. Previous work identified clinical and biological predictors but a major, coordinated approach is needed to validate them so they can be used clinically. The EU has ~17.8 million people living with a prior diagnosis of cancer of whom ~7 million received radiotherapy. In the long-term, potentially 20% of those suffering with mild to severe side-effects (~1.4 million) might benefit from alleviation of symptoms, with resulting reductions in the cost of care in the EU. REQUITE aims to develop validated clinical models and incorporate biomarkers to identify before treatment cancer patients at risk of side-effects and use the models to design interventional trials aimed at reducing side-effects and improving QoL in cancer survivors who underwent radiotherapy. REQUITE will: 1. carry out a multi-centre, longitudinal, observational study to collect standardised data and samples in breast, prostate and lung cancer patients; 2. validate biomarkers with published evidence of predictive value; 3. replicate published clinical models and incorporate replicated biomarkers to create validated predictive algorithms; 4. use the prospectively validated models and biomarkers to design interventional trial protocols aiming to reduce side-effects and improve QoL in high-risk patients. REQUITE builds on collaborations with a proven history of data sharing, enlarged to a consortium with expertise in patient recruitment, knowledge management, biomarker testing and predictive model development. SME involvement for biomarker assays will facilitate future clinical implementation and commercial exploitation. The outcome of this project will be validated predictive models for three common cancers and trial protocols using the models to investigate interventions aimed at reducing long-term side-effects and improving the QoL of cancer survivors.


PubMed | Center Francois Baclesse, Besancon University Hospital Center, Roche Holding AG, Institute Paoli Calmettes and 11 more.
Type: | Journal: European journal of cancer (Oxford, England : 1990) | Year: 2016

To investigate whether adding bevacizumab to neoadjuvant carboplatin-paclitaxel (CP) helps achieve optimal debulking, measured by complete resection rate (CRR) at interval debulking surgery (IDS), in patients with initially unresectable International Federation of Gynecology and Obstetrics stage IIIC/IV ovarian, tubalor peritoneal adenocarcinoma.Multicentre, open-label, non-comparative phase II study. Ninety-five patients randomised (2:1) to receive four cycles of neoadjuvant CP 3 concomitant cycles of bevacizumab 15mg/kg (BCP) followed by IDS. Primary objectiveis to evaluate the CRR at IDS in the BCP group (reference CRR rate defined as 45% CRR). A stopping rule based on bevacizumab-related adverse events (AEs) of special interest was implemented.In the BCP group (N=58), IDS was performed in 40 (69%) patients, of whom 85% had a complete resection. The CRR of this group was therefore 58.6% (34 patients), statistically over pre-defined 45%. The CRR in the CP group was 51.4%: 22 (60%) patients underwent IDS (85% had a complete resection). Grade 3 adverse events occurred in 62% of the BCP-treated patients and 63% of the CP-treated patients: mainly blood and lymphatic, gastrointestinaland vascular disorders, without more toxicity with BCP. Postoperative complications (mainly wound, infectiousand gastrointestinal complications) occurred in 28% and 36% of the patients, respectively. The pre-specified safety stopping rule was not reached.The primary objective was met as the CRR with BCP was significantly higher than the reference rate. Bevacizumab may be safely added to a preoperative program in patients deemed non-optimally resectable, whatever the final surgical decision. Bevacizumabs role in this setting should be further investigated.


Bianga J.,French National Center for Scientific Research | Bouslimani A.,Montpellier University | Bec N.,Montpellier University | Quenet F.,Institute Regional Du Cancer Of Montpellier | And 6 more authors.
Metallomics | Year: 2014

The follow-up of the Heated Intraoperative Chemotherapy (HIPEC) of peritoneal carcinomatosis would benefit from the monitoring of the penetration, distribution and metabolism of the drug within the tumor. As tumor nodules can be resected during the therapy, mass spectrometry imaging is a suitable tool for the evaluation of treatment efficacy, and, as a result, the therapy can be re-optimized. In this work we demonstrate the complementarity of laser ablation (LA) ICP mass spectrometry and MALDI imaging to study the penetration and distribution of two Pt-based metallodrugs (cisplatin and oxaliplatin) in human tumor samples removed from patients diagnosed with colorectal or ovarian peritoneal carcinomatosis. LA ICP MS offered sensitive (LOD for 195Pt 4.8 pg s-1) imaging of platinum quasi-independently of the original species and the sample matrix and thus an ultimate way of verifying the penetration of the Pt-containing drug or its moieties into the tumor. MALDI imaging was found to suffer in some cases from signal suppression by the matrix leading to false negatives. In the case of the oxaliplatin metallodrug, the results obtained from ICP and MALDI MS imaging were coherent whereas in the case of cisplatin, species detected by ICP MS imaging could not be validated by MALDI MS. The study is the first application of the dual ICP and MALDI MS imaging to the follow-up of metallodrugs in human tumors. This journal is © the Partner Organisations 2014.


Patent
French National Center for Scientific Research, Institute Regional Du Cancer Of Montpellier and Montpellier University | Date: 2013-02-26

The present invention relates to an association of poly (N-acryloyl glycinamide) with at least one active principle and/or at least one product which is visible in medical imaging, in a physiologically acceptable aqueous medium.


Background: Mounting evidence indicates an enhanced lymphocytic reaction as an informative prognostic indicator in colon cancer (CC). The IM methodology has been defined to quantify the in situ immune infiltrate. Methods: A Society for Immunotherapy of Cancer-led international consortium of 23 pathology expert centers from 17 countries was initiated to evaluate the standardized IM assay in routine clinical settings. Patient (pt) eligibility criteria were CC Stages I/II/III and no neo-adjuvant treatment. 1336 pts split into a training set (TS) and internal validation set (IVS) were quantified for IM using standardized procedure, immunohistochemistry using CD3 and CD8 antibodies, and quantification using digital pathology on whole slide section of primary CCs. Statistical analysis plan was predefined and all statistical analyses performed by blinded external statisticians. Primary study endpoint was timeto- recurrence (TTR); analyses were by Cox models stratified by enrolling center. Results: Median recurrent follow-up duration across centers was 5.9 years. Overall pts: 51% male, median age 69 years, 19%/56%/25% stage I/II/III. Among pts with stages I/II/III CC, in the TS TTR was shorter among 332 pts (48.1%) with low-IM CC vs 358 pts with high-IM CC (HR (95% CI), 0.35 (0.23-0.52); P<0.0001). In the IVS (630 pts) TTR was also shorter among 303 pts with low-IM CC vs 327 pts with high- IM CC (HR (95% CI), 0.54 (0.34-0.84); P=0.006). In both groups, results were independent of pt age, sex, tumor stage and sidedness. Among pts with stage II CC, the difference in TTR between low and high-IM was significant both in the TS (HR (95% CI), 0.27 (0.14-0.51); P<0.0001) and in the IVS (HR (95% CI), 0.46 (0.24-0.87) P=0.014); multivariate results similar (TS HR (95% CI), 0.28 (0.14-0.54); P<0.0001 and IVS HR (95% CI), 0.46 (0.24-0.87); P=0.0142)). Reproducibility of the standardized IM assay was validated across centers. Conclusions: The primary endpoint of the worldwide prespecified IM study was reached. TTR was significantly longer in pts stages I/II/III with high-IM. Low-IM identified a subgroup of patients with high-risk stage II CC. © 2016 Lavoisier


Patent
Sanofi S.A., French Institute of Health, Medical Research, Institute Regional Du Cancer Of Montpellier and Montpellier University | Date: 2014-01-02

The present invention relates to a method for identifying a cellular target involved in a cell phenotype comprising identifying an intrabody which can modify a cell phenotype and identifying a direct or indirect cellular target of the intrabody. The present invention also relates to intrabodies 3H2-1, 3H2-VH and 5H4 which are capable of inhibiting the degranulation reaction in mast cells triggered by an allergic stimulus, and especially to intrabodies 3H2-1 and 5H4 which are capable of directly or indirectly targeting a protein of the ABCF1 family and of the C120RF4 family respectively. The present invention also relates to ABCF1 and C120RF4 inhibitors for use in therapy, in particular for treating allergic and/or inflammatory conditions.


Patent
Montpellier University and Institute Regional Du Cancer Of Montpellier | Date: 2014-03-28

The present invention relates to a method for the in vitro determination of the radiosensitivity of a subject. More particularly, the invention relates to a method comprising a step of inducing an exogenous stress on a biological sample from a subject, followed by the comparison of the presence or level of at least one compound chosen in a group of defined compounds, in said biological sample and in a reference sample. The present invention also relates to the use of said at least one compound as predictive biomarker of the radio-sensitivity of a subject. The invention also relates to a kit for the detection of the presence or level of at least one of said compounds, usable in a method according to the invention.


Patent
Montpellier University and Institute Regional Du Cancer Of Montpellier | Date: 2014-06-18

The present invention relates generally to the fields of reproductive medicine. More specifically, the present invention relates to in vitro non invasive methods and kits for determining the quality of an embryo by determining the level of the cell free nucleic acids and/or determining the presence and/or expression level of at least one specific nucleic acid sequence in the nude is acid extraction.


PubMed | Institute Regional Du Cancer Of Montpellier
Type: Journal Article | Journal: Virchows Archiv : an international journal of pathology | Year: 2016

DNA mismatch repair (MMR) protein analysis by immunohistochemistry (IHC) can identify colorectal cancer (CRC) with microsatellite instability (MSI). As MLH1-deficient CRC can be hereditary or sporadic, markers to distinguish between them are needed. MLH1 promoter methylation assay is the reference method; however, sometimes, it is challenging on formalin-fixed paraffin-embedded tissue samples. We assessed by IHC the expression of BRAFV600E, p16, MGMT, and CDX2 in 55 MLH1-deficient MSI CRC samples (of which 8 had a germline MLH1 mutation) to determine whether this panel differentiates between sporadic and hereditary CRCs. We also analyzed MLH1 promoter methylation by methylation-specific PCR and pyrosequencing and BRAF status by genotyping. None of the hereditary CRCs showed MLH1 methylation, BRAF mutation, BRAFV600E-positive immunostaining, or loss of p16 expression. We detected MLH1 promoter methylation in 67% and a BRAF mutation in 42% of CRC, all showing MLH1 promoter methylation. BRAFV600E IHC and BRAF genotyping gave concordant results in all but two samples. Loss of expression of p16 was found in 30% of CRC with methylation of the MLH1 promoter, but its expression was retained in all non-methylated and part of MLH1-methylated tumors (100% specificity, 30% sensitivity). CDX2 and MGMT expression was not associated with MLH1 status. Thus, BRAFV600E and p16 IHC may help in differentiating sporadic from hereditary MLH1-deficient CRC with MSI. Specifically, p16 IHC might be used as a surrogate marker for MLH1 promoter methylation, because all p16-negative CRCs displayed MLH1 methylation, whereas hereditary CRCs were all p16-positive.


Patent
French Institute of Health, Medical Research, Montpellier University and Institute Regional Du Cancer Of Montpellier | Date: 2014-07-22

The present invention relates to anti-claudin 1 antibodies and their uses thereof. In particular, the present invention relates to an anti-Claudin 1 (CLDN1) antibody comprising n heavy chain variable region comprising SEQ ID NO:2 in the H-CDR1 region, SEQ ID NO:3 in the H-CDR2 region and SEQ ID NO:4 in the H-CDR3 region; and a light chain variable region comprising SEQ ID NO:6 in the L-CDR1 region, SEQ ID NO:7 in the L-CDR2 region and SEQ ID NO:8 in the L-CDR3 region.

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