Les cancers de l’orbite etude retrospective à propos de 31 cas

locorégionale rendant le traitement difficile et mutilant. Dans ce travail, nous rapportons notre expérience dans la prise en charge diagnostique et thérapeutique de ces tumeurs. Matériels et méthodes : Notre étude rétrospective a concerné 31 cas de cancers de l’orbite colligés sur 13 ans (1993- 2005). Tous les patients ont bénéficié d’un examen clinique complet, d’une imagerie du massif facial (TDM et/ou IRM) et d’une biopsie de la tumeur. Le traitement a été basé sur la chirurgie, la radiothérapie et/ou la chimiothérapie. Résultats : La symptomatologie clinique était dominée par les signes ophtalmologiques et les algies faciales. L’imagerie a montré dans tous les cas un processus expansif tissulaire à point de départ orbitaire, avec lyse osseuse orbitaire chez 16 patients (51,6%), une extension au massif facial chez 7 patients (22,6%), endocrâniennes chez 6 patients (19,4%) et des formes bilatérales atteignant les deux orbites dans 3 cas (9,7%) l’anatomopathologie montrait une prédominance des lymphomes malins non hodgkiniens (32,3%) et des carcinomes épidermoïdes (32,3%), suivis des rhabdomyosarcomes embryonnaires (19,4 %). Douze patients ont été traités par chirurgie et radiothérapie postopératoire, dix patients par une association radio-chimiothérapie, et neuf autres par une chimiothérapie néo-adjuvante. La survie globale était de 67,8% à 3 ans, 48,4% à 5 ans et 22,6% à 10 ans. Conclusion : Les cancers de l’orbite sont de mauvais pronostic. Un diagnostic précoce et un traitement radical et adapté au type histologique permet d’améliorer la survie et la qualité de vie chez les patients atteints de ces tumeurs.Mots-clés : Orbite, cancer, lymphome, carcinome épidermoïde, rhabdomyosarcom

Uncovering the clinical relevance of unclassified variants in DNA repair genes: a focus on BRCA negative Tunisian cancer families

Introduction: Recent advances in sequencing technologies have significantly increased our capability to acquire large amounts of genetic data. However, the clinical relevance of the generated data continues to be challenging particularly with the identification of Variants of Uncertain Significance (VUSs) whose pathogenicity remains unclear. In the current report, we aim to evaluate the clinical relevance and the pathogenicity of VUSs in DNA repair genes among Tunisian breast cancer families.Methods: A total of 67 unsolved breast cancer cases have been investigated. The pathogenicity of VUSs identified within 26 DNA repair genes was assessed using different in silico prediction tools including SIFT, PolyPhen2, Align-GVGD and VarSEAK. Effects on the 3D structure were evaluated using the stability predictor DynaMut and molecular dynamics simulation with NAMD. Family segregation analysis was also performed.Results: Among a total of 37 VUSs identified, 11 variants are likely deleterious affecting ATM, BLM, CHEK2, ERCC3, FANCC, FANCG, MSH2, PMS2 and RAD50 genes. The BLM variant, c.3254dupT, is novel and seems to be associated with increased risk of breast, endometrial and colon cancer. Moreover, c.6115G>A in ATM and c.592+3A>T in CHEK2 were of keen interest identified in families with multiple breast cancer cases and their familial cosegregation with disease has been also confirmed. In addition, functional in silico analyses revealed that the ATM variant may lead to protein immobilization and rigidification thus decreasing its activity. We have also shown that FANCC and FANCG variants may lead to protein destabilization and alteration of the structure compactness which may affect FANCC and FANCG protein activity.Conclusion: Our findings revealed that VUSs in DNA repair genes might be associated with increased cancer risk and highlight the need for variant reclassification for better disease management. This will help to improve the genetic diagnosis and therapeutic strategies of cancer patients not only in Tunisia but also in neighboring countries

Fight against cancer around the Mediterranean area: "Many hands make light work!"

The geopolitical and strategic importance of the Mediterranean area is evident since a long time. In terms of health programs and means for cancer care, significant disparities have been reported between countries that borders the Mediterranean basin. AROME project began modestly in 2006 with a group of leaders who recognized the need to promote practical training of young people and, thus, contribute to reduce these inacceptable inequalities in terms of early diagnosis and management. Moreover, our project has been built from our belief that the socio-cultural specificity of this region, its epidemiology, availability of means for diagnosis and treatment, should impose a sustained regional research and better knowledge of tumor biology and identify the specificities that may require particular strategies of care that should not be based only on Western and Asian research data. We must thus take advantage of advances in the identification of intimate biological tumors to provide answers to our ignorance of the specific Mediterranean biology. In this paper, we illustrate this issue describing some particular cancers in this region such as breast and nasopharyngeal cancers. (C) 2012 Elsevier Ireland Ltd. All rights reserved

Leptin decreases BC cell susceptibility to NK lysis via PGC1A pathway

International audienceLarge prospective studies established a link between obesity and breast cancer (BC) development. Yet, the mechanisms underlying this association are not fully understood. Among the diverse adipocytokine secreted by hypertrophic adipose tissue, leptin is emerging as a key candidate molecule linking obesity and cancer, since it promotes proliferation and invasiveness of tumors. However, the potential implication of leptin on tumor escape mechanisms remains unknown. This study aims to explore the effect of leptin on tumor resistance to NK lysis and the underlying mechanism. We found that leptin promotes both BC resistance to NK92-mediated lysis and β oxidation on MCF-7, by the up-regulation of a master regulator of mitochondrial biogenesis, the peroxisome proliferator activated receptor coactivator-1 α (PGC1A). Using adenoviral approaches, we show that acute elevation of PGC1A enhances the fatty acid oxidation pathway and decreases the susceptibility of BC cells to NK92-mediated lysis. Importantly, we identified the involvement of PGC1A and leptin in the regulation of hypoxia inducible factor-1 alpha (HIF1A) expression by tumor cells. We further demonstrate that basal BC cells MDA-MB-231 and BT-20 exhibit an increased PGC1A mRNA level and an enhanced oxidative phosphorylation activity; in comparison with luminal BC cells MCF7 and MDA-361, which are associated with more resistance NK92 lysis. Altogether, our results demonstrate for the first time how leptin could promote tumor resistance to immune attacks. Reagents blocking leptin or PGC1A activity might aid in developing new therapeutic strategies to limit tumor development in obese BC patients

Clinicopathologic and Prognostic Significance of Gelatinase A in Tunisian Colorectal Cancer: A Case-Control Study.

International audienceMatrix metalloproteinase-2 (gelatinase A) is a well-known mediator of cancer metastasis, but it is also thought to be involved in several aspects of cancer development, including cell growth and inflammation. In the present study, we investigate whether MMP-2 SNP, MMP-2 mRNAs, and MMP-2 protein are associated with the susceptibility to colorectal cancer in the Tunisian population. The TaqMan allele discrimination assay and DNA sequencing techniques were used for genotyping; MMP-2 expression of each genotype was analyzed by semiquantitative RT-PCR, and MMP-2 protein expression was analyzed by immunohistochemistry staining. Our result showed that the levels of MMP-2 mRNA expression in patients containing the CC genotype were much higher compared with cells with the CT genotype. The frequency of the MMP-2 CC genotype was significantly higher in colorectal cancer patients when compared with controls (OR=1.94; 95% CI, 1.117-3.680). A higher intensity of staining of MMP-2 was observed in regions of invasion of the muscularis mucosa compared with superficial portions of the tumor. In addition, we found a significant progressive increase in total MMP-2 plasma levels with progression from adenomatous polyps through advancing Dukes stages (P=0.0001). Our data suggest that MMP-2 may be associated with colorectal cancer development and invasion in the Tunisian population; moreover, SNP and levels of MMP-2 could be a predictive value for colorectal cancer prevention and invasiveness

Multiple Primary Cancers in North Tunisia, 2000 - 2009

Aim: to evaluate and report the frequency, epidemiologic and antaomo -clinical features of patients who developed MPM from the data of North Tunisia Cancer Registry, during the period 2000-2009.Materials and methods: From a population of 53757 new patients of the North Tunisia National Cancer Registry database presenting new cases of cancers during the period 2000-2009 in North Tunisia, we collected and analyzed those with MPMTs. We used for MPMT the international IARC diagnosis criteria are published in ICD-O Third Edition. Results:  In the 53757 new cancer cases registered from 2000-2009, we collected 528 cases (1.0%) of MPM. Mean age at diagnosis of the 1st cancer was 61 years (22-99) and sex-ratio at  1.08 (275M/253F) while mean age at the 2nd cancer diagnosis was 62 years(29 to 99). Among the 528 cases, the most frequent 1st cancer site was breast in females (147 pts, 58.1%) and urinary tract for males (56 patients, 20.4%). In the 528 MPM cases, 321 (60.8%) were synchronous and 207 cases (39.2%) were metachronous tumors. The median time from 1st to 2nd cancer was 1.98 months (range 0-140). The most associated 1st-2nd cancer sites were breast in 110 patients (43.3%) in females and for males’ urinary tract -prostate cancers (45 patients, 16.3%). Conclusions: The coexistence of a synchronous or metachronous MPM is possible and have to be considered during pretreatment evaluation. A close follow-up should be recommended to detect second malignancies in patients treated for a 1st cancer.Keywords: Multiple primary malignancies , clinical features , North Tunisi