Mohamed Gasmi

Hôpital Européen, Marseille, Marsiglia, Provence-Alpes-Côte d'Azur, France

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Publications (60)204.98 Total impact

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    ABSTRACT: Pancreatic Ductal Adenocarcinoma (PDAC) is a disease with a great heterogeneity in the response to treatments. To improve the responsiveness to treatments there are two different approaches, the first one consist to develop new and more efficient drugs that intent to cure all patients and the second one is to use already-approved drugs, alone or in combination, but selecting beforehand the most sensitive patients. In this work we explored the efficiency of the second possibility. We developed a collection of 17 PDAC samples collected by Endoscopic Ultrasound-Guided Fine-Needle Aspiration (EUS-FNA) or surgery and preserved as xenografts and as primary cultures. This collection was characterized at molecular level by a transcriptomic analysis using an Affymetrix approach. In this paper we present data demonstrating that a subgroup of PDAC responds to low doses of 5-aza-dC. These tumors show a specific RNA expression profile that could serve as a marker, but there is no correlation with Dnmt1, Dnmt3A or Dnmt3B expression. Responder tumors corresponded to well-differentiated samples and longer survival patients. In conclusion, we present data obtained with the well-known drug 5-aza-dC as a proof of concept that a drug that seems to be inefficient in solid tumors in general could be applicable to a particular subgroup of patients with PDAC.
    Oncotarget 12/2014; · 6.64 Impact Factor
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    ABSTRACT: The management of post-operative anastomotic leakage and fistulas of the upper GI tract remains challenging. Fully covered stents are used despite a high risk of migration because of a better removability. The goal of our study was to evaluate the effectiveness of this new type of endoscopic stent in this indication. The secondary objective was to determine the ability of withdrawing this stent.
    Surgical endoscopy. 10/2014;
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    ABSTRACT: Chemoradiotherapy (CHRT) is often advocated for locally-advanced biliary tract cancer (LABTC). However there was not comparative study with chemotherapy alone (CH).
    European journal of cancer (Oxford, England: 1990) 09/2014; · 4.12 Impact Factor
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    ABSTRACT: Adrenomedullin (AM) is a multifunctional peptide vasodilator that transduces its effects through calcitonin receptor-like receptor/receptor activity-modifying protein-2 and -3 (CLR/RAMP2 and CLR/RAMP3). In this study, real-time quantitative reverse transcription demonstrated a significant expression of AM mRNA in tumor samples from colorectal cancer (CRC) patients in clinical stage II, III, and IV when compared with normal colorectal tissue. AM, CLR, RAMP2, and RAMP3 proteins were immunohistochemically localized in the carcinomatous epithelial compartment of CRC tissue. Tissue microarray analysis revealed a clear increase of AM, CLR, RAMP2, and RAMP3 staining in lymph node and distant metastasis when compared with primary tumors. The human colon carcinoma cells HT-29 expressed and secreted AM into the culture medium with a significant increase under hypoxia. Treatment of HT-29 cells with synthetic AM stimulated cell proliferation and invasion in vitro. Incubation with anti-AM antibody (αAM), anti-AM receptors antibodies (αAMR), or AM antagonist AM22-52 inhibited significantly basal levels of proliferation of HT-29 cells, suggesting that AM may function as an autocrine growth factor for CRC cells. Treatment with αAM significantly suppressed the growth of HT-29 tumor xenografts in vivo. Histological examination of αAM-treated tumors showed evidence of disruption of tumor vascularity with decreased microvessel density, depletion of endothelial cells and pericytes, and increased tumor cell apoptosis. These findings highlight the potential importance of AM and its receptors in the progression of CRC and support the conclusion that αAM treatment inhibits tumor growth by suppression of angiogenesis and tumor growth, suggesting that AM may be a useful therapeutic target.
    Cancer Medicine 04/2013; 2(2):196-207.
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    ABSTRACT: PURPOSEElderly patients form a heterogeneous population. Evaluation of geriatric factors may help evaluate a patient's health status to better adapt treatment. PATIENTS AND METHODS Elderly patients with previously untreated metastatic colorectal cancer (mCRC) were randomly assigned to receive fluorouracil (FU) -based chemotherapy either alone or in combination with irinotecan (IRI) in the Fédération Francophone de Cancérologie Digestive (FFCD) 2001-02 study. Sites participating in the geriatric substudy completed geriatric screening tools to perform prognostic factor analyses for treatment safety during the first 4 months after treatment initiation.ResultsThe geriatric score was calculated in 123 patients (44%). Median age was 80 years (range, 75 to 91 years). The Charlson comorbidity index was ≤ 1 in 75%, Mini-Mental State Examination (MMSE) score was ≤ 27/30 in 31%, and Instrumental Activities of Daily Living (IADL) showed impairment in 34% of the patients. Seventy-one patients (58%) had grade 3 to 4 toxicity, 41 (33%) had a dose-intensity reduction of more than 33%, and 54 (44%) had at least one unexpected hospitalization during the first 4 months after starting treatment. In multivariate analysis, significant predictive factors for grade 3-4 toxicity were IRI arm (odds ratio [OR], 5.03), MMSE ≤ 27/30 (OR, 3.84), and impaired IADL (OR, 4.67); for dose-intensity reduction of > 33%, the significant predictive factors were alkaline phosphates > 2 × upper limit of normal (OR, 4.16) and IRI arm (OR, 6.85); and for unexpected hospitalization, significant predictive factors were MMSE ≤ 27/30 (OR, 4.56) and Geriatric Depression Scale ≤ 2 (OR, 5.52). CONCLUSION Geriatric factors (MMSE and IADL) are predictive of severe toxicity or unexpected hospitalization (MMSE) in a randomized prospective phase III study in mCRC. These results suggest that cognitive function and autonomy impairment should be taken into account when choosing a regimen for chemotherapy.
    Journal of Clinical Oncology 03/2013; · 18.04 Impact Factor
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    ABSTRACT: Background Sorafenib is an oral anticancer agent targeting Ras-dependent signaling and angiogenic pathways. A phase I trial demonstrated that the combination of gemcitabine and sorafenib was well tolerated and had activity in advanced pancreatic cancer (APC) patients. The BAYPAN study was a multicentric, placebo-controlled, double-blind, randomized phase III trial comparing gemcitabine/sorafenib and gemcitabine/placebo in the treatment of APC. Patients and methods The patient eligibility criteria were locally advanced or metastatic pancreatic adenocarcinoma, no prior therapy for advanced disease and a performance status of zero to two. The primary end point was progression-free survival (PFS). The patients received gemcitabine 1000 mg/m(2) i.v., weekly seven times followed by 1 rest week, then weekly three times every 4 weeks plus sorafenib 200 mg or placebo, two tablets p.o., twice daily continuously. Results Between December 2006 and September 2009, 104 patients were enrolled on the study (52 pts in each arm) and 102 patients were treated. The median and the 6-month PFS were 5.7 months and 48% for gemcitabine/placebo and 3.8 months and 33% for gemcitabine/sorafenib (P = 0.902, stratified log-rank test), respectively. The median overall survivals were 9.2 and 8 months, respectively (P = 0.231, log-rank test). The overall response rates were similar (19 and 23%, respectively). Conclusion The addition of sorafenib to gemcitabine does not improve PFS in APC patients.
    Annals of Oncology 07/2012; 23(11):2799-805. · 7.38 Impact Factor
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    ABSTRACT: To report the results of a medical management of sphincter of oddi dysfunction (SOD) after an intermediate follow-up period. A total of 59 patients with SOD (2 men and 57 women, mean age 51 years old) were included in this prospective study. After medical treatment for one year, the patients were clinically re-evaluated after an average period of 30 mo. The distribution of the patients according to the Milwaukee's classification was the following: 11 patients were type 1, 34 were type 2 and 14 were type 3. Fourteen patients underwent an endoscopic sphincterotomy (ES) after one year of medical treatment. The median intermediate follow-up period was 29.8 ± 3 mo (3-72 mo). The initial effectiveness of the medical treatment was complete, partial and poor among 50.8%, 13.5% and 35%, respectively, of the patients. At the end of the follow-up period, 37 patients (62.7%) showed more than 50% improvement. The rate of improvement in patients who required ES was not significantly different compared with the patients treated conservatively (64.2% vs 62.2%, respectively). Our study confirms that conservative medical treatment could be an alternative to endoscopic sphincterotomy because, after an intermediate follow-up period, the two treatments show the same success rates.
    World Journal of Gastroenterology 04/2012; 18(14):1610-5. · 2.55 Impact Factor
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    ABSTRACT: We aimed to analyze the feasibility and efficacy of a new transperineal access to treat anorectal sepsis (fistulae and abscesses) under endoanal ultrasonography guidance. Twenty-five patients (80% Crohn disease) were included retrospectively. Twenty-one patients had fistulae (perianal, urethroanal, and anovaginal) treated by injection of heterologous fibrin glue and cyanoacrylate. Four patients with abscesses were treated by irrigation-injection of normal saline solution and an aminoglycoside antibiotic. Twenty-five patients underwent 32 treatment sessions. At 4 weeks' evaluation, 19 patients (90.5%) with anal fistulae ultimately achieved a 4-week short-term success. Of these, 5 patients (26%) showed resolution of symptoms and persistent occlusion of the fistula track at long-term follow-up (>6 mo). At 4-week follow-up, the treatment of abscesses was successful in 3 of 4 cases. However, a relapse was observed in 2 cases after a mean period of 3 months. No serious adverse events were observed. Endoanal ultrasonography-assisted percutaneous transperineal injection represents a sphincter-sparing alternative to the surgical route, with interesting outcomes and excellent tolerability for the treatment of anorectal sepsis.
    Surgical laparoscopy, endoscopy & percutaneous techniques 04/2012; 22(2):148-53. · 0.88 Impact Factor
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    ABSTRACT: We analyzed the influence of 8 germinal polymorphisms of candidate genes potentially related to EGFR signalling (EGFR, EGF, CCND1) or antibody-directed cell cytotoxicity (FCGR2A and FCGR3A) on outcome of colorectal cancer (CRC) patients receiving cetuximab-based therapy. Fifty-eight advanced CRC patients treated with cetuximab-irinotecan salvage therapy between 2001 and 2007 were analyzed (mean age 60; 50 PS 0-1). The following polymorphisms were analyzed on blood DNA: EGFR (CA repeats in intron 1, -216 G > T, -191C > A, R497K), EGF (A61G), CCND1 (A870G), FCGR2A (R131H), FCGR3A (F158V). Statistical analyses were conducted on the total population and on patients with wt KRas tumors. All SNPs were considered as ternary variables (wt/wt vs wt/mut vs mut/mut), with the exception of -191C > A EGFR polymorphism (AA patient merged with CA patients). Analysis of skin toxicity as a function of EGFR intron 1 polymorphism showed a tendency for higher toxicity in patients with a low number of CA-repeats (p = 0.058). CCND1 A870G polymorphism was significantly related to clinical response, both in the entire population and in KRas wt patients, with the G allele being associated with a lack of response. In wt KRas patients, time to progression (TTP) was significantly related to EGFR -191C > A polymorphism with a longer TTP in CC patients as compared to others, and to CCND1 A870G polymorphism with the G allele being associated with a shorter TTP; a multivariate analysis including these two polymorphisms only retained CCND1 polymorphism. Overall survival was significantly related to CCND1 polymorphism with a shorter survival in patients bearing the G allele, and to FCGR3A F158V polymorphism with a shorter survival in VV patients (in the entire population and in KRas wt patients). FCGR3A F158V and CCND1 A870G polymorphisms were significant independent predictors of overall survival. Present original data obtained in wt KRas patients corresponding to the current cetuximab-treated population clearly suggest that CCND1 A870G polymorphism may be used as an additional marker for predicting cetuximab efficacy, TTP and overall survival. In addition, FCGR3A F158V polymorphism was a significant independent predictor of overall survival.
    BMC Cancer 11/2011; 11:496. · 3.33 Impact Factor
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    ABSTRACT: The optimum use of cytotoxic drugs for advanced colorectal cancer has not been defined. Our aim was to investigate whether combination treatment is better than the sequential administration of the same drugs in patients with advanced colorectal cancer. In this open-label, randomised, phase 3 trial, we randomly assigned patients (1:1 ratio) with advanced, measurable, non-resectable colorectal cancer and WHO performance status 0-2 to receive either first-line treatment with bolus (400 mg/m(2)) and infusional (2400 mg/m(2)) fluorouracil plus leucovorin (400 mg/m(2)) (simplified LV5FU2 regimen), second-line LV5FU2 plus oxaliplatin (100 mg/m(2)) (FOLFOX6), and third-line LV5FU2 plus irinotecan (180 mg/m(2)) (FOLFIRI) or first-line FOLFOX6 and second-line FOLFIRI. Chemotherapy was administered every 2 weeks. Randomisation was done centrally using minimisation (minimisation factors were WHO performance status, previous adjuvant chemotherapy, number of disease sites, and centre). The primary endpoint was progression-free survival after two lines of treatment. Analyses were by intention-to-treat. This trial is registered at ClinicalTrials.gov, NCT00126256. 205 patients were randomly assigned to the sequential group and 205 to the combination group. 161 (79%) patients in the sequential group and 161 (79%) in the combination group died during the study. Median progression-free survival after two lines was 10·5 months (95% CI 9·6-11·5) in the sequential group and 10·3 months (9·0-11·9) in the combination group (hazard ratio 0·95, 95% CI 0·77-1·16; p=0·61). All six deaths caused by toxic effects of treatment occurred in the combination group. During first-line chemotherapy, significantly fewer severe (grade 3-4) haematological adverse events (12 events in 203 patients in sequential group vs 83 events in 203 patients in combination group; p<0·0001) and non-haematological adverse events (26 events vs 186 events; p<0·0001) occurred in the sequential group than in the combination group. Upfront combination chemotherapy is more toxic and is not more effective than the sequential use of the same cytotoxic drugs in patients with advanced, non-resectable colorectal cancer. Sanofi-Aventis France.
    The Lancet Oncology 09/2011; 12(11):1032-44. · 25.12 Impact Factor
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    ABSTRACT: Chemotherapy combinations and addition of cetuximab or bevacizumab to chemotherapy have been shown to improve overall survival of metastatic colorectal cancer (CRC) patients. However, the efficacy of cetuximab when administered after bevacizumab failure is still unknown. Fifty-eight consecutive patients diagnosed with advanced colorectal cancer between treated with cetuximab following irinotecan failure were included in our analysis. A multivariate Cox model analysis was performed to estimate the effect of previous bevacizumab regimen on survival. Thirteen (22.4%) were pre-treated with anti-VEGF agents. None of them responded to cetuximab, and this subgroup presented a significantly decreased disease-specific survival as compared to treatment-naïve patients (9.1 months vs. 4.9 months; p=0.026). This difference remained statistically significant in a multivariate Cox model after adjusting for age, sex, performance status (PS), and K-RAS status (RR=2.2; 95% CI: 1.1-4.5, p=0.03). These study results suggest that a previous anti-VEGF therapy decrease cetuximab efficiency.
    Digestive and Liver Disease 07/2011; 43(11):917-9. · 3.16 Impact Factor
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    ABSTRACT: Gemcitabine is the standard chemotherapy for patients with metastatic pancreatic adenocarcinoma. Although the 5-fluorouracil (5FU), folinic acid and cisplatin combination (LV5FU2-CDDP) is an option, the optimal order of the regimens must be determined. The first strategic phase III trial comparing LV5FU2-CDDP followed by gemcitabine versus gemcitabine followed by LV5FU2-CDDP was conducted. Patients with metastatic pancreatic adenocarcinoma, performance status (PS) 0-2, without prior chemotherapy were randomly assigned (1:1) to receive either LV5FU2-CDDP followed by gemcitabine at disease progression or toxicity (Arm A), or the opposite sequence (Arm B). 202 patients had to be included and 170 deaths had to be observed to detect an expected improvement in median overall survival (OS) from 6.5 to 10 months in Arm A (two-sided α = 5% and β = 20%). 202 patients were included (Arm A, 102; Arm B, 100). Median age, male/female ratio, PS 0-1 and previous surgery were similar in the two arms. After a median follow-up of 44 months, median OS in Arm A was 6.6 months versus 8.0 months in Arm B (p = 0.85). Median progression-free survival was similar between Arms A and B. More grade 3/4 toxicities were observed when LV5FU2-CDDP was administered as a first-line treatment compared with gemcitabine: 79% versus 64% (p = 0.018). This trial did not show any strategic advantage to using LV5FU2-CDDP as a first-line treatment and suggests that gemcitabine remains the standard first-line treatment. Sixty-one per cent of patients were able to receive a second line of chemotherapy.
    Gut 11/2010; 59(11):1527-34. · 10.73 Impact Factor
  • Endoscopy 03/2010; 42(03). · 5.74 Impact Factor
  • Endoscopy 03/2009; 41(03). · 5.74 Impact Factor
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    ABSTRACT: Introduction La qualité de prise en charge des hémorragies digestives dans les services d’urgence des hôpitaux reste discutable avec une grande hétérogénéité de pratique Patients et Méthodes 90 patients ont été adressés aux urgences avec un diagnostic final d’hémorragie digestive haute parmi 38 889 patients consultants aux urgences durant l’année 2006 (0,002 %). L’âge moyen était de 56 ans (15-90 ans) avec 60 hommes pour 30 femmes. Résultats 63 patients présentaient une hématémèse, 37 un méléna et 12 des rectorragies. Le délai de prise en charge était supérieur à 24 heures chez 18 patients (20 %). 17 patients avaient une consommation d’alcool significative dont 9 cirrhoses avec hypertension portale. 30 patients (33 %) prenaient des antiagregants ou anticoagulants. 7 patients (6 %) étaient en état de choc. 65 patients ont été hospitalisés et 13 transfusés. 20 patients seulement ont eu 2 voies veineuses périphériques, l’ECG n’a pas été fait chez 47 patients, un avis gastroentérologique n’a été demandé que dans 44 % des cas la nuit et 65 % le jour. 51 patients ont reçu une injection d’IPP en urgence. 49 patients ont eu une endoscopie digestive haute dans les 24H (17 saignements actifs), 14 sont sortis sans endoscopie et 2 patients l’ont refusée. 6 patients parmi les 65 hospitalisés sont décédés (10 %). Conclusion Malgré des efforts pour rendre sa prise en charge rigoureuse, des éléments essentiels de la surveillance, de la prise en charge hospitalière et endoscopique ne sont pas appliqués. Une « feuille de route » type mériterait d’être mise au point et appliquées dans les SAU.
    Gastroentérologie Clinique et Biologique 03/2009; 33(3):A49. · 1.14 Impact Factor
  • Gastroentérologie Clinique et Biologique 03/2009; 33(3). · 1.14 Impact Factor
  • Endoscopy 03/2009; 41(03). · 5.74 Impact Factor
  • Gastroenterologie Clinique Et Biologique - GASTROEN CLIN BIOL. 01/2009; 33(3).
  • Gastroenterologie Clinique Et Biologique - GASTROEN CLIN BIOL. 01/2009; 33(3).
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    ABSTRACT: Introduction Le cétuximab est un anticorps monoclonal anti- EGFR qui a prouvé son efficacité dans les CCRM en association à une chimiothérapie à base d’irinotecan ou en monothérapie [1]. De nombreuses études ont montré que la mutation KRAS est associée à un échec du traitement par cétuximab mais une faible proportion de patients KRAS sauvage sont répondeurs (10 à 49 %) [2]. Le but de ce travail rétrospectif multicentrique était d’évaluer la valeur prédictive des polymorphismes liés à l’EGFR sur la réponse au cétuximab sur une série de patients atteints d’un CCRM. Patients et Méthodes Les patients inclus rétrospectivement dans deux centres universitaires avaient un adénocarcinome colorectal métastatique traité par cétuximab. La mutation KRAS était analysée sur l’ADN tumoral des prélèvements inclus en paraffine et les polymorphismes EGFR R497K, intron 1 EGFR, EGFR - 216 G/T, EGFR -191 C/A, FCGR2A H131R, FCGR3 V158F, EGF G61A et Cycline D1 A870G étaient étudiés par PCR-RFLP sur ADN extrait de culots leucocytaires ou de prélèvement tissulaires inclus en paraffine. Résultats De décembre 2001 à décembre 2007, 58 patients ont été inclus. Parmi eux 86,2 % étaient en échappement thérapeutique à l’irinotecan et à l’oxaliplatine, et 22,4 % étaient prétraités par un anti-VEGF. La mutation KRAS a été retrouvée chez 16 patients (27,6 %). L’influence des polymorphismes a été testée chez les 43 patients ayant reçu au moins 6 cycles de cétuximab. Le taux de réponse était significativement amélioré chez les patients homozygotes pour l’allèle A de la CCND1 (50 % νs 8,6 %, p = 0,031). La survie sans progression (SSP médiane 2,7 mois) et la survie globale (SG médiane 8,4 mois) étaient significativement corrélées au polymorphisme EGFR-191 C/A avec une meilleure survie chez les patients homozygotes CC par rapport aux autres (p = 0,012 et 0,015 ; RR = 2,63 et 2,78, IC 95 % : 1,2 - 5,6 et 1,2 - 6,4, respectivement pour la SSP et la SG). Les autres polymorphismes n’influençaient ni la réponse ni la survie. La toxicité cutanée était significativement corrélée au polymorphisme de l’intron 1, avec une toxicité cutanée grade 2 et 3 plus importante chez les patients ayant un faible nombre de répétition dinucléotidique CA (85,7 % chez les patients avec une somme de CA ≤ 35 νs 55 % chez les patients avec une somme de CA > 35, p = 0,043, Odds ratio 4,9, IC 95 % CI : 1,1 - 22,1). Par ailleurs, la survie spécifique était significativement abaissée chez les patients traités antérieurement par un anti-VEGF de 9,1 à 4,9 mois (p = 0,03 RR = 2,2 ; IC 95 % : 1,1 - 4,5 p = 0,03). Conclusion Nos résultats suggèrent que les polymorphismes cycline D1 A870G, et EGFR -191C/A influencent significativement la réponse au cétuximab, la survie sans progression et la survie spécifique et confirment l’impact de l’intron 1 sur l’intensité de la toxicité cutanée. Un traitement antérieur par une thérapie anti VEGF est associé à une diminution significative de la survie spécifique.
    Gastroenterologie Clinique Et Biologique - GASTROEN CLIN BIOL. 01/2009; 33(3).

Publication Stats

380 Citations
204.98 Total Impact Points

Institutions

  • 2011
    • Hôpital Européen, Marseille
      Marsiglia, Provence-Alpes-Côte d'Azur, France
  • 2009
    • Polytech Marseille
      Marsiglia, Provence-Alpes-Côte d'Azur, France
  • 2002–2006
    • Assistance Publique Hôpitaux de Marseille
      Marsiglia, Provence-Alpes-Côte d'Azur, France
  • 2004
    • Hospital Drome Nord
      Romans, Rhône-Alpes, France