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1.
Cacheux W Seksik P Lemann M Marteau P Nion-Larmurier I Afchain P Daniel F Beaugerie L Cosnes J 《The American journal of gastroenterology》2008,103(3):637-642
OBJECTIVES: Cyclosporine is an effective rescue therapy in steroid-refractory ulcerative colitis (UC) and may avoid immediate colectomy. However, the individual's response to cyclosporine is poorly predictable. The aim of this study was to identify predictive factors of the response to cyclosporine in steroid-refractory UC. METHODS: One hundred thirty-five patients with steroid-refractory UC, admitted consecutively between 1992 and 2004, were included. Data were collected on the first day of the cyclosporine therapy. Colonoscopy was performed within 2 days preceding or following the cyclosporine treatment in 118 patients for assessing the presence of severe endoscopic lesions. RESULTS: The actuarial rate of colectomy was 0.45 at 6 months. Cox analysis in the whole population selected three predictive criteria of colectomy: body temperature >37.5 degrees C (adjusted hazard ratio = 1.94, 95% confidence interval 1.51-2.49), heart rate >90 bpm (1.86, 1.45-2.38), and C-reactive protein (CRP) >45 mg/L (1.70, 1.34-2.16). In the 118 patients who underwent colonoscopy, the presence of severe endoscopic lesions was an independent predictive factor of colectomy (2.38, 1.80-3.14). Colonoscopy was decisive and changed the therapeutic decision in patients with one or two criteria: 71% of the patients with severe endoscopic lesions were colectomized versus 17% of the patients without severe endoscopic lesions (P < 0.001). Finally, the clinical, biological, and endoscopic criteria allowed the classification of the patients into two different groups (80%vs 20% colectomy at 6 months). CONCLUSION: In patients with steroid-refractory UC, the combination of simple criteria is useful to predict the response to cyclosporine. Colonoscopy is crucial in patients with intermediate clinical and biological severity. 相似文献
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Maud Kamal Sonia Lameiras Marc Deloger Adeline Morel Sophie Vacher Charlotte Lecerf Clia Dupain Emmanuelle Jeannot Elodie Girard Sylvain Baulande Coraline Dubot Gemma Kenter Ekaterina S. Jordanova Els M. J. J. Berns Guillaume Bataillon Marina Popovic Roman Rouzier Wulfran Cacheux Christophe Le Tourneau Alain Nicolas Nicolas Servant Suzy M. Scholl Ivan Biche RAIDs Consortium 《British journal of cancer》2021,124(4):777
Background Cervical cancer (CC) remains a leading cause of gynaecological cancer-related mortality with infection by human papilloma virus (HPV) being the most important risk factor. We analysed the association between different viral integration signatures, clinical parameters and outcome in pre-treated CCs.Methods Different integration signatures were identified using HPV double capture followed by next-generation sequencing (NGS) in 272 CC patients from the BioRAIDs study []. Correlations between HPV integration signatures and clinical, biological and molecular features were assessed.Results Episomal HPV was much less frequent in CC as compared to anal carcinoma (p < 0.0001). We identified >300 different HPV-chromosomal junctions (inter- or intra-genic). The most frequent integration site in CC was in MACROD2 gene followed by MIPOL1/TTC6 and TP63. HPV integration signatures were not associated with histological subtype, FIGO staging, treatment or PFS. HPVs were more frequently episomal in PIK3CA mutated tumours (p = 0.023). Viral integration type was dependent on HPV genotype (p < 0.0001); HPV18 and HPV45 being always integrated. High HPV copy number was associated with longer PFS (p = 0.011).Conclusions This is to our knowledge the first study assessing the prognostic value of HPV integration in a prospectively annotated CC cohort, which detects a hotspot of HPV integration at MACROD2; involved in impaired PARP1 activity and chromosome instability.Subject terms: NCT02428842Oncology, Molecular medicine, Biomarkers, Molecular biology 相似文献
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Abderaouf Hamza Julien Masliah-Planchon Cindy Neuzillet Jérémie H. Lefèvre Magali Svrcek Sophie Vacher Christine Bourneix Matthieu Delaye Diane Goéré Peggy Dartigues Emmanuelle Samalin Marc Hilmi Julien Lazartigues Elodie Girard Jean-François Emile Eugénie Rigault Virginie Dangles-Marie Nathalie Rioux-Leclercq Christelle de la Fouchardière David Tougeron Andrea Casadei-Gardini Pascale Mariani Frédérique Peschaud Wulfran Cacheux Astrid Lièvre Ivan Bièche 《International journal of cancer. Journal international du cancer》2024,154(3):504-515
The management of anal squamous cell carcinoma (ASCC) has yet to experience the transformative impact of precision medicine. Conducting genomic analyses may uncover novel prognostic biomarkers and offer potential directions for the development of targeted therapies. To that end, we assessed the prognostic and theragnostic implications of pathogenic variants identified in 571 cancer-related genes from surgical samples collected from a homogeneous, multicentric French cohort of 158 ASCC patients who underwent abdominoperineal resection treatment. Alterations in PI3K/AKT/mTOR, chromatin remodeling, and Notch pathways were frequent in HPV-positive tumors, while HPV-negative tumors often harbored variants in cell cycle regulation and genome integrity maintenance genes (e.g., frequent TP53 and TERT promoter mutations). In patients with HPV-positive tumors, KMT2C and PIK3CA exon 9/20 pathogenic variants were associated with worse overall survival in multivariate analysis (Hazard ratio (HR)KMT2C = 2.54, 95%CI = [1.25,5.17], P value = .010; HRPIK3CA = 2.43, 95%CI = [1.3,4.56], P value = .006). Alterations with theragnostic value in another cancer type was detected in 43% of patients. These results suggest that PIK3CA and KMT2C pathogenic variants are independent prognostic factors in patients with ASCC with HPV-positive tumors treated by abdominoperineal resection. And, importantly, the high prevalence of alterations bearing potential theragnostic value strongly supports the use of genomic profiling to allow patient enrollment in precision medicine clinical trials. 相似文献
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Romain Coriat Olivier Mir Anatole Cessot Catherine Brezault Stanislas Ropert Jean-Philippe Durand Wulfran Cacheux Stanislas Chaussade Fran?ois Goldwasser 《Investigational new drugs》2012,30(1):376-381
Purpose The only drug that improves survival in hepatocellular carcinoma is sorafenib. FOLFOX-4 regimen is safe and widely used in
patients with colorectal cancer, yielding interesting results with little toxicity. We conducted a retrospective study to
evaluate the safety and the effectiveness of FOLFOX-4 in cirrhotic or liver transplanted patients with hepatocellular carcinoma
ineligible for sorafenib. Methods Thirty seven patients were enrolled in the study. The medical record of either cirrhotic patients or liver transplanted patients
with advanced hepatocellular carcinoma receiving FOLFOX-4 regimen between November 1999 and March 2006 were retrospectively
analyzed. Patients received oxaliplatin 85 mg/m2 as a 2-hour infusion on day one, and leucovorin 200 mg/m2 as a 2-hour infusion followed by bolus 5-fluorouracil 400 mg/m2 and a 48-hours infusion of 5-fluorouracil 2400 mg/m2. Treatment was repeated every 2 weeks until disease progression or unacceptable adverse effects occurred. Results Patients had a Child-Pugh class A (n = 16), class B cirrhosis (n = 10) or a liver transplant (n = 11) and received 2 to 37 cycles of chemotherapy (total of 310 cycles). Two (5.4%) cirrhotic patients developed neutropenic
sepsis and one (2.7%) toxic death occurred. At first assessment, five patients from Child-Pugh class A (33%) and two from
Child-Pugh class B group (20%) achieved a radiological response and/or alpha foeto-protein decrease, and no patient achieved
a complete response. Conclusions In conclusion, with a manageable toxicity profile in cirrhotic Child-Pugh class A-B or liver transplanted patients, the FOLFOX-4
regimen appears to be a feasible treatment option for patients with advanced hepatocellular carcinoma unfit for sorafenib.
These data need to be confirmed in a prospective study. 相似文献
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Mariani P Lae M Degeorges A Cacheux W Lappartient E Margogne A Pierga JY Girre V Mignot L Falcou MC Salmon RJ Delattre O De Cremoux P 《Anticancer research》2010,30(10):4229-4235
KRAS somatic mutations are the main predictive factor for non response to EGFR-targeted monoclonal antibodies in metastatic colorectal cancer (mCRC) patients. We compared KRAS mutational status in the primary tumour and the corresponding metastases (1 to 4 sites) in 38 mCRC patients. KRAS mutational status was analysed using direct sequencing, SNAPShot multiplex PCR and Scorpion Taqman PCR analysis. Results showed 54% of primary tumours had KRAS mutations. A concordance of 97% between primaries and metastatic sites was observed. A tumour heterogeneity was also demonstrated in 5% of mCRC. One case with three different primary tumours harboured three different KRAS mutations, and only one was represented in the unique metastasis of this patient. We concluded there was a high concordance in the KRAS status between the primary tumour and metastases. More than one informative block and more sensitive assay may increase the accuracy of KRAS status determination. 相似文献
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HPV circulating tumor DNA to monitor the efficacy of anti‐PD‐1 therapy in metastatic squamous cell carcinoma of the anal canal: A case report 下载免费PDF全文
Luc Cabel François‐Clément Bidard Vincent Servois Wulfran Cacheux Pascale Mariani Emanuela Romano Mathieu Minsat Ivan Bieche Fereshteh Farkhondeh Emmanuelle Jeannot Bruno Buecher 《International journal of cancer. Journal international du cancer》2017,141(8):1667-1670
Squamous cell carcinoma of the anal canal (SCCA) is a rare HPV‐associated cancer with limited sensitivity to standard chemotherapy. In a phase 2 study, nivolumab, an anti PD‐1 immune checkpoint inhibitor, demonstrated significant efficacy as single‐agent therapy in metastatic SCCA patients. Nevertheless, imaging assessment by standard RECIST criteria of the efficacy of immune therapy can be difficult in some patients due to tumor immune cell infiltration, and biomarkers of treatment efficacy are needed. We have previously developed a quantitative droplet digital PCR (ddPCR) technique to detect HPV circulating tumor DNA (HPV ctDNA), with excellent sensitivity and specificity. Here, we report, for the first time, the kinetics of HPV ctDNA during therapy in a patient with metastatic SCCA, who obtained sustained partial response to single‐agent nivolumab. We observed an early and very significant decrease of HPV ctDNA during therapy from the baseline level of 3713 copies/ml plasma to 564 copies/ml plasma at 4 weeks, and 156 copies/ml at 6 weeks, followed by a plateau. This observation provides proof‐of‐concept that HPV ctDNA can be used as a noninvasive early dynamic biomarker to monitor the efficacy of new immunotherapy agents. 相似文献
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Tolerance of 4-aminosalicylic acid enemas in patients with inflammatory bowel disease and 5-aminosalicylic-induced acute pancreatitis 总被引:1,自引:0,他引:1
Derivatives of 5-aminosalicylic acid (5-ASA) used for the treatment of inflammatory bowel disease may induce acute pancreatitis of immunoallergic origin. 4-aminosalicylic acid (4-ASA) differs from its 5-ASA counterpart by the position of the NH2 group and has shown efficacy in ulcerative colitis. The risk of cross intolerance reaction between 5-ASA and 4-ASA has currently never been evaluated. We report three cases of 5-ASA-induced pancreatitis, with no recurrence of pancreatitis during subsequent treatment with 4-ASA enemas. We conclude that 4-ASA enemas are a safe and well-tolerated therapeutic alternative whenever 5-ASA-induced pancreatitis occurs. 相似文献
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Gefitinib, an EGFR inhibitor, prevents hepatocellular carcinoma development in the rat liver with cirrhosis 总被引:8,自引:0,他引:8
Schiffer E Housset C Cacheux W Wendum D Desbois-Mouthon C Rey C Clergue F Poupon R Barbu V Rosmorduc O 《Hepatology (Baltimore, Md.)》2005,41(2):307-314
Epidermal growth factor receptor (EGFR) binds transforming growth factor alpha (TGF-alpha) which is mitogenic for hepatocytes. Diverse lines of evidence suggest that activation of the TGF-alpha /EGFR pathway contributes to hepatocellular carcinoma (HCC) formation. Herein, we developed an experimental model of cirrhosis giving rise to HCC and tested the antitumoral effect of gefitinib, a selective EGFR tyrosine kinase inhibitor, in this model. Rats received weekly intraperitoneal injections of diethylnitrosamine (DEN) followed by a 2-week wash-out period that caused cirrhosis in 14 weeks and multifocal HCC in 18 weeks. Hepatocyte proliferation was increased in diseased tissue at 14 weeks compared with control liver and at even higher levels in HCC nodules compared with surrounding diseased tissues at 18 weeks. Increased proliferation was paralleled by upregulation of TGF-alpha messenger RNA expression. A group of DEN-treated rats received daily intraperitoneal injections of gefitinib between weeks 12 and 18. In rats treated with gefitinib, the number of HCC nodules was significantly lower than in untreated rats (18.1 +/- 2.4 vs. 3.7 +/- 0.45; P < .05), while EGFR was activated to a lesser extent in the diseased and tumoral tissues of these animals compared with untreated rats. HCC nodules from both untreated and gefitinib-treated animals displayed insulin-like growth factor 2 overexpression that contributed to tumor formation in treated animals. In conclusion, the blockade of EGFR activity by gefitinib has an antitumoral effect on the development of HCC in DEN-exposed rats, suggesting that it may provide benefit for the chemoprevention of HCC. 相似文献
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Wulfran Bougouin Lionel Lamhaut Eloi Marijon Daniel Jost Florence Dumas Nicolas Deye Frankie Beganton Jean-Philippe Empana Emilie Chazelle Alain Cariou Xavier Jouven 《Intensive care medicine》2014,40(6):846-854