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| 1 | Caspase-1 activation by NLRP3 inflammasome dampens IL-33-dependent house dust mite-induced allergic lung inflammation显示文摘The cysteine protease caspase-1(Casp-1)contributes to innate immunity through the assembly of NLRP3,NLRC4,AIM2,and NLRP6 inflammasomes.Here we ask whether caspase-1 activation plays a regulatory role in house dust mite(HDM)-induced experimental allergic airway inflammation.We report enhanced airway inflammation in caspase-1-deficient mice exposed toHDMwith a marked eosinophil recruitment,increased expression of IL-4,IL-5,IL-13,aswell as full-length and bioactive IL-33.Furthermore,mice deficient for NLRP3 failed to control eosinophil influx in the airways and displayed augmented Th2 cytokine and chemokine levels,suggesting that the NLPR3 inflammasome complex controls HDM-induced inflammation.IL-33 neutralization by administration of soluble ST2 receptor inhibited the enhanced allergic inflammation,while administration of recombinant IL-33 during challenge phase enhanced allergic inflammation in caspase-1-deficient mice.Therefore,we show that caspase-1,NLRP3,and ASC,but not NLRC4,contribute to the upregulation of allergic lung inflammation.Moreover,we cannot exclude an effect of caspase-11,because caspase-1-deficient mice are deficient for both caspases.Mechanistically,absence of caspase-1 is associated with increased expression of IL-33,uric acid,and spleen tyrosine kinase(Syk)production.This study highlights acritical role of caspase-1 activation andNLPR3/ASCinflammasomecomplex in the down-modulation of IL-33 in vivo and in vitro,thereby regulating Th2 response in HDM-induced allergic lung inflammation. | Fahima Madouri Noelline Guillou Louis Fauconnier Tiffany Marchiol Nathalie Rouxel Pauline Chenuet Aurelie Ledru Lionel Apetoh Franc¸ois Ghiringhelli Mathias Chamaillard Song Guo Zheng Fabrice Trovero Valerie F.J.Quesniaux Bernhard Ryffel Dieudonnee Togbe | 2015 | Journal of Molecular Cell Biology2015，7，4： | 8 |
| 2 | Hepatic arterial infusion of gemcitabine-oxaliplatin in a large metastasis from colon cancer显示文摘Hepatic arterial infusion (HAI) of chemotherapy can be performed in cases of liver-confined metastatic disease,resulting in increased local drug concentrations.Here we report the case of a 61-year-old man who presented with an isolated large unresectable liver metastasis of colon cancer after failure of surgery and multiple administration of systemic chemotherapy.The patient was treated with a combination of gemcitabine and oxaliplatin using HAI.The tolerance was excellent and a radiological complete response was obtained after 8 cycles of HAI.The rationale for the use of gemcitabine and oxaliplatin as well as that for the combination of the 2 drugs is discussed in this paper.HAI of gemcitabine-oxaliplatin should be evaluated in further clinical trials. | Boris Guiu Julie Vincent Séverine Guiu Sylvain Ladoire Pablo Ortega-Deballon Jean-Pierre Cercueil Bruno Chauffert Franois Ghiringhelli | 2010 | World Journal of Gastroenterology2010，16，9： | 4 |
| 3 | Degarelix as a new antiangiogenic agent for metastatic colon cancer?显示文摘Recently,follicle stimulating hormone receptor was found to be selectively expressed by endothelial cells on tumor-associated blood vessels in a wide range of human cancers.In this context,we hypothesized that degarelix,a new gonadotropin-releasing hormone receptor antagonist developed for patients with prostate cancer,may have antiangiogenic effects via its capacity to block follicle stimulating hormone(FSH)production. We report the case of a patient with metastatic colon cancer exhibiting tumor progression after failure of all conventional chemotherapeutic regimens.The addition of degarelix to the last chemotherapeutic regimen was proposed as compassionate treatment.Degarelix induced a rapid decrease in FSH level.This treatment induced radiological stabilization and carcinoembryonic antigen stabilization during 1 year.Contrast-enhanced ultrasonography demonstrated reduction of tumor vas-clature.This case represents the first report of an antitumoral effect of degarelix in metastatic colon cancer and suggests an antiangiogenic property of this drug. | Francois Ghiringhelli Nicolas Isambert Sylvain Ladoire | 2013 | World Journal of Gastroenterology2013，19，5： | 2 |
| 4 | FOLFIRI plus bevacizumab as a second-line therapy for metastatic intrahepatic cholangiocarcinoma显示文摘AIM:To evaluate the efficacy and tolerance of FOLFIRI plus bevacizumab treatment outcome as second-line treatment for metastatic intrahepatic cholangiocarcinoma.METHODS:Thirteen consecutive patients with metastatic intrahepatic cholangiocarcinoma who were refractory tofirst-line therapy consisting of gemcitabine plus oxaliplatinbased first-line chemotherapy given intravenously via intra-arterial infusion were treated with FOLFIRI[irinotecan(180 mg/m2 i.v.over 90 min)concurrently with folinic acid(400 mg/m2 i.v.over 120 min)followed by fluorouracil(400 mg/m2 i.v.bolus)then fluorouracil 2400 mg/m2 intravenous infusion over 46 h]and bevacizumab(5mg/kg)every 2 wk.Tumor response was evaluated by computed tomography scan every 4 cycles.RESULTS:The best tumor responses using response evaluation criteria in solid tumor criteria were:complete response for 1 patient,partial response for 4 patients,and stable disease for 6 patients after 6 mo of follow-up.The response rate was 38.4%(95%CI:12.5-89)and the disease control rate was 84.5%(95%CI:42-100).Seven deaths occurred at the time of analysis,progression free survival was 8 mo(95%CI:7-16),and median overall survival was 20 mo(95%CI:8-48).No grade 4toxic events were observed.Four grade 3 hematological toxicities and one grade 3 digestive toxicity occurred.An adaptive reduction in chemotherapy dosage was required in 2 patients due to hematological toxicity,and a delay in chemotherapy cycles was required for 3 patients.CONCLUSION:FOLFIRI plus bevacizumab combination treatment showed promising efficacy and safety as second-line treatment for metastatic intrahepatic cholangiocarcinoma after failure of the first-line treatment of gemcitabine plus oxaliplatin chemotherapy. | Jean-Florian Guion-Dusserre Veronique Lorgis Julie Vincent Leila Bengrine Francois Ghiringhelli | 2015 | World Journal of Gastroenterology2015，21，7： | 2 |
| 5 | Folfirinox in elderly patients with pancreatic or colorectal cancer-tolerance and efficacy显示文摘AIM To study the tolerance and the efficiency of FOLFIRINOX in elderly patients diagnosed with colorectal or pancreatic cancer.METHODS This retrospective study included elderly patients aged over 70 years of age treated at Georges-Francois Leclerc Center by FOLFIRINOX for histological proved colorectal or pancreatic cancer between January 2009 and January 2015. Chemotheapy regimen consisted of oxaliplatin(85 mg/m2 in over 120 min) followed by leucovorin(400 mg/m2 in over 120 min), with the addition, after 30 min of irinotecan(180 mg/m2 in over 90 min) then 5 fluorouracil(5FU)(400 mg/m2 administred intravenous bolus), followed by 5FU(2400 mg/m2 intraveinous infusion over 46 h) repeated every 2 wk. Geriatric parameters were recorded at the beginning. Toxicities were evaluated with the Common Terminology Criteria for Adverse Events 4.03. Tumor response was evaluated by CT scan. Treatment continued until disease progression, unacceptable toxicities or patient refusal.RESULTS Fifty-two patients aged from 70 to 87 years were treated by FOLFIRINOX, 34 had colorectal cancer and 18 had pancreatic cancer. Most of them were in good general condition, 82.7% had a 0-1 performance status and 61.5% had a Charlson Comorbidity Index < 10. The most frequent severe toxicities were neutropenia(17 patients, n = 32.7%) and diarrhea(35 patients n = 67.3%); 10 of the case of neutropenia and 5 of diarrhea registered a grade 4 toxicity. Thirty-nine patients(75%) initially received an adapted dose of chemotherapy. The dosage was adjusted for 26% of patients during the course of treatment. Tumor response evaluated by RECIST criteria showed a controlled disease for 25 patients(48.1%), a stable disease for 13 and a partial response for 12 patients. Time under treatment was higher for colorectal cancer with a median time of 2.44 mo(95%CI: 1.61-3.25). Overall survival was 43.88 mo for colorectal cancer and 12.51 mo for pancreatic cancer. In univariate or multivariate analysis, none of geriatric parameters were linked to overall survival. Only the type of tumor(pancreatic/colorectal) was linked in both analysis.CONCLUSION For people over 70 years old, FOLFIRINOX regimen seems to induce manageable toxicities but similar, even higher, median survival rates compared to younger people. | Jean-Florian Guion-Dusserre Aurélie Bertaut Fran?ois Ghiringhelli Julie Vincent Valérie Quipourt Sophie Marilier Zoé Tharin Leila Bengrine-Lefevre | 2016 | World Journal of Gastroenterology2016，22，42： | 2 |
| 6 | Prognostic value of chemotherapy-induced hematological toxicity in metastatic colorectal cancer patients显示文摘AIM: To establish whether chemotherapy-induced neutropenia is predictive of better outcome in patients with metastatic colorectal cancer(mCRC). METHODS: Survival and patient characteristics from consecutive mCRC patients treated in the Centre Georges Francois Leclerc, Dijon, France between January 2001 and December 2011 were analyzed. Patient and tumor characteristics, hematological toxicity(neutropenia, anemia, and thrombocytopenia), and type of chemotherapy received were recorded. RESULTS: We retrospectively analyzed data from 399 consecutive patients with mCRC who received at least one line of chemotherapy. Median follow up was 6.3 years. Eighty-eight percent of the patients received more than two lines of chemotherapy. By univariate analysis, whatever their grade, neutropenia and thrombocytopenia occurring during the first two lines of chemotherapy were significantly associated with better overall survival(HR = 0.55, 95%CI: 0.43-0.70, P < 0.0001 and HR = 0.70, 95%CI: 0.56-0.88, P = 0.025 respectively). In contrast, anemia during chemotherapy was significantly associated with poorer overall survival(HR = 1.9, 95%CI: 1.22-2.97, P = 0.005). Multivariate analysis revealed that both neutropenia and thrombocytopenia were significantly associated with better overall survival: HR = 0.43, 95%CI: 0.29-0.64, P < 0.0001 and HR = 0.69, 95%CI: 0.49-0.98, P = 0.036, respectively. CONCLUSION: These data suggest that occurrence of neutropenia or thrombocytopenia during first- or second-line chemotherapy for mCRC is associated with better survival. | Laurie Rambach Aurelie Bertaut Julie Vincent Veronique Lorgis Sylvain Ladoire Francois Ghiringhelli | 2014 | World Journal of Gastroenterology2014，20，6： | 2 |
| 7 | Sirolimus,bevacizumab,5-Fluorouracil and irinotecan for advanced colorectal cancer:A pilot study显示文摘AIM:To evaluate the efficacy and the safety of combined 5-Fluorouracil,irinotecan,bevacizumab and sirolimus in refractory advanced colorectal carcinoma. METHODS:We initiated a regimen with at day 1 an injection(iv)of bevacizumab at 5 mg/kg,followed by 180 mg/m 2 irinotecan,followed by Leucovorin 400 mg/m 2 ,followed by a 5-Fluorouracil bolus 400 mg/m 2 and a 46-h infusion 2400 mg/m 2 .Sirolimus was given orally as continuous administration of 2 mg twice a day every days.This treatment was repeated every 14 d. RESULTS:A total of 12 patients were enrolled. All patients presented with metastatic disease that had failed at least three lines of chemotherapy that contained oxaliplatin,irinotecan and bevacizumab. Cetuximab failure was also observed in all K-Ras wildtype patients.The median number of cycles was 8.5 (range 2-20)and clinical benefit was observed in eight patients.The median time to progression was 5 mo and the median survival was 8 mo.Grade 3 neutropenia developed in four patients,and grade 3 diarrhea and stomatitis in two. CONCLUSION:The combination regimen of 5-Fluorouracil,irinotecan,bevacizumab and sirolimus in advanced colorectal carcinoma after failure of classical treatment is feasible and promising.Further evaluation of this combination is required. | Francois Ghiringhelli Boris Guiu Bruno Chauffert Sylvain Ladoire | 2009 | World Journal of Gastroenterology2009，15，34： | 2 |
| 8 | Retrospective evaluation of FOLFIRI3 alone or in combination with bevacizumab or aflibercept in metastatic colorectal cancer显示文摘BACKGROUND The treatment of metastatic colorectal cancer(mCRC) relies of chemotherapy. The efficacy of the standard FOLFIRI-therapy could be improved by a modification of the regimen by splitting the dose of irinotecan on day 1 and day 3 in the FOLFIRI3 regimen.AIM To determine safety and efficacy of FOLFIRI3 regimen.METHODS This is a monocentric retrospective study evaluating the efficacy and safety of the FOLFIRI3 regimen given alone or in combination with bevacizumab or aflibercept in patients with previously treated mCRC.RESULTS One hundred and fifty-three consecutive patients were included(18 treated with FOLFIRI3, 99 with FOLFIRI3 plus bevacizumab and 36 with FOLFIRI3 plus aflibercept). The overall response rate(ORR) and disease control rate were 51%and 62%, respectively. Similar ORRs were observed in all 3 cohorts. Median progression-free survival(PFS) and overall survival(OS) were 3.9 mo(95%CI:3.2-4.9) and 9.4 mo(95%CI: 6.6-12), respectively. Median PFS and OS values were improved in the FOLFIRI3 plus aflibercept group. The most common grade 3-4 adverse events were diarrhoea(21.6%) and neutropenia(11.8%), and these toxicities were more frequent in the FOLFIRI3 plus aflibercept group. According to the multivariate Cox proportional model, previous surgery of metastasis andaflibercept were associated with outcomes.CONCLUSION The modification of the FOLFIRI regimen impacted treatment response of mCRC patients. The addition of an antiangiogenic agent, in particular aflibercept,enhanced the clinical benefit and improved survival. | Madeline Devaux Laura Gerard Corentin Richard Leila Bengrine-Lefevre Julie Vincent Antonin Schmitt Fran?ois Ghiringhelli | 2019 | World Journal of Clinical Oncology2019，10，2： | 2 |
| 9 | Immunogenic death of colon cancer cells treated with oxaliplatin显示文摘 | Tesniere A Schlemmer F Boige V Kepp O Martins I Ghiringhelli F | 2010 | Oncogene2010，29，： | 1 |
| 10 | Tumor cell death and ATP release prime dendritic cells and efficient anticancer immunity显示文摘 | Aymeric L Apetoh L Ghiringhelli F | 2010 | Cancer Res2010，70，： | 1 |
| 11 | 'I3ae interaction between hmgbl and tlr4 dictates the outcome of antieaneer chemo- therapy and radiotherapy显示文摘 | Apetoh L Ghiringhelli F Tesniere A | 2007 | lmmunol Rev2007，220，12： | 1 |
| 12 | Metronomic cy-clophosphamide regimen selectively depletes CD4 +CD25 + regulatory T cells and restores T and NK effectorfunctions in end stage cancer patients 显示文摘 | Ghiringhelli F Menard C Puig PE | 2007 | Cancer Immu-nol Immunother2007，56，5： | 1 |
| 13 | Caspase-dependent immunogenicity of doxorubicin-induced tumor cell death显示文摘 | Casares N Pequignot M O Tesniere A Ghiringhelli F Roux S Chapu N | 2005 | J Exp Med2005，202，： | 1 |
| 14 | Calreticulin exposure dictates the immunogenicity of cancer cell death显示文摘 | Obeid M Tesniere A Ghiringhelli F Fimia G M Apetoh L Perfettini J L | 2007 | Nat Med2007，13，： | 1 |
| 15 | Calreticulin exposure dictates the immunogenicity of cancer cell death显示文摘 | Obeid M Tesniere A Ghiringhelli F A ct al | 2007 | Nat Med2007，13，1： | 1 |
| 16 | Toll-like receptor 4-dependent contribution of the immune system to anticancer chemotherapy and radiotherapy显示文摘 | Apetoh L Ghiringhelli F Tesniere A Obeid M Ortiz C Criollo A | 2007 | Nat Med2007，13，： | 1 |
| 17 | Prognostic role of FOXP3^+ regn-latory T cells infiltrating human carcinomas:the paradox of colorectal cancer 显示文摘 | Ladoire S Martin F Ghiringhelli F | 2011 | Cancer Immunol Immunother2011，60，7： | 1 |
| 18 | Prognostic role of FOXP3 + regulatory T cells infiltrating human carcinomas:the paradox of colorectal cancer显示文摘 | Ladoire S Martin F Ghiringhelli F | 2011 | Cancer Immunol Immunother2011，60，7： | 1 |
| 19 | Metronomic cyclophosphamide regimen selectively depletes CD4+CD25+ regulatory T cells and restores T and NK effector functions in end stage cancer patients显示文摘 | Fran?ois Ghiringhelli Cedric Menard Pierre Emmanuel Puig Sylvain Ladoire Stephan Roux Fran?ois Martin Eric Solary Axel Le Cesne Laurence Zitvogel Bruno Chauffert | 2007 | Cancer Immunology Immunotherapy2007，，5： | 1 |
| 20 | Calretieulin exposure dictates the immunogenicity of cancer cell death 显示文摘 | Obeid M Tesniere A Ghiringhelli F | 2007 | Nat Meal2007，13，1： | 1 |
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