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FOLFIRI plus bevacizumab as a second-line therapy for metastatic intrahepatic cholangiocarcinoma

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World Journal of Gastroenterology 2015年第7期21卷 2096-2101页

作者： Jean-Florian Guion-Dusserre Veronique Lorgis julie vincent Leila Bengrine Francois Ghiringhelli Department of Medical Oncology Centre Georges-Fran?ois Leclerc Institut National de la Santé et de la Recherche Médicale University of Burgundy

AIM:To evaluate the efficacy and tolerance of FOLFIRI plus bevacizumab treatment outcome as second-line treatment for metastatic intrahepatic ***: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 *** 90 min)concurrently with folinic acid(400 mg/m2 *** 120 min)followed by fluorouracil(400 mg/m2 ***)then fluorouracil 2400 mg/m2 intravenous infusion over 46 h]and bevacizumab(5mg/kg)every 2 *** response was evaluated by computed tomography scan every 4 ***: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 *** 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 *** grade 3 hematological toxicities and one grade 3 digestive toxicity *** adaptive reduction in chemotherapy dosage was required in 2 patients due to hematological toxicity,and a delay in chemotherapy cycles was required for 3 ***: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.

关键词： Biliary tract cancer Intrahepatic cholangiocarcino

Safety and efficacy of a docetaxel-5FU-oxaliplatin regimen with or without trastuzumab in neoadjuvant treatment of localized gastric or gastroesophageal junction cancer: A retrospective study

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World Journal of Gastrointestinal Oncology 2019年第8期11卷 634-641页

作者： Valeria Basso David Orry Jean Fraisse julie vincent Audrey Hennequin Leila Bengrine Francois Ghiringhelli Department of Surgery Centre Georges Francois LeclercDijon 21000France Department of Medical Oncology Centre Georges Francois LeclercDijon 21000France

BACKGROUND Triplet chemotherapy,with docetaxel-5FU-oxaliplatin FLOT regimen recently became the standard perioperative treatment for localized gastric cancer(GC).An adapted regimen called TeFOX was recently tested in metastatic setting and gave promising *** To determine safety and efficacy of TeFOX perioperative *** This monocentric retrospective study aims to test efficacy and safety of the perioperative TeFOX regimen given alone or in combination with trastuzumab in patients with localized *** consist in docetaxel(50 mg/m^2)with oxaliplatin 85 mg/m^2 and and leucovorin(400mg/m^2^)5 FU bolus(400mg/m^2)on day 1,followed by continuous infusion of 5FU for 46h(2400mg/m^2)every 2 *** Thirty-three consecutive patients were included in this retrospective *** patients have a gastroesophageal junction cancer and 11 have a *** follow-up of surviving patients was 32 mo.R0 resection was obtained in 30(91)*** patients(36)had a pathological complete response and 8(24)patients a nearly complete pathological *** OS and PFS were not reached at data base *** have observed 6 metastatic relapses and 1 localized *** relapse was observed in patients with pathological complete *** most common grade 3-4 adverse events were peripheral neuropathy(21)and asthenia(20).CONCLUSION TeFOX regimen could be safely administrated in perioperative treatment of localized *** and the FLOT regimen have comparable efficacy and safety profiles.

关键词： Gastric cancer Neoadjuvant chemotherapy TeFOX Retrospective study

Hepatic arterial infusion of gemcitabine-oxaliplatin in a large metastasis from colon cancer

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World Journal of Gastroenterology 2010年第9期16卷 1150-1154页

作者： Boris Guiu julie vincent Séverine Guiu Sylvain Ladoire Pablo Ortega-Deballon Jean-Pierre Cercueil Bruno Chauffert Franois Ghiringhelli Department of Radiology INSERM U866University of BurgundyUniversity Hospital Department of Hepatology INSERM U866University of BurgundyUniversity Hospital Department of Oncology INSERM U866AVENIR TeamUniversity of Burgundy Department of Digestive Surgery INSERM U866University of BurgundyUniversity Hospital

Hepatic arterial infusion (HAI) of chemotherapy can be performed in cases of liver-confined metastatic disease,resulting in increased local drug *** 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 *** patient was treated with a combination of gemcitabine and oxaliplatin using *** tolerance was excellent and a radiological complete response was obtained after 8 cycles of *** rationale for the use of gemcitabine and oxaliplatin as well as that for the combination of the 2 drugs is discussed in this *** of gemcitabine-oxaliplatin should be evaluated in further clinical trials.

关键词： Hepatic artery Chemotherapy Colon cancer Liver metastasis Gemcitabine Oxaliplatin Contrast media Computed tomography

Folfirinox in elderly patients with pancreatic or colorectal cancer-tolerance and efficacy

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World Journal of Gastroenterology 2016年第42期22卷 9378-9386页

作者： Jean-Florian Guion-Dusserre Aurélie Bertaut Fran?ois Ghiringhelli julie vincent Valérie Quipourt Sophie Marilier Zoé Tharin Leila Bengrine-Lefevre Department of Medical Oncology Centre Georges-Fran?ois Leclerc Institut National de la Santé et de la Recherche Médicale University of Burgundy

AIM To study the tolerance and the efficiency of FOLFIRINOX in elderly patients diagnosed with colorectal or pancreatic *** 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 *** 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 pa

关键词： Elderly patients Feasibility treatment Pancreatic cancer Colorectal cancer FOLFIRINOX

Retrospective evaluation of FOLFIRI3 alone or in combination with bevacizumab or aflibercept in metastatic colorectal cancer

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World Journal of Clinical Oncology 2019年第2期10卷 75-85页

作者： Madeline Devaux Laura Gerard Corentin Richard Leila Bengrine-Lefevre julie vincent Antonin Schmitt Fran?ois Ghiringhelli Department of Medical Oncology Centre George Fran?ois Leclerc Platform of Transfer in Biological Oncology Centre George Fran?ois Leclerc

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 *** To determine safety and efficacy of FOLFIRI3 *** 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 *** 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 *** 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.

关键词： Colorectal cancer Chemotherapy Irinotecan Second-line Aflibercept

Oligodendroglial heterogeneity in health,disease,and recovery:deeper insights into myelin dynamics

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Neural Regeneration Research 2025年第11期20卷 3179-3192页

作者： Pieter-Jan Serneels julie D.De Schutter Lies De Groef Lieve Moons Steven Bergmans KU Leuven Leuven Brain InstituteDepartment of BiologyAnimal Physiology and Neurobiology DivisionNeural Circuit Development&Regeneration Research GroupLeuvenBelgium KU Leuven Leuven Brain InstituteDepartment of BiologyAnimal Physiology and Neurobiology DivisionCellular Communication&Neurodegeneration Research GroupLeuvenBelgium

Decades of research asserted that the oligodendroglial lineage comprises two cell types:oligodendrocyte precursor cells and ***,recent studies employing single-cell RNA sequencing techniques have uncovered novel cell states,prompting a revision of the existing *** forward,the oligodendroglial lineage should be delineated into five distinct cell states:oligodendrocyte precursor cells,committed oligodendrocyte precursor cells,newly formed oligodendrocytes,myelin-forming oligodendrocytes,and mature *** new classification system enables a deeper understanding of the oligodendroglia in both physiological and pathological *** this uniform terminology will facilitate comparison and integration of data across ***,including the consolidation of findings from various demyelinating models,is essential to better understand the pathogenesis of demyelinating ***,comparing injury models across species with varying regenerative capacities can provide insights that may lead to new therapeutic strategies to overcome remyelination ***,by standardizing terminology and synthesizing data from diverse studies across different animal models,we can enhance our understanding of myelin pathology in central nervous system disorders such as multiple sclerosis,Alzheimer's disease,and amyotrophic lateral sclerosis,all of which involve oligodendroglial and myelin dysfunction.

关键词： animal models demyelination fish mammals multiple sclerosis myelin neurodegeneration oligodendrocytes oligodendroglial lineage remyelination

SNAP23-Kif5 complex controls mGlu1 receptor trafficking

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Journal of Molecular Cell Biology 2018年第5期10卷 423-436页

作者： Fabrice Raynaud vincent Homburger Martial Seveno Oana Vigy Enora Moutina Laurent Fagni julie Perroy IGF CNRS INSERM Univ. Montpel[ier F-34094 Montpellier France BioCampus Montpellier CNRS INSERM Univ. Montpellier F-34094 Montpellier France Present address: INSERM U1046 PhyMedExp CNRS UMR9214 Univ. Montpellier F-34094 Montpellier France

Metabotropic glutamate receptors are expressed at excitatory synapses and control synaptic transmission in mammalian brain. These receptors are involved in numerous patho-physiological functions. However, little is known about the molecular determinants responsible for their intracellular transport and membrane targeting. Here we investigated the nature of the molecular motor and adaptor protein responsible for trafficking and membrane localization of the group I metabotropic glutamate mGlu1 postsynaptic receptor in cultured hippocampal neurons. In proteomic studies, we identified the synaptosome-associated protein 23 （SNAP23） and the molecular motor Kif5 kinesin as proteins interacting with mGlu1 receptor. We showed that SNAP23, but not Kif5, directly interacts with mGlu1 receptor carboxyl terminus. Using a recombination approach to impair or enhance the interaction between SNAP23 and KifS, we found that the SNAP23-Kif5 complex controls the trafficking of mGlu1 receptor along microtubules. Additional fluorescence recovery after cleavage experiments allowed us to identify a role of the complex in the receptor cell surface targeting. In conclusion, our study indicates that along dendritic processes Kif5-SNAP23 complex contributes to proper mGlu1 receptor trafficking and cell surface expression.

关键词： mGlu1 SNARE kinesin neuron traffic

Colon cancer stemness as a reversible epigenetic state:Implications for anticancer therapies

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World Journal of Stem Cells 2019年第11期11卷 920-936页

作者： Audrey vincent Aicha Ouelkdite-Oumouchal Mouloud Souidi julie Leclerc Bernadette Neve Isabelle Van Seuningen Lille University Institut National de la Sante et de la Recherche MédicaleCHU LilleUMR-S 1172-Jean-Pierre Aubert Research CenterLille F-59000France Department of Biochemistry and Molecular Biology Lille University HospitalLille F-59000France

The recent discovery of cancer cell plasticity,*** ability to reprogram into cancer stem cells(CSCs)either naturally or under chemotherapy and/or radiotherapy,has changed,once again,the way we consider cancer *** cancer stemness is a reversible epigenetic state rather than a genetic identity,opportunities will arise for therapeutic strategies that remodel epigenetic landscapes of ***,the systematic use of DNA methyltransferase and histone deacetylase inhibitors,alone or in combination,in advanced solid tumors including colorectal cancers,regardless of their molecular subtypes,does not seem to be the best *** this review,we first summarize the knowledge researchers have gathered on the epigenetic signatures of CSCs with the difficulty of isolating rare populations of *** raise questions about the relevant use of currently available epigenetic inhibitors(epidrugs)while the expression of numerous cancer stem cell markers are often repressed by epigenetic *** markers include the three cluster of differentiation CD133,CD44 and CD166 that have been extensively used for the isolation of colon ***,we describe current treatment strategies using epidrugs,and we hypothesize that,using correlation tools comparing associations of relevant CSC markers with chromatin modifier expression,we could identify better candidates for epienzyme targeting.

关键词： Cancer stem cells Colon cancer Epigenetics Chromatin modifying enzymes CD44 CD133 CD166

A MEASURE OF SUPPLY CHAIN COMPLEXITY INCORPORATING VIRTUAL ARCS

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Journal of Systems Science and Systems Engineering 2015年第4期24卷 486-499页

作者： julie Drzymalski Department of Industrial Engineering and Engineering Management Western New England University

Increased globalization, as well as the ability to have virtual supply chain partners, has had numerous effects on supply chains. While some of these effects are positive, making more resilient supply chains, there are also the negative effects of scale ~nd complexity, making these supply chains more challenging than ever to manage. Having a means to measure the complexity is crucial for today＇s managers to make more informed decisions. This measure must not only account for the number of arcs, but the amount of information and material carried on it, as well as incorporate the benefit that virtual arcs add to the network by increasing efficiency and reducing information, product and financial transfer costs and time. This research utilizes newer models in network clustering and complexity theory to make them applicable to supply chains and creates a new, practical approach to measuring supply chain complexity which can be easily implemented by practitioners.

关键词： Supply chain complexity clustering virtual networks