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Biomarkers of cetuximab resistance in patients with head and neck squamous cell carcinoma

Cancer Biology & Medicine 2020年第1期17卷 208-217页

作者： Olivia Leblanc sophie Vacher Charlotte Lecerf emmanuelle Jeannot Jerzy Klijanienko Frederique Berger Caroline Hoffmann Valentin Calugaru Nathalie Badois Anne Chilles Maria Lesnik Samar Krhili IvanBieche Christophe Le Tourneau Maud Kamal Department of Genetics Curie InstitutePSL Research UniversityParis 75005France Department of Drug Development and Innovation(D3i) Curie InstitutePSL Research UniversityParis 75005France Department of Pathology Curie InstitutePSL Research UniversityParis 75005France Department of Biostatistics Curie InstitutePSL Research UniversityParis 75005France Department of Surgery Curie InstitutePSL Research UniversityParis 75005France INSeRM U932 Research Unit Paris 75005France Department of Radiotherapy Curie InstitutePSL Research UniversityParis 75005France eA7331 Faculty of Pharmaceutical and Biological SciencesParis Descartes UniversityParis 75005France INSeRM U900 Research Unit Curie InstituteParis 75005France

Objective:In patients with head and neck squamous cell carcinoma(HNSCC),cetuximab[a monoclonal antibody targeting epidermal growth factor receptor(eGFR)]has been shown to improve overall survival when combined with radiotherapy in the locally advanced setting or with chemotherapy in first-line recurrent and/or metastatic(R/M)setting,*** biomarkers of resistance to cetuximab have been identified in metastatic colorectal cancer,no biomarkers of efficacy have been identified in ***,we aimed to identify biomarkers of cetuximab sensitivity/resistance in ***:HNSCC patients treated with cetuximab at the Curie Institute,for whom complete clinicopathological data and formalin-fixed paraffin-embedded(FFPe)tumor tissue collected before cetuximab treatment were available,were *** analyses of PTeN and eGFR were performed to assess protein expression ***3 CA and H/N/KRAS mutations were analyzed using high-resolution melting(HRM)and Sanger *** evaluated the predictive value of these alterations in terms of progression-free survival(PFS).Results:Hot spot activating PIK3 CA and KRAS/HRAS mutations were associated with poor PFS among HNSCC patients treated with cetuximab in the first-line R/M setting,but not among HNSCC patients treated with cetuximab in combination with *** of PTeN protein expression had a negative predictive value among HNSCC patients treated with cetuximab and *** eGFR expression did not predict cetuximab sensitivity in our patient ***:Hot spot activating PIK3 CA and RAS mutations predicted cetuximab resistance among HNSCC patients in the firstline R/M setting,whereas loss of PTeN protein expression predicted resistance to cetuximab when combined to radiotherapy.

关键词： Head and neck squamous cell carcinoma cetuximab biomarker PIK3CA RAS

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Comparison of open and closed hyperthermic intraperitoneal chemotherapy: Results from the United States hyperthermic intraperitoneal chemotherapy collaborative

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World Journal of Gastrointestinal Oncology 2020年第7期12卷 756-767页

作者： Jennifer L Leiting Jordan M Cloyd Ahmed Ahmed Keith Fournier Andrew J Lee sophie Dessureault Seth Felder Jula Veerapong Joel M Baumgartner Callisia Clarke Harveshp Mogal Charles A Staley Mohammad Y Zaidi Sameer H Patel Syed A Ahmad Ryan J Hendrix Laura Lambert Daniel e Abbott Courtney Pokrzywa Mustafa Raoof Christopher J LaRocca Fabian M Johnston Jonathan Greer Travis e Grotz Division of Hepatobiliary and Pancreas Surgery Mayo ClinicRochesterMN 55901United States Division of Surgical Oncology Department of SurgeryThe Ohio State University Wexner Medical CenterColumbusOH 43210United States Department of Surgical Oncology University of Texas MD Anderson Cancer CenterHoustonTX 77030United States Department of Gastrointestinal Oncology Moffitt Cancer CenterDepartment of Oncologic SciencesMorsani College of MedicineTampaFL 33612United States Division of Surgical Oncology Department of SurgeryUniversity of CaliforniaSan DiegoCA 92093United States Division of Surgical Oncology Department of SurgeryMedical College of WisconsinMilwaukeeWI 53226United States Division of Surgical Oncology Winship Cancer InstituteEmory UniversityAtlantaGA 30322United States Department of Surgery University of Cincinnati College of MedicineCincinnatiOH 45267United States Division of Surgical Oncology Department of SurgeryUniversity of Massachusetts Medical SchoolWorcesterMA 01655United States Peritoneal Surface Malignancy Program Section of Surgical Oncology Huntsman Cancer InstituteUniversity of UtahSalt Lake CityUT 84112United States Division of Surgical Oncology Department of SurgeryUniversity of WisconsinMadisonWI 53792United States Christopher La Rocca Division of Surgical OncologyDepartment of SurgeryCity of Hope National Medical CenterDuarteCA 91010United States Department of Surgery Johns Hopkins UniversityBaltimoreMD 21287United States

BACKGROUND Cytoreductive surgery(CRS)with hyperthermic intraperitoneal chemotherapy(HIPeC)for peritoneal carcinomatosis can be performed in two ways:Open or closed abdominal *** To evaluate the impact of HIPeC method on post-operative and long-term survival *** Patients undergoing CRS with HIPeC from 2000-2017 were identified in the United States HIPeC collaborative ***-operative,recurrence,and overall survival outcomes were compared between those who received open vs closed *** Of the 1812 patients undergoing curative-intent CRS and HIPeC,372(21%)patients underwent open HIPeC and 1440(79%)underwent closed *** was no difference in re-operation or severe complications between the two *** HIPeC had higher rates of 90-d readmission while open HIPeC had a higher rate of 90-d *** multi-variable analysis,closed HIPeC technique was not a significant predictor for overall survival(hazards ratio:0.75,95%confidence interval:0.51-1.10,P=0.14)or recurrence-free survival(hazards ratio:1.39,95%confidence interval:1.00-1.93,P=0.05)in the entire *** findings remained consistent in the appendiceal and the colorectal *** In this multi-institutional analysis,the HIPeC method was not independently associated with relevant post-operative or long-term *** technique may be left to the discretion of the operating surgeon.

关键词： Mucinous appendiceal carcinoma Cytoreductive surgery Multi-institutional

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家庭之约

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作者： (美)雷·摩尔(e. Ray moore) (美)吉尔·摩尔(Gail Pinckney moore)

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evaluation of a Preventive effect of a Lotion on the Formation of Stretch Marks. Quantification of Contractile Forces Developed by Fibroblasts from early Stretch Marks (Red Color) and from Healthy Surrounding Skin Using GlasBoxPlusDevice

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Journal of Cosmetics, Dermatological Sciences and Applications 2017年第2期7卷 177-188页

作者： Carol Courderot-Masuyer sophie Robin Ferial Fanian Philippe Humbert Bioexigence SAS Espace Lafayette Besan&ccedil on France Research and Studies Center on the Integument (CeRT) Department of Dermatology Clinical Investigation Center (CIC INSERM 1431) Besan&ccedil on University Hospital INSeRM UMR1098 FED4234 IBCT University of Franche-Comté Besan&ccedil on France

Stretch marks are cutaneous lesions occurring frequently in weight gain during puberty and early adult life. Previous studies showed that highest contractile forces were developed by fibroblasts from early stretch marks (SMF) compared to those developed by fibroblasts from normal healthy skin (HF) of the same patient. The aim of the present study was to evaluate a possible preventive effect of a topical preparation (containing vitamins C and e and botanical extracts including natural extract of Calendula, Aloe Vera and evening Primrose Oil) on the formation of stretch marks using GlasboxPlus? device. In the presence of the tested mixture, a significant overall decrease in contractile forces of SMF was noted for 24 hours of measurements compared to control SMF and made it possible to restore their capacity to the same level as HF indicating a possible preventive effect of the tested mixture. The synergistic effects of these components are certainly responsible for the decrease in contractile forces of early stretch marks fibroblasts.

关键词： Stretch Marks Fibroblasts Mechanical Forces Preventive effect

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A comparative pattern of lectin-binding in the endometrial glands of the uterus and placenta of healthy buffaloes and bovines at early gestation

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BIOCeLL 2021年第2期45卷 331-337页

作者： SeRGIO GASTÓN CASPe JOSÉLUIS KONRAD DADIN PRANDO moore JUAN MANUeL SALA LILIAN LISCHINSKY CARLOS MANUeL CAMPeRO CLAUDIO GUSTAVO BARBeITO Laboratory of Pathology Experimental Station MercedesInstituto Nacional de Tecnología AgropecuariaCorrientes3470Argentina Laboratory of Theriogenology School of Veterinary SciencesUniversidad Nacional del NordesteCorrientesW3402BKGArgentina Animal Health Group Experimental Station BalcarceInstituto Nacional de Tecnología AgropecuariaBalcarceB7620EMAArgentina Laboratory of Histology and embryology School of Veterinary SciencesUniversidad Nacional de La PlataLa Plata1900Argentina

Water buffalo(Bubalus bubalis)and domestic cattle(Bos taurus)are closely related ***,embryo transfer interspecies has been attempted without any *** failure in hybrid embryo-implantation is associated with the glycocode in the maternal-fetal *** patterns have been studied in different species of ruminants;however,in ***,only the binucleated cells(BNC)have been *** glycocode is essential for a successful embryo-implantation and can be defined by Lectin-Histochemistry(LHC).The aim of this study is to compare the glycosylation pattern of placenta and uterus in water buffaloes and cattle by *** samples of placenta and uterus from pregnant Mediterranean female water buffaloes(Buf1)and Angus cows(Bov1)were *** animals were euthanized at 98 days of *** was carried out using twelve lectins(Con A,LCA,PSA,sWGA,PHA-e,SBA,UeA-1,WGA,RCA-1,PNA,DBA,BSA-1).The intensity of lectin binding was semiquantitatively scored using a scale of 0(negative)to 3(strongly positive).Difference between species was found in trophoblast layer by PSA,SWGA,PNA and BSA-1,in BNC,and in the mononuclear cells by LCA,PSA,PHA-e,DBA,BSA-1,*** utero,differences in the apical cellular membrane and the secretion of glands were identified by DBA and RCA-1,and in the cytoplasm of those glandular epithelial cells by PHA-e,BSA-1,WGA,and *** both species,BNC presented a strong positive reaction with DBA and SBA,a moderate response by LCA,PHA-e,BSA-1 and PNA lectin,and a low reaction by PSA,UeA-1,SWGA,WGA,Con A and *** results found in this study suggest that although both species are closely related,glycosylation patterns in the placenta and uterus are different,thus providing a possible reason for embryo transfer not being possible between these species.

关键词： Lectin-histochemistry Water buffalo Placenta Glycosylation pattern

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SHP2 regulates skeletal cell fate by modifying SOX9 expression and transcriptional activity

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Bone Research 2018年第2期6卷 132-144页

作者： Chunlin Zuo Lijun Wang Raghavendra M.Kamalesh Margot e.Bowen Douglas C.moore Mark S.Dooner Anthony M.Reginato Qian Wu Christoph Schorl Yueming Song Matthew L.Warman Benjamin G.Neel Michael G.ehrlich Wentian Yang Department of Orthopaedics Brown University Alpert Medical School and Rhode Island HospitalProvidenceRI 02903USA Orthopaedic Research Laboratories and Howard Hughes Medical Institute Boston Children's Hospital and Department of GeneticsHarvard Medical SchoolBostonMA 02115USA Division of Hematology and Oncology Brown University Alpert Medical School and Rhode Island HospitalProvidenceRI 02903USA Division of Rheumatology Brown University Alpert Medical School and Rhode Island HospitalProvidenceRI 02903USA Department of Pathology and Laboratory Medicine University of Connecticut Health CenterFarmingtonCT 06030USA Department of Molecular and Cell Biology and Biochemistry Brown University70 Ship StreetProvidenceRI 02912USA Department of Orthopedic Surgery West China Hospital of Sichuan UniversityChengdu 610041 Laura and Issac Perlmutter Cancer Center NYU Langone Medical CenterNew YourkNY 10016USA Department of endocrinology the First Affiliated Hospital of Anhui Medical UniversityHefei 230022China

Chondrocytes and osteoblasts differentiate from a common mesenchymal precursor, the osteochondroprogenitor（OCP）, and help build the vertebrate skeleton. The signaling pathways that control lineage commitment for OCPs are incompletely understood. We asked whether the ubiquitously expressed protein-tyrosine phosphatase SHP2（encoded by Ptpn11） affects skeletal lineage commitment by conditionally deleting Ptpn11 in mouse limb and head mesenchyme using ＂Cre-lox P＂-mediated gene ***2-deficient mice have increased cartilage mass and deficient ossification, suggesting that SHP2-deficient OCPs become chondrocytes and not osteoblasts. Consistent with these observations, the expression of the master chondrogenic transcription factor SOX9 and its target genes Acan, Col2a1, and Col10a1 were increased in SHP2-deficient chondrocytes, as revealed by gene expression arrays, q RT-PCR, in situ hybridization, and immunostaining. Mechanistic studies demonstrate that SHP2 regulates OCP fate determination via the phosphorylation and SUMOylation of SOX9, mediated at least in part via the PKA signaling pathway. Our data indicate that SHP2 is critical for skeletal cell lineage differentiation and could thus be a pharmacologic target for bone and cartilage regeneration.

关键词： SHP2 regulates skeletal cell modifying SOX9 expression transcriptional activity SOX

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Loss of Notch signaling in skeletal stem cells enhances bone formation with aging

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Bone Research 2023年第4期11卷 737-750页

作者： Lindsey H.Remark Kevin Leclerc Malissa Ramsukh Ziyan Lin Sooyeon Lee Backialakshmi Dharmalingam Lauren Gillinov Vasudev V.Nayak Paulo el Parente Margaux Sambon Pablo J.Atria Mohamed A.e.Ali Lukasz Witek Alesha B.Castillo Christopher Y.Park Ralf H.Adams Aristotelis Tsirigos sophie M.Morgani Philipp Leucht Department of Orthopaedic Surgery NYU Robert I.Grossman School of MedicineNew YorkNYUSA Applied Bioinformatics Laboratories NYU Grossman School of MedicineNew YorkNYUSA Institute of Comparative Molecular endocrinology Ulm UniversityUlmGermany Max Planck Institute for Molecular Biomedicine Department of Tissue Morphogenesisand University of MünsterFaculty of MedicineD-48149 MünsterGermany Department of Biochemistry and Molecular Biology University of Miami Miller School of MedicineMiamiFLUSA Department of Pathology NYU Robert I.Grossman School of MedicineNew YorkNYUSA Biomaterials Division New York University College of DentistryNew YorkNYUSA Hansjörg Wyss Department of Plastic Surgery NYU Grossman School of MedicineNew York UniversityNew YorkNYUSA Department of Biomedical engineering Tandon School of EngineeringNew York UniversityBrooklynNYUSA Department of Cell Biology NYU Robert I.Grossman School of MedicineNew YorkNYUSA

Skeletal stem and progenitor cells(SSPCs) perform bone maintenance and repair. With age, they produce fewer osteoblasts and more adipocytes leading to a loss of skeletal integrity. The molecular mechanisms that underlie this detrimental transformation are largely unknown. Single-cell RNA sequencing revealed that Notch signaling becomes elevated in SSPCs during aging. To examine the role of increased Notch activity, we deleted Nicastrin, an essential Notch pathway component, in SSPCs in vivo. Middle-aged conditional knockout mice displayed elevated SSPC osteo-lineage gene expression, increased trabecular bone mass, reduced bone marrow adiposity, and enhanced bone repair. Thus, Notch regulates SSPC cell fate decisions, and moderating Notch signaling ameliorates the skeletal aging phenotype, increasing bone mass even beyond that of young mice. Finally, we identified the transcription factor ebf3 as a downstream mediator of Notch signaling in SSPCs that is dysregulated with aging, highlighting it as a promising therapeutic target to rejuvenate the aged skeleton.

关键词： Notch skeletal elevated

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干扰素

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国外医学.外科学分册 1982年第1期09卷 11-15页

作者： moore G e 鲁泽清

病毒专家认为第一次病毒感染通常被后继的病毒感染所干扰,1957年 Isaacs 和 Lindenmann 对此进行了令人鼓舞的连续观察,他们称由感染细胞释放的因子为干扰素。简短地说,热灭活的流感病毒与经绒毛筷尿囊培养过夜。若将培养液的上层清液... 详细信息

病毒专家认为第一次病毒感染通常被后继的病毒感染所干扰,1957年 Isaacs 和 Lindenmann 对此进行了令人鼓舞的连续观察,他们称由感染细胞释放的因子为干扰素。简短地说,热灭活的流感病毒与经绒毛筷尿囊培养过夜。若将培养液的上层清液加入新鲜组织培养物,则活病毒的生长受到抑制。早在1935年 Hoskins 就曾确切地描述了这一现象,但是实验未阐述清楚。已知干扰素的机制是一种特殊病毒可干扰继发感染:破坏受体;感染使与缺陷颗粒竞争;内在性竟争核糖核甙酸节段的配对;竞争必要的生长元素,以及生产抑制性激素——干扰素。

关键词：干扰素人类恶性疾病淋巴样恶性细胞肿瘤细胞抗病毒药细胞毒性 IFN

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枫长镰管蚜气味结合蛋白OBP3的cDNA克隆和序列分析及其成虫嗅觉行为反应测定

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昆虫学报 2011年第9期54卷 975-981页

作者：范佳 sophie VANDeRMOTeN Frederic FRANCIS 刘勇陈巨莲程登发中国农业科学院植物保护研究所植物病虫害生物学国家重点实验室北京100193 Functional and evolutionary entomology Gembloux Agro-Bio TechUniversity of LiegePassage des Deportes2B-5030 GemblouxBelgium 山东农业大学植物保护学院山东泰安271018

枫长镰管蚜Drepanosiphum platanoidis是少数几种不分泌e-β-法尼烯(e-β-farnesene,eBF)的蚜虫之一。ApisOBP3是首个被鉴定的特异结合eBF的昆虫气味结合蛋白,来自于豌豆蚜Acyrthosiphum pisum。本研究通过基因克隆技术,在枫长镰管蚜体... 详细信息

枫长镰管蚜Drepanosiphum platanoidis是少数几种不分泌e-β-法尼烯(e-β-farnesene,eBF)的蚜虫之一。ApisOBP3是首个被鉴定的特异结合eBF的昆虫气味结合蛋白,来自于豌豆蚜Acyrthosiphum pisum。本研究通过基因克隆技术,在枫长镰管蚜体内获得2个表达ApisOBP3类似蛋白的cDNA序列,长度均为426bp,其中,5'末端的69bp为信号肽编码序列。编码的成熟蛋白分别命名为DplaOBP3-1和DplaOBP3-2,两个蛋白均由119个氨基酸残基组成,序列一致性为95.8%。与ApisOBP3的序列一致性分别为95.8%和98.3%。DplaOBP3-1,DplaOBP3-2及ApisOBP33个蛋白具有数量和位置完全一致的6个保守的半胱氨酸残基。以测得3D结构的马德拉蜚蠊Leucophaea maderae的信息素结合蛋白LmadPBP为模板比较建模,结果显示两个蛋白在疏水中心均具有与ApisOBP3一致的关键疏水残基及芳香族氨基酸残基Tyr84。利用四臂嗅觉仪测定枫长镰管蚜的嗅觉行为反应,结果显示:枫长镰管蚜残体挥发物及外源eBF对该蚜均有显著的驱避作用(P=0.01)。本研究提示,枫长镰管蚜具有种内报警信息素,该蚜残体挥发物即为其种内报警信息素;枫长镰管蚜尽管并不分泌eBF,但具有表达2种OBP3蛋白的基因,并可识别环境中的eBF且对其作出行为反应。

关键词：枫长镰管蚜气味结合蛋白报警信息素 e-β-法尼烯(eBF) cDNA克隆四臂嗅觉仪

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Impact of Celosia cristataextract on Adipogenesis of Native Human CD34+/CD31-Cells

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Journal of Cosmetics, Dermatological Sciences and Applications 2013年第3期3卷 55-63页

作者： Richard Fitoussi David estève Anne-sophie Delassus Katell Vié Centre de Recherche Clarins Pontoise France Inserm UMR1048 Team 1 Institute of Metabolic and Cardiovascular Diseases Toulouse France

Background: The adipose tissue mainly consists of adipocytes but also contains non-adipose cells. Among them, progenitor cells represent a local pool of immature cells that, in vitro, can undergo various lineage differentiation processes. These cells are thought to contribute to normal homeostasis of the adipose tissue through adipogenesis but also to the growth of the adipose tissue under chronic energy overload. The aim of the present study is to evaluate in vitro the capacity of a Celosia cristata extract to impact the adipogenic potential of native human adipose tissue progenitor cells, i.e. commitment and differentiation towards adipogenic lineage. Methods: Native adipose tissue progenitor cells were isolated by immunoselection/depletion approaches from human subcutaneous adipose tissues. Two distinct cell culture conditions were used to assess the effect of Celosia cristata extract on commitment and differenciation of progenitor cells. Cells were cultured either in differentiation medium for 10 days in the presence/absence of Celosia cristata extracts to study the impact on differentiation or first cultured in a commitment-inducing medium, with or without Celosia cristata extract, for 48 h and then cultured 10 days in differentiation medium to assess the impact on commitment. In both experimental series, the fate of progenitor cells was studied by quantification of lipids and by determining the expression of key genes involved in adipogenesis. Results: Data show that Celosia cristata extract reduces lipid content of progenitor cells undergoing differentiation. This reduction correlates with a reduced expression of C/eBPα. When progenitor cells are placed in commitment-inducing conditions, Celosia cristata extract induces a more potent reduction of lipid content. This reduction correlates with a decrease in the expression levels of master genes involved in adipogenesis: the genes of transcription factors PPARγ2 and C/eBPα as well as marker genes coding for LPL

关键词： Adipose Tissue Stem/Progenitor Cells Adipogenic Commitment Adipogenic Differentiation

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