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Activation of PI3K/AKT pathway is a potential mechanism of treatment resistance in small cell lung cancer

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Activation of PI3K/AKT pathway is a potential mechanism of t...

Activation of PI3K/AKT pathway is revealed as a mechanism of chemoresistance in small cell lung cancer

2022CCTB中国肿瘤标志物学术大会暨中国整合肿瘤学大会暨第十六届肿瘤标志物青年科学家论坛暨中国肿瘤标志物产业创新大会

作者： Ying Jin Yamei Chen Huarong Tang Xiao Hu Shawna m.hubert Qian Li Dan Su Haimiao Xu Yun Fan Xinmin Yu Qixun Chen Jinshi Liu Wei Hong Yujin Xu HuanDeng Dapeng Zhu Pansong Li Yuhua Gong Xuefeng Xia Carl m.Gay Jianjun Zhang ming Chen Zhejiang Cancer Hospital Department of Thoracic/Head and Neck medical Oncology the University of Texas MD Anderson Cancer Center 中山大学肿瘤防治中心

Purpose:Here we have investigated treatment resistance mechanisms in small-cell lung cancer(SCLC) by focusing on comparing the genotype and phenotype in tumor samples of treatment-resistant and treatment-sensitive ***:We conducted whole-exome sequencing(WES) on paired tumor samples at diagnosis and relapse from 11 limited-stage(LS)-SCLC patients and targeted sequencing of 1,021cancer-related genes on cell free DNA(cfDNA) at baseline and paired relapsed samples from9 additional LS-SCLC ***,we performed label-free mass spectrometry-(mS-) based proteomics on tumor samples from 28 chemo-resistant and 23 chemo-sensitive patients with extensive-stage(ES)-*** main findings were validated in vitro in chemo-sensitive versus chemo-resistant SCLC cell lines and analyses of transcriptomic data of SCLC cell lines from a public ***:Genomic analyses demonstrated that at relapse of LS-SCLC,genes in the PI3K/AKT signaling pathway were enriched for acquired somatic mutations or high frequency acquired *** analysis on differentially upregulated proteins from ES-SCLC cohort revealed enrichment in the HIF-1 signaling ***,7 of 62 PI3K/AKT pathway genes containing acquired somatic copy number amplifications were enriched in HIF-1 *** of transcriptomic data of SCLC cell lines from public databases confirmed upregulation of PI3K/AKT and HIF-1 pathways in chemo-resistant SCLC cell ***,chemotherapy-resistant cell lines could be sensitive to PI3K inhibitors in ***:PI3K/AKT pathway activation may be one potential mechanism underlying therapeutic resistance of *** finding warrants further investigation and provides a possible approach to reverse resistance to chemo/radiotherapy.

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Activation of PI3K/AKT pathway is revealed as a mechanism of...

Influence of irritable bowel syndrome on treatment outcome in gastroesophageal reflux disease

2021年中国肿瘤标志物学术大会暨第十五届肿瘤标志物青年科学家论坛

作者： Ying Jin Yamei Chen Huarong Tang Xiao Hu Shawna m.hubert Qian Li Dan Su Haimiao Xu Yun Fan Xinmin Yu Qixun Chen Jinshi Liu Wei Hong Yujin Xu Huan Deng Dapeng Zhu Pansong Li Yuhua Gong Xuefeng Xia Carl m.Gay Jianjun Zhang ming Chen The Cancer Hospital of the University of Chinese Academy of Sciences 中国科学院肿瘤与基础医学研究所浙江省放射肿瘤学重点实验室 Department of Thoracic/Head and Neck medical Oncology the University of Texas MD Anderson Cancer Center Department of Genomic medicine the University of Texas MD Anderson Cancer Center 中山大学肿瘤防治中心(中山大学附属肿瘤医院中山大学肿瘤研究所)

Purpose: There is an urgent need to elucidate mechanisms involved in chemoresistance in SCLC. Here we have investigated the mechanisms of chemoresistance in SCLC, focusing on comparing the genotype and phenotype in tumor samples of chemo-resistant and chemo-sensitive ***: We conducted whole-exome sequencing(WES) on paired tumor samples at diagnosis and relapse collected from 11 patients with SCLC treated with standard chemoradiation to investigate mechanisms of chemoresistance. Additionally, we performed targeted sequencing of 1,021 cancerrelated genes on cell free DNA(cfDNA) obtained at baseline from 9 additional patients and paired relapsed samples. Furthermore, we performed label-free mass spectrometry-(mS-) based proteomics on tumor samples derived from 28 chemo-resistant and 23 chemo-sensitive patients with ***: We found that numerous previously reported mutated genes were identified both in treatmentna?ve and post-treatment SCLCs in our cohort, while numerous relapse-specific mutations and copy number variants(CNVs) were also identified. At relapse, genes in the PI3 K/ATK signaling pathway were enriched for acquired somatic mutations or high frequency acquired CNVs. Pathway analysis found that genes with differentially upregulated expressed proteins were enriched in HIF-1 signaling pathway. Interestingly, 12 of 96 PI3 K/AKT pathway genes containing acquired somatic copy number amplification were enriched in HIF-1 pathway, and most of them were located upstream of ***, in vitro-derived chemo-resistant SCLC cell lines demonstrate reversal of chemotherapy resistance upon PI3 ***: Overall, our findings point to an important role for PI3 K/AKT pathway activation in SCLC chemoresistance. PI3 K/ATK pathway targeting could be a viable strategy to reverse chemoresistance.

关键词： small cell lung cancer whole-exome sequencing mechanism of chemoresistance PI3K/AKT pathway

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World Journal of Gastroenterology 2011年第27期17卷 3235-3241页

作者： hubert mnnikes Robert C Heading Holger Schmitt hubert Doerfler Department of medicine Martin-Luther HospitalAcademic Teaching Hospital of CharitéUniversitts-medizin14193 BerlinGermany Edinburgh EH10 7ARScotlandUnited Kingdom Nycomed GmbH 78467 ConstanceGermany Nycomed International management GmbH 8152 ZurichSwitzerland

AIm: To investigate the influence of irritable bowel syndrome (IBS)-like symptoms on treatment outcomes with pantoprazole in gastroesophageal reflux disease (GERD) in a real life setting. mETHODS: For this prospective, open-label, multinational, multicentre study, 1888 patients assessed by the investigators as suffering from GERD were recruited. The patients were additionally classified as with or without IBS-like symptoms at baseline. They were treated with pantoprazole 40 mg once daily and completed the Reflux Questionnaire (ReQuest) short version daily. Response rates and symptom scores were compared after 4 and 8 wk of treatment for subgroups defined by the subclasses of GERD [erosive(ERD) and non-erosive reflux disease (NERD)] and the presence of IBS-like symptoms. RESULTS: IBS-like symptoms were more prevalent in NERD than in ERD (18.3% vs 12.7%, P = 0.0015). Response rates after 4 and/or 8 wk of treatment were lower in patients with IBS-like symptoms than in patients without IBS-like symptoms in both ERD (Week 4: P minal com- plaints" symptom scores were highest in NERD patients with IBS-like symptoms. Additionally, these patients had the strongest symptom improvement after treatment compared with all other subgroups. CONCLUSION: IBS-like symptoms influence treatment outcome and symptom burden in GERD and should be considered in management. Proton pump inhibitors can improve IBS-like symptoms, particularly in NERD.

关键词： Pantoprazole ReQuestTm Clinical practice Irritable bowel syndrome Gastroesophageal reflux disease

Turbulence and suspended sediment processes in the Garonne River tidal bore in November 2016

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International Journal of Sediment Research 2019年第5期34卷 496-508页

作者： David Reungoat Xinqian Leng hubert Chanson Université de Bordeaux I2MLaboratoire TREFLE CNRS UmR 5295 The University of Queensland School of Civil Engineering

A tidal bore is a water discontinuity at the leading edge of a flood tide wave in estuaries with a large tidal range and funneling topography. New measurements were done in the Garonne River tidal bore on14–15 November 2016, at a site previously investigated between 2010 and 2015. The data focused on long, continuous, high-frequency records of instantaneous velocity and suspended sediment concentration(SSC) estimate for several hours during the late ebb, tidal bore passage and flood tide. The bore passage drastically modified the flow field, with very intense turbulent and sediment mixing. This was evidenced with large and rapid fluctuations of both velocity and Reynolds stress, as well as large SSCs during the flood tide. Granulometry data indicated larger grain sizes of suspended sediment in water samples compared to sediment bed material, with a broader distribution, shortly after the tidal bore. The tidal bore induced a sudden suspended sediment flux reversal and a large increase in suspended sediment flux magnitude. The time-variations of turbulent velocity and suspended sediment properties indicated large fluctuations throughout the entire data set. The ratio of integral time scales of SSC to velocity in the x-direction was on average TE,SSC/TE,～0.16 during the late ebb tide, compared to TE,SSC/TE,～0.09 during the late flood tide. The results imply different time scales between turbulent velocities and suspended sediment concentrations.

关键词： Tidal bore Garonne River Hydrodynamics Suspended sediment Field observations Turbulence-sediment suspension interactions

The Quaternary fault in Jiamu area,the Xinjiang Uygur Autonomous Region

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Chinese Science Bulletin 2002年第6期47卷 494-499页

作者： A.hubert-Feram J.Suppe Department of Geosciences Princeton UniversityPrincetonDepartment of GeosciencesPrinceton UniversityPrinceton New Jersey 08544USANew Jersey 08544USA

The Quaternary Tailan River fault has been found in the Tianshan foothills area, the Xinjiang Uygur Autonomous Region. It is the recent boundary fault of the Tarim Basin coupling with the West Tianshan mountains. In the light of measurement data of the slip which cuts the Quaternary deposits of different ages, the Quaternary kinematic figures of the Tailan River fault are estimated as follows: crustal shortening 3.7 km and shortening rate 1.59 mm/a, uplift of Tianshan mountains 1.34 km and uplift rate 0.56 mm/a, and additional relief of 900 m. Considering the contribution of the Gumubiezi anticline close to the south of the Tailan River fault, the Quaternary crustal shortening and shortening rate of the Jiamu area are 4.8 km and 2 mm/a respectively. The above-mentioned data coincide with the crustal shortening rate calculated from the growth strata in the Kuqa area, as well as the GPS measurements in the Lake Issyk area and the Korla-Urumqi area, reflecting the fast thrusting period within the

关键词： coupling mechanics in the formation of basin and moun-tains of the Tarim basin-Tianshan mountains moraine Quaternary fault crustal shortening.

Separation,speciation and quantification of both chromium(Ⅵ)and chromium(Ⅲ)in tanned leather samples:a comparative study and validation of analytical methods

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Collagen and Leather 2023年第2期5卷 51-66页

作者： mónica Gisel Arellano-Sánchez Juliette Vievard Lamia moufarrej Christine Devouge-Boyer marie hubert-Roux Carlos Afonso mélanie mignot COBRA UmR CNRS 6014 INSANormandie UniversityUNIROUENAvenue de l'Université76800 Saint-Etienne-du-RouvrayFrance COBRA UMR CNRS 6014IRCOFNormandie UniversityUNIROUEN76821 Mont-Saint-Aignan CedexFrance

In the present work,a comparative study of analytical methods for the simultaneous and quantitative determination of trivalent and hexavalent chromium is *** the analysis by ion chromatography-inductively coupled plasma-mass spectrometry,two different columns were tested,as well as different mobile phases and different pH of the *** optimized analytical method permitted the separation of Cr(Ⅲ)and Cr(Ⅵ)using 75 mmol/L NH_(4)NO_(3)pH 3 as chromatographic *** method was validated and applied to real samples,allowing the determination of both species simultaneously,even when there is a huge difference of concentration between Cr(Ⅲ)and Cr(Ⅵ).Limit of detection and limit of quantification for Cr(Ⅲ)were found to be 0.016 and 0.054μg/L(0.3 and 1.1μg/kg),respectively,and for Cr(Ⅵ)0.13 and 0.43μg/L(7 and 22μg/kg),*** species interconversions were monitored through the use of chromium isotopic standards,which confirmed that the optimized methodology preserves chromium speciation during extraction and ***-transform ion cyclotron resonance-mass spectrometry permitted the structure elucidation of the complex formed during ethylenediaminetetraacetic acid extraction.

关键词： Chromium speciation Tanned leather Interconversions Ion chromatography Inductively coupled plasmamass spectrometry Fourier-transform ion cyclotron resonance mass spectrometry

Screening for hepatocellular carcinoma by Egyptian physicians

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World Journal of Gastrointestinal Oncology 2015年第9期7卷 161-171页

作者： Sahar m Hassany Ehab F Abdou moustafa mohamed El Taher Afaf Adel Abdeltwab hubert E Blum Department of Tropical medicine and Gastroenterology Assiut University Assiut Hospital for Febrile Illnesses Department of Internal medicine Ⅱ Freiburg University

AIm: To assess the practice of Egyptian physicians in screening patients for hepatocellular carcinoma(HCC). mETHODS: The study included 154 physicians from all over Egypt caring for patients at risk for HCC. The study was based on a questionnaire with 20 items. Each questionnaire consisted of two parts:(1) personal information regarding the physician(name, age, specialty and type of health care setting); and(2) professional experience in the care of patients at risk for HCC development(screening, knowledge about the cause and natural course of liver diseases and HCC risk). RESULTS: Sixty-eight percent of doctors with an mD degree, 48% of doctors with a master degree or a diploma and 40% of doctors with a Bachelor of medicine, Bachelor of Surgery certificate considered the hepatitis C virus(HCV) genotype as risk factor for HCC development(P medicine, internal medicine or gastroenterology and 67% of physicians in other specialties advise patients to undergo screening for HCV and hepatitis B virus infection as well as liver cirrhosis(P ministry of Health(mOH) doctors consider HCV infection as the leading cause of HCC in Egypt(P mD degree, 55% of doctors with a master degree or a diploma, 56% of doctors with an mBBCH certificate, 74% of doctors in University Hospitals and 46% of mOH hospital doctors consider abdominal ultrasonography as the most important investigation in HCC screening(P medicine, internal medicine or gastroenterology and 37% of physicians in other specialties recommend as HCC screening interval of 3 mo(P mD degree, 50% of doctors with a master degree or diploma and 60% of doctors with an mBBCH certificate follow the same ***: In Egypt, physicians spe

关键词： Hepatocellular carcinoma Egyptian physicians Scree

Evaluation of Radarsat-2 quad-pol SAR time-series images for monitoring groundwater irrigation

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International Journal of Digital Earth 2019年第10期12卷 1177-1197页

作者： Amit Kumar Sharma Laurence hubert-moy Buvaneshwari Sriramulu m.Sekhar Laurent Ruiz S.Bandyopadhyay Shiv mohan Samuel Corgne Univ Rennes UMR LETG CNRSRennesFrance Indo-French Cell for Water Science Indian Institute of ScienceBangaloreIndia Department of Civil Engineering Indian Institute of ScienceBangaloreIndia UmR 1069 SAS INRAAgro-campus OuestRennesFrance Géosciences Environnement Toulouse Universitéde ToulouseCNRSIRDToulouseFrance EOS Indian Space Research OrganizationBangaloreIndia PLANEX Physical Research LaboratoryAhmedabadIndia

Groundwater assists farmers to irrigate crops for fulfilling the crop-water *** agriculture system is characterized by three cropping seasons known as Kharif(monsoon),Rabi(post-monsoon)and summer(pre-monsoon).In tropical countries like India,monitoring cropping practices using optical remote sensing during Kharif and Rabi seasons is constraint due to the cloud cover,which can be well addressed by microwave remote *** the proposed research,the strength of C-band polarimetric Synthetic Aperture Radar(SAR)time series images were evaluated to classify groundwater irrigated croplands for the Kharif and Rabi cropping seasons of the year *** present study was performed in the Berambadi experimental watershed of Kabini river basin,southern peninsular India.A total of fifteen polarimetric variables were estimated includes four backscattering coefficients(HH,HV,VH,VV)and eleven polarimetric indices for all Radarsat-2 SAR *** cumulative temporal sum(seasonal and dual-season)of these parameters was supervised classified using Support Vector machine(SVm)classifier with intensive ground observation *** results using the best equation(highest accuracy and kappa)shows that the Kharif,Rabi and irrigated double croplands are respectively 9.58 km2(20.6%),16.14 km2(34.7%)and 6.22 km2(13.4%)with a kappa coefficient respectively 0.84,0.74 and 0.94.

关键词： Radarsat-2 Synthetic Aperture Radar Polarimetric Indices Irrigated Cropland Support Vector machine Classifier Kabini Critical Zone Observatory

How rotational speed of planetary ball mill and polymer load influence the performance and water vapor sorption in solid dispersions composed of tadalafil and soluplus

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Particuology 2023年第2期73卷 37-46页

作者： Karol Kubat Anna Krupa Witold Brniak Agnieszka Węgrzyn Dorota majda Agata Bogdał hubert Harańczyk Department of medical Physics Faculty of PhysicsInstitute of PhysicsJagiellonian UniversityCracowPoland Department of Pharmaceutical Technology and Biopharmaceutics Faculty of PharmacyCollegium MedicumJagiellonian UniversityCracowPoland Faculty of Chemistry Jagiellonian UniversityCracowPoland

The presence of residual water may deteriorate the performance of amorphous solid dispersions prepared by ball milling,affecting molecular mobility,crystallinity,particle size and finally,the drug dissolution *** the stability of these metastable systems depend on both formulation and process variables,the aim of this study was to assess for the first time,the impact that the polymer load and the rotational speed applied upon high energy ball milling could have on the performance of binary co-milled solid dispersions composed of tadalafil(a hydrophobic crystalline drug)and Soluplus(an amphiphilic,hygroscopic amorphous polymer).Each of these variables was tested at three *** electron microscopy,laser diffraction and X-ray powder diffraction were used to analyze morphology,particle size distribution and crystallinity of ball milled formulations *** studies were also carried *** tools of applied physics,namely solid state 1H NmR and relaxometry were used to assess the structure and water mobility upon gaseous phase hydration on *** was shown that both tested variables determined the particle size of the *** the rotational speed of 400 rpm was used,all solid dispersion were XRD-amorphous,but to ensure the immediate release of tadalafil its micellar solubilization in Soluplus was *** the formulation was exposed to water vapor,the hydration level increased with an increasing polymer load as ***,the rotational speed governed the space available for the adsorption of water molecules and their organization in a monolayer or *** behavior may have impact on the kinetics of the amorphous drug recrystallization,and finally deteriorate its dissolution.

关键词： Tadalafil Soluplus Solid dispersion Relaxation time milling NmR