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Spectrum of EGFR aberrations and potential clinical implications:insights from integrative pan-cancer analysis

Cancer Communications 2020年第1期40卷 43-59页

作者： Haijing Liu Bo Zhang Zhifu Sun Department of Pathology School of Basic Medical SciencesThird HospitalPeking University Health Science CenterBeijing100191P.R.China Division of Biomedical Statistics and Informatics Department of Health Sciences ResearchMayo ClinicRochesterMN55905USA

Background:Human epidermal growth factor receptor(EGFR)is an oncogenic gene and one of top targets of precision therapy in lung cancer with EGFR *** there are many reports for some individual cancers,comprehensive profiling of EGFR mutations,overexpression,amplification,DNA methylation,and their clinical associations across many different cancers simultaneously was not *** study aimed to fill the gap and provide insights to the alteration spectrum of EGFR and its therapeutic and prognostic ***:The Cancer Genome Atlas(TCGA)datasets for 32 cancer types involving 11,314 patients were analyzed for alterations(mutations and amplification/deletion),abnormal expression and DNA methylation in EGFR *** frequency,genomic location distribution,functional impact,and clinical targeted therapy implication were compared among different cancer types,and their associations with patient survival were ***:EGFR alteration frequency,mutation sites across functional domains,amplification,overexpression,and DNA methylation patterns differed greatly among different cancer *** overall mutation frequency in all cancers combined was relatively *** mutations,mainly in lung cancer,were primarily found in the Pkinase_Tyr *** multiforme had the highest rate of alterations,but it was dominated by gene amplification and most mutations were in the Furin-like domain where targeted therapy was less ***-grade glioma often had gene amplification and increased EGFR expression which was associated with poor *** and pancreatic adenocarcinoma had very few EGFR mutations;however,high EGFR expression was significantly associated with short patient *** cell carcinoma regardless of their sites(the head and neck,lung,or esophagus)exhibited similar characteristics with an alteration frequency of about 5.0%,was dominated by gene amplification,and had increased EGFR expression general

关键词： EGFR expression EGFR mutation epidermal growth factor receptor pan-cancer profiling patient survival targeted therapy The Cancer Genome Atlas(TCGA)

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Scaffold protein MAPK8IP2 expression is a robust prognostic factor in prostate cancer associated with AR signaling activity

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Asian Journal of Andrology 2023年第2期25卷 198-207页

作者： Jian Huang Wang Liu Bi-Yun Lin Jean C Li Jane Lu Ben-Yi Li Center for Pathological Diagnosis and Research The Affiliated Hospital of Guangdong Medical UniversityZhanjiang 524001China Department of Urology The University of Kansas Medical CenterKansas CityKS 66160USA

Mitogen-activated protein kinase-8-interacting protein 2(MAPK8IP2)is a scaffold protein that modulates MAPK signal *** MAPK pathways were heavily implicated in prostate cancer progression,the regulation of MAPK8IP2 expression in prostate cancer is not yet *** assessed MAPK8IP2 gene expression in prostate cancer related to disease progression and patient survival ***8IP2 expression was analyzed using multiple genome-wide gene expression datasets derived from The Cancer Genome Atlas(TCGA)RNA-sequence project and complementary DNA(cDNA)*** Cox regressions and log-rank tests were used to analyze the overall survival outcome and progression-free ***8IP2 protein expression was evaluated using the immunohistochemistry *** quantitative PCR and Western blot methods analyzed androgen-stimulated MAPK8IP2 expression in LNCaP *** primary prostate cancer tissues,MAPK8IP2 mRNA expression levels were significantly higher than those in the case-matched benign prostatic *** MAPK8IP2 expression was strongly correlated with late tumor stages,lymph node invasion,residual tumors after surgery,higher Gleason scores,and preoperational serum prostate-specific antigen(PSA)***8IP2 upregulation was significantly associated with worse overall survival outcomes and progression-free *** castration-resistant prostate cancers,MAPK8IP2 expression strongly correlated with androgen receptor(AR)signaling *** cell culture-based experiments,MAPK8IP2 expression was stimulated by androgens in AR-positive prostate cancer ***,MAPK8IP2 expression was blocked by AR antagonists only in androgen-sensitive LNCaP but not castration-resistant C4-2B and 22RV1 *** results indicate that MAPK8IP2 is a robust prognostic factor and therapeutic biomarker for prostate *** potential role of MAPK8IP2 in the castration-resistant progression is under further investigation.

关键词： cell cycle regulation disease progression mitogen-activated protein kinase-8-interacting protein 2 patient survival prostate cancer

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Cancer chemotherapy and beyond:Current status,drug candidates,associated risks and progress in targeted therapeutics

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Genes & Diseases 2023年第4期10卷 1367-1401页

作者： Uttpal Anand Abhijit Dey Arvind K.Singh Chandel Rupa Sanyal Amarnath Mishra Devendra Kumar Pandey Valentina De Falco Arun Upadhyay Ramesh Kandimalla Anupama Chaudhary Jaspreet Kaur Dhanjal Saikat Dewanjee Jayalakshmi Vallamkondu José M.Pérez de la Lastra Department of Life Sciences Ben-Gurion University of the NegevBeer-Sheva 84105Israel Department of Life Sciences Presidency UniversityKolkataWest Bengal 700073India Center for Disease Biology and Integrative Medicine Faculty of MedicineThe University of TokyoTokyo 113-0033Japan Department of Botany Bhairab Ganguly College(affiliated to West Bengal State University)KolkataWest Bengal 700056India Faculty of Science and Technology Amity Institute of Forensic SciencesAmity University Uttar PradeshNoida 201313India Department of Biotechnology School of Bioengineering and BiosciencesLovely Professional UniversityPhagwaraPunjab 144411India Institute of Endocrinology and Experimental Oncology(IEOS) National Research Council(CNR)Department of Molecular Medicine and Medical Biotechnology(DMMBM)University of Naples Federico IINaples 80131Italy Department of Biochemistry School of Life SciencesCentral University of RajasthanBandar SindariKishangarh AjmerRajasthan 305817India CSIR-Indian Institute of Chemical Technology HyderabadTelangana 500007India Department of Biochemistry Kakatiya Medical CollegeWarangalTelangana 506007India Orinin-BioSystems LE-52Lotus Road 4CHD CityKarnalHaryana 132001India Department of Computational Biology Indraprastha Institute of Information Technology Delhi(IIIT-D)Okhla Industrial EstatePhase IIINew Delhi 110020India Advanced Pharmacognosy Research Laboratory Department of Pharmaceutical TechnologyJadavpur UniversityKolkata 700032India Department of Physics National Institute of Technology-WarangalWarangalTelangana 506004India Biotechnology of Macromolecules Research Group Instituto de Productos Naturales y AgrobiologíaIPNA-CSICSan Cristóbal de La Laguna 38206TenerifeSpain

Cancer is an abnormal state of cells where they undergo uncontrolled proliferation and produce aggressive malignancies that causes millions of deaths every *** the new understanding of the molecular mechanism(s)of disease progression,our knowledge about the disease is snowballing,leading to the evolution of many new therapeutic regimes and their successive *** the past few decades,various combinations of therapies have been pro-posed and are presently employed in the treatment of diverse *** drug therapy,immunotherapy,and personalized medicines are now largely being employed,which were not common a few years *** field of cancer discoveries and therapeutics are evolving fast as cancer type-specific biomarkers are progressively being identified and several types of cancers are nowadays undergoing systematic therapies,extending patients’disease-free survival *** growing evidence shows that a systematic and targeted approach could be the future of cancer medicine,chemotherapy remains a largely opted therapeutic option despite its known side effects on the patient’s physical and psychological ***-apeutic agents/pharmaceuticals served a great purpose over the past few decades and have remained the frontline choice for advanced-stage malignancies where surgery and/or radiation therapy cannot be prescribed due to specific *** present report succinctly reviews the existing and contemporary advancements in chemotherapy and assesses the status of the enrolled drugs/pharmaceuticals;it also comprehensively discusses the emerging role of specific/targeted therapeutic strategies that are presently being employed to achieve better clinical success/survival rate in cancer patients.

关键词： Antimicrobial peptides Cancer therapies Clinical trials Combination therapy Immunotherapy patient survival Personalized medicine Targeted drug delivery

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Can composite performance measures predict survival of patients with colorectal cancer?

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World Journal of Gastroenterology 2014年第42期20卷 15805-15814页

作者： Kuo-Piao Chung Li-Ju Chen Yao-Jen Chang Yun-Jau Chang Graduate Institute of Health Policy and Management College of Public Health National Taiwan University Department of Ophthalmology Heping Branch Taipei City Hospital Department of General Surgery Buddhist Xindian Tzu Chi General Hospital Department of General Surgery National Taiwan University Hospital Department of General Surgery Zhongxing Branch Taipei City Hospital

AIM: To assess the relationship between long-term colorectal patient survival and methods of calculating composite performance scores.

关键词： Performance measure Composite performance score Colon cancer Rectal cancer patient survival Analytic hierarchy process Principal component analysis

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Qualifying the suitability of living donor livers for pediatric liver transplantation:are we doing the right thing?

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Hepatobiliary Surgery and Nutrition 2023年第3期12卷 462-464页

作者： Henkjan J.Verkade Frans C.J.Cuperus Aad P.van den Berg Division of Pediatric Gastroenterology and Hepatology Department of PediatricsUniversity of GroningenBeatrix Children’s HospitalUniversity Medical Center GroningenGroningenThe Netherlands Department of Gastroenterology and Hepatology University of GroningenUniversity Medical Center GroningenGroningenThe Netherlands

Over the last decades,liver transplantation has become the standard care for many forms of end-stage liver disease,both in adults and in *** prognosis after pediatric liver transplantation(pLT)has steadily increased up to a patient survival at 5 years of 85%and an estimated graft half life of 31 years(1,2).In the early days of pLT,the transplanted organ originated from deceased *** 1990,adult-to-child living donor liver transplantation(LDLT)programs have developed,which rapidly gained popularity,particularly in Europe and Asia(2,3).A major stimulus for LDLT has been the limited availability of deceased *** indications for liver transplantation have expanded,particularly for adult patients,at a higher rate than the availability of donor ***,the quality of donor organs has steadily declined,resulting in a decreased utilization of livers from deceased donors for transplantation(4).The limited availability of qualified deceased donor livers has further stimulated LDLT:in Europe,for example,the percentage of living donor organs used for pLT increased from 7%before 2000 to 40%since 2010(1).

关键词： Steatosis graft survival pediatric liver transplantation(pLT) patient survival

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Exocrine drainage in pancreas transplantation:Complications and management

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World Journal of Transplantation 2020年第12期10卷 392-403页

作者： Joana Ferrer-Fàbrega Laureano Fernández-Cruz HepatoBiliaryPancreatic Surgery and Liver and Pancreas Transplantation Department ICMDMHospital Clinic BarcelonaUniversity of BarcelonaBarcelona Clinic Liver Cancer GroupAugust Pi i Sunyer Biomedical Research InstituteBarcelona 08036BarcelonaSpain Department of Surgery ICMDMHospital Clinic BarcelonaBarcelona 08036BarcelonaSpain

The aim of this minireview is to compare various pancreas transplantation exocrine drainage techniques i.e.,bladder vs *** techniques have different difficulties and *** comparisons have been made in the literature between exocrine drainage techniques throughout the history of pancreas transplantation,detailing complications and their impact on graft and patient *** emphasis has been made on the early postoperative management of these complications and the related surgical infections and their *** light of the results,a number of bladder-drained pancreas grafts required conversion to enteric *** a result of technical improvements,outcomes of the varied enteric exocrine drainage techniques(duodenojejunostomy,duodenoduodenostomy or gastric drainage)have also been discussed i.e.,assessing specific risks vs *** exocrine secretions can be drained to the urinary or intestinal *** the late 1990s the bladder drainage technique was used in the majority of transplant centers due to ease of monitoring urine amylase and lipase levels for evaluation of possible ***,bladder drainage was associated at that time with fewer surgical complications,which in contrast to enteric drainage,could be managed with conservative ***,the most commonly used technique for proper driving of exocrine pancreatic secretions is enteric drainage due to the high rate of urological and metabolic complications associated with bladder *** note,10%to 40%of bladder-drained pancreata eventually required enteric conversion at no detriment to overall graft *** surgical techniques were originally described using the small bowel for enteric anastomosis with Roux-en-Y loop or a direct side-to-side *** the improvements in surgery,enteric drainage complication rates ranging from 2%-20%have been *** depends on the presence of any associated complicati

关键词： Graft survival patient survival Anastomotic leak Morbidity Infection Surgery

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Long-term outcomes of pediatric liver transplantation in acute liver failure vs end-stage chronic liver disease:A retrospective observational study

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World Journal of Transplantation 2023年第3期13卷 96-106页

作者： Amr M Alnagar Abdul R Hakeem Khaled Daradka Eirini Kyrana Marumbo Methga KarthikeyanPalaniswamy Sanjay Rajwal Jamila Mulla Moira O'meara Vivek Upasani Dhakshinamoorthy Vijayanand Raj Prasad Magdy S Attia Department of General Surgery Faculty of MedicineAlexandria UniversityAlexandria 21615Egypt Liver and Transplant Surgery The Leeds Teaching HospitalsNHS Foundation TrustLeeds LS97TFUnited Kingdom

BACKGROUND Children with acute liver failure(ALF)who meet the criteria are eligible for super-urgent transplantation,whereas children with end-stage chronic liver disease(ESCLD)are usually transplanted *** liver transplantation(PLT)in ALF and ESCLD settings has been well described in the literature,but there are no studies comparing the outcomes in these two *** To determine if there is a difference in post-operative complications and survival outcomes between ALF and ESCLD in *** This was a retrospective observational study of all primary PLTs performed at a single center between 2000 and *** and ESCLD groups were compared for pretransplant recipient,donor and operative parameters,and post-operative outcomes including graft and patient *** Over a 20-year study period,232 primary PLTs were performed at our center;195 were transplanted for ESCLD and 37 were transplanted for *** ALF recipients were significantly older(median 8 years vs 5.4 years;P=0.031)and heavier(31 kg vs 21 kg;P=0.011).Living donor grafts were used more in the ESCLD group(34 vs 0;P=0.006).There was no difference between the two groups concerning vascular complications and rejection,but there were more bile leaks in the ESCLD ***-transplant patient survival was significantly higher in the ESCLD group:1-,5-,and 10-year survival rates were 97.9%,93.9%,and 89.4%,respectively,compared to 78.3%,78.3%,and 78.3%in the ALF group(P=0.007).However,there was no difference in 1-,5-,and 10-year graft survival between the ESCLD and ALF groups(90.7%,82.9%,77.3%vs 75.6%,72.4%,and 66.9%;P=0.119).CONCLUSION patient survival is inferior in ALF compared to ESCLD recipients;the main reason is death in the 1st year post-PLT in ALF *** the ALF children overcome the 1st year after transplant,their survival stabilizes,and they have good long-term outcomes.

关键词： Pediatric liver transplantation Acute liver failure End-stage chronic liver disease Graft failure patient survival Complications

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Treatment of patients with advanced gastrointestinal stromal tumor of small bowel: Implications of imatinib mesylate

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World Journal of Gastroenterology 2006年第23期12卷 3760-3765页

作者： Chun-Nan Yeh Tsung-Wen Chen Ting-Jung Wu Swei Hsueh Yi-Yin Jan Department of Surgery Chang Gung Memorial HospitalChang Gung University5 Fu-Hsing StreetKwei-ShanTaoyuanTaiwanChina Department of Pathology Chang Gung Memorial HospitalChang Gung University5 Fu-Hsing StreetKwei-ShanTaoyuanTaiwan China

AIM： To examine the impact of imatinib mesylate （Glivec） on patient survival and response and its safety, and the correlation of the response rate with the kit gene mutation status. METHODS： Thirty-three of 74 （44.6%） small bowel gastrointestinal stromal tumor （GIST） patients who developed recurrence after curative resection and not treated with Glivec were classified as group A patients. Twenty-two advanced small bowel GIST patients treated with Glivec were classified as group B patients. Clinicopathological features, post-recurrence and overall survival rates were compared. Each tumor in group B patients was investigated for mutations of kit or plateletderived growth factor alpha （PDGFRA）. The mutation type was correlated with clinical outcomes. The antitumor effect and safety of Glivec in group B patients were also assessed. RESULTS： Advanced small bowel GIST patients treated with Glivec had substatntially longer post-recurrence survival and higher overall survival rates than those not treated with Glivec. A total of 15 patients had a partial response （PR）（67.8%）. Activated mutations of c-kit were found in 16 of 19 tested patients and no PDGFRA mutant was identified. In 13 patients with GISTs harboring exon 11 kit mutations, the partial response rate （PR） was 69.3%, whereas two of three patients with tumors containing an exon 9 kit mutation had an overall response rate （ORR） of 66.7% （not significant）. CONCLUSION： Glivec significantly prolongs the postrecurrence and overall survival of Asian patients with advanced GISTs. Glivec induces a sustained objective response in more than half of Asian patients withadvanced small bowel GISTs. Activated mutations of kit exon 11 are detectable in the vast majority of GISTs. There is no difference in the PR rate for patients whose GISTs have kit exon 9 and exon 11 mutations.

关键词： Gastrointestinal stromal tumor Glivec patient survival Kit gene mutation

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Portal vein thrombosis in liver transplantation: radiologic evaluation, risk factors, and occult diagnosis

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Hepatoma Research 2016年第1期2卷 36-41页

作者： Adam Hauch Carl Winkler Eric Katz Peter W.Lundberg Mary Killackey Anil S.Paramesh Luis A.Balart Nathan J.Shores Martin Moehlen Ward Miller Douglas P.Slakey Joseph F.Buell Bob H.Saggi Tulane Transplant Institute Tulane University School of MedicineNew OrleansLA 70112USA Department of Gastroenterology Section of HepatologyTulane University School of MedicineNew OrleansLA 70112USA

Aim:Portal vein thrombosis(PVT)in the liver transplant recipient poses many ***,the risk factors and effects on outcomes of PVT are not ***:This study analyzed the experience with PVT in liver transplant program from 2007 to *** included the effectiveness of PVT diagnostics and its risk factors using logistical *** primary endpoints were Kaplan-Meir patient and graft *** secondary endpoints were the length of stay(LOS),transfusion rate,and overall *** predictors of survival were identified using a Cox’s proportional hazards ***:Two hundred and sixteen consecutive liver transplant recipients were examined,and 30(13.8%)had either a total or partial *** hundred and five patients had imaging within 1 year of liver transplantation with only 7(23.3%)of the 30 PVTs identified *** sensitivity(4.8-50%)and negative predictive values(10.5-22.2%)were ***,age significantly predicted PVT[P=0.037/hazard ratio(HR)=0.95].Ninety-day-patient and graft survival for PVT was similar at 6 months,although 1-year survival was significantly lower.“Occult”PVT was not associated with inferior *** for end-stage liver disease score>25(P=0.001,HR=0.49/P=0.004,HR=0.52)and age>60 years(P=0.017,HR=0.64/P=0.013,HR=0.67)were significant predictors of patient and graft *** the transfusion rate was significantly greater with PVT,LOS,and morbidity were ***:Older recipients had a greater likelihood of *** studies were not effective at excluding PVT,and occult diagnosis did not affect the *** was not an independent predictor of mortality or graft loss,but was associated with greater blood loss but not increased LOS or morbidity.

关键词： Advanced age graft survival patient survival post-transplant outcomes resource utilization

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CIB1 as a Potential Diagnosis and Prognosis Biomarker in Uveal Melanoma

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Yangtze Medicine 2023年第2期7卷 116-133页

作者： Xianwang Wang Xiao Zhang Shujuan Hu Lei Ge Zhiming Zou Yingying Lu Department of Biochemistry and Molecular Biology Health Science Center Yangtze University Jingzhou China Institute of Education and Sports Sciences Yangtze University Jingzhou China Department of Ophtalmology The Second School of Clinical Medicine & Jingzhou Central Hospital Yangtze University Jingzhou China The Seventh Affiliated Hospital Sun Yat-sen University Shenzhen China

Background: Uveal melanoma (UVM) is the most common primary intraocular tumor in adults. However, identification of the effective biomarker for the diagnosis and treatment of UVM remains to be explored. Calcium and integrin-binding protein 1 (CIB1) is emerging as an important factor in tumor progression. Purpose: To determine the contribution of CIB1 in the diagnosis of UVM. Method: Immunohistochemical staining is used to detect the CIB1 expression level, while Gene Expression Profiling Interactive Analysis 2 (GEPIA2) and UALCAN online tools were used to analyze patient survival and CIB1 correlation genes in UVM. Integrative analysis using STRING and GeneMANIA predicted the correlated genes with CIB1 in UVM. Results: CIB1 expression level in UVM was significantly enhanced when compared with that in paracancerous tissues. A higher CIB1 expression level resulted in a significantly worse disease-free survival as well as overall survival. Moreover, the survival probability of patients was associated with body weight and gender of the patients with UVM. The correlated genes with CIB1 in UVM, and the similarity of the genes in UVM expression and survival heatmap were verified. Furthermore, Gene ontology enrichment analysis revealed that CIB1 and its correlated genes are significantly enriched in ITGA2B-ITGB3-CIB1 complex, regulation of intracellular protein transport and regulation of ion transport. Conclusions: Our novel findings suggested that CIB1 might be a potential diagnostic predictor for UVM, and might contribute to the potential strategy for UVM treatment by targeting CIB1.

关键词： CIB1 Uveal Melanoma TCGA Prognostic Biomarker patient survival

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