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ATM Activation is Key in Vasculogenic Mimicry Formation by Glioma Stem-like Cells

Biomedical and Environmental Sciences 2024年第8期37卷 834-849页

作者： Jing Xie Jiaxin Tang Yuan Li Xue Kong Wei Wang Haibo Wu department of pathology the First Affiliated Hospital of USTCDivision of Life Sciences and MedicineUniversity of Science and Technology of ChinaHefei 230036AnhuiChina Intelligent pathology Institute Division of Life Sciences and MedicineUniversity of Science and Technology of ChinaHefei 230036AnhuiChina

Objective Vasculogenic mimicry(VM)is a novel vasculogenic process integral to glioma stem cells(GSCs)in glioblastoma(GBM).However,the relationship between VM and ataxia-telangiectasia mutated(ATM)serine/threonine kinase activation,which confers chemoradiotherapy resistance,remains *** We investigated VM formation and phosphorylated ATM(pATM)levels by CD31/GFAPperiodic acid-Schiff dual staining and immunohistochemical staining in 145 GBM *** stem-like cells(GSLCs)derived from the formatted spheres of U87 and U251 cell lines and their pATM level and VM formation ability were examined using western blot and three-dimensional *** the examination of the function of pATM in VM formation by GSLCs,ATM knockdown by shRNAs and deactivated via ATM phosphorylation inhibitor KU55933 were *** VM and high pATM expression occurred in 38.5% and 41.8% of tumors,respectively,and were significantly associated with reduced progression-free and overall *** with VM-positive GBMs exhibited higher pATM levels(r_(s)=0.425,P=0.01).The multivariate analysis established VM as an independent negative prognostic factor(P=0.002).Furthermore,GSLCs expressed high levels of pATM and formed vascular-like networks in *** inactivation or knockdown hindered VM-like network formation concomitant with the downregulation of pVEGFR-2,VE-cadherin,and laminin *** VM may predict a poor GBM prognosis and is associated with pATM *** propose that pATM promotes VM through extracellular matrix modulation and VE-Cadherin/pVEGFR-2 activation,thereby highlighting ATM activation as a potential target for enhancing anti-angiogenesis therapies for GBM.

关键词： Glioblastoma Vasculogenic mimicry Ataxia-telangiectasia mutated(ATM) Glioma stem-like cell

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World Journal of Clinical Cases 2024年第1期12卷 176-179页

作者： Hsin-Chia Angela Lin Kam-Fai Lee Tzu Hao Huang division of General Surgery Department of SurgeryChang Gung Memorial HospitalChiayi 613Taiwan department of Anatomic pathology Chang Gung Memorial HospitalChiayi 613Taiwan

BACKGROUND Gastric IgG4-related disease(IgG4-RD)is rarely encountered in clinical practice,and especially more so among pediatric *** our knowledge,this is the first report of IgG4-RD presenting as a calcifying gastric mass in a *** describe how this entity was difficult to differentiate from a gastrointestinal stromal tumor(GIST)imaging-based ***,this case highlights the importance of considering IgG4-RD in the differential diagnosis of gastric tumor before performing surgical resection,especially to distinguish it from malignancy to avoid unnecessary *** SUMMARY The patient suffered from epigastric pain for several *** and computed tomography scan revealed a submucosal *** diagnoses included GIST,leiomyoma,teratoma,and mucinous ***,laparoscopic proximal gastrectomy allowed for the definitive diagnosis of IgG4-related stomach *** We emphasize the importance of considering IgG4-RD in the differential diagnosis of gastric submucosal tumors before performing surgical resection.

关键词： IgG4-related disease Gastrointestinal stromal tumor Child Pediatric Case report

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Melanocortin 3,5 receptors immunohistochemical expression in colonic mucosa of inflammatory bowel disease patients:A matter of disease activity?

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World Journal of Gastroenterology 2024年第9期30卷 1132-1142页

作者： Antonietta Gerarda Gravina Iacopo Panarese Maria Consiglia Trotta Michele D'Amico Raffaele Pellegrino Franca Ferraraccio Marilena Galdiero Roberto Alfano Paolo Grieco Alessandro Federico Hepatogastroenterology division Department of Precision MedicineUniversity of Campania Luigi VanvitelliNaples 80138Italy pathology division Department of Mental and Physical Health and Preventive MedicineUniversity of Campania Luigi VanvitelliNaples 80138Italy department of Experimental Medicine Division of PharmacologyUniversity of Campania Luigi VanvitelliNaples 80138Italy department of Advanced Medical and Surgical Sciences(DAMSS) University of Campania Luigi VanvitelliNaples 80138Italy department of Pharmacy University of Naples Federico IINaples 80131Italy

BACKGROUND Melanocortin 3 and 5 receptors(i.e.,MC3R and MC5R)belong to the melanocortin ***,data regarding their role in inflammatory bowel diseases(IBD)are currently *** This study aims to ascertain their expression profiles in the colonic mucosa of Crohn’s disease(CD)and ulcerative colitis(UC),aligning them with IBD disease endoscopic and histologic *** Colonic mucosal biopsies from CD/UC patients were sampled,and immunohisto-chemical analyses were conducted to evaluate the expression of MC3R and *** sampling was performed on both traits with endoscopic scores(Mayo endoscopic score and CD endoscopic index of severity)consistent with inflamed mucosa and not consistent with disease activity(i.e.,normal appearing mucosa).RESULTS In both CD and UC inflamed mucosa,MC3R(CD:+7.7 fold vs normal mucosa,P<0.01;UC:+12 fold vs normal mucosa,P<0.01)and MC5R(CD:+5.5 fold vs normal mucosa,P<0.01;UC:+8.1 fold vs normal mucosa,P<0.01)were significantly more expressed compared to normal *** MC3R and MC5R are expressed in the colon of IBD ***,expression may differ according to disease endoscopic activity,with a higher degree of expression in the traits affected by disease activity in both CD and UC,suggesting a potential use of these receptors in IBD pharmacology.

关键词： Melanocortin 3 receptor Melanocortin 5 receptor Ulcerative colitis Crohn's disease Inflammatory bowel disease

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Unique presentation of neonatal liver failure:A case report

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World Journal of Clinical Pediatrics 2024年第2期13卷 221-226页

作者： Eman Al Atrash Amer Azaz Samar Said Mohammad Miqdady department of Pediatrics Division of Pediatric GastroenterologySheikh Khalifa Medical CityAbu Dhabi 971United Arab Emirates department of pathology Mayo ClinicRochesterMN 55905United States

BACKGROUND Acute fulminant liver failure rarely occurs in the neonatal *** etiologies include viral infection(15%),metabolic/genetic disease(10%),hematologic disorders(15%),and ischemic injury(5%).Gestational alloimmune liver disease usually manifests as severe neonatal liver failure,with extensive hepatic and extrahepatic iron overload,sparing the reticuloendothelial *** liver failure is a rare cause of liver failure where a patient presents with liver failure in the neonatal period with no hepatocytes in liver *** SUMMARY A 5-week-old male presented with *** examination revealed an alert but deeply icteric *** data demonstrated direct hyperbilirubinemia,a severely deranged coagulation profile,normal transaminase,and normal *** resonance imaging of the abdomen was suggestive of perinatal *** biopsy showed histiocytic infiltration with an absence of *** hemosiderin deposition was identified in a buccal mucosa *** Neonatal liver failure in the absence of hepatocellular regeneration potentially reflects an acquired or inborn defect in the regulation of hepatic regeneration.

关键词： Liver Hyperbilirubinemia Le foie vide Neonatal hemochromatosis Case report

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Autoimmune pancreatitis:Cornerstones and future perspectives

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World Journal of Gastroenterology 2024年第8期30卷 817-832页

作者： Camilla Gallo Giulia Dispinzieri Nicola Zucchini Pietro Invernizzi Sara Massironi division of Gastroenterology and Center for Autoimmune Liver Diseases Department of Medicine and SurgeryFondazione IRCCS San Gerardo dei TintoriUniversity of Milano-BicoccaMonza 20900Italy department of pathology Fondazione IRCCS San Gerardo dei TintoriMonza 20900Italy

Autoimmune pancreatitis(AIP)is an autoimmune subtype of chronic pancreatitis resulting from the aberrant immune response against the pancreas,leading to inflammation and *** AIP is rare,its incidence is increasing and is often misdiagnosed as other pancreatic *** is commonly classified into two *** 1 AIP(AIP-1)is typically associated with elevated serum immunoglobulin G4(IgG4)levels and systemic manifestations,while type 2 AIP is typically a more localized form of the disease,and may coexist with other autoimmune disorders,especially inflammatory bowel ***,there is emerging recognition of a third type(type 3 AIP),which refers to immunotherapy-triggered AIP,although this classification is still gaining acceptance in medical *** clinical manifestations of AIP mainly include painless jaundice and weight *** serum IgG4 levels are particularly characteristic of *** relies on a combination of clinical,laboratory,radiological,and histological findings,given the similarity of AIP symptoms to other pancreatic *** mainstay of treatment for AIP is steroid therapy,which is effective in most *** cases might require additional imm-unosuppressive *** review aims to summarize the current knowledge of AIP,encompassing its epidemiology,etiology,clinical presentation,diagnosis,and treatment *** also address the challenges and controversies in diagnosing and treating AIP,such as distinguishing it from pancreatic cancer and managing long-term treatment,highlighting the need for increased awareness and knowledge of this complex disease.

关键词： Autoimmunity Pancreatitis Autoimmune pancreatitis Immunoglobulin G4 Steroids Relapse

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Sporophytic control of tapetal development and pollen fertility by a mitogen-activated protein kinase cascade in rice

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Journal of Integrative Plant Biology 2024年第7期66卷 1500-1516页

作者： Jianguo Zeng Manman Duan Yiqing Wang Guangtao Li Yujing You Jie Shi Changhao Liu Jinyang Zhang Juan Xu Shuqun Zhang Jing Zhao department of Plant pathology Nanjing Agricultural UniversityNanjing 210095China State Key Laboratory of Plant Physiology and Biochemistry College of Life SciencesZhejiang UniversityHangzhou 310058China division of Biochemistry University of MissouriColumbia65211MOUSA

Tapetum,the innermost layer of the anther wall,provides essential nutrients and materials for pollen *** degradation of anther tapetal cells is a prerequisite for normal pollen development in flowering *** cells facilitate male gametogenesis by providing cellular contents after highly coordinated programmed cell death(PCD).Tapetal development is regulated by a transcriptional ***,the signaling pathway(s)involved in this process are poorly *** this study,we report that a mitogen-activated protein kinase(MAPK)cascade composed of OsYDA1/OsYDA2-OsMKK4-OsMPK6 plays an important role in tapetal development and male gametophyte *** of function of this MAPK cascade leads to anther indehiscence,enlarged tapetum,and aborted pollen *** cells in osmkk4 and osmpk6 mutants exhibit an increased presence of lipid body-like structures within the cytoplasm,which is accompanied by a delayed occurrence of *** of a constitutively active version of OsMPK6(CA-OsMPK6)can rescue the pollen defects in osmkk4 mutants,confirming that OsMPK6 functions downstream of OsMKK4 in this *** crosses also demonstrated that the MAPK cascade sporophyticly regulates pollen *** study reveals a novel function of rice MAPK cascade in plant male reproductive biology.

关键词： degradation MAPK cascade pollen fertility rice tapetum

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New insights into ATR inhibition in muscle invasive bladder cancer:The role of apolipoprotein B mRNA editing catalytic subunit 3B

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Oncology Research 2024年第6期32卷 1021-1030页

作者： HYUNHO KIM UIJU CHO SOOK HEE HONG HYUNG SOON PARK IN-HO KIM HO JUNG AN BYOUNG YONG SHIM JIN HYOUNG KANG division of Medical Oncology Department of Internal MedicineSt.Vincent’s HospitalCollege of MedicineThe Catholic University of KoreaSuwonKorea department of pathology St.Vincent’s HospitalCollege of MedicineThe Catholic University of KoreaSuwonKorea division of Medical Oncology Department of Internal MedicineSeoul St.Mary’s HospitalCollege of MedicineThe Catholic University of KoreaSeoulKorea

Background:Apolipoprotein B mRNA editing catalytic polypeptide(APOBEC),an endogenous mutator,induces DNA damage and activates the ataxia telangiectasia and Rad3-related(ATR)-checkpoint kinase 1(Chk1)*** cisplatin-based therapy is the mainstay for muscle-invasive bladder cancer(MIBC),it has a poor survival ***,this study aimed to evaluate the efficacy of an ATR inhibitor combined with cisplatin in the treatment of APOBEC catalytic subunit 3B(APOBEC3B)expressing ***:Immunohistochemical staining was performed to analyze an association between APOBEC3B and ATR in patients with *** APOBEC3B expression in MIBC cell lines was assessed using real-time polymerase chain reaction and western blot *** blot analysis was performed to confirm differences in phosphorylated Chk1(pChk1)expression according to the APOBEC3B *** viability and apoptosis analyses were performed to examine the anti-tumor activity of ATR inhibitors combined with ***:There was a significant association between APOBEC3B and ATR expression in the tumor tissues obtained from patients with *** with higher APOBEC3B expression showed higher pChk1 expression than cells expressing low APOBEC3B *** treatment of ATR inhibitor and cisplatin inhibited cell growth in MIBC cells with a higher APOBEC3B *** to cisplatin single treatment,combination treatment induced more apoptotic cell death in the cells with higher APOBEC3B ***:Our study shows that APOBEC3B’s higher expression status can enhance the sensitivity of MIBC to cisplatin upon ATR *** result provides new insight into appropriate patient selection for the effective application of ATR inhibitors in MIBC.

关键词： Apolipoprotein B mRNA editing catalytic polypeptide(APOBEC) Ataxia telangiectasia and Rad3-related(ATR) Bladder cancer DNA damage response DNA replication stress

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Hepatocellular carcinoma presenting as an extrahepatic mass:A case report and review of literature

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World Journal of Gastrointestinal Oncology 2024年第5期16卷 2241-2252页

作者： Wei Kelly Wu Krutika Patel Chandrasekhar Padmanabhan Kamran Idrees department of Surgery Vanderbilt University Medical CenterNashvilleTN 37232United States department of pathology Microbiology and ImmunologyVanderbilt University Medical CenterNashvilleTN 37232United States division of Surgical Oncology and Endocrine Surgery Department of SurgeryVanderbilt University Medical CenterNashvilleTN 37232United States

BACKGROUND Hepatocellular carcinoma(HCC)is a primary liver tumor generally diagnosed based on radiographic *** disease is typically associated with increased tumor diameter,multifocality,and vascular *** report a case of a patient who presented with extrahepatic HCC metastasis to a portocaval lymph node with occult hepatic primary on computed tomography(CT).We review the literature for cases of extrahepatic HCC presentation without known hepatic lesions and discuss strategies to differentiate between metastatic and ectopic *** SUMMARY A 67-year-old male with remotely treated hepatis C was referred for evaluation of an enlarging portocaval,mixed cystic-solid *** CT evaluations demonstrated steatosis,but no cirrhosis or liver *** ultrasound demonstrated a normal-appearing pancreas,biliary tree,and *** needle aspiration yielded atypical *** differential diagnosis included duodenal or pancreatic cyst,lymphoproliferative cyst,stromal or mesenchymal lesions,nodal involvement from gastrointestinal or hematologic malignancy,or duodenal gastrointestinal stromal *** review by a multidisciplinary tumor board,the patient underwent open surgical resection of a 5.2 cm×5.5 cm retroperitoneal mass with pathology consistent with moderately-differentiated *** resonance imaging(MRI)subsequently demonstrated a 1.2 cm segment VIII hepatic lesion with late arterial enhancement,fatty sparing,and intrinsic T1 *** fetoprotein was 23.3 ng/*** patient was diagnosed with HCC with portocaval nodal ***:We surveyed the literature for HCC presenting as extrahepatic masses without history of concurrent or prior intrahepatic *** identified 18 cases of extrahepatic HCC ultimately found to represent metastatic lesions,and 30 cases of extrahepatic HCC found to be primary,ectopic *** Hepatocellular carcinoma can seldomly present with extrahepatic metastasis in the setting of

关键词： Extrahepatic Metastasis Portocaval Lymph node Case report

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Mucinous neoplasm of the appendix:A case report and review of literature

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World Journal of Gastrointestinal Surgery 2024年第3期16卷 944-954页

作者： Hao-Cheng Chang Jung-Cheng Kang Ta-Wei Pu Ruei-Yu Su Chao-Yang Chen Je-Ming Hu department of Surgery Tri-Service General HospitalTaipei 114TaiwanChina division of Colon and Rectal Surgery Department of SurgeryTaiwanChina Adventist HospitalTaipei 105TaiwanChina division of Colon and Rectal Surgery Department of SurgeryTri-Service General Hospital Songshan BranchNational Defense Medical CenterTaipei 105TaiwanChina division of Colon and Rectal Surgery Department of SurgeryTri-Service General HospitalNational Defense Medical CenterTaipei 114TaiwanChina department of pathology Tri-Service General HospitalNational Defense Medical CenterTaipei 105TaiwanChina department of pathology and Laboratory Medicine Taoyuan Armed Forces General HospitalTaoyuan 325TaiwanChina

BACKGROUND Appendiceal mucinous neoplasms(AMNs),although not classified as rare,are relatively uncommon tumors most often discovered incidentally during colorectal *** identification of AMNs is difficult due to non-specific sym-ptoms,overlapping tumor markers with other conditions,and the potential for *** underscores the urgent need for precision in diagnosis to pre-vent severe *** SUMMARY This case report describes the unexpected discovery and treatment of a low-grade AMN(LAMN)in a 74-year-old man undergoing laparoscopic hemicolectomy for transverse colon adenocarcinoma(AC).Preoperatively,non-specific gastroin-testinal symptoms and elevated tumor markers masked the presence of *** tumor,presumed to be an AMN peritoneal cyst intraoperatively,was con-firmed as LAMN through histopathological *** neoplasm exhibited mucin accumulation and a distinct immunohistochemical profile:Positive for Ho-meobox protein CDX-2,Cytokeratin 20,special AT-rich sequence-binding protein 2,and Mucin 2 but negative for cytokeratin 7 and Paired box gene *** profile aids in distinguishing appendiceal and ovarian mucinous *** recovery was uncomplicated,and the patient initiated adjuvant chemotherapy for the colon *** This case highlights the diagnostic complexity of AMNs,emphasizing the need for vigilant identification to avert potential complications,such as pseudomyxoma peritonei.

关键词： Adenocarcinoma Appendiceal neoplasms Low-grade appendiceal mucinous neoplasm Peritoneal neoplasms Pseudomyxoma peritonei Case report

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Multidisciplinary management of ulcerative colitis complicated by immune checkpoint inhibitor-associated colitis with life-threatening gastrointestinal hemorrhage:A case report

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World Journal of Gastrointestinal Surgery 2024年第7期16卷 2329-2336页

作者： Na Hong Bo Wang Hang-Cheng Zhou Zheng-Xiang Wu Hua-Ying Fang Geng-Qing Song Yue Yu department of Gastroenterology The First Affiliated Hospital of University of Science and Technology of ChinaDivision of Life Sciences and MedicineUniversity of Science and Technology of ChinaHefei 230001Anhui ProvinceChina department of pathology The First Affiliated Hospital of University of Science and Technology of ChinaDivision of Life Sciences and MedicineUniversity of Science and Technology of ChinaHefei 230036Anhui ProvinceChina Intelligent pathology Institute Division of Life Sciences and MedicineUniversity of Science and Technology of ChinaHefei 230036Anhui ProvinceChina department of Gastroenterology and Hepatology Metro Health Medical CenterCase Western Reserve UniversityClevelandOH 44109United States

BACKGROUND Programmed cell death 1(PD-1)inhibitors are immune checkpoint inhibitors(ICI)that have demonstrated significant efficacy in treating various advanced malignant *** most patients tolerate treatment well,several adverse drug reactions,such as fatigue,myelosuppression,and ICI-associated colitis,have been *** SUMMARY This case involved a 57-year-old male patient with ulcerative colitis complicated by hepatocarcinoma who underwent treatment with tirelizumab(a PD-1 inhibitor)for six *** treatment led to repeated life-threatening lower gastrointestinal *** patient received infliximab,vedolizumab,and other salvage procedures but ultimately required subtotal colectomy due to uncontrollable massive lower gastrointestinal ***,postoperative gastrointestinal bleeding has stopped,the patient’s stool has turned yellow,and his full blood cell count has returned to *** This case highlights the necessity of early identification,timely and adequate treatment of ICI-related colitis,and rapid escalation to achieve the goal of improving prognosis.

关键词： Ulcerative colitis Hepatocarcinoma Immune checkpoint inhibitor-associated colitis Colectomy Case report

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