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Nrf2 and Her3 co-expression in cholangiocarcinoma:Possible biological pathways for potential therapeutic approach

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Hepatobiliary & Pancreatic Diseases International 2024年第3期23卷 317-321页

作者： Paola Parente Valentina Angerilli Giuseppe Zamboni Angelo Sparaneo Fabiola Fiordelisi Leonarda Di Candia Matteo Fassan Paolo Graziano pathology unit Fondazione IRCCS Casa Sollievo della Sofferenza71013San Giovanni Rotondo(Foggia)Italy Department of Medicine(DIMED) Surgical Pathology UnitUniversity of Padua35128Padua(Padua)Italy pathology unit IRCCS Ospedale Sacro Cuore Don Calabria37024Negrar(Verona)Italy Laboratory of Oncology Fondazione IRCCS Casa Sollievo della Sofferenza71013San Giovanni Rotondo(Foggia)Italy Veneto Institute of Oncology IOV-IRCCS 35124Padua(Padua)Italy

To the Editor:Cholangiocarcinomas(CCAs)are heterogeneous group of malignancies,encompassing intrahepatic CCA(iCCA),and extrahepatic CCA(eCCA);they are also classified into common hepatic duct cholangiocarcinoma(CHDCCA),choledocus extrapancreatic cholangiocarcinoma(EPCCA)and choledocus intrapancreatic cholangiocarcinoma(IPCCA)and,finally,gallbladder carcinoma(GBCCA).CCAs are relatively uncommon but.

关键词： carcinoma gallbladder Nrf2

Digital pathology-based artificial intelligence models for differential diagnosis and prognosis of sporadic odontogenic keratocysts

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International Journal of Oral Science 2024年第2期16卷 349-358页

作者： Xinjia Cai Heyu Zhang Yanjin Wang Jianyun Zhang Tiejun Li Department of Oral pathology Peking University School and Hospital of Stomatology&National Center of Stomatology&National Clinical Research Center for Oral Diseases&National Engineering Research Center of Oral Biomaterials and Digital Medical DevicesBeijingChina Central Laboratory Peking University School and Hospital of StomatologyBeijingChina Department of Oral pathology Shanghai Stomatological Hospital&School of StomatologyFudan UniversityShanghaiChina Research unit of Precision Pathologic Diagnosis in Tumors of the Oral and Maxillofacial Regions Chinese Academy of Medical Sciences(2019RU034)BeijingChina

Odontogenic keratocyst(OKC)is a common jaw cyst with a high recurrence *** combined with basal cell carcinoma as well as skeletal and other developmental abnormalities is thought to be associated with Gorlin ***,OKC needs to be differentiated from orthokeratinized odontogenic cyst and other jaw *** of the different prognosis,differential diagnosis of several cysts can contribute to clinical *** collected 519 cases,comprising a total of 2157 hematoxylin and eosinstained images,to develop digital pathology-based artificial intelligence(AI)models for the diagnosis and prognosis of *** Inception_v3 neural network was utilized to train and test models developed from patch-level ***,whole slide imagelevel AI models were developed by integrating deep learning-generated pathology features with several machine learning *** AI models showed great performance in the diagnosis(AUC=0.935,95%CI:0.898–0.973)and prognosis(AUC=0.840,95%CI:0.751–0.930)of *** advantages of multiple slides model for integrating of histopathological information are demonstrated through a comparison with the single slide ***,the study investigates the correlation between AI features generated by deep learning and pathological findings,highlighting the interpretative potential of AI models in the ***,we have developed the robust diagnostic and prognostic models for *** AI model that is based on digital pathology shows promise potential for applications in odontogenic diseases of the jaw.

关键词： diagnosis pathology prognosis

The role of polymorphic cytochrome P450 gene(CYP2B6)in B-chronic lymphocytic leukemia(B-CLL)incidence and outcome among Egyptian patients

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Oncology Research 2024年第4期32卷 785-797页

作者： MENNA AL-ADL MAGDY MYOUSSEF AHMED EL-SEBAIE SHERIF REFAAT AFAF EL-SAID Division of Biochemistry Department of ChemistryFaculty of ScienceMansoura UniversityMansoura35511Egypt Hematology unit Department of Clinical PathologyFaculty of MedicineMansoura UniversityMansoura35511Egypt Medical Oncology unit Oncology Center Mansoura UniversityMansoura35511Egypt Department of Genetics Mansoura University Children’s HospitalMansoura35511Egypt

Cytochromes P450(CYPs)play a prominent role in catalyzing phase I xenobiotic biotransformation and account for about 75%of the total metabolism of commercially available drugs,including *** gene expression and enzyme activity of CYPs are variable between individuals,which subsequently leads to different patterns of susceptibility to carcinogenesis by genotoxic xenobiotics,as well as differences in the efficacy and toxicity of clinically used *** research aimed to examine the presence of the CYP2B6*9 polymorphism and its possible association with the incidence of B-CLL in Egyptian patients,as well as the clinical outcome after receiving cyclophosphamide *** was isolated from whole blood samples of 100 de novo B-CLL cases and also from 100 sex-and age-matched healthy *** presence of the CYP2B6*9(G516T)polymorphism was examined by PCR-based allele specific amplification(ASA).Patients were further indicated for receiving chemotherapy,and then they were followed *** CYP2B6*9 variant indicated a statistically significant higher risk of B-CLL under different genetic models,comprising allelic(T-allele vs.G-allele,OR=4.8,p<0.001)and dominant(GT+TT ***,OR=5.4,p<0.001)*** cyclophosphamide chemotherapy,we found that the patients with variant genotypes(GT+TT)were less likely to achieve remission compared to those with the wild-type genotype(GG),with a response percentage of(37.5%vs.83%,respectively).In conclusion,our findings showed that the CYP2B6*9(G516T)polymorphism is associated with B-CLL susceptibility among Egyptian *** variant greatly affected the clinical outcome and can serve as a good therapeutic marker in predicting response to cyclophosphamide treatment.

关键词： B-CLL Xenobiotics Cytochromes P450 CYP2B6

Comparison of mismatch repair and immune checkpoint protein profile with histopathological parameters in pancreatic,periampullary/ampullary,and choledochal adenocarcinomas

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World Journal of Gastrointestinal Oncology 2024年第3期16卷 875-882页

作者： Arzu Hazal Aydın Nesrin Turhan Department of pathology Aksaray University Aksaray Training and Research HospitalAksaray 68200Turkey Department of pathology University of Health Sciences Ankara City HospitalAnkara 06800Turkey

BACKGROUND Pancreatic,periampullary/ampullary,and choledochal adenocarcinomas are aggressive malignancies with a poor *** checkpoint blockade is a promising treatment option for several tumor types.H long terminal repeatassociating 2(HHLA2),which is analogous to programmed death-ligand 1(PDL1),is a recently discovered member of the B7/cluster of differentiation 28 family and is expressed in many *** To analyze the expression of HHLA2 and its association with the pathologic biomarkers that predict sensitivity to *** Ninety-two adenocarcinoma cases located in the pancreas,ampulla,and distal common bile duct were *** study assessed 106 pancreaticoduodenectomy and distal/total pancreatectomy samples that were delivered to Ankara City Hospital between 2019 and *** was conducted to examine the expression of DNA mismatch repair(MMR),PD-L1,and HHLA2 *** Patients with high HHLA2 expression had a higher mean age than those with low *** HHLA2 expression was associated with high perineural ***2 expression was low in pathological stage T3(pT)3 cases and high in pathological stage T1,T2,and T4 *** was no correlation between HHLA2 expression and the expression of MMR proteins and *** Evaluation of HHLA2 expression in microsatellite stable and PD-L1-negative tumors may be useful for predicting the response of individuals to immunotherapy and may serve as a novel therapeutic target for immunotherapy in advanced-stage disease.

关键词： H long terminal repeat-associating 2 Programmed death-ligand 1 Adenocarcinoma Pancreas Ampulla of Vater Distal common bile duct

Liver biopsy in the post-hepatitis C virus era in Japan

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World Journal of Gastroenterology 2024年第14期30卷 1949-1957页

作者： Yoshihiro Ikura Takako Okubo Yasuhiro Sakai Department of pathology Takatsuki General HospitalTakatsuki 569-1192Osaka PrefectureJapan Department of pathology Kansai Medical University Medical CenterMoriguchi 570-8507Japan

In Japan,liver biopsies were previously crucial in evaluating the severity of hepatitis caused by the hepatitis C virus(HCV)and diagnosing HCV-related hepatocellular carcinoma(HCC).However,due to the development of effective antiviral treatments and advanced imaging,the necessity for biopsies has significantly *** change has resulted in fewer chances for diagnosing liver disease,causing many general pathologists to feel less confident in making liver biopsy *** article provides a comprehensive overview of the challenges and potential solutions related to liver biopsies in ***,it highlights the importance of considering steatotic liver diseases as independent conditions that can coexist with other liver diseases due to their increasing ***,it emphasizes the need to avoid hasty assumptions of HCC in nodular lesions,because clinically diagnosable HCCs are not targets for ***,the importance of diagnosing hepatic immune-related adverse events caused by immune checkpoint inhibitors is increasing due to the anticipated widespread use of these *** conclusion,pathologists should be attuned to the changing landscape of liver diseases and approach liver biopsies with care and attention to detail.

关键词： Liver biopsy Alteration Post-hepatitis C virus era Steatotic liver disease Hepatic tumors Immune checkpoint inhibitors

Blastomas of the digestive system in adults:A review

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World Journal of Gastrointestinal Surgery 2024年第4期16卷 1030-1042页

作者： Yu Liu Tony El Jabbour Jonathan Somma Yukihiro Nakanishi Saverio Ligato Hwajeong Lee Zhi-Yan Fu Department of pathology LSU Health Sciences Center School of MedicineNew OrleansLA 70112United States Department of pathology Hartford HealthCareHartfordCT 06102United States Department of pathology Moffitt Cancer CenterTampaFL 33612United States Department of pathology and Laboratory Medicine Albany Medical CenterAlbanyNY 12208United States

Blastomas,characterized by a mixture of mesenchymal,epithelial,and undifferentiated blastematous components,are rare malignant neoplasms originating from precursor blast *** review focuses on digestive system blastomas in adult patients,including gastroblastoma,hepatoblastoma,and *** is a biphasic,epitheliomesenchymal tumor,with only sixteen cases reported to *** addition to the characteristic histology,metastasisassociated lung adenocarcinoma transcript 1-glioma-associated oncogene homolog 1 gene fusion is typical,although recently novel ewing sarcoma breakpoint region 1-c-terminal binding protein 1 and patched 1-glioma-associated oncogene homolog 2 fusions have been *** is exceptionally rare in adults and can show a variety of histologic patterns which may cause diagnostic ***,primarily a pediatric tumor,displays acinar differentiation and squamoid nests with other lines of differentiation also present,especially *** approaches for these blastomas include a combination of imaging modalities,histopathological examination,and molecular *** treatment generally involves surgical resection,which may be supplemented by chemotherapy or radiotherapy in some *** vary with gastroblastoma generally showing favorable outcomes post-surgery whereas hepatoblastoma and pancreatoblastoma often have poorer outcomes,particularly in the setting of *** review highlights the complexity of diagnosing and managing these rare adult blastomas as well as the need for ongoing research to better understand their pathogenesis and improve treatment strategies.

关键词： Adult blastomas Gastroblastoma Hepatoblastoma Pancreatoblastoma Digestive system

Role of ACLY in the development of gastric cancer under hyperglycemic conditions

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Quantitative Biology 2024年第1期12卷 100-116页

作者： Keran Sun Jingyuan Ning Keqi Jia Xiaoqing Fan Hongru Li Jize Ma Meiqi Meng Cuiqing Ma Lin Wei Department of Immunology Immunology Department of Hebei Medical UniversityShijiazhuangChina Department of pathology Pathology Department of the Fourth Hospital of Hebei Medical UniversityShijiazhuangChina

To investigate the impact of hyperglycemia on the prognosis of patients with gastric cancer and identify key molecules associated with high glucose levels in gastric cancer development,RNA sequencing data and clinical features of gastric cancer patients were obtained from The Cancer Genome Atlas(TCGA)*** glucose-related genes strongly associated with gastric cancer were identified using weighted gene co-expression network and differential analyses.A gastric cancer prognosis signature was constructed based on these genes and patients were categorized into high-and low-risk *** immune statuses of the two patient groups were *** citrate lyase(ACLY),a gene significantly related to the prognosis,was found to be upregulated upon high-glucose *** and molecular analyses confirmed high ACLY expression in gastric cancer tissues and *** Set Enrichment Analysis(GSEA)revealed the involvement of ACLY in cell cycle and DNA replication *** of ACLY affected the proliferation and migration of gastric cancer cells induced by high glucose *** findings suggest that ACLY,as a high glucose-related gene,plays a critical role in gastric cancer progression.

关键词： ACLY gastric cancer high glucose immune microenvironment

Microbiome changes in esophageal cancer:implications for pathogenesis and prognosis

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Cancer Biology & Medicine 2024年第2期21卷 163-174页

作者： Yi Li Bing Wei Xia Xue Hongle Li Jun Li Department of Molecular pathology Clinical Pathology CenterAffiliated Cancer Hospital of Zhengzhou University and Henan Cancer HospitalZhengzhou 450003China Henan Key Laboratory of Molecular pathology Zhengzhou 450003China Henan Key Laboratory of Helicobacter pylori&Microbiota and Gastrointestinal Cancer Marshall Medical Research CenterThe Fifth Affiliated Hospital of Zhengzhou UniversityZhengzhou 450052China

Esophageal cancer(EC)is an aggressive malignancy with a poor *** factors,including dietary habits,and antacid and antibiotic use,have been shown to influence the esophageal ***,enrichment and diversity of the esophageal microbiome can also impact its *** studies have revealed prevalent changes in the esophageal microbiome among patients with EC,thus suggesting the potential contribution of the esophageal microbiome to EC ***,distinct microbiome compositions have been observed in patients with different responses to radiotherapy and chemotherapy,indicating the role of the esophageal microbiome in modulating treatment *** this review,we have examined previous studies on the esophageal microbiome in healthy individuals and patients with EC or other esophageal diseases,with a focus on identifying microbial communities associated with EC pathogenesis and *** the role of the microbiome in EC may aid in early detection and optimized treatment strategies,ultimately leading to better outcomes for patients.

关键词： Esophageal cancer microbiome dysbiosis microenvironment carcinogenesis

Correlation of tumor-associated macrophage density and proportion of M2 subtypes with the pathological stage of colorectal cancer

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World Journal of Gastrointestinal Oncology 2024年第5期16卷 1878-1889页

作者： Fouzia Fazal Muhammad Arsalan Khan Sumayya Shawana Rahma Rashid Muhammed Mubarak Department of pathology Jinnah Medical and Dental CollegeKarachi 74800SindhPakistan Department of General Surgery Sindh Institute of Urology&Transplantation(SIUT)Karachi 74200SindhPakistan Department of pathology Bahria University of Health SciencesKarachi 74400SindhPakistan Department of pathology SIUTKarachi 74200SindhPakistan

BACKGROUND Colorectal cancer(CRC)is a prevalent global malignancy with complex prognostic ***-associated macrophages(TAMs)have shown paradoxical associations with CRC survival,particularly concerning the M2 *** We aimed to establish a simplified protocol for quantifying M2-like TAMs and explore their correlation with clinicopathological *** A cross-sectional study included histopathological assessment of paraffinembedded tissue blocks obtained from 43 CRC *** CD68 and CD163 immunohistochemistry,we quantified TAMs in tumor stroma and front,focusing on M2 ***,histopathological,and clinical parameters were *** TAM density was significantly higher at the tumor front,with the M2 proportion three times greater in both *** tumor front had a higher M2 proportion,which correlated significantly with advanced tumor stage(P=0.04),pathological nodal involvement(P=0.04),and lymphovascular invasion(LVI,P=0.01).However,no significant association was found between the M2 proportion in the tumor stroma and clinicopathological *** Our study introduces a simplified protocol for quantifying M2-like TAMs in CRC tissue *** demonstrated a significant correlation between an increased M2 proportion at the tumor front and advanced tumor stage,nodal involvement,and *** suggests that M2-like TAMs might serve as potential indicators of disease progression in CRC,warranting further investigation and potential clinical application.

关键词： Colorectal cancer Macrophages Tumor stroma M2 subset Tumor front Tumor stage Lymphovascular invasion Prognosis Tumor-associated macrophages Immunohistochemistry