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Tissue inhibitor of metalloproteinase-3 expression affects clinicopathological features and prognosis of aflatoxin B1-related hepatocellular carcinoma

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World Journal of Hepatology 2024年第8期16卷 1131-1144页

作者： Qiu-Ju Liang Qin-Qin Long Feng-Qin Tian Qun-Ying Su Xiao-Ying Zhu Xi-Dai Long Clinicopathological Diagnosis and Research Center The Affiliated Hospital of Youjiang Medical University for NationalitiesBaise 533000Guangxi Zhuang Autonomous RegionChina department of tumor pathology Key Laboratory of Tumor Molecular Pathology of Guangxi Higher Education InstitutesBaise 533000Guangxi Zhuang Autonomous RegionChina

BACKGROUND The dysregulation of tissue inhibitor of metalloproteinase-3(TIMP3)was positively correlated with the progression of hepatocellular carcinoma(HCC).However,it is not clear whether TIMP3 expression is associated with the clinico-pathological features and prognosis of aflatoxin B1(AFB1)-related HCC(AHCC).A retrospective study,including 182 patients with AHCC,was conducted to explore the link between TIMP3 expression in cancerous tissues and the clinico-pathological characteristics and prognosis of ***3 expression was detected by immunohistochemistry and its effects on the clinicopathological features and prognosis of AHCC were evaluated by Kaplan-Meier survival analysis and Cox regression survival *** ratio,hazard ratio(HR),median overall survival time(MST),median tumor recurrence-free survival time(MRT),and corresponding 95%confidential interval(CI)was calculated to RESULTS Kaplan-Meier survival analysis showed that compared with high TIMP3 expression,low TIMP3 expression in tumor tissues significantly decreased the MST(36.00 mo vs 18.00 mo)and MRT(32.00 mo vs 16 mo)of patients with *** Cox regression survival analysis further proved that decreased expression of TIMP3 increased the risk of death(HR=2.85,95%CI:2.04-4.00)and tumor recurrence(HR=2.26,95%CI:1.57-3.26).Furthermore,decreased expression of TIMP3 protein in tissues with AHCC was significantly correlated with tumor clinicopatho-logical features,such as tumor size,tumor grade and stage,tumor microvessel density,and tumor blood ***,TIMP3 protein expression was also negatively associated with amount of AFB1-DNA adducts in tumor *** These findings indicate that the dysregulation of TIMP3 expression is related to AHCC biological behaviors and affects tumor outcome,suggesting that TIMP3 may act as a prognostic biomarker for AHCC.

关键词： Tissue inhibitor of metalloproteinase-3 expression Aflatoxin B1 Hepatocellular carcinoma Clinicopathological feature Prognosis

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Myocardial metastasis from ZEB1-and TWIST-positive spindle cell carcinoma of the esophagus:A case report

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World Journal of Gastroenterology 2024年第11期30卷 1636-1643页

作者： Yoshihiro Shibata Hirofumi Ohmura Kazuki Komatsu Kosuke Sagara Atsuji Matsuyama Ryuji Nakano Eishi Baba department of Medical Oncology Fukuoka Wajiro HospitalFukuoka 811-0213Japan department of Oncology and Social Medicine Kyushu University Graduate School of Medical SciencesFukuoka 812-8582Japan department of pathology and Oncology University of Occupational and Environmental HealthKitakyushu 807-8555Japan department of diagnostic pathology Fukuoka Wajiro HospitalFukuoka 811-0213Japan

BACKGROUND Metastatic cardiac tumors are known to occur more frequently than primary cardiac tumors,however,they often remain asymptomatic and are commonly dis-covered on *** tumors with a relatively high frequency of cardiac metastasis include mesothelioma,melanoma,lung cancer,and breast cancer,whereas reports of esophageal cancer with cardiac metastasis are *** SUMMARY The case of a 60-year-old man who complained of dysphagia is *** gastrointestinal endoscopy showed a submucosal tumor-like elevated lesion in the esophagus causing ***-enhanced computed tomography showed left atrial compression due to the esophageal tumor,multiple liver and lung metastases,and a left pleural *** examination of a biopsy speci-men from the esophageal tumor showed spindle-shaped cells,raising suspicion of esophageal *** disease progressed rapidly,and systemic chemotherapy was deemed necessary,however,due to his poor general condition,adminis-tration of cytotoxic agents was considered *** his high Combined Positive Score,nivolumab was administered,however,the patient soon died from the *** autopsy confirmed spindle cell carcinoma(SCC)of the esophagus and cardiac metastasis with similar histological *** stem cell markers,ZEB1 and TWIST,were positive in both the primary tumor and the cardiac *** To the best of our knowledge,there have been no prior reports of cardiac metastasis of esophageal *** case highlights our experience with a patient with esophageal SCC who progressed rapidly and died from the disease,with the autopsy examination showing cardiac metastasis.

关键词： Spindle cell carcinoma Esophagus Myocardial metastasis Epithelial-mesenchymal transition Case report

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Distinct clinical profiles and mutation landscapes of gliomas originating from the neocortex,mesocortex,and cerebellum

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Genes & Diseases 2024年第1期11卷 53-56页

作者： Ye Cheng Lei Zhang Xiaolong Wu Hiroaki Wakimoto Haoming Geng Yukui Wei Geng Xu Xinru Xiao Jie Bai Yaming Wang Zeliang Hu Leiming Wang Qingtang Lian department of Neurosurgery Xuanwu HospitalCapital Medical UniversityBeijing 100053China Brain tumor Research Center Massachusetts General HospitalDepartment of NeurosurgeryHarvard Medical SchoolBostonMA02134USA department of pathology Xuanwu HospitalCapital Medical UniversityBeijing 100053China

Gliomas originating from anatomically and developmentally distinct brain regions have different clinical ***,the molecular landscape underlying this difference remains *** analyzed key molecular mutations via sequencing and correlated them with clinical characteristics in 180 adult patients with gliomas originating from the neocortex,mesocortex,and *** of cerebellar origin had significantly longer survival than those of supratentorial origin,consistent with higher rates of mutation in key genes associated with supratentorial gliomas.

关键词： clinical cortex glioma

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Clinical and molecular significance of homologous recombination deficiency positive non-small cell lung cancer in Chinese population:An integrated genomic and transcriptional analysis

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Chinese Journal of Cancer Research 2024年第3期36卷 282-297页

作者： Yifei Wang Yidan Ma Lei He Jun Du Xiaoguang Li Peng Jiao Xiaonan Wu Xiaomao Xu Wei Zhou Li Yang Jing Di Changbin Zhu Liming Xu Tianlin Sun Lin Li Dongge Liu Zheng Wang department of pathology department of Minimally Invasive tumor Therapies Center department of Thoracic Surgery department of Oncology department of Respiratory and Critical Care Medicine Beijing HospitalNational Center of GerontologyInstitute of Geriatric MedicineChinese Academy of Medical SciencesBeijing 100730China Amoy diagnostics Co. Ltd.Xiamen 361027China

Objective:The clinical significance of homologous recombination deficiency(HRD)in breast cancer,ovarian cancer,and prostate cancer has been established,but the value of HRD in non-small cell lung cancer(NSCLC)has not been fully *** study aimed to systematically analyze the HRD status of untreated NSCLC and its relationship with patient prognosis to further guide clinical ***:A total of 355 treatment-naïve NSCLC patients were retrospectively *** status was assessed using the AmoyDx Genomic Scar Score(GSS),with a score of≥50 considered ***,transcriptomic,tumor microenvironmental characteristics and prognosis between HRD-positive and HRDnegative patients were ***:Of the patients,25.1%(89/355)were *** to HRD-negative patients,HRDpositive patients had more somatic pathogenic homologous recombination repair(HRR)mutations,higher tumor mutation burden(TMB)(Ptumor proliferation and immunosuppression ***-negative NSCLC showed activated signatures of major histocompatibility complex(MHC)-II,interferon(IFN)-γand effector memory CD8+T ***-positive patients had a worse prognosis and shorter progressionfree survival(PFS)to targeted therapy(first-and third-generation EGFR-TKIs)(P=0.042).Additionally,HRDpositive,EGFR/ALK wild-type patients showed a numerically lower response to platinum-free immunotherapy ***:Unique genomic and transcriptional characteristics were found in HRD-positive *** prognosis and poor response to EGFR-TKIs and immunotherapy were observed in HRD-positive *** study highlights potential actionable alterations in HRD

关键词： Non-small cell lung cancer homologous recombination deficiency genetic alterations transcriptional analysis tumor microenvironment prognosis

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A Case of Warthin’s tumor Together with IgG4-Related Sialadenitis

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Open Journal of pathology 2024年第3期14卷 81-89页

作者： Ryogo Aoki Risa Ito Asuka Ohashi Riyoko Niwa Masashi Matsuyama Sachiko Oka Naomi Kawaguchi Toshimasa Sakakima Daichi Kodama Naoki Watanabe Daisuke Okamoto Takafumi Naiki Takuji Tanaka department of diagnostic pathology (DDP) & Research Center of diagnostic pathology (RC-DiP) Gifu Municipal Hospital Gifu Japan department of Central Clinical Laboratory Gifu Municipal Hospital Gifu Japan department of Hematology Gifu Municipal Hospital Gifu Japan

Warthin’s tumor is the second most frequent neoplasm next to pleomorphic adenoma in the salivary gland. The tumor contains the epithelial oncocyte cells with the presence of rich-mitochondria and their surrounding abundant lymphocytes. A relatively new disease entity of IgG4-related disease frequently occurs in the salivary gland. However, the coexistence of Warthin’s tumor and IgG4-related disease is scarcely observed. We have recently experienced a rare case of Warthin’s tumor with IgG4-related sialadenitis. A 51-year-old man presented to our hospital, complaining of a mass with right submandibular tenderness and spontaneous pain. A computed tomography scan of the cervical region revealed a suspicion of lymph node proliferative disease, including malignant lymphoma. Elevated serum levels of IL-2R: 1843 U/ml (reference value 122 - 496 U/ml), IgG: 3430 mg/dl (reference value 861 - 1747 mg/dl), and IgG4: 3140 mg/dl (reference value 11 - 121 mg/dl) were observed. Other laboratory data showed within normal ranges. The cervical tumor was diagnosed as Warthin’s tumor by the findings of fine-needle aspiration cytology and biopsy examination. Immunohistochemistry revealed numerous IgG4- and IgG-positive cells with fibrosis surrounding the epithelial component of Warthin’s tumor, suggesting IgG4-rerated sialadenitis. Finally, we diagnosed the cervical tumor as Warthin tumor with IgG4-related sialadenitis. This is the second report describing a case of Warthin’s tumor with possible involvement of IgG4-related sialadenitis.

关键词： Warthin’s tumor Sialadenitis IgG4-Related Disease Immunohistochemistry

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PLAU plays a functional role in driving lung squamous cell carcinoma metastasis

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Genes & Diseases 2024年第2期11卷 554-557页

作者： Pengbo Ning Fuyu Du Xiaocheng Gong Jingtong Yuan Caixia Ding Xilian Zhao Wei Li School of Life Science and Technology Xidian UniversityXi'anShaanxi 710071China Engineering Research Center of Molecular & Neuroimaging Ministry of EducationXi'anShaanxi 710071China department of Medical Oncology Zhongshan HospitalFudan UniversityShanghai 200032China department of pathology Shaanxi Provincial Tumor HospitalXi'an Jiaotong UniversityXi'anShaanxi 710061China

The high mortality of patients with lung squamous cell carcinoma(LUSC)results from metastasis rather than primary tumors,1 whereas the molecular pathogenesis of cancer metastasis remains poorly *** encodes urokinase-type plasminogen activator(uPA)which is closely related to tumor diagnosis,treatment target,and prognosis of patients.2.3 We previously predicted that PLAU is a key gene negatively associated with overall survival by integrated multidimensional analyses of The Cancer Genome Atlas(TCGA)datasets from 504 samples of LUSC tumor tissues and 46 samples of adjacent non-tumorous lung tissues.4 However,whether the role of PLAU contributes to the metastasis of LUC remains ***,we analyzed the association between uPA levels and LUSC and found that uPA levels were associated with pathological variations in LUSC patients.

关键词： metastasis lung squamous

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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

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Aspartoacylase suppresses prostate cancer progression by blocking LYN activation

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Military Medical Research 2024年第2期11卷 180-205页

作者： Hong Weng Kang-Ping Xiong Wang Wang Kai-Yu Qian Shuai Yuan Gang Wang Fang Yu Jun Luo Meng‑Xin Lu Zhong‑Hua Yang Tao Liu Xing Huang Hang Zheng Xing-Huan Wang department of Urology Zhongnan Hospital of Wuhan UniversityWuhan 430071China Center for Evidence‑Based and Translational Medicine Zhongnan Hospital of Wuhan UniversityWuhan 430071China department of Biological Repositories Zhongnan Hospital of Wuhan UniversityWuhan 430071China Hubei Key Laboratory of tumor Biological Behaviors Wuhan 430071China department of pathology Zhongnan Hospital of Wuhan UniversityWuhan 430071China Center for pathology and Molecular diagnostics Wuhan UniversityWuhan 430071China Wuhan Research Center for Infectious Diseases and Cancer Chinese Academy of Medical SciencesWuhan 430071China

Background:Globally,despite prostate cancer(PCa)representing second most prevalent malignancy in male,the precise molecular mechanisms implicated in its pathogenesis remain ***,elucidating the key molecular regulators that govern disease progression could substantially contribute to the establishment of novel therapeutic strategies,ultimately advancing the management of ***:A total of 49 PCa tissues and 43 adjacent normal tissues were collected from January 2017 to December 2021 at Zhongnan Hospital of Wuhan *** advanced transcriptomic methodologies were employed to identify differentially expressed mRNAs in *** expression of aspartoacylase(ASPA)in PCa was thoroughly evaluated using quantitative real-time PCR and Western blotting *** elucidate the inhibitory role of ASPA in PCa cell proliferation and metastasis,a comprehensive set of in vitro and in vivo assays were conducted,including orthotopic and tumor-bearing mouse models(n=8 for each group).A combination of experimental approaches,such as Western blotting,luciferase assays,immunoprecipitation assays,mass spectrometry,glutathione S-transferase pulldown experiments,and rescue studies,were employed to investigate the underlying molecular mechanisms of ASPA's action in *** Student‘s t-test was employed to assess the statistical significance between two distinct groups,while one-way analysis of variance was utilized for comparisons involving more than two groups.A two-sided P<0.05 was deemed to indicate statistical ***:ASPA was identified as a novel inhibitor of PCa *** expression of ASPA was found to be significantly down-regulated in PCa tissue samples,and its decreased expression was independently associated with patients’prognosis(HR=0.60,95%CI 0.40–0.92,P=0.018).Our experiments demonstrated that modulation of ASPA activity,either through gain-or loss-of-function,led to the suppression or enhancement of PCa cell proliferation,mig

关键词： Prostate cancer Aspartoacylase LYN JNK AP-1 C-Jun Phosphorylation

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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

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Cellular zinc metabolism and zinc signaling:from biological functions to diseases and therapeutic targets

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Signal Transduction and Targeted Therapy 2024年第2期9卷 401-441页

作者： Bonan Chen Peiyao Yu Wai Nok Chan Fuda Xie Yigan Zhang Li Liang Kam Tong Leung Kwok Wai Lo Jun Yu Gary M.K.Tse Wei Kang Ka Fai To department of Anatomical and Cellular pathology State Key Laboratory of Translational OncologyPrince of Wales HospitalThe Chinese University of Hong KongHong KongChina State Key Laboratory of Digestive Disease Institute of Digestive DiseaseThe Chinese University of Hong KongHong KongChina CUHK-Shenzhen Research Institute The Chinese University of Hong KongShenzhenChina department of pathology Nanfang Hospital and Basic Medical CollegeSouthern Medical UniversityGuangdong Province Key Laboratory of Molecular Tumor PathologyGuangzhouChina Institute of Biomedical Research Taihe HospitalHubei University of MedicineShiyanChina department of Pediatrics The Chinese University of Hong KongHong KongChina department of Medicine and Therapeutics The Chinese University of Hong KongHong KongChina

Zinc metabolism at the cellular level is critical for many biological processes in the body.A key observation is the disruption of cellular homeostasis,often coinciding with disease *** an essential factor in maintaining cellular equilibrium,cellular zinc has been increasingly spotlighted in the context of disease *** research suggests zinc’s involvement in promoting malignancy and invasion in cancer cells,despite its low tissue *** has led to a growing body of literature investigating zinc’s cellular metabolism,particularly the functions of zinc transporters and storage mechanisms during cancer *** transportation is under the control of two major transporter families:SLC30(ZnT)for the excretion of zinc and SLC39(ZIP)for the zinc ***,the storage of this essential element is predominantly mediated by metallothioneins(MTs).This review consolidates knowledge on the critical functions of cellular zinc signaling and underscores potential molecular pathways linking zinc metabolism to disease progression,with a special focus on *** also compile a summary of clinical trials involving zinc *** the main localization of zinc transporters at the cell membrane,the potential for targeted therapies,including small molecules and monoclonal antibodies,offers promising avenues for future exploration.

关键词： metabolism invasion involvement

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