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Liquid biopsy for gastric cancer:Techniques,applications,and future directions

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World Journal of Gastroenterology 2024年第12期30卷 1680-1705页

作者： Cristina Díaz del Arco M Jesús Fernández Aceñero Luis Ortega Medina department of Surgical pathology Health Research Institute of the Hospital Clínico San CarlosHospital Clínico San CarlosMadrid 28040Spain department of Legal Medicine Psychiatry and PathologyUniversidad Complutense de MadridMadrid 28040Spain

After the study of circulating tumor cells in blood through liquid biopsy(LB),this technique has evolved to encompass the analysis of multiple materials originating from the tumor,such as nucleic acids,extracellular vesicles,tumor-educated platelets,and other ***,research has extended to include the examination of samples other than blood or plasma,such as saliva,gastric juice,urine,or *** techniques are diverse,intricate,and *** must be highly sensitive,and pre-analytical,patient,and tumor-related factors significantly influence the detection threshold,diagnostic method selection,and potential ***,the implementation of LB in clinical practice still faces several *** potential applications of LB range from early cancer detection to guiding targeted therapy or immunotherapy in both early and advanced cancer cases,monitoring treatment response,early identification of relapses,or assessing patient *** the other hand,gastric cancer(GC)is a disease often diagnosed at advanced *** recent advances in molecular understanding,the currently available treatment options have not substantially improved the prognosis for many of these *** application of LB in GC could be highly valuable as a non-invasive method for early diagnosis and for enhancing the management and outcomes of these *** this comprehensive review,from a pathologist’s perspective,we provide an overview of the main options available in LB,delve into the fundamental principles of the most studied techniques,explore the potential utility of LB application in the context of GC,and address the obstacles that need to be overcome in the future to make this innovative technique a game-changer in cancer diagnosis and treatment within clinical practice.

关键词： Liquid biopsy Gastric cancer Circulating tumor cells Cell-free DNA Circulating tumor DNA Molecular

Targeting stroma and tumor,silencing galectin 1 treats orthotopic mouse hepatocellular carcinoma

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Acta Pharmaceutica Sinica B 2024年第1期14卷 292-303页

作者： Tahereh Setayesh Ying Hu Farzam Vaziri Xin Chen Jinping Lai Dongguang Wei Yu-Jui Yvonne Wan department of Medical pathology and Laboratory Medicine University of CaliforniaDavisSacramentoCA 95817USA Cancer Biology Program the University of Hawaii Cancer CenterHonoluluHI 96813USA department of pathology and Laboratory Medicine Kaiser Permanente Sacramento Medical CenterSacramentoCA 95825USA

This study examines inhibiting galectin 1(Gal1)as a treatment option for hepatocellular carcinoma(HCC).Gal1 has immunosuppressive and cancer-promoting *** data showed that Gal1 was highly expressed in human and mouse *** levels of Gal1 positively correlated with the stages of human HCC and negatively with *** roles of Gal1 in HCC were studied using overexpression(OE)or silencing using Igals1 siRNA delivered by *** to HCC initiation induced by RAS and AKT mutations,lgals1-OE and silencing had opposite impacts on tumor *** treatment effect of lgals1 siRNAwas further demonstrated by intersecting HCC at different time points when the tumor load had already reached 9%or even 42%of the body *** spatial transcriptomic profiles of Gal1 silenced and OE HCC,inhibiting matrix formation and recognition of foreign antigen in CD45t cell-enriched areas located at tumor-margin likely contributed to the anti-HCC effects of Gal1 *** the tumors,silencing Gal1 inhibited translational initiation,elongation,and ***,Gal1 silencing increased immune cells as well as expanded cytotoxic T cells within the tumor,and the anti-HCC effect of lgals1 siRNAwas ***,Gal1 silencing has a promising potential for HCC treatment.

关键词： Liver Hepatocellular carcinoma Carbohydrate-binding lectin Galectin 1 Extracellular matrix Translation Spatial transcriptomics Tumor-margin

The Largest Chinese Cohort Study Indicates Homologous Recombination Pathway Gene Mutations as Another Major Genetic Risk Factor for Colorectal Cancer with Heterogeneous Clinical Phenotypes

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Research 2024年第3期6卷 191-203页

作者： Yun Xu Kai Liu Cong Li Minghan Li Fangqi Liu Xiaoyan Zhou Menghong Sun Megha Ranganathan Liying Zhang Sheng Wang Xin Hu Ye Xu department of Colorectal Surgery Fudan University Shanghai Cancer CenterShanghaiP.R.China department of pathology Fudan University Shanghai Cancer CenterShanghaiP.R.China department of pathology Tissue BankFudan University Shanghai Cancer CenterShanghaiP.R.China department of Medicine Memorial Sloan Kettering Cancer CenterNew YorkNYUSA department of pathology and Laboratory Medicine David Geffen School of MedicineUniversity of CaliforniaLos AngelesCAUSA Precision Cancer Medical Center Fudan University Shanghai Cancer CenterShanghaiP.R.China

While genetic factors were associated with over 30% of colorectal cancer (CRC) patients, mutations in CRC-susceptibility genes were identified in only 5% to 10% of these patients. Besides, previous studies on hereditary CRC were largely designed to analyze germline mutations in patients with single genetic high-risk factor, which limited understanding of the association between genotype and phenotypes. From January 2015 to December 2018, we retrospectively enrolled 2,181 patients from 8,270 consecutive CRC cases, covering 5 categories of genetic high-risk factors. Leukocyte genomic DNA was analyzed for germline mutations in cancer predisposition genes. The germline mutations under each category were detected and analyzed in association with CRC susceptibility, clinical phenotypes, and prognoses. A total of 462 pathogenic variants were detected in 19.3% of enrolled CRC patients. Mismatch repair gene mutation was identified in 9.1% of patients, most prevalent across all high-risk groups. Homologous recombination (HR) gene mutations were detected in 6.5% of cases, penetrated in early-onset and extra-colonic cancer risk groups. Mutations in HR genes, including BARD1, RAD50, and ATM, were found to increase CRC risk with odds ratios of 2.8-, 3.1-, and 3.1-fold, respectively. CRC patients with distinct germline mutations manifested heterogeneous phenotypes in clinicopathology and long-term prognoses. Thus, germline mutation screenings should be performed for CRC patients with any of those genetic risk factors. This study also reveals that HR gene mutations may be another major driver for increased CRC risk.

关键词： susceptibility category Major

Arginine methylation of ALKBH5 by PRMT6 promotes breast tumorigenesis via LDHA-mediated glycolysis

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Frontiers of Medicine 2024年第2期18卷 344-356页

作者： Xue Han Chune Ren Aifang Jiang Yonghong Sun Jiayi Lu Xi Ling Chao Lu Zhenhai Yu department of Reproductive Medicine Affiliated Hospital of Weifang Medical UniversityWeifang261053China department of pathology Affiliated Hospital of Weifang Medical UniversityWeifang261053China

ALKBH5 is a master regulator of N6-methyladenosine(m6A)modification,which plays a crucial role in many biological ***,we show that ALKBH5 is required for breast tumor ***,PRMT6 directly methylates ALKBH5 at R283,which subsequently promotes breast tumor ***,arginine methylation of ALKBH5 by PRMT6 increases LDHA RNA stability via m6A demethylation,leading to increased aerobic ***,PRMT6-mediated ALKBH5 arginine methylation is confirmed in PRMT6-knockout ***,these findings identify a PRMT6-ALKBH5-LDHA signaling axis as a novel target for the treatment of breast cancer.

关键词： PRMT6 ALKBH5 N6-methyladenosine glycolysis tumor growth

Single nucleotide polymorphism within chromosome 8q24 is associated with prostate cancer development in Saudi Arabia

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Asian Journal of Urology 2024年第1期11卷 26-32页

作者： Awad Elsid Osman Sahar Alharbi Atif Ali Ahmed Asim Ali Elbagir pathology and Clinical Laboratory Management department(PCLM) King Fahad Medical CityRiyadhSaudi Arabia department of pathology and Laboratory Medicine University of Missouri at Children's Mercy HospitalKansas CityMOUSA

Objective: Genome-wide association studies have demonstrated that single nucleotide polymorphisms (SNPs) are important risk factors for the development of prostate cancer (PCa). Preliminary studies have suggested that the incidence of PCa in Saudi males is low but is probably familial or genetically ***: To identify any possible association of SNP with PCa development in Saudi patients, we investigated a group of SNPs in Saudi PCa patients (n=85) and compared the outcomes to healthy normal controls (n=115) and nodular hyperplasia patients (n=120). DNA was extracted from paraffin-embedded formalin fixed tissue or whole blood from both patients’ groups and healthy control group. A total of thirteen SNPs were genotyped using TaqMan® minor groove binder polymerase chain reaction ***: The rs16901979A, s629242T and rs1447295A alleles were found at significantly higher frequency in PCa patients than controls (p< 0.05). The rs16901979 CA genotype was found at significantly greater frequency in PCa patients than in healthy controls (43% vs. 14%, odds ratio=4.6, p=0.0001) and benign hyperplasia group (43% vs. 25%, odds ratio=2.2, p=0.009).Conclusion: Our study has highlighted the association of rs16901979 SNP with PCa in Saudi males. Such findings have important implications in the PCa diagnosis and in screening unaffected family members of Saudi patients.

关键词： Prostatecancer Saudi Singlenucleotide polymorphism Allele

A systematic review of salivary biomarkers in Parkinson's disease

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Neural Regeneration Research 2024年第12期19卷 2613-2625页

作者： Maria Ilenia De Bartolo Daniele Belvisi Romina Mancinelli Matteo Costanzo Claudia Caturano Giorgio Leodori Alfredo Berardelli Giovanni Fabbrini Giorgio Vivacqua IRCCS Neuromed PozzilliItaly department of Human Neurosciences Sapienza University of RomeRomeItaly department of Anatomical HistologicalForensic Medicine and Orthopedics SciencesSapienza University of RomeRomeItaly department of Experimental Morphology and Microscopy-Integrated Research Center(PRAAB)-Campus Biomedico University of Rome RomeItaly

The search fo r reliable and easily accessible biomarkers in Parkinson's disease is receiving a growing emphasis,to detect neurodegeneration from the prodromal phase and to enforce disease-modifying *** the need for non-invasively accessible biomarke rs,the majo rity of the studies have pointed to cerebrospinal fluid or peripheral biopsies biomarkers,which require invasive collection *** represents an easily accessible biofluid and an incredibly wide source of molecular *** the present study,after presenting the morphological and biological bases for looking at saliva in the search of biomarkers for Parkinson's disease,we systematically reviewed the results achieved so far in the saliva of different cohorts of Parkinson's disease patients.A comprehensive literature search on PubMed and SCOPUS led to the discovery of *** screening and exclusion,34 relevant articles were derived fo r systematic ***-synuclein,the histopathological hallmark of Parkinson's disease,has been the most investigated Parkinson's disease biomarker in saliva,with oligomeric alphasynuclein consistently found increased in Parkinson's disease patients in comparison to healthy controls,while conflicting results have been reported regarding the levels of total alpha-synuclein and phosphorylated alpha-synuclein,and few studies described an increased oligomeric alpha-synuclein/total alpha-synuclein ratio in Parkinson's *** alpha-synuclein,other biomarkers to rgeting diffe rent molecular pathways have been explored in the saliva of Parkinson's disease patients:total tau,phosphorylated tau,amyloid-β1-42(pathological protein aggregation biomarkers);DJ-1,heme-oxygenase-l,metabolites(alte red energy homeostasis biomarkers);MAPLC-3beta(aberrant proteostasis biomarker);cortisol,tumor necrosis factor-alpha(inflammation biomarkers);DNA methylation,miRNA(DNA/RNA defects biomarkers);acetylcholinesterase activity(synaptic and neuronal network

关键词： alpha-synuclein amyloid-beta autophagy DJ-1 neurodegeneration neuroinflammation Parkinson's disease salivary biomarkers tau

Distinguished biological adaptation architecture aggravated population differentiation of Tibeto-Burman-speaking people

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Journal of Genetics and Genomics 2024年第5期51卷 517-530页

作者： Yuntao Sun Mengge Wang Qiuxia Sun Yan Liu Shuhan Duan Zhiyong Wang Yunyu Zhou Jun Zhong Yuguo Huang Xinyu Huang Qingxin Yang Xiangping Li Haoran Su Yan Cai Xiucheng Jiang Jing Chen Jiangwei Yan Shengjie Nie Liping Hu Junbao Yang Renkuan Tang Chuan-Chao Wang Chao Liu Xiaohui Deng Libing Yun Guanglin He West China School of Basic Science&forensic Medicine Sichuan UniversityChengduSichuan 610041China Institute of Rare Diseases West China Hospital of Sichuan UniversitySichuan UniversityChengduSichuan 610000China Center for Archaeological Science Sichuan UniversityChengduSichuan 610000China Faculty of forensic Medicine Zhongshan School of MedicineSun Yat-sen UniversityGuangzhouGuangdong 510275China Guangzhou forensic Science Institute GuangzhouGuangdong 510055China department of forensic Medicine College of Basic MedicineChongqing Medical UniversityChongqing 400331China School of Clinical Medical Sciences North Sichuan Medical CollegeNanchongSichuan 637100China School of Basic Medical Sciences North Sichuan Medical CollegeNanchongSichuan 637100China School of forensic Medicine Kunming Medical UniversityKunmingYunnan 650500China School of Stomatology North Sichuan Medical CollegeNanchongSichuan 637100China department of Medical Laboratory North Sichuan Medical CollegeNanchongSichuan 637007China School of Life Sciences Xiamen UniversityXiamenFujian 361005China Anti-Drug Technology Center of Guangdong Province GuangzhouGuangdong 510230China School of forensic Medicine Shanxi Medical UniversityJinzhongShanxi030600China

Tibeto-Burman(TB)people have endeavored to adapt to the hypoxic,cold,and high-UV high-altitude environments in the Tibetan Plateau and complex disease exposures in lowland rainforests since the late Paleolithic ***,the full landscape of genetic history and biological adaptation of geographically diverse TB-speaking people,as well as their interaction mechanism,remain ***,we generate a whole-genome meta-database of 500 individuals from 39 TB-speaking populations and present a comprehensive landscape of genetic diversity,admixture history,and differentiated adaptative features of geographically different TB-speaking *** identify genetic differentiation related to geography and language among TB-speaking people,consistent with their differentiated admixture process with incoming or indigenous ancestral source populations.A robust genetic connection between the Tibetan-Yi corridor and the ancient Yellow River people supports their Northern China origin *** finally report substructure-related differentiated biological adaptative signatures between highland Tibetans and Loloish *** signatures associated with the physical pigmentation(EDAR and SLC24A5)and metabolism(ALDH9A1)are identified in Loloish people,which differed from the high-altitude adaptative genetic architecture in ***-related genomic resources provide new insights into the genetic basis of biological adaptation and better reference for the anthropologically informed sampling design in biomedical and genomic cohort research.

关键词： Tibeto-Burman people Genetic profile Natural selection Genetic diversity Biological adaptation

Nanotechnology’s frontier in combatting infectious and inflammatory diseases:prevention and treatment

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Signal Transduction and Targeted Therapy 2024年第3期9卷 998-1047页

作者： Yujing Huang Xiaohan Guo Yi Wu Xingyu Chen Lixiang Feng Na Xie Guobo Shen department of Biotherapy Cancer Center and State Key Laboratory of BiotherapyWest China Hospitaland West China School of Basic Medical Sciences and Forensic MedicineSichuan Universityand Collaborative Innovation Center for BiotherapyChengdu 610041China

Inflammation-associated diseases encompass a range of infectious diseases and non-infectious inflammatory diseases,which continuously pose one of the most serious threats to human health,attributed to factors such as the emergence of new pathogens,increasing drug resistance,changes in living environments and lifestyles,and the aging *** rapid advancements in mechanistic research and drug development for these diseases,current treatments often have limited efficacy and notable side effects,necessitating the development of more effective and targeted anti-inflammatory *** recent years,the rapid development of nanotechnology has provided crucial technological support for the prevention,treatment,and detection of inflammation-associated *** types of nanoparticles(NPs)play significant roles,serving as vaccine vehicles to enhance immunogenicity and as drug carriers to improve targeting and *** can also directly combat pathogens and *** addition,nanotechnology has facilitated the development of biosensors for pathogen detection and imaging techniques for inflammatory *** review categorizes and characterizes different types of NPs,summarizes their applications in the prevention,treatment,and detection of infectious and inflammatory *** also discusses the challenges associated with clinical translation in this field and explores the latest developments and *** conclusion,nanotechnology opens up new possibilities for the comprehensive management of infectious and inflammatory diseases.

关键词： prevention inflammatory treatment

Pathologic assessment of hepatocellular carcinoma in the era of immunotherapy:a narrative review

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Hepatobiliary Surgery and Nutrition 2024年第3期13卷 472-493页

作者： Han Wang You-Wen Qian Hui Dong Wen-Ming Cong department of pathology Shanghai Eastern Hepatobiliary Surgery HospitalNaval Medical UniversityShanghaiChina

Background and Objective:Immune checkpoint inhibitor(ICI)-based therapy has achieved impressive success in various cancer *** ICIs have been unprecedentedly approved as the treatment regimens for advanced hepatocellular carcinoma(HCC)in recent ***,numerous clinical trials are being performed to exploit more ICIs into initially unresectable HCC and postoperative HCC to expectantly induce adequate tumor downstaging for further resection or implement adjuvant treatment for relapse-free survival,*** this review,we aim to summarize some pragmatic histomorphologic,immunohistochemical,and molecular pathologic parameters which promisingly indicate the response of neoadjuvant/conversion ICI-related therapy and predict the efficacy of adjuvant/therapeutic ICI-related therapy for ***:We searched PubMed using the terms hepatocellular carcinoma,immunotherapy,immune checkpoint inhibitor,immune checkpoint blockade,conversion therapy,neoadjuvant therapy,adjuvant therapy,biomarker,pathologic evaluation,pathologic assessment till February *** Content and Findings:Although there is no consensus regarding the pathologic evaluation of relevant HCC specimens,it is encouraging that a few of studies have concentrated on this field,and moreover,the methods and parameters noted on other cancer types are also worthy of *** the pathologic assessment of HCC specimens underwent immunotherapy,a suitable sampling scheme,identifying immunotherapy-related pathologic response,and quantification of pathologic response rate should be *** the patients of HCC who are scheduled to receive immunotherapy,tumor-infiltrating lymphocyte,intratumoral tertiary lymphoid structure,programmed cell death ligand 1,Wnt/β-catenin,microsatellite instability and mismatch repair,tumor mutational burden and tumor neoantigen,as well as some other signaling pathways are the potential predictive biomarkers of treatment response of ***:The managem

关键词： Hepatocellular carcinoma(HCC) immune checkpoint blockade pathologic evaluation neoadjuvant therapy conversion therapy adjuvant therapy