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Journal of Zhejiang University-Science B(Biomedicine & Biotechnology) 2022年第8期23卷 617-624页

作者： Sergey VTORUSHIN Anastasia DULESOVA Nadezhda KRAKHMAL department of pathology Siberian State Medical University Ministry of Health of RussiaTomsk 634050Russia department of General and molecular pathology Cancer Research InstituteTomsk National Research Medical Center of the Russian Academy of SciencesTomsk 634009Russia department of pathology Republican Clinical Oncological Dispensary Ministry of HealthTatarstan RepublicKazan 420029Russia

According to the classification presented by Lehmann BD(2016),triple-negative breast cancer(TNBC)is a heterogeneous group of malignant tumors with four specific subtypes:basal-like(subtype 1 and subtype 2),mesenchymal,and luminal androgen receptor(LAR)subtypes.The basal-like subtypes of carcinomas predominate in this group,accounting for up to 80%of all cases.Despite the significantly lower proportions of mesenchymal and LAR variants in the group of breast carcinomas with a TNBC profile,such tumors are characterized by aggressive biological behavior.To this end,the LAR subtype is of particular interest,since the literature on such tumors presents different and even contradictory data concerning the disease course and prognosis.This review is devoted to the analysis of the relevant literature,reflecting the main results of studies on the molecular properties and clinical features of the disease course of LAR-type TNBC carcinomas.

关键词： Luminal androgen receptor(LAR)subtype Triple-negative breast cancer(TNBC) Androgen receptor(AR) Prognosis

Next-generation sequencing and its clinical application

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Cancer Biology & Medicine 2019年第1期16卷 4-10页

作者： Dahui Qin molecular Diagnostic Laboratory Department of Pathology Moffitt Cancer Center

Next-generation sequencing (NGS) is a new technology used for DNA and RNA sequencing and variant/mutation detection. NGS can sequence hundreds and thousands of genes or whole genome in a short period of time. The sequence variants/mutations detected by NGS have been widely used for disease diagnosis, prognosis, therapeutic decision, and follow up of patients. The capacity of its massive parallel sequencing offers new opportunities for personalized precision medicine.

关键词： NGS DNA capacity

Multiple pathological components in gliosarcoma

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The Journal of Biomedical Research 2021年第5期35卷 408-410页

作者： Nan NJiang Ramiro Larrazabal Waleed Alsunbul Jian-Qiang Lu department of Radiology department of Surgery/Neurosurgery department of pathology and molecular

Dear Editor:Our recent article"Angiosarcomatous component in Glioblastoma:case report and consideration of diagnostic challenge and hemorrhagic propensity"published in The Journal of Biomedical Research[1]demonstrated an interesting case of gliosarcoma with alternating gliomatous and angiosarcomatous components,which on imaging,displayed unique intratumorally piliform enhancement pattern and clinically,exhibited an increased tendency for intraoperative hemorrhage.Indeed,gliosarcoma may be composed of various different pathological components and may dictate the radiological features and clinical presentations that make preoperative diagnosis extremely difficult.

关键词： sarcoma diagnosis pathological

Synergistic effect of MTHFR C677T and F2 G20210A polymorphisms on ischemic stroke

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Neuroscience Bulletin 2013年第6期29卷 725-730页

作者： Thierry Paluku They-They Omar Battas Sellama Nadifi department of clinical Neuroscience and Biological Psychiatry Hassan Ⅱ University Laboratory of Genetic and molecular pathology Faculty of MedicineHassan Ⅱ University

The predisposition to stroke might involve interactive effects among variants in several genes.We tested this hypothesis by examining the influence of polymorphisms in methylenetetrahydrofolate reductase（MTHFR）（C677T） and prothrombin（F2）（G20210A） as risk factors for stroke in Morocco.The polymerase chain reaction-restriction fragment length polymorphism methods were used to analyze DNA from 91 stroke patients and 182 controls.Association between the two polymorphisms and the risk of stroke was estimated by four-level models for the analysis of genetic interaction.Neither the MTHFR 677TT nor the F2 20210GA genotype showed any significant association compared to the MTHFR CC and F2 GG genotypes,respectively.An interactive effect between the MTHFR 677TT and F2 20210GA polymorphisms showed an increased risk of stroke.The odds ratios,in univariate and multivariate analysis,for the combined polymorphisms were 4.99（95% CI,1.75–14.2,P = 0.001） and 5.29（95% CI,1.63–17.1,P = 0.005）,respectively.

关键词： genotyping prothrombotic polymorphisms risk factor MTHFR F2 stroke

Trisomy 3 may predict a poor response of gastric MALT lymphoma to Helicobacter pylori eradication therapy

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World Journal of Gastroenterology 2005年第1期11卷 89-93页

作者： Sawako Taji Kenichi Nomura Yosuke Matsumoto Hideaki Sakabe Naohisa Yoshida Shoji Mitsufuji Kazuhiro Nishida Shigeo Horiike Shigeo Nakamura Masuji Morita Masafumi Taniwaki molecular Gastroenterology and Hepatology molecular Hematology and Oncology department of Internal Medicine department of pathology and clinical Laboratories School of Nursing clinical molecular Genetics and Laboratory Medicine

AIM: To investigate the relation of the response to Helicobacter pylori eradication therapy to the depth of tumor invasion and chromosome abnormalities in patients with mucosaassociated lymphoid tissue (MALT) lymphoma and to determine the clinical value of aneuploidy.METHODS: We studied 13 patients with localized gastric MALT lymphoma of stage E1. Before eradication therapy,the depth of tumor invasion was assessed by endoscopic ultrasonography in 8 patients and by endoscopic examination and gastrointestinal series in the remaining patients. To detect chromosomal abnormalities, paraffin-embedded tissue sections of diagnostic biopsy specimens underwent tissuefluorescence in situ hybridization (FISH), using chromosomespecific α-satellite DNA probes for chromosomes 3,7,12,and 18 and YAC clones for t(11;18)(q21;q21).RESULTS: Seven of the 13 patients had complete regression(CR) in response to H pylori eradication therapy. No patient with CR had submucosal tumor invasion. Trisomy 18 was seen in 1 patient with CR, and both trisomies 12 and 18 were present in another patient with CR. All patients with no response or progressive disease had deep submucosal tumor invasion and showed t(11;18)(q21;q21) or trisomy 3. Trisomy 7 was not detected in this series of patients.CONCLUSION: The depth of tumor invasion is an accurate predictor of the response of stage E1 MALT lymphoma to H pylori eradication therapy and is closely associated with the presence of chromosomal abnormalities. Trisomy 3 may predict the aggressive development of MALT lymphoma.

关键词：三体型3 胃淋巴瘤 MALT 哈比特属肿瘤

Fatty acid-binding protein 5(FABP5)-related signal transduction pathway in castration-resistant prostate cancer cells:a potential therapeutic target

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Precision clinical Medicine 2019年第3期2卷 192-196页

作者： Abdulghani ANaeem Saud A.Abdulsamad Philip S.Rudland Mohammed IMalki Youqiang Ke The molecular pathology Laboratory Department of Molecular and Clinical Cancer Medicine department of Biochemistry Liverpool UniversityLiverpool L693GAUK College of Medicine Qatar UniversityDoha 2713Qatar

In this short communication,a novel fatty acid-binding protein 5(FABP5)-related signal transduction pathway in prostate cancer is reviewed.In castration-resistant prostate cancer(CRPC)cells,the FABP5-related signal transduction pathway plays an important role during transformation of the cancer cells from androgen-dependent state to androgen-independent state.The detailed route of this signal transduction pathway can be described as follows:when FABP5 expression is increased as the increasing malignancy,excessive amounts of fatty acids from intra-and extra-cellular sources are transported into the nucleus of the cancer cells where they act as signalling molecules to stimulate their nuclear receptor peroxisome proliferator-activated receptor gamma(PPARγ).The phosphorylated or biologically activated PPARγthen modulates the expression of its downstream target regulatory genes to trigger a series of molecular events that eventually lead to enhanced tumour expansion and aggressiveness caused by an overgrowth of the cancer cells with a reduced apoptosis and an increased angiogenesis.Suppressing the FABP5-related pathway via RNA interference against FABP5 has produced a 63-fold reduction in the average size of the tumours developed from CRPC cells in nude mice,a seven-fold reduction of tumour incidence,and a 100%reduction of metastasis rate.Experimental treatments of CRPC with novel FABP5 inhibitors have successfully inhibited the malignant progression of CRPC cells both in vitro and in nude mouse.These studies suggest that FABP5-related signal transduction pathway is a novel target for therapeutic intervention of CRPC cells.

关键词： FABP5 CRPC fatty acids PPARγ tumorigenicity metastasis

Iron dysregulation in beta-thalassemia

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Asian Pacific Journal of Tropical Medicine 2016年第11期9卷 1013-1021页

作者： Kamonlak Leecharoenkiat Pathrapol Lithanatudom Wannapa Sornjai Duncan R.Smith department of clinical Microscopy Faculty of Allied Health SciencesChulalongkorn University department of Biology Faculty of ScienceChiang Mai University molecular pathology Laboratory.Institute of molecular Biosciences Mahidol University

Iron deficiency anemia and iron overload conditions affect more than one billion people worldwide.Iron homeostasis involves the regulation of cells that export iron into the plasma and cells that utilize or store iron.The cellular iron balance in humans is primarily mediated by the hepcidin-ferroportin axis.Ferroportin is the sole cellular iron export protein,and its expression is regulated transcriptionally,post-transcriptionally and posttranslationally.Hepcidin,a hormone produced by liver cells,post-translationally regulates ferroportin expression on iron exporting cells by binding with ferroportin and promoting its internalization by endocytosis and subsequent degradation by lysosomes.Dysregulation of iron homeostasis leading to iron deposition in vital organs is the main cause of death in betathalassemia patients.Beta-thalassemia patients show marked hepcidin suppression,ineffective eiythropoiesis,anemia and iron overload.Beta-thalassemia is common in the Mediterranean region,Southeast Asia and the Indian subcontinent,and the focus of this review is to provide an update on the factors mediating hepcidin related iron dysregulation in beta-thalassemia disease.Understanding this process may pave the way for new treatments to ameliorate iron overloading and improve the long term prognosis of these patients.

关键词： Beta-thalassemia Hepcidin Iron overload Ferroportin

Light chain cardiac amyloidosis in a nonagenarian

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Journal of Geriatric Cardiology 2022年第1期19卷 83-89页

作者： Koji Takahashi Mina Yamashita Tomoki Sakaue Daijiro Enomoto Shigeki Uemura Takafumi Okura Shuntaro Ikeda Takanori Senba Akira Saijo Nobuhisa Yamamura Sohei Kitazawa department of Community Emergency Medicine Ehime University Graduate School of MedicineEhimeJapan department of Cardiology Yawatahama City General HospitalEhimeJapan department of Hematology Yawatahama City General HospitalEhimeJapan department of clinical pathology Yawatahama City General HospitalEhimeJapan department of molecular pathology Ehime University Graduate School of MedicineEhimeJapan

Cardiac amyloidosis is an infiltrative and restrictive cardiomyopathy caused by the extracellular deposition of amyloid fib-rils within the heart as systemic amyloidosis,lead-ing to heart failure,reduced quality of life,and death.[1]There are two major amyloid fibril proteins that af-fect the heart:amyloid immunoglobulin light chain(AL)and amyloid transthyretin(ATTR).The latter is further subdivided into wild-type ATTR and variant types based on the presence of a mutation in the transthyretin gene.

关键词： amyloid death. cardiomyopathy

Frequency, localization, and types of gastrointestinal stromal tumor-associated neoplasia

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World Journal of Gastroenterology 2019年第30期25卷 4261-4277页

作者： Johanna Waidhauser Anne Bornemann Martin Trepel Bruno Markl Institute of pathology and molecular Diagnostics University Medical Center AugsburgAugsburg 86156Germany department of Hematology and clinical Oncology University Medical Center AugsburgAugsburg 86156Germany

BACKGROUND In recent years,increasing evidence of second neoplasms associated with gastrointestinal stromal tumors(GIST)has been found.Numerous case reports,mostly retrospective studies and a few reviews,have been published.To our knowledge,however,no systematic review or meta-analysis of the existing data has been performed so far.AIM To prepare a compilation,as complete as possible,of all reported second tumor entities that have been described in association with GIST and to systematically analyze the published studies with regard to frequency,localization,and types of GIST-associated neoplasms.METHODS The MEDLINE and EBSCO databases were searched for a combination of the keywords GIST/secondary,synchronous,coincident/tumor,neoplasm,and relevant publications were selected by two independent authors.RESULTS Initially,3042 publications were found.After deletion of duplicates,1631 remained,and 130 papers were selected;22 of these were original studies with a minimum of 20 patients,and 108 were case reports.In the 22 selected studies,comprising a total number of 12050 patients,an overall rate of GIST-associated neoplasias of 20%could be calculated.Most second neoplasias were found in the gastrointestinal tract(32%)and in the male and female urogenital tract(30%).The specific risk scores of GISTs associated with other tumors were significantly lower than those without associated neoplasias.CONCLUSION In this first systematic review,we could confirm previously reported findings of a more than coincidental association between GIST and other neoplasias.The question whether there is an underlying causal association will need further investigation.Our data suggest that even GIST with a very low risk of disease progression should prompt screening for second neoplasia and subsequent frequent controls or extended staging.

关键词： Gastrointestinal stromal tumor Associated Secondary Neoplasia Tumor

Big DNA as a tool to dissect an age-related macular degeneration-associated haplotype

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Precision clinical Medicine 2019年第1期2卷 1-7页

作者： Jon M.Laurent Xin Fu Sergei German Matthew T.Maurano Kang Zhang Jef D.Boeke Institute for Systems Genetics department of Biochemistry and molecular pathology department of pathology NYU Langone Health Shiley Eye Institute UCSD School of Medicine

Age-related Macular Degeneration(AMD)is a leading cause of blindness in the developed world,especially in aging populations,and is therefore an important target for new therapeutic development.Recently,there have been several studies demonstrating strong associations between AMD and sites of heritable genetic variation at multiple loci,including a highly significant association at 10q26.The 10q26 risk region contains two genes,HTRA1 and ARMS2,both of which have been separately implicated as causative for the disease,as well as dozens of sites of non-coding variation.To date,no studies have successfully pinpointed which of these variant sites are functional in AMD,nor definitively identified which genes in the region are targets of such regulatory variation.In order to efficiently decipher which sites are functional in AMD phenotypes,we describe a general framework for combinatorial assembly of large‘synthetic haplotypes’along with delivery to relevant disease cell types for downstream functional analysis.We demonstrate the successful and highly efficient assembly of a first-draft 119kb wild-type‘assemblon’covering the HTRA1/ARMS2 risk region.We further propose the parallelized assembly of a library of combinatorial variant synthetic haplotypes covering the region,delivery and analysis of which will identify functional sites and their effects,leading to an improved understanding of AMD development.We anticipate that the methodology proposed here is highly generalizable towards the difficult problem of identifying truly functional variants from those discovered via GWAS or other genetic association studies.

关键词： CRISPR gene editing synthetic biology age related macular degeneration HTRA1