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Identification of differentially expressed genes after partial rat liver ischemia/reperfusion by suppression subtractive hybridization

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World Journal of Gastroenterology 2005年第9期11卷 1303-1316页

作者： Christine Fallsehr Christina Zapletal Michael Kremer Resit Demir Magnus von Knebel Doeberitz Ernst Klar Institute of molecular pathology Department of Surgery

AIM: To identify potential diagnostic target genes in early reperfusion periods following warm liver ischemia before irreversible liver damage occurs. METHODS: We used two strategies (SSH suppression subtractive hybridization and hybridization of cDNA arrays) to determine early changes in gene expression profiles in a rat model of partial WI/R, comparing postischemic and adjacent nonischemic liver lobes. Differential gene expression was verified (WI/R; 1 h/2 h) and analyzed in more detail after warm ischemia (1 h) in a reperfusion time kinetics (0, 1, 2 and 6 h) and compared to untreated livers by Northern blot hybridizations. Protein expression was examined on Western blots and by immunohistochemistry for four differentially expressed target genes (Hsp70, Hsp27, Gadd45a and IL-1rI). RESULTS: Thirty-two individual WI/R target genes showing altered RNA levels after confirmation by Northern blot analyzes were identified. Among them, six functionally uncharacteristic expressed sequences and 26 known genes (12 induced in postischemic liver lobes, 14 with higher transcriptional expression in adjacent nonischemic liver lobes). Functional categories of the verified marker genes indicate on the one hand cellular stress and tissue damage but otherwise activation of protective cellular reactions (AP-1 transcription factors, apoptosis related genes, heat shock genes). In order to assign the transcriptional status to the biological relevant protein level we demonstrated that Hsp70, Hsp27, Gadd45a and IL-1rI were clearly up-regulated comparing postischemic and untreated rat livers, suggesting their involvement in the WI/R context. CONCLUSION: This study unveils a WI/R response gene set that will help to explore molecular pathways involved in the tissue damage after WI/R. In addition, these genes especially Hsp70 and Gadd45a might represent promising new candidates indicating WI/R liver damage.

关键词： Organ injury Liver ischemia AP-1 transcription factor Heat shock protein Gadd45A Suppression subtractive hybridization

Prognostic significance of BMP and activin membrane-bound inhibitor in colorectal cancer

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World Journal of Gastroenterology 2008年第31期14卷 4880-4888页

作者： Nozomi Togo Susumu Ohwada Shinji Sakurai Hiroyuki Toya Ichiro Sakamoto Tatsuya Yamada Tetsuhiro Nakano Ken Muroya Izumi Takeyoshi Takashi Nakajima Takashi Sekiya Yusuke Yamazumi Tsutomu Nakamura Tetsu Akiyama departments of Surgery Graduate School of Medicine Gunma University Gunma 371-8511 Japan departments of Tumor pathology Graduate School of Medicine Gunma University Gunma 371-8511 Japan Laboratory of molecular and Genetic Information Institute for Molecular and Cellular Biosciences University of Tokyo Tokyo 113-0032 Japan

AIM： To investigate the clinical significance of BMP and activin membrane-bound inhibitor （BAMBI） which is a pseudoreceptor of transforming growth factorbeta （TGF-β） type 1 receptors and acts as a negative regulator of TGF-β signaling and expression aberrantly elevated in colorectal cancers （CRCs）. We studied BAMBI expression in CRCs. METHODS： We studied BAMBI expression in 183 surgically resected CRCs by immunochemical and immunoblotting analyses using a generated monoclonal anti-BAMBI antibody. Commercially available anti-β- catenin and anti-p53 antibodies were also applied for immunochemical analyses as a comparison ***： Immunohistochemical analysis revealed that BAMBI expression was observed in 148 （80.8%）, and strong BAMBI expression was observed in 46% of the CRCs. Strong BAMBI expression was positively correlated with histological type, depth of invasion, lymph node metastases, and tumor node metastasis （TNM） stage （P 〈 0.05）. Clear associations were found between BAMBI and β-catenin （P = 0.035） and p53 （P =0.049） expression. In curatively resected CRC, 5-year recurrence-free survival was 51.9% （P = 0.037） for strong BAMBI expression compared to 79.8% for weak BAMBI expression. In the Cox＇s multivariate analysis, lymph node metastases （relative risk 6.685; P 〈 0.001） and depth of invasion （RR 14.0; P = 0.013） were significant indicators for recurrence, and strong BAMBI expression （RR 2.26; P = 0.057） tended to be significant. CONCLUSION： BAMBI was linked to a potentially aggressive tumor phenotype and predicted tumor recurrence and cancer-related death in CRC. BAMBI expression might be applicable in the routine clinical setting of CRC.

关键词： BMP and activin membrane-bound inhibitor Colorectal cancer Transforming growth factor-beta signal Prognosis Wnt signal

Purinergic signaling systems across comparative models of spinal cord injury

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Neural Regeneration Research 2022年第3期17卷 2391-2398页

作者： Eva E.Stefanova Angela L.Scott Department of pathology and molecular Medicine McMaster UniversityHamiltonONCanada

Within the last several decades,the scientific community has made substantial progress in elucidating the complex pathophysiology underlying spinal cord ***,despite the many advances using conventional mammalian models,both cellular and axonal regeneration following spinal cord injury have remained out of *** this sense,turning to non-mammalian,regenerative species presents a unique opportunity to identify pro-regenerative cues and chara cterize a spinal cord microenvironment permissive to *** the signaling pathways hypothesized to be dysregulated during spinal cord injury is the purinergic signaling *** addition to its well-known role as energy currency in cells,ATP and its metabolites are small molecule neurotransmitte rs that mediate many diverse cellular processes within the central nervous *** our unde rstanding of the roles of the purinergic system following spinal cord injury is limited,this signaling pathway has been implicated in all injury-induced secondary processes,including cellular death,inflammation,reactive gliosis,and neural *** that the purinergic system is also evolutionarily conserved between mammalian and non-mammalian species,comparisons of these roles may provide important insights into conditions responsible for recovery ***,we compare the secondary processes between key model species and the influence of purinergic signaling in each *** our understanding of this signaling system and pro-regenerative conditions continues to evolve,so does the potential for the development of novel therapeutic interventions for spinal cord injury.

关键词： cell death differenriation glia inflammation neurogenesis proliferation purinergic signaling reactive gliosis regeneration spinal cord injury teleost

Nestin:A novel angiogenesis marker and possible target for tumor angiogenesis

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World Journal of Gastroenterology 2013年第1期19卷 42-48页

作者： Yoko Matsuda Masahito Hagio Toshiyuki Ishiwata departments of pathology and Integrative Oncological pathology Nippon Medical SchoolTokyo 113-8602Japan

Abnormal vasculature,termed tumor vessels,is a hallmark of solid *** degree of angiogenesis is associated with tumor aggressiveness and clinical ***,exact quantification of tumor vessels is useful to evaluate ***,selective detection of newly formed tumor vessels within cancer tissues using specific markers raises the possibility of molecular targeted therapy via the inhibition of tumor ***,an intermediate filament protein,is reportedly expressed in repair processes,various neoplasms,and proliferating vascular endothelial *** expression is detected in endothelial cells of embryonic capillaries,capillaries of the corpus luteum,which replenishes itself by angiogenesis,and proliferating endothelial progenitor cells,but not in mature endothelial ***,expression of nestin is relatively limited to proliferating vascular endothelial cells and endothelial progenitor *** expression is also reported in blood vessels within glioblastoma,prostate cancer,colorectal cancer,and pancreatic cancer,and its expression is more specific for newly formed blood vessels than other endothelial cell ***-positive blood vessels form smaller vessels with high proliferation activity in *** of nestin in vascular endothelial cells suppresses endothelial cell growth and tumor formation ability of pancreatic cancers in *** nestin to more accurately evaluate microvessel density in cancer specimens may be a novel prognostic ***,nestin-targeted therapy may suppress tumor proliferation via inhibition of angiogenesis in numerous malignancies,including pancreatic *** this review article,we focus on nestin as a novel angiogenesis marker and possible therapeutic target via inhibition of tumor angiogenesis.

关键词： Nestin Angiogenesis molecular targeting therapy Gastrointestinal cancer Pancreatic cancer Microvessel density CD34 CD31 Factor VIII

Chemically oligomerizable TDP-43:a novel chemogenetic tool for studying the pathophysiology of amyotrophic lateral sclerosis

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Neural Regeneration Research 2022年第11期17卷 2434-2436页

作者： Kohsuke Kanekura Yoshiaki Yamanaka Tamami Miyagi Masahiko Kuroda Department of molecular pathology Tokyo Medical University

Amyotrophic lateral sclerosis (ALS) is a devastating neurodegenerative disease characterized by the progressive loss of both upper and lower motor *** ALS cases are sporadic,but approximately 5-10%of patients have a f... 详细信息

关键词： sclerosis familial

Amyloid-β-induced disruption of axon-initial-segment mitochondria localization:consequences for TAU missorting in Alzheimer's disease pathology

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Neural Regeneration Research 2025年第5期20卷 1407-1408页

作者： Daniel Adam Felix Langerscheidt Hans Zempel Institute of Human Genetics University Hospital CologneCologneGermany Center for molecular Medicine Cologne(CMMC) University of CologneCologneGermany

TAU is a neuronal microtubule-associated protein preferentially located in *** a battery of neurodegenerative diseases termed"tauopathies,"including Alzheimer's disease (AD),TAU is missorted and abnormally phosphorylated,leading to filamentous accumulations of hyperphosphorylated TAU,a pathological hallmark and potential disease driver of AD and related tauopathies (Zempel,2024).

关键词： Alzheimer tau diseases

Examination of in vivo mutagenicity of sodium arsenite and dimethylarsinic acid in gpt delta rats

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Journal of Environmental Sciences 2016年第11期28卷 125-130页

作者： Masaki Fujioka Min Gi Satoko Kawachi Kumiko Tatsumi Naomi Ishii Kenichiro Doi Anna Kakehashi Hideki Wanibuchi Department of molecular pathology Osaka City University Graduate School of Medicine

Arsenic is a well-known human bladder and liver carcinogen, but its exact mechanism of carcinogenicity is not fully understood. Dimethylarsinic acid（DMAV） is a major urinary metabolite of sodium arsenite（i As~Ⅲ） and induces urinary bladder cancers in rats. DMAVand i As~Ⅲare negative in in vitro mutagenicity tests. However, their in vivo mutagenicities have not been determined. The purpose of present study is to evaluate the in vivo mutagenicities of DMAVand i As~Ⅲin rat urinary bladder epithelium and liver using gpt delta F344 ***-week old male gpt delta F344 rats were randomized into 3 groups and administered 0,92 mg/L DMAV, or 87 mg/L i As~Ⅲ（each 50 mg/L As） for 13 weeks in the drinking water. In the mutation assay, point mutations are detected in the gpt gene by 6-thioguanine selection（gpt assay） and deletion mutations are identified in the red/gam genes by Spi-selection（Spi-assay）. Results of the gpt and Spi-assays showed that DMAVand i As~Ⅲhad no effects on the mutant frequencies or mutation spectrum in urinary bladder epithelium or liver. These findings indicate that DMAVand i As~Ⅲare not mutagenic in urinary bladder epithelium or liver in rats.

关键词： Dimethylarsinic acid Sodium arsenite In vivo mutagenicity Urinary bladder epithelium gpt delta rat

The next generation of cancer management

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Cancer Biology & Medicine 2016年第1期13卷 1-2页

作者： Wayne W.Grody Divisions of Medical Genetics and molecular Diagnostics Departments of Pathology & Laboratory Medicine Pediatrics and Human Genetics UCLA School of Medicine UCLA Institute for Society and Genetics Molecular Diagnostic Laboratories and Clinical Genomics Center UCLA Medical Center

As readers of Cancer Biology and Medicine well know,there has been a seismic shift in human molecular biology over the past few years,as momentous in its own way as the discovery of the double-helical structure of DNA by Watson and Crick 60 years ago,the elucidation of the genetic code shortly thereafter,the advent of recombinant DNA and gene cloningin the 1970s, and the introduction of the polymerase chain reaction in the mid-1980s.

关键词： Next-generation sequencing tumor sequencing targeted sequencing incidental findings variants of uncertain significance

Gastrointestinal B-cell lymphomas:From understanding B-cell physiology to classification and molecular pathology

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World Journal of Gastrointestinal Oncology 2012年第12期4卷 238-249页

作者： Xavier Sagaert Thomas Tousseyn Rhonda K Yantiss Department of pathology University Hospitals Leuven Department of pathology and Laboratory Medicine Weill Cornell Medical College

The gut is the most common extranodal site where lymphomas arise. Although all histological lymphoma types may develop in the gut, small and large B-cell lymphomas predominate. The sometimes unexpected finding of a lymphoid lesion in an endoscopic biopsy of the gut may challenge both the clinician (who is not always familiar with lymphoma pathogenesis) and the pathologist (who will often be hampered in his/her diagnostic skill by the limited amount of available tissue). Moreover, the past 2 decades have spawned an avalanche of new data that encompasses both the function of the reactive B-cell as well as the pathogenic pathways that lead to its neoplastic counterpart, the B-cell lymphoma. Therefore, this review aims to offer clinicians an overview of B-cell lymphomas in the gut, and their pertinent molecular features that have led to new insights regarding lymphomagenesis. It addresses the question as how to incorporate all presently available information on normal and neoplastic B-cell differentiation, and how this knowledge can be applied in daily clinical practice (e.g., diagnostic tools, prognostic biomarkers or therapeutic targets) to optimalise the managment of this heterogeneous group of neoplasms.

关键词： B-cell Non-Hodgkin’s lymphomas Gut molecular pathology