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Apples to oranges:environmentally derived,dynamic regulation of serotonin neuron subpopulations in adulthood?

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Neural Regeneration Research 2025年第9期20卷 2596-2597页

作者： Christopher J.O’Connell Matthew J.Robson Department of genetics College of MedicineHarvard UniversityBostonMAUSA James L.Winkle College of Pharmacy Division of Pharmaceutical SciencesUniversity of CincinnatiCincinnatiOHUSA Neuroscience Graduate program College of MedicineUniversity of CincinnatiCincinnatiOHUSA

Traumatic brain injury(TBI)is a public health problem with an undue economic burden that impacts nearly every age,ethnic,and gender group across the globe(Capizzi et al.,2020).TBIs are often sustained during a dynamic range of exposures to energetic environmental forces and as such outcomes are typically heterogeneous regarding severity and pathology(Capizzi et al.,2020).

关键词： sustained orange dynamic

Novel translational strategies in colorectal cancer research

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World Journal of Gastroenterology 2007年第44期13卷 5902-5910页

作者： Ignacio Gil-Bazo cancer Biology & genetics program Memorial Sloan-Kettering Cancer Center New York NY 10021 United States

Defining translational research is still a complex task. In oncology, translational research implies using our basic knowledge learnt from in vitro and in vivo experiments to directly improve diagnostic tools and therapeutic approaches in cancer patients. Moreover, the better understanding of human cancer and its use to design more reliable tumor models and more accurate experimental systems also has to be considered a good example of translational research. The identification and characterization of new molecular markers and the discovery of novel targeted therapies are two main goals in colorectal cancer translational research. However, the straightforward translation of basic research findings, specifically into colorectal cancer treatment and vice versa is still underway. In the present paper, a summarized view of some of the new available approaches on colorectal cancer translational research is provided. Pros and cons are discussed for every approach exposed.

关键词： Translational research Colorectal cancer Genomics Proteomics Targeted therapies

cancer epigenetics: a perspective on the role of DNA methylation in acquired endocrine resistance

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Chinese Journal of cancer 2011年第11期30卷 749-756页

作者： Michael P. Trimarchi Mary Mouangsavanh Tim Hui-Ming Huang Human cancer genetics program Department of Molecular Virology Immunology and Medical Genetics The Ohio State University Columbus Ohio 43210 USA

Epigenetic mechanisms, including DNA methylation, are responsible for determining and maintaining cell fate, stably differentiating the various tissues in our bodies. Increasing evidence shows that DNA methylation plays a significant role in cancer, from the silencing of tumor suppressors to the activation of oncogenes and the promotion of metastasis. Recent studies also suggest a role for DNA methylation in drug resistance. This perspective article discusses how DNA methylation may contribute to the development of acquired endocrine resistance, with a focus on breast cancer. In addition, we discuss DNA methylome profiling and how recent developments in this field are shedding new light on the role of epigenetics in endocrine resistance. Hormone ablation is the therapy of choice for hormone-sensitive breast tumors, yet as many as 40% of patients inevitably relapse, and these hormone refractory tumors often have a poor prognosis. Epigenetic studies could provide DNA methylation biomarkers to predict and diagnose acquired resistance in response to treatment. Elucidation of epigenetic mechanisms may also lead to the development of new treatments that specifically target epigenetic abnormalities or vulnerabilities in cancer cells. Expectations must be tempered by the fact that epigenetic mechanisms of endocrine resistance remain poorly understood, and further study is required to better understand how altering epigenetic pathways with therapeutics can promote or inhibit endocrine resistance in different contexts. Going forward, DNA methylome profiling will become increasingly central to epigenetic research, heralding a network-based approach to epigenetics that promises to advance our understanding of the etiology of cancer in ways not previously possible.

关键词： DNA甲基化作用表观遗传学内分泌癌症收购甲基化分析遗传机制肿瘤抑制

Cervical cancer:a tale from HPV infection to PARP inhibitors

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Genes & Diseases 2023年第4期10卷 1445-1456页

作者： Minakshi Mann Vikram Pratap Singh Lalit Kumar Department of Medical Oncology Dr.B.R.A.Institute Rotary Cancer HospitalAll India Institute of Medical SciencesNew Delhi 110029India Department of Oncoanaesthesia and Palliative Medicine Dr.B.R.A.Institute Rotary Cancer HospitalAll India Institute of Medical SciencesNew Delhi 110029India Epigenetics Section Mouse Cancer Genetics ProgramCenter for Cancer ResearchNational Cancer InstituteFrederickMD 21702USA

Globally,cervical cancer(CxCa)ranks 4th common cancer among females and led to 569,847 incidences and 311,365 deaths in 2018.80%of CxCa cases occur due to persistent infection with a high-risk subtype of human papillomavirus(HPV-16 and 18).Smoking,high par-ity,and co-infection with type 2 herpes simplex or HIV are other known risk factors for *** histological subtypes are squamous(70%)and adenocarcinoma(25%).Presently,concur-rent radiation plus cisplatin(CDDP)-based chemotherapy is the standard treatment for CxCa ***,CDDP resistance and toxic side effects limit its efficacy,leading to a poorer response rate and an expected overall survival ranging from 10 to 17.5 *** drug uptake,increased DNA damage repair,increased CDDP inactivation,and overexpressed Bcl-2 or caspase inhibition,are primarily accountable mechanisms for CDDP resistance and improving CDDP’s efficacy remains the major ***(ADP-ribosyl)polymerase-1,an effective mediator of nucleotide excision repair pathway,is involved in DNA repair as well as maintaining genomic stability and is significantly expressed in malignant lymphomas,hepa-tocellular-,cervical-and colorectal carcinoma,which has been approved effective in mainte-nance therapy and may serve as an effective target to enhance CDDP sensitivity in ***,we summarize the etiology and epidemiology of and treatment for CxCa,the mechanism responsible for chemotherapy resistance,PARP inhibitor as a possible therapy for CxCa,and other possible chemotherapeutic options for CxCa treatment.

关键词： Cervical cancer Chemotherapy Cisplatin Disease etiology and histology PARP inhibitors Resistance

HPV18 Utilizes Two Alternative Branch Sites for E6*I Splicing to Produce E7 Protein

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Virologica Sinica 2019年第2期34卷 211-221页

作者： Ayslan Castro Brant Vladimir Majerciak Miguel Angelo Martins Moreira Zhi-Ming Zheng Tumor Virus RNA Biology Section RNA Biology Laboratory Center for Cancer Research National Cancer Institute NIH Frederick MD 21702 USA genetics Post-Graduation program Rio de Janeiro Federal University Rio de Janeiro Brazil genetics program Nacional Cancer Institute INCA Rio de Janeiro 20231-050 Brazil

Human papillomavirus 18(HPV18) E6 and E7 oncogenes are transcribed as a single bicistronic E6 E7 pre-mRNA. The E6 ORF region in the bicistronic E6 E7 pre-mRNA contains an intron. Splicing of this intron disrupts the E6 ORF integrity and produces a spliced E6*I RNA for efficient E7 translation. Here we report that the E6 intron has two overlapped branch point sequences(BPS) upstream of its 30 splice site, with an identical heptamer AACUAAC, for E6*I splicing. One heptamer has a branch site adenosine(underlined) at nt 384 and the other at nt 388. E6*I splicing efficiency correlates to the expression level of E6 and E7 proteins and depends on the selection of which branch site. In general, E6*I splicing prefers the 30 ss-proximal branch site at nt 388 over the distal branch site at nt 384. Inactivation of the nt 388 branch site was found to activate a cryptic acceptor site at nt 636 for aberrant RNA splicing. Together, these data suggest that HPV18 modulates its production ratio of E6 and E7 proteins by alternative selection of the two mapped branch sites for the E6*I splicing, which could be beneficial in its productive or oncogenic infection according to the host cell environment.

关键词： Human papillomavirus 18 (HPV18) HPV splicing Branch point E6,E7,E6 intron HPV oncogenes

ezQTL:A Web Platform for Interactive Visualization and Colocalization of QTLs and GWAS Loci

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Genomics, Proteomics & Bioinformatics 2022年第3期20卷 541-548页

作者： Tongwu Zhang Alyssa Klein Jian Sang Jiyeon Choi Kevin M.Brown Division of cancer Epidemiology and genetics National Cancer InstituteBethesdaMD 20892USA

Genome-wide association studies(GWAS)have identified thousands of genomic loci associated with complex diseases and traits,including *** vast majority of common traitassociated variants identified via GWAS fall in non-coding regions of the genome,posing a challenge in elucidating the causal variants,genes,and mechanisms *** quantitative trait locus(eQTL)and other molecular QTL studies have been valuable resources in identifying candidate causal genes from GWAS loci through statistical colocalization *** QTL colocalization is becoming a standard analysis in post-GWAS investigation,an easy web tool for users to perform formal colocalization analyses with either user-provided or public GWAS and eQTL datasets has been ***,we present ezQTL,a web-based bioinformatic application to interactively visualize and analyze genetic association data such as GWAS loci and molecular QTLs under different linkage disequilibrium(LD)patterns(1000 Genomes Project,UK Biobank,or user-provided data).This application allows users to perform data quality control for variants matched between different datasets,LD visualization,and two-trait colocalization analyses using two state-of-the-art methodologies(eCAVIAR and HyPrColoc),including batch *** is a free and publicly available cross-platform web tool,which can be accessed online at https://***/ezqtl.

关键词： Genome-wide association study Expression quantitative trait locus Colocalization Linkage disequilibrium Visualization

A novel Rad gene polymorphism combined with obesity increases risk for type 2 diabetes mellitus

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Chinese Medical Journal 2004年第5期117卷 770-771页

作者：王国英牛天华陈常忠李琼芳徐希平 Department of Endocrinology program for Population genetics

The ras-associated diabetes (Rad) was initially identified by subtraction cloning from the skeletal muscle of humans with non-insulin dependent diabetes mellitus (type 2 DM).1 Rad mRNA expression is markedly increased... 详细信息

关键词： Rad gene·obesity · polymorphism·type 2 diabetes mellitus

A revision of the InfiniumPurify R package for genome-wide correction of tumor purity in Infinium DNA methylation array data

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Genes & Diseases 2023年第3期10卷 698-700页

作者： Phuc H.Hoang Division of cancer Epidemiology and genetics National Cancer InstituteBethesdaMD 20892USA

Understanding DNA methylation(DNAm)alterations in tumors is important to develop novel therapeutic targets and powerful biomarkers,and to gain insights into tumorigenesis *** many studies have highlighted the confounding effects of tumor purity in DNAm analyses,1,2,3 various tools have also been developed to tackle the issue.2,3,4 Among them,InfiniumPurify R package is a popular and widely cited tool,2,3,5 consisting of a set of statistical methods to estimate and account for tumor purity in cancer DNAm analyses.

关键词： alterations purity correction

Beyond tumorigenesis: cancer stem cells in metastasis

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Cell Research 2007年第1期17卷 3-14页

作者： Benjamin Tiede JoanMassagué Department of Molecular Biology Princeton University Washington Road PrincetonNJ 08544USA cancer Biology and genetics program and Howard Hughes Medical Institute Memorial Sloan-Kettering Cancer CenterNew YorkNY 10021USA

The importance of cancer stem cells (CSCs) in tumor-initiation has been firmly established in leukemia and recentlyreported for a variety of solid ***,the role of CSCs in multistage cancer progression,particularly withrespect to metastasis,has not been *** metastasis requires the seeding and successful colonization ofspecialized CSCs at distant *** biology of normal stein cells and CSCs share remarkable similarities and mayhave important implications when applied to the study of cancer ***,overlapping sets of moleculesand pathways have recently been identified to regulate both stem cell migration and cancer *** moleculesconstitute a complex network of cellular interactions that facilitate both the initiation of the pre-metastasis niche by theprimary tumor and the formation of a nurturing organ microenvironment for migrating *** this review,we surveyedthe recent advances in this dynamic field and propose a unified model of cancer progression in which CSCs assume acentral role in both tumorigenesis and *** understanding of CSCs as a fundamental component of themetastatic cascade will lead to novel therapeutic strategies against metastatic cancer.

关键词： stem cells cancer stem cells metastasis metastasis roche mouse model