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Identification of differentially expressed microRNAs by microarray： a possible role for microRNAs gene in medulloblastomas

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Chinese Medical Journal 2009年第20期122卷 2405-2411页

作者： LIU Wei GONG Yan-hua CHAO Teng-fei PENG Xiao-zhong YUAN Jian-gang MA Zhen-yu JIA Ge ZHAO Ji-zong Department of Neurosurgery Beijing Tiantan Hospital Capital Medical University Beijing 100050 China National Laboratory of Medical Molecular Biology Institute of Basic Medical Sciences Peking Union Medical College & Chinese Academy of Medical Sciences Beijing 100005 China

Background MicroRNAs （miRNAs） are small noncoding regulatory RNAs whose aberrant expression may be observed in many malignancies. However, few data are yet available on human primary medulloblastomas. This work aimed to identify that whether miRNAs would be aberrantly expressed in tumor tissues compared with non-tumorous cerebellum tissues from same patients, and to explore a possible role during carcinogenesis. Methods A high throughput microRNA microarray was performed in human primary medulloblastoma specimens to investigate differentially expressed miRNAs, and some miRNAs were validated using real-time quantitative RT-PCR method. In addition, the predicted target genes for the most significantly downor up-regulated miRNAs were analyzed by using a newly modified ensemble algorithm. Results Nine miRNA species were differentially expressed in medulloblastoma specimens versus normal non-tumorous cerebellum tissues. Of these, 4 were over expressed and 5 were under expressed. The changes ranged from 0.02-fold to 6.61-fold. These findings were confirmed using real-time quantitative RT-PCR for most significant deregulated miRNAs （miR-17, miR-100, miR-106b, and miR-218） which are novel and have not been previously published. Interestingly, most of the predicted target genes for these miRNAs were involved in medulloblastoma carcinogenesis. Conclusions MJRNAs are differentially expressed between human medulloblastoma and non-tumorous cerebellum tissue. MiRNAs may play a role in the tumorigenesis of medulloblastoma and maybe serve as potential targets for novel therapeutic strategies in future.

关键词： microRNA oncogenes medulloblastoma target mRNA carcinogenesis

Mutated Genes in Pancreatic Cancer

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Chinese Journal of Cancer Research 2010年第2期22卷 93-98页

作者： Song-bing He De-chun Li Department of General Surgery the First Affiliated Hospital Soochow University Suzhou 215006 China

Pancreatic cancer continues to be a deadly malignancy with still high mortality and poor survival. Little progress has been made on the treatment of advanced pancreatic cancer despite the significant advances in understanding, diagnosis, and access to conventional and novel treatments. Molecular pathology of the lesion is the key of our understanding of the mechanisms underlying the development of this cancer and will probably help us in earlier diagnosis and better therapeutic results. New treatment strategies and a more careful evaluation of innovative therapies are clearly needed for this disease. In view of many findings pancreatic cancer should be regarded as a systemic disease, and over the last several years, investigators have gained a better understanding of the molecular biology and events that lead to the development of malignancies. We here review the novel developments in the systemic exploring for commonly mutated genes in pancreatic cancer.

关键词： Pancreatic cancer Epithelial growth factor Matrix metalloproteinases oncogenes

Cytogenetic and molecular genetic alterations in hepatocellular carcinoma

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Acta Pharmacologica Sinica 2005年第6期26卷 659-665页

作者： Sze-hang LAU, Xin-yuan GUAN~1 Department of Clinical Oncology, Faculty of Medicine, The University of Hong Kong, Hong Kong, China Department of Clinical Oncology Faculty of Medicine The University of Hong Kong Hong Kong China

Specific chromosome aberrations are frequently detected during the development of hepatocellular carcinoma. Molecular cytogenetic approaches such as comparative genomic hybridization and loss of heterozygosity analyses have provided fruitful information on changes in HCC cases at the genomic level. Mapping of chromosome gains and losses have frequently resulted in the identification of oncogenes and tumor suppressors, respectively. In this review, we summarize some frequently detected chromosomal aberrations reported for hepatocellular carcinoma cases using comparative genomic hybridization and loss of heterozygosity studies. Focus will be on gains of lq, 8q, and 20q, and losses of 4q, 8p, 13q, 16q, and 17p. We then examine the candidate oncogenes and tumor suppressors located within these regions, and explore their possible functions in hepatocarcinogenesis. Finally, the impact of microarray-based screening platforms will be discussed.

关键词： hepatocellular carcinoma chromosome aberrations oncogenes tumor suppressor genes

Genetic alterations in pancreatic cancer

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World Journal of Gastroenterology 2007年第33期13卷 4423-4430页

作者： Muhammad Wasif Saif Lena Karapanagiotou Kostas Syrigos Yale University School of Medicine Section of Medical Oncology 333 Cedar Street NewHaven CT 06520-8032 United States Oncology Unit Third Department of MedicineAthens Medical SchoolSotiria General HospitalMesogion 152 11526 AthensGreece

The diagnosis of pancreatic patients and their relatives cancer is devastating for as the incidence rate is approximately the same as mortality rate. Only a small percentage, which ranges from 0.4% to 4% of patients who have been given this diagnosis, will be alive at five years. At the time of diagnosis, 80% of pancreatic cancer patients have unresectable or metastatic disease. Moreover, the therapeutic alternatives offered by chemotherapy or radiotherapy are few, if not zero. For all these reasons, there is an imperative need of analyzing and understanding the primitive lesions that lead to invasive pancreatic adenocarcinoma. Molecular pathology of these lesions is the key of our understanding of the mechanisms underlying the development of this cancer and will probably help us in earlier diagnosis and better therapeutic results. This review focuses on medical research on pancreatic cancer models and the underlying genetic alterations.

关键词： Carcinogenesis Telomerase p21 p16 oncogenes Epidermal growth factor

Effect of phosphorylation of MAPK and Stat3 and expression of c-fos and c-jun proteins on hepatocarcinogenesis and their clinical significance

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World Journal of Gastroenterology 2001年第1期7卷 33-36页

作者： De Yun Feng Hui Zheng Yi Tan Rui Xue Cheng Department of Pathology, Hunan Medical University, Changsha 410078, Hunan Province, China New England Biolab, MA, USA Department of Pathology Hunan Medical University Changsha 410078 Hunan Province China. cslj4841401@***

AIM To study the effect of phosphorylation ofMAPK and Stat3 and the expression of c-fos andc-jun proteins on hepatocellular carcinogenesisand their clinical *** SP immunohistochemistry was usedto detect the expression of p42/44MAPK, p-Stat3,c-fos and c-jun proteins in 55 hepatocellularcarcinomas (HCC) and their surrounding *** The positive rates and expressionlevels of p42/44MAPK, p-Stat3, c-fos and c-junproteins in HCCs were significantly higher thanthose in pericarcinomatous liver tissues (PCLT).A positive correlation was observed between theexpression of p42/44MAPK and c-fos proteins, andbetween p-Stat3 and c-jun, but there was nosignificant correlation between p42/44MAPK and p-Stat3 in HCCs and their surrounding *** The abnormalities of Ras/Rat/MAPK and JAKs/ Stat3 cascade reaction maycontribute to malignant transformation ofhepatocytes. Hepatocytes which are positive forp42/ 44MAPK, c-fos or c-jun proteins may bepotential malignant pre-cancerous *** of MAPK and Stat3 proteins may be anearly event in hepatocellular carcinogenesis.

关键词： liver neoplasms mitogen-activated protein kinases signal transduction trans-activators oncogenes immunohistochemistry precancerous conditions

Clinical and genetic characteristics of Chinese hereditary nonpolyposis colorectal cancer families

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World Journal of Gastroenterology 2006年第25期12卷 4074-4077页

作者： Xu-Lin Wang Ying Yuan Su-Zhan Zhang Shan-Rong Cai Yan-Qin Huang Qiang Jiang Shu Zheng Cancer Institute the 2nd Affiliated Hospital College of Medicine Zhejiang University 88 Jie-Fang Road Hangzhou 310009 Zhejiang Province China

AIM： To analyze the clinical characteristics of Chinese hereditary nonpolyposis colorectal cancer （HNPCC） families and to screen the germline mutations of human mismatch repair genes hMLH1 and hMSH2 in the probands. METHODS： Thirty-one independent Chinese HNPCC families were collected in Zhejiang Province. All of them met Chinese HNPCC criteria. Clinical data about patient gender, site of colorectal cancer, age of onset, history of multiple colorectal cancer, associated extracolonic cancer were recorded. PCR and denaturing high performance liquid chromatography （DHPLC） were employed to screen the mutations. Sequencing analysis was used to find out the exact mutation site and characteristics of the samples showing abnormal DHPLC profiles. RESULTS： One hundred and thirty-six malignant neoplasms were found in 107 patients including 14 multiple cancers. One hundred and six of the 136 neoplasms （77.9%） were diagnosed as colorectal cancer, with an average age of onset at 48.57 ±29.00 years. Gastric cancer was the most common extracolonic cancer （10.3%） in these families. Twenty-three different sequence variations in hMLHI and hMSH2 genes were detected in these 17 families. Fifteen sequence variations were located in the exons, including 5 SNPs, 3 silent mutations, 3 missense mutations, 2 nonsense mutations and 2 frameshift mutations. The latter seven mutations seemed to be pathogenic. CONCLUSION： Germline mutations of hMLH1 and hMSH2 genes are identified in about one-third HNPCC kindreds fulfilling Chinese HNPCC criteria. Chinese HNPCC families have some particular clinical characteristics, such as a left-sided predominance, less synchronous or metachronous colorectal cancer, and frequent occurrence of gastric cancer.

关键词： Colorectal cancer Hereditary nonpolyposis DNA mutation analysis High pressure liquid Chromatography oncogenes

Eosinophil MBP Extract Modulates Oncogene Expression in Prostate Tumor Cells: A Preliminary Study with Monolayer Cultures

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Journal of Cancer Therapy 2015年第6期6卷 482-492页

作者： Christine A. Clarke Michael A. Smith Ibrahim Laniyan Theresa R. Vaughn Debra Parish-Gause William Green Paulette M. Furbert-Harris Department of Microbiology Howard University College of Medicine Washington DC USA Howard University Cancer Center Howard University College of Medicine Washington DC USA Carolina’s Hospital System Marion Mullins SC USA Department of Pathology Howard University College of Medicine Washington DC USA National Human Genome Center at Howard University Howard University College of Medicine Washington DC USA

Prostate cancer is the second leading cause of cancer deaths in the United States and remains a significant health concern for men throughout the world. Despite the discovery of promising immunotherapeutic strategies, curative outcomes remain elusive. We have investigated eosinophils as potential anti-cancer effector cells, and have reported the ability of their toxic granular proteins (MBP, EPO, ECP, EDN) to inhibit prostate tumor cell growth?in vitro. This study investigates the effect of eosinophil MBP extract on the expression of oncogenes p53, bcl-xl, bax, and c-myc, which modulate tumor growth, proliferation, and apoptosis. Briefly, granular proteins were differentially extracted from GRC.014.22 and GRC.014.24, eosinophilic cell lines established in our laboratory from a patient with moderate asthma. Protein extracts were fractionated on Sephadex G-50 columns, and prostate tumor cell lines DU-145, LNCaP, PC-3, and HPC8L (established in our laboratory from a tumor resected from an African American patient) were treated with MBP extracts from the pooled third peaks. Colony formation and monolayer cell growth inhibition assays were used to evaluate the protein’s growth inhibitory activity against prostate tumor cells;and gene expression analyses, to determine p53, bcl-xl, bax, and c-myc oncogene expression. We show that the granular proteins were potent in their action on HPC8L, inhibiting colony formation in a dose-dependent manner. Treated prostate tumor cell lines trended toward apoptosis-induction, as evident in bcl-xl/bax ratios oncogenes associated with prostate tumor proliferation and apoptosis. More importantly, this study offers insights into possible applications of eosinophilic mediators in oncogenic-targeted

关键词： Eosinophils Major Basic Protein (MBP) Prostate Cancer HPC8L oncogenes

Molecular genetics of early-onset colorectal cancer

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World Journal of Biological Chemistry 2023年第2期14卷 13-27页

作者： Olivia Marx Marc Mankarious Gregory Yochum Department of Biochemistry&Molecular Biology Pennsylvania State University College of MedicineHersheyPA 17033United States Department of Surgery Division of Colon&Rectal SurgeryPennsylvania State University Milton S.Hershey Medical CenterHersheyPA 17033United States Department of Biochemistry&Molecular Biology&Surgery Pennsylvania State University College of MedicineHersheyPA 17033United States

Early-onset colorectal cancer(EOCRC)has been rising in global prevalence and incidence over the past several *** influences,including generational lifestyle changes and rising obesity,contribute to these increased *** the rise in EOCRC is best documented in western countries,it is seen throughout the world,although EOCRC may have distinct genetic mutations in patients of different ethnic *** and molecular characterizations show that EOCRC has a distinct presentation compared with later-onset colorectal cancer(LOCRC).Recent studies have identified DNA,RNA,and protein-level alterations unique to EOCRC,revealing much-needed biomarkers and potential novel therapeutic *** molecular EOCRC studies have been performed with Caucasian and Asian EOCRC cohorts,however,studies of other ethnic backgrounds are *** addition,certain molecular characterizations that have been conducted for LOCRC have not yet been repeated in EOCRC,including high-throughput analyses of histone modifications,mRNA splicing,and proteomics on large *** propose that the complex relationship between cancer and aging should be considered when studying the molecular underpinnings of *** this review,we summarize current EOCRC literature,focusing on sporadic molecular alterations in tumors,and their clinical *** conclude by discussing current challenges and future directions of EOCRC research efforts.

关键词： Early-onset colorectal cancer Later-onset colorectal cancer Mutations oncogenes Molecular characteristics Transcriptomics

Oncogenic driver mutations in non-small cell lung cancer: Past, present and future

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World Journal of Clinical Oncology 2021年第4期12卷 217-237页

作者： Mathieu Chevallier Maxime Borgeaud Alfredo Addeo Alex Friedlaender Department of Oncology University Hospital GenevaGeneva 1205Switzerland Department of Oncology Clinique Générale BeaulieuGeneva 1206Switzerland

Lung cancer,of which non-small lung cancer is the most common subtype,represents the leading cause of cancer related-death *** is now recognized that a significant proportion of these patients present alterations in certain genes that drive *** recent years,more of these so-called oncogenic drivers have been identified,and a better understanding of their biology has allowed the development new targeted *** review aims to provide an update about the current landscape of driver mutation in non-smallcell lung *** in Kirsten rat sarcoma,epidermal growth factor receptor,MET,anaplastic lymphoma kinase,c-ROS oncogene 1,v-raf murine sarcoma viral oncogene homolog B,neurotrophic receptor tyrosine kinase,human epidermal growth factor 2,neuregulin-1 and rearranged during transfection are discussed,as well as agents targeting these *** standards of treatment as well as promising future strategies are ***,more than fifteen targeted agents are food and Drug administration-approved for seven oncogenic drivers in non-small-cell lung cancer,highlighting the importance of actively searching for these *** and future efforts made in defining the biology of each of these alterations will help to elucidate their respective resistance mechanisms,and to define the best treatment strategy and therapeutic sequence.

关键词： Non-small cell lung cancer Driver mutations Tyrosine kinase inhibitors Targeted agents oncogenes