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antisense oligodeoxynucleotides inhibit bcl-2 expression and induce apoptosis in acute lymphocytic leukemia cells

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中国实验血液学杂志 1997年第3期5卷 329-329页

作者： Zhao Wang, Ying ChangDepartment of Hematology, Beijing Friendship Hospital,Capital Medical University

Previous studies have shown that the bcl-2protooncogene encodes a mitochondrial protein thatpromotes cell survival by blocking programmed celldeath. High levels of bcl-2 expression were found inmurine myeloid leukemic cell lines resistant to apoptosisinduced by variety of agents. In addition artificialelevation of bcl-2 expression in a human pre-B leukemiccell line resulted in enhanced resistance to chemo-therapcutic drugs. We reported here on the effect ofbcl-2 antisense phosphorothiate

关键词： lymphocytic inhibit myeloid mitochondrial programmed antisense blocking RNA oligo ASON

Current status of gene therapy in gastroenterology

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World Journal of Gastroenterology 1998年第1期4卷 90-94页

作者： XU Chang Tai 1 and PAN Bo Rong 2

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ＣｕｒｅｎｔｓｔａｔｕｓｏｆｇｅｎｅｔｈｅｒａｐｙｉｎｇａｓｔｒｏｅｎｔｅｒｏｌｏｇｙＸＵＣｈａｎｇＴａｉ１ａｎｄＰＡＮＢｏＲｏｎｇ２Ｓｕｂｊｅｃｔｈｅａｄｉｎｇｓｇａｓｔｒｏｅｎｔｅｒｏｌｏｇｙ；ｇｅｎｅｔｈｅｒａｐｙ；ｇｅｎｅｔｒａｎｓｆｅｒ...

关键词： gastroenterology gene therapy gene transfer gene expression DNA, antisense genes, surpressor, tumor oncogenes neoplasms

Depletion of telomerase RNA inhibits growth of gastrointestinal tumors transplanted in mice

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World Journal of Gastroenterology 2013年第15期19卷 2340-2347页

作者： Xue-Cheng Sun Jing-Yi Yan Xiao-Lei Chen Ying-Peng Huang Xian Shen Xiao-Hua Ye Department of Gastroenterology and Hepatology the First Affiliated Hospital of Wenzhou Medical College Department of Gastroenterology and General Surgery the First Affiliated Hospital of Wenzhou Medical College

AIM: To explore effects of telomerase RNA-targeting phosphorothioate antisense oligodeoxynucleotides (PS-ASODN) on growth of human gastrointestinal stromal tumors transplanted in mice. METHODS: A SCID mouse model for transplantation of human gastrointestinal stromal tumors (GISTs) was established using tumor cells from a patient who was diagnosed with GIST and consequently had been treated with imatinib. GIST cells cultured for 10 passages were used for inoculation into mice. Transfection of PS-ASODN was carried out with Lipotap Liposomal Transfection Reagent. GISTs that subsequently developed in SCID mice were subjected to intratumoral injection once daily from day 7 to day 28 postinoculation, and mice were divided into the following four groups according to treatment: PS-ASODN group (5.00 μmoL/L of oligonucleotide, each mouse received 0.2 mL once daily); imatinib group (0.1 mg/g body weight); liposome negative control group (0.01 mL/g); and saline group (0.01 mL/g). On day 28, the mice were sacrificed, and tumor attributes including weight and longest and shortest diameters were measured. Tumor growth was compared between treatment groups, and telomerase activity was measured by enzyme-linked immunosorbent assay. Apoptosis was examined by flow cytometry. Real-time polymerase chain reaction was used to detect expression of the mRNA encoding the apoptosis inhibition B-cell leukemia/lymphoma 2 (bcl-2 ) gene. RESULTS: In the PS-ASODN group, tumor growth was inhibited by 59.437%, which was markedly higher than in the imatinib group (11.071%) and liposome negative control group (2.759%) [tumor inhibition=(mean tumor weight of control group - mean tumor weight of treatment group)/(mean tumor weight of control group) × 100%]. Telomerase activity was significantly lower (P < 0.01) in the PS-ASODN group (0.689 ± 0.158) compared with the imatinib group (1.838 ± 0.241), liposome negative control group (2.013 ± 0.273), and saline group (2.004 ± 0.163). Flow cytometry revealed that the apoptosis rate of tumor cells treated w

关键词： Gastrointestinal stromal tumor Phosphorothioate antisense oligonucleotides Imatinib Tumor inhibitory rate Telomerase activity

Clusterin:Review of research progress and looking ahead to direction in hepatocellular carcinoma

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World Journal of Gastroenterology 2015年第27期21卷 8262-8270页

作者： Peng Xiu Xiao-Feng Dong Xin-Ping Li Jie Li Department of General Surgery Shandong Provincial Qianfoshan Hospital Shandong University Department of Hepatobiliary Surgery The People’s Hospital of Guangxi Zhuang Autonomous Region

Liver cancer, a large proportion of which is hepatocellular carcinoma(HCC), is diagnosed in more than 700000 people each year worldwide. Liver cancer is particularly prevalent in Asia, Sub-Saharan Africa and the South Pacific, where hepatitis B and hepatitis C infection rates are very high. However, due to resistance to chemotherapy, patients with intermediate and advanced-stage disease cannot benefit from this treatment. Clusterin, which is overexpressed in many different cancers, is a stress-induced cytoprotective protein that confers treatment resistance. Custirsen(OGX-011) is a novel 2'-methoxyethyl modified phosphorothioate antisense oligonucleotide that targets secretory clusterin protein expression and is currently in clinical trials for patients with different cancers. In recent years, a number of different clinical trials have been performed, and two phase Ⅲ clinical trials of custirsen evaluating combinations with chemotherapy in patients with metastatic castration-resistant prostate cancer and metastatic non-small cell lung cancer are currently in progress. The aims of this review are to summarize the current state of research on clusterin, predict future research directions and analyze the potential of the clinical application of custirsen in HCC.

关键词： Hepatocellular carcinoma Clusterin Custirsen Chemotherapy antisense oligonucleotides

Gene therapy of cancer

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中国实验血液学杂志 1997年第3期5卷 287-288页

作者： Robert E.Sobol M.D. Director of Clinical Science Sidney Kimmel Cancer Center San DiegoCAUSA

The essence of gene therapy is to placefunctioning genes into a patient’s cells for therapeuticpurposes. Gene therapy may be employed to ①enhance anti-tumor immune responses; ②

关键词： essence correct cancerous cytokine antisense inhibit repair destruction vaccination cytotoxic

Gene therapy for rat myelodysplastic syndrome (MDS)

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中国实验血液学杂志 1997年第3期5卷 323-324页

作者： Baozhung Feng, Jianlin Lei, Zc.xi Lin Institute of Hematology, Chinese Academy of Medical Sciences, Peking Union Medical College, Tianjin 300020

During the past ten years. our molecular studies haddemonstrated that myelodysplasia of MDS bone marrowwas associated with the rearrangement/amplification ofc-erbB and deletion/ inactivation of c-erbA and identifiedthe sites of the rearrangement by v-erbB PCR genediagnosis of MDS and confirmed their etiogenicsignificance by the follow-up of MDS cases. These resultsprovided 2 target sequences of c-erbB.The

关键词： antisense deletion rearrangement amplification targeted curative DMBA usefulness reproduced briefly

Gene therapy and liver diseases

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World Journal of Gastroenterology 1998年第S1期4卷 26-27页

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关键词： liver diseases/therapy gene therapy hepatocytes gene expression antisense DNA hepatitis B virus hepatitis C virus

C-myc antisense transcripts acceleratec differentiation and start apoptosis in human leukemia cells

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中国实验血液学杂志 1997年第3期5卷 324-324页

作者： X.J. Hao, P.M. Tang, D.L. Du, N. Mao, M. Wu Beijing Institute of Basic Medical Sciences, Beijing100850

To demonstrate that low c-myc expression mightexert the effects on differentiation and survival ofleukemic cells, antisense technique was used. Human 2. 7kb c-myc DNA fragment containing exon l, intron 1 and127nt exon... 详细信息

关键词： antisense transcripts plasmid transfection DNA intron exogenous staining morphological RNA

Prospects for nucleic acid-based therapeutics against hepatitis C virus

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World Journal of Gastroenterology 2013年第47期19卷 8949-8962页

作者： Chang Ho Lee Ji Hyun Kim Seong-Wook Lee Department of Molecular Biology Institute of Nanosensor and BiotechnologyDankook UniversityYongin 448-701South Korea

In this review,we discuss recent advances in nucleic acid-based therapeutic technologies that target hepatitis C virus(HCV)infection.Because the HCV genome is present exclusively in RNA form during replication,various nucleic acid-based therapeutic approaches targeting the HCV genome,such as ribozymes,aptamers,siRNAs,and antisense oligonucleotides,have been suggested as potential tools against HCV.Nucleic acids are potentially immunogenic and typically require a delivery tool to be utilized as therapeutics.These limitations have hampered the clinical development of nucleic acid-based therapeutics.However,despite these limitations,nucleic acid-based therapeutics has clinical value due to their great specificity,easy and large-scale synthesis with chemical methods,and pharmaceutical flexibility.Moreover,nucleic acid therapeutics are expected to broaden the range of targetable molecules essential for the HCV replication cycle,and therefore they may prove to be more effective than existing therapeutics,such as interferon-αand ribavirin combination therapy.This review focuses on the current status and future prospects of ribozymes,aptamers,siRNAs,and antisense oligonucleotides as therapeutic reagents against HCV.

关键词： Hepatitis C virus Nucleic acid-based therapeutics Ribozyme Aptamer siRNA antisense oligonucleotide