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Chinese Science Bulletin 1997年第2期42卷 159-162页

作者： Gao, ZQ Gao, ZP Liu, XF Department of Pathology Beijing Medical University Beijing China

DRUG resistance of tumor is a very common phenomenon in clinical tumor treatment. Most patients with lung cancers, one of the most common malignant tumors in China, have no response to chemotherapy, so it is very important to study the resistant biology of lung cancer for treatment. The rate of drug sensitivity in non-small cell lung cancer (NSCLC) is lower than in small cell lung cancer (SCLC). The drug resistance, besides the effects of MDR1 gene and GST-π, is also closely correlated with the effect of another novel gene MRP (multidrug resistance-related gene).In the previous study on a doxorubicin-selected human NSCLC cell line, GAOK, we found that MDR1 gene overexpressed and MDR1 Antisense RNA mediated by retrovirus could not completely reverse the phenotype of multidrug resistance, and

关键词： lung cancer reversal of drug resistance MRP Antisense RNA retrovirus.

INHIBITED NEOPLASTIC PHENOTYPE BY THE c-Ha-ras Antisense RNA

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Science China Chemistry 1991年第12期34卷 1485-1491页

作者：路桂荣武纯静柯杨熊辛李延钧刘景梅许毅胥薇李吉友邓国仁鄂征 Beijing Institute for Cancer Research Beijing 100034 PRC

A 2.0 kb fragment DNA plasmid which expresses Antisense to the upstream first exon of c-Ha-ras oncogene was transfected into Ha-ras transformed cell lines, GCM-3T3 and REF-4.3. The transfection leads to the inhibition of malignant behaviour, shown by decreasing of growth speed, colony forming ability on soft agar, tumorigenicity in nude mice and increasing ot differentiation degree. In GCM-3T3 cells the lung metastasis frequency became much less (from 60% to 12.5%) after the transfection and the expression of ras oncogene product, and p21 protein was obviously decreased in the transfected cells. This work has first shown the inhibitory effect of Antisense RNA on neoplastic behaviour in China.

关键词： Antisense RNA malignant cell reversion c-Ha-ras oncogene cell transfection.

Co-transfection of MRP and bcl-2 Antisense S-oligodeoxynucleotides reduces drug resistance in cisplatin-resistant lung cancer cells

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Chinese Medical Journal 2000年第10期 93-96页

作者：王洁刘叙仪蒋薇 Department of Internal Medicine School of OncologyBeijing Medical University

Obejctive To detect the influence of Antisense s oligodeoxynucleotides (S ODNs) of bd 2 and multidrug resistamce associated protein (MRP) genes multidrug resistance associated protein gene and bcl 2 Antisense S oligodeoxynucleotides on cisplatin resistant lung adenocarcinoma cell line A 549 DDP which overexpresses both bcl 2 and MRP Methods A 549 DDP cells were treated with sense and Antisense S ODN mediated by lipofection Expression of MRP and bcl 2 mRNA and protein in the treated cells was measured by RT PCR and flow cytometry (FCM), respectively Apoptosis was identified by DNA electrophoresis and terminal deoxynucleotidyl transferase (TdT) mediated biotin dUTP nick end labeling(TUNEL) The degree of drug resistance of the treated cells was detected by a cell viability 3' [4,5 dimethylthiazol 2 yl] 2,5 diphenyl tefrazolium bromide thiazolylblue (MTT) assay Results Expression of bcl 2 and MRP significantly decreased in the cells treated with bcl 2 or/and MRP Antisense S ODN for 48h as compared to the cells untreated and sense treated ( P Antisense S ODN decreased by 60 6% (6 5 times), 56 4% (7 2 times) and 71 0% (4 8 times), respectively, which paralleled the decrease of bcl 2 and MRP expression Similarly, the resistance to etoposide and epirubicin in Antisense treated cells also reduced in parallel to decreases of the two gene expressions The drug resistance in sense treated cells was similar to that in untreated cells Statistically significant dose and concentration dependent increases of apoptotic cells were observed in the groups exposed to 100?μmol/L cisplatin for 48?h after treatment by bcl 2 or/and MRP Antisense Conclusion Bcl 2 and MRP were at least additive and possibly synergistic in conferring drug resistance in a cisplatin resistant lung adenocarcinoma cell line Antisense S ODN could attenuate drug resistance by promoting cells apoptos

关键词： A_(549) and A_(549)^(DDP) cell lines drug resistance apoptosis lung neoplasms Antisense S-oligodeoxynucleotide

Antisense to cyclin D1 reverses the transformed phenotype of human gastric cancer cells

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World Journal of Gastroenterology 1999年第1期5卷 23-26页

作者： CHEN Bing 1, ZHANG Xue Yong 2, ZHANG Yu Jing 3, ZHOU Ping 3, GU Yan 4 and FAN Dai Ming 2

ＩＮＴＲＯＤＵＣＴＩＯＮＳｔｕｄｉｅｓｏｎｔｈｅｆｕｎｃｔｉｏｎｓｏｆｃｅｌｕｌａｒｐｒｏｔｏｏｎｃｏｇｅｎｅｓａｎｄｔｕｍｏｒｓｕｐｐｒｅｓｏｒｇｅｎｅｓｉｎｄｉｃａｔｅｔｈａｔｍｏｓｔｏｆｔｈｅｓｅｇｅｎｅｓｍ... 详细信息

ＩＮＴＲＯＤＵＣＴＩＯＮＳｔｕｄｉｅｓｏｎｔｈｅｆｕｎｃｔｉｏｎｓｏｆｃｅｌｕｌａｒｐｒｏｔｏｏｎｃｏｇｅｎｅｓａｎｄｔｕｍｏｒｓｕｐｐｒｅｓｏｒｇｅｎｅｓｉｎｄｉｃａｔｅｔｈａｔｍｏｓｔｏｆｔｈｅｓｅｇｅｎｅｓｍｅｄｉａｔｅｓｉｇｎａｌｔｒａｎｓ...

关键词： stomach neoplasms cyclin D1 RNA, Antisense gene therapy

Transduction of Fas gene or Bcl-2 Antisense RNA sensitizes cultured drug resistant gastric cancer cells to chemotherapeutic drugs

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World Journal of Gastroenterology 1998年第5期4卷 58-62页

作者： XIAO Bing, SHI Yong Quan, ZHAO Yan Qiu, YOU Han, WANG Zuo You, LIU Xian Ling, YIN Fang, QIAO Tai Dong and FAN Dai Ming

ＩＮＴＲＯＤＵＣＴＩＯＮＣｈｅｍｏｔｈｅｒａｐｙｉｓｏｎｅｏｆｔｈｅｍａｊｏｒｍｅｔｈｏｄｓｉｎｔｕｍｏｒｔｒｅａｔｍｅｎｔ，ｂｕｔｉｔｏｆｔｅｎｄｏｅｓｎｏｔｗｏｒｋｄｕｅｔｏｍｕｌｔｉｄｒｕｇｒｅｓｉｓｔａｎｃｅ... 详细信息

ＩＮＴＲＯＤＵＣＴＩＯＮＣｈｅｍｏｔｈｅｒａｐｙｉｓｏｎｅｏｆｔｈｅｍａｊｏｒｍｅｔｈｏｄｓｉｎｔｕｍｏｒｔｒｅａｔｍｅｎｔ，ｂｕｔｉｔｏｆｔｅｎｄｏｅｓｎｏｔｗｏｒｋｄｕｅｔｏｍｕｌｔｉｄｒｕｇｒｅｓｉｓｔａｎｃｅ（ＭＤＲ）．Ｒｅｃｅｎｔｓｔｕｄｉ...

关键词： stomach neoplasms Fas gene Bcl 2 gene Antisense nucleic acid drug resistance, multiple gene transduction apoptosis

Retrovirus-mediated Antisense RNA to bcl-2 alter the biological behavior of stomach carcinoma MGC-803 cell lines

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World Journal of Gastroenterology 1998年第S1期4卷 53-56页

ＩＮＴＲＯＤＵＣＴＩＯＮＢｃｌ２ｇｅｎｅ，ｆｉｒｓｔｄｅｔｅｃｔｅｄａｓａｐｕｔｕｔｉｖｅｏｎｃｏｇｅｎｅｌｏｃａｔｅｄｎｅａｒｔｏｔｈｅｂｒｅａｋｐｏｉｎｔｏｆｔ（１４，１８）（ｑ３２，ｑ２１）ｔｒａｎｓｌｏｃａ... 详细信息

ＩＮＴＲＯＤＵＣＴＩＯＮＢｃｌ２ｇｅｎｅ，ｆｉｒｓｔｄｅｔｅｃｔｅｄａｓａｐｕｔｕｔｉｖｅｏｎｃｏｇｅｎｅｌｏｃａｔｅｄｎｅａｒｔｏｔｈｅｂｒｅａｋｐｏｉｎｔｏｆｔ（１４，１８）（ｑ３２，ｑ２１）ｔｒａｎｓｌｏｃａｔｉｏｎｓｉｎｈｕｍａｎｆｏｌｉｃ...

关键词： stomach neoplasms RNA, Antisense bcl 2 gene MGC 803 cell lines gene therapy

Effects of Antisense oligodeoxynucleotides to NR1 on suppression of seizures and protection of cortical neurons from excitotoxicity in vivo and in vitro

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Chinese Medical Journal 1997年第8期 3-7页

作者：单巍松吴希如张国荣张月华王朝晖

Objective To investigate the effects of NR1 subunit on the initiation and development of seizures and protection of cortical neurons from excitotoxicity by using Antisense oligodeoxynucleotides (ODN) to NR1 in vivo and in vitro. Methods Intracerebroventricular injection, temporal cortex slices discharge, cerebral cortical neuronal culture, induction of neurotoxicity and MK 801 binding were used in this study. Results After an Antisense ODN for NR1 was administered intracerebroventricularly (i.c.v. 100 μg in 10 μl) once daily, for three days in genetically epilepsy prone rats (GEPR, P77PMC), the animals did not develop any clonic and tonic convulsions and their seizure scores were significantly lower compared to the control groups. The frequency and amplitude of early seizure like events (SLEs) and late reccurrent discharges (LRD), induced by lowering Mg 2+ , were reduced in entorhinal cortex (EC) of the temporal cortex slice treated by Antisense ODNs. Pretreatment with Antisense ODN (2 μM) protected more than 52% of glutamate sensitive neurons and reduced the MK 801 binding to 50% in cultured cerebral cortical neurons. Conclusions N methy D aspartate receptors(NMDAR), specifically the NR1 subunit, may participate and play important roles in the initiation and propagation of epilepsy in the P77PMC rat.

关键词： vivo excitotoxicity Antisense Effects

Sequencing of PCR amplified HBV DNA pre-c and c regions in 2.2.15 cells and antiviral action by targeted Antisense oligonucleotide directed against sequence

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World Journal of Gastroenterology 1998年第5期4卷 71-73页

作者： ZHOUG Sen 1, WEN Shou Ming 2, ZHANG Ding Feng 3, WANG Quan Li 4, WANG Seng Qi 4 and REN Hong 3

ＩＮＴＲＯＤＵＣＴＩＯＮＭａｎｙｓｔｕｄｉｅｓｈａｖｅｓｈｏｗｎｔｈａｔａｎｔｉｓｅｎｓｅｏｌｉｇｏｎｕｃｌｅｏｔｉｄｅｓ（ＡＳＯＮｓ）ｃａｎｅｆｆｉｃｉｅｎｔｌｙｉｎｈｉｂｉｔＨＢＶＤＮＡｒｅｐｌｉｃａｔｉｏｎａｎ... 详细信息

ＩＮＴＲＯＤＵＣＴＩＯＮＭａｎｙｓｔｕｄｉｅｓｈａｖｅｓｈｏｗｎｔｈａｔａｎｔｉｓｅｎｓｅｏｌｉｇｏｎｕｃｌｅｏｔｉｄｅｓ（ＡＳＯＮｓ）ｃａｎｅｆｆｉｃｉｅｎｔｌｙｉｎｈｉｂｉｔＨＢＶＤＮＡｒｅｐｌｉｃａｔｉｏｎａｎｄｅｘｐｒｅｓｉｏｎｉｎｖｉｔｒｏ...

关键词： hepatitis B virus gene, viral DNA, viral Antisense oligonucleotide gene expression polymerase chain reaction

PEGylation of therapeutic oligonucletides： From linear to highly branched PEG architectures

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Nano Research 2018年第10期11卷 5519-5534页

作者： Xueguang Lu Ke Zhang Department of Chemistry and Chemical Biology Northeastern University Boston Massachusetts 02115 USA

PEGylation, the attachment of poly（ethylene glycol）（PEG）, has been adopted to improve the pharmacokinetic properties of oligonucleotide therapeutics for nearly 30 years. Prior efforts mainly focused on the investigation of linear or slightly branched PEG having different molecular weights, terminal functional groups, and possible oligonucleotide sites for functionalization. Recent studies on highly branched PEG （including brush, star, and micellar structures） indicate superior properties in several areas including cellular uptake, gene regulation efficac~ reduction of side effects, and biodistribution. This review focuses on comparing the effects of PEG architecture on the physiochemical and biological properties of the PEGylated oligonucleotide.

关键词： PEGylation oligonucleotide brush polymer Antisense small interfering RNA aptamer phosphorothioate

Introduction of Antisense waxy gene into main parent lines of indica hybrid rice

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Chinese Science Bulletin 2002年第14期47卷 1192-1197页

作者： CHEN Xiuhua LIU Qiaoquan WANG Zongyang WANG Xingwen CAI Xiuling ZHANG Jingliu GU Minghong Key Laboratory of Biotechnology of Jiangsu Province Yangzhou UniversityYangzhou 225009China Shanghai Institute of Plant Physiology and Ecology Chinese Academy of ScienceShanghai 200032China

Amylose content in rice endosperm is one of the key determinants of rice eating and cooking quality, and the poor quality of indica hybrid rice is closely related to the high amylose level in rice grains. In order to improve the grain quality of the indica hybrid rice by genetic engineering, an Antisense fragment of rice waxy gene, driven by the 5’-franking sequences of the rice waxy gene, was successfully introduced into three major parent lines of indica hybrid rice, all contain a high amylose level in the grains, via Agrobacte-rium, and more than 100 hygromycin-resistant plants were regenerated. The analysis of PCR amplification and Southern blots indicated that the T-DNA containing the Antisense waxy gene had been integrated into the genome of transgenic rice plants. Most of the primary transgenic rice plants grew normally, and the mature seeds from these transgenic plants were performed for analysis of the amylose content. The results showed that the amylose content in the endosperm of some grains

关键词： transgenic rice indica rice maintain line Antisense waxy gene amylose content.