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Developing aptamers into tumor diagnostics and therapeutics

Mi JING ; Bryan M. Clary ; Bruce A. Sullenger

Chinese Journal of Cancer Biotherapy.2008;15(4):301-304. doi:10.3872/j.issn.1007-385X.2008.04.001

Aptamers are small single-stranded nucleic acid molecules that bind a target protein with high affinity and specificity. Due to their stability, low toxicity and immunogenicity, as well as improved safety, aptamers are attractive alternatives to antibody and are therefore suitable for in vivo applications. Aptamers are typically isolated, through a process termed SELEX (systematic evolution of ligands by exponential enrichment), from combinatorial libraries with desired proteins. In the present review, the recent non-conventional aptamer selection process will be discussed together with an overview on the aptamer application in cancer diagnosis and therapy.

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Paclitaxel-octreotide conjugates inhibit growth of human non-small cell lung cancer cells

Meili SUN ; Xiuwen WANG ; Pu WANG ; Junmin WEI ; Lei LI

Chinese Journal of Cancer Biotherapy.1996;0(04):-.

Objective: To evaluate the cytotoxicity and targeting ability of self-developed paclitaxel-octreotide (PTX-OCT) conjugates on A549 non-small cell lung cancer (NSCLC) cells and Calu-6 NSCLC cells. Methods: Conjugates PTX-OCT and 2PTX-OCT were synthesized by our school. Reverse transcription-polymerase chain reaction was used to detect mRNA of human somatostatin receptor subtypes (SSTRs) using specific primers. The cells were treated with different concentrations (1, 100 nmol/L and 1 ?mol/L) of paclitaxel and the conjugates for different time periods (24-72 h); we also set up a control group. MTT assay was used to evaluate the cell viability after treatment; cell cycle perturbations were determined by FAC Scan flow cytometer 24 h after treatment with 1 ?mol/L paclitaxel, PTX-OCT, and 2PTX-OCT. Results: Both A549 cell and Calu-6 cell expressed the mRNA of SSTR2 and SSTR5; no SSTR mRNA was detected in the fibroblasts. The conjugates had a similar cytotoxicity to paclitaxel; they both effectively inhibited the growth of A549 cells and Calu-6 cells in a concentration-and time-dependent manner. After 72 h treatment with 1 ?mol/L paclitaxel, PTX-OCT and 2PTX-OCT, the survival rates of A549 cells were (26.9?7.3)%, (26.6?9.2)% and (35.7?4.3)%, respectively; the survival rates of Calu-6 cells were (29.5?5.0)%, (28.2?9.7)% and (26.5?4.9)%, respectively. The survival rate A549 cells at 72 h after treatment was lower than that at 24 h after treatment(P

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Inhibitory effects of angiostatin gene combined with antisense hypoxia inducible factor-1? gene transfection on implanted human ovarian carcinoma in nude mice

Ping SUN ; Dianning DONG ; Beihua KONG

Chinese Journal of Cancer Biotherapy.1996;0(04):-.

Objective: To observe the synergistic inhibitory effect of angiostatin gene combined with antisense hypoxia inducible factor-1? (aHIF-1?) gene on implanted human ovarian carcinoma in nude mice. Methods: BALB/C nude mice were subcutaneously transplanted with SKOV3 tumor cells and the tumors were allowed to grow till the diameter reached 0.4 cm, then the mice were randomly divided into 4 groups: PcDNA3 control group, PcDNA3-Angiostatin group, PcDNA3B-aHIF-1? group and PcDNA3-Angiostatin+PcDNA3B-aHIF-1? group; plamids PcDNA3, PcDNA3-Angiostatin, PcDNA3B-aHIF-1? and PcDNA3-Angiostatin+PcDNA3B-aHIF-1? were injected intra-tumorally in the above groups, respectively. The tumor samples were harvested on the 7 th day after gene transfer. Angiostatin, HIF-1?, vascular endothelial growth factor (VEGF) and microvessel density (MVD) of tumors were determined by immunohistochemical methods. Tumor cell apoptosis was determined with TUNEL staining. Results:The growth of tumors of PcDNA3-Angiostatin+PcDNA3B-aHIF-1? group was significantly inhibited, with local low expression of HIF-1? and VEGF (lower than those of the other 3 groups). MVD in combined transfection group(13.6?2.3) was lower than that of Angiostain group (24.5?2.7); the apoptosis index in combined transfection group (5.32?0.62)was higher than those of Angiostatin group(2.89?0.45), aHIF-1? group(2.98?0.51)and contrl group(1.56?0.41). Conclusion: Our results suggest a synergestic effect between Angiostain gene and aHIF-1? gene in inhibiting implanted human ovarian tumors in nude mice, which may contribute to drug resistance in antiangiogenic therapy of tumors.

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Effects of anti-HPV16E6-ribozyme on telomerase activity in cervical carcinoma cells and the related mechanisms

Zhiguo RAO ; Jiren ZHANG ; Yanfang ZHENG

Chinese Journal of Cancer Biotherapy.1996;0(04):-.

Objective: To investigate the effects of HPV16E6-ribozyme on telomerase activity in cervical carcinoma cell line CaSKi and the related mechanisms. Methods: Anti-HPV16E6-ribozyme and blank eucaryotic plasmids were transfected into CaSKi cells via lipofectin, and the resultant cells were named as CaSKi-R and CaSKi-P, respectively. The expression of ribozyme in transfected cells was observed by RNA dot blotting. The expression of E6 mRNA and protein in the 3 kinds of cells were detected by Northern blotting and Western blotting, respectively. Telomerase activity was determined by TRAP-Elisa method; the expression of P53, c-myc, hTERT and hRT mRNA were examined by RT-PCR.Results: RNA dot blotting showed that anti-HPV16E6-ribozyme was stably expressed in transfected CaSKi-R cells. Western blotting showed that the expression of E6 mRNA and protein in CaSKi-R cells was obviously lower than that in CaSKi and CaSKi-P cells. The telomerase activities in CaSKi,CaSKi-P and CaSKi-R cells were (0.89?0.14), (0.90?0.11) and(0.36?0.06),respectively. The inhibitory rate of telomerase activity in CaSKi-R cells was 59.55%, which was significantly lower than those in CaSKi and CaSKi-P cells (P

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Inhibitory effect of Trichinella spiralis polypide protein on hepatic cancer cells H7402

Xuelin WANG

Chinese Journal of Cancer Biotherapy.2006;0(05):-.

Objective:To investigate the inhibitory effect of Trichinella spiralis polypide protein on H7402 cell line in vitro and to assess its anti-tumor effect against hepatocellular carcinoma(HCC).Methods:The Trichinella spiralis polyp- ide protein was isolated from adult worms and newborn mixture.Trichinella spiralis polypide protein was prepared through homogenization and centrifugation,and its concentrations were determined by UV-visable spectrometers.H7402 cells trea- ted with Trichinella spiralis polypide protein(at 0.035,0.070,0.140 mg/ml)served as treatment group,and normal he- patic cell line HL-7702 treated with Trichinella spiralis polypide protein served as control group.Cell proliferation was de- tected by MTT;the effect of Trichinella spiralis polypide protein on migration and invasion ability of H7402 cell line was assessed by scarification test and invasion test.Cell apoptosis was observed by TUNEL.Apoptosis and cell cycle were ana- lyzed by FCM.Results:Trichinella spiralis polypide protein was successfully prepared.The protein at 0.035,0.070,0. 140 mg/ml inhibited H7402 cells proliferation by(22.40?13.80)%,(29.45?16.80)%,and(39.38?17.80)%, respectively.Apoptosis was observed by TUNEL and FCM,with an apoptosis rate of(39.07?0.90)%;the cell cycle was blocked at S phase.Scarification test and invasion test suggested that Trichinella spiralis polypide protein inhibited the migration and invasion of H7402 cell line,with the inhibition rate being(63.79?13.71)%.Conclusion:Trichinella spiralis polypide protein can inhibit the proliferation,migration,invision of H7402 cell line,and it might be a potential anti-cancer agent.

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Adenovirus enhances adeno-associated virus expression in drug-sensitive and drug-resistant tumor cells and the related mechanism

Shenghai ZHANG

Chinese Journal of Cancer Biotherapy.2006;0(05):-.

Objective:To investigate the enhancing effect of low dose adenovirus on rAAV2 expression in drug-sensi- tive and drug-resistant tumor cells and to explore the related mechanism.Methods:Human small cell lung cancer NCI- H446 cells,human lung adenocarcinoma A549 cells,human gastric cancer SGC7901 cells,human oral epithelial cancer KB cells,and VCR-resistant KB cells(KB/VCR)were transfected with rAAV2-GFP alone or combined with AdS-RFP or with AdS-TERT-RFP.GFP expression in the infected tumor cells was observed and analyzed by fluorescence microscope and fluorescence activated cell sorting(FACS).GFP protein and phosphorylation level of ERK and AKT in the infected tumor cells were detected by Western blotting.Quantitative analysis of DNA copies of GFP and mRNA expression of GFP, HSPG,?_v integrin,FGFR-1 in the infected tumor cells were performed by Real-time PCR.Results:The results of FACS demonstrated that the mean intensity of GFP fluorescence and the GFP positive rate after infection with rAAV2-GFP com- bined with Ad5-RFP or Ad5-TERT-RFP increased by 0.3-3 and 4-8 folds,respectively.GFP expression in the tumor cells with combined infection showed 4-6 folds increase and the phosphorylation level of ERK and AKT also increased.GFP mRNA expression in the combined infection tumor cells increased by 3.83-7.33 folds;there was no differences in the GFP DNA copies between rAAV2-GFP group and rAAV2-GFP plus Ad5-RFP group.Cellular receptors HSPG,?_v integrin and FGFR-1 mRNA expression was slightly increased in rAAV2-GFP plus Ad5-RFP.Conclusion:Lower dose of recombinant adenovirus can obviously enhance the expression of rAAV2 in drug-sensitive and drug-resistant tumor cells,which might be related to the activation of signal transduction pathway and increase of intracellular transcription.

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Inhibitory effects of bone sialoprotein monoclonal antibody on bone-seeking breast cancer cells adhering to bone matrix

Yingjing GONG ; Jie WANG ; Huixue SONG ; Bing XIA

Chinese Journal of Cancer Biotherapy.2006;0(06):-.

Objective: To determine the inhibitory effects of anti-bone sialoprotein(BSP) antibody on human breast cancer cells adhering to bone matrix in vitro.Methods: Expression of BSP in 3 different cancer cell lines(bone seeking breast cancer cell MDA-MB-231-BO,lung adenocarcinoma cell SPCA-1 and colon carcinoma cell LOVO)was detected immunohistochemically.Cells adhering test was carried out to investigate the adhering of the 3 different cancer cell lines to mouse bone matrix in vitro and the inhibitory effect of anti-BSP antibody on MDA-MB-231-BO cells adhering to mouse bone matrix;Enzyme-linked immunosorbent assay was carried out for quantitative detection of TGF-?.Results: BSP immunostaining was positive in MDA-MB-231-BO cells and negative in SPCA-1 and Lovo cells.The number of MDA-MB-231-F10 cells adhering to mouse bone matrix was significantly more than SPCA-1 or Lovo cells(P

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Bcl-XL siRNA sensitizes ovary cancer cells in TRAIL-induced apoptosis

Jingzi HU ; Hongbo ZHU ; Xuefeng HUANG ; Chao HE

Chinese Journal of Cancer Biotherapy.2006;0(06):-.

Objective: To investigate the role of Bcl-XL siRNA in sensitizing ovary cancer cells for TRAIL-induced apoptosis and the underlying mechanisms.Methods: Western blotting analysis was performed to confirm whether Bcl-XL siRNA could effectively down-regulate Bcl-XL protein after SKOV3 cells were transfected with Bcl-XL siRNA and then the cells were treated with TRAIL.Flow cytometry analysis and cell counting were used for assessment of apoptotic rate and survival rate,respectively.Western blotting analysis was performed to determine the changes of apoptosis-related protein in SKOV3 cells.Results: Compared with control group,Bcl-XL siRNA transfection effectively down-regulated the expression of Bcl-XL protein and suppressed the growth of SKOV3 cells;the suppression peaked at 96 h after transfection,being 43.9% that of the control group(P

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Expression of Raf-1 in colon carcinoma tissue and its clinical significance

Ningning ZHANG ; Wenchao LIU ; Yan XUE

Chinese Journal of Cancer Biotherapy.2006;0(06):-.

Objective: To investigate the relationship between the expression of Raf-1 and tumor angiogenesis,and to discuss its clinical significance.Methods: Tissue microarray technique was used to detect the expression of Raf-1 in 87 specimens of human colon carcinoma,their corresponding adjacent tissues,and incision margins.The patients were from the Department of Pathology of Xijing Hospital between 2005 and 2006.Microvessel density(MVD) was detected using immunohistochemistry with CD34 labeling.The correlation between Raf-1 expression and MVD with the tumor size,metastasis,and differentiation was analyzed.Results: The positive rates of Raf-1 in colon carcinoma tissues,adjacent tissues and incision margins were 86.47%,37.34% and 11.03%,respectively;there were significant difference among the 3 values(P

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Tumor antigen-pulsed dendritic cell vaccine for treatment of patients with advanced malignant tumor:a clinical observation

Liming ZHU ; Yiping ZHANG ; Xiaojia WANG ; Haijun ZHONG ; Yun FAN ; Xinmin YU ; Qinghua DENG ; Xiangming KONG ; Jieer YING ; Tie LI ; Guangyuan LOU ; Zhibing WU ; Zhongzhu TANG ; Shengling MA

Chinese Journal of Cancer Biotherapy.2006;0(06):-.

Objective: To observe the safety and clinical efficacy of tumor antigen-pulsed dendritic cell(DC) vaccine in treatment of advanced malignant tumor.Methods: Ninety-one patients with non-small cell lung cancer,colon and rectal cancer,melanoma,renal carcinoma,breast cancer and other malignant tumors were enrolled in this study.All patients met the selecting standard and signed informed consent.Human dendritic cells were obtained from peripheral blood monocytes by culturing them with granulocyte macrophage-colony stimulating factor and interleukin-4.DC vaccine was prepared from tumor antigen pulsed immature dendritic cells in vitro.Patients received the vaccine therapy once every week and one cycle was defined as once every week for 3 weeks.Results: All the patients received 96 cycles of DC vaccine treatment.Symptoms of toxicity included fever,shivering,aching pain of muscle,asthenia,itching,stifle and transient fatigue;most of the symptoms automatically recovered.Clinical efficacy of the treatment was evaluated in 76 patients.Thirty-one of the 76 patients were stable after treatment and 45 were in progressive situation,with the clinical benefiting rate being 40.8%.Eighty-five patients were followed up.The median time for progression was 2.6 months;the overall survival time was 0.9-30.6 months;and the median survival period was 4.5 months,with the one year survival rate being 9.2%.Conclusion: The results suggest that the DC vaccine therapy is well tolerated in treating patients with advanced malignant tumors and has satisfactory clinical benefit;the clinical value of DC vaccine therapy needs to be further observed.

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