Telomerase-related advances in hepatocellular carcinoma:A bibliometric and visual analysis

BACKGROUND As a critical early event in hepatocellular carcinogenesis,telomerase activation might be a promising and critical biomarker for hepatocellular carcinoma(HCC)patients,and its function in the genesis and treatment of HCC has gained much attention over the past two decades.AIM To perform a bibliometric analysis to systematically assess the current state of research on HCC-related telomerase.METHODS The Web of Science Core Collection and PubMed were systematically searched to retrieve publications pertaining to HCC/telomerase limited to“articles”and“reviews”published in English.A total of 873 relevant publications related to HCC and telomerase were identified.We employed the Bibliometrix package in R to extract and analyze the fundamental information of the publications,such as the trends in the publications,citation counts,most prolific or influential writers,and most popular journals;to screen for keywords occurring at high frequency;and to draw collaboration and cluster analysis charts on the basis of coauthorship and co-occurrences.VOSviewer was utilized to compile and visualize the bibliometric data.RESULTS A surge of 51 publications on HCC/telomerase research occurred in 2016,the most productive year from 1996 to 2023,accompanied by the peak citation count recorded in 2016.Up to December 2023,35226 citations were made to all publications,an average of 46.6 citations to each paper.The United States received the most citations(n=13531),followed by China(n=7427)and Japan(n=5754).In terms of national cooperation,China presented the highest centrality,its strongest bonds being to the United States and Japan.Among the 20 academic institutions with the most publications,ten came from China and the rest of Asia,though the University of Paris Cité,Public Assistance-Hospitals of Paris,and the National Institute of Health and Medical Research(INSERM)were the most prolific.As for individual contributions,Hisatomi H,Kaneko S,and Ide T were the three most prolific authors.Kaneko S ranked first by H-index,G-index,and overall publication count,while Zucman-Rossi J ranked first in citation count.The five most popular journals were the World Journal of Gastroenterology,Hepatology,Journal of Hepatology,Oncotarget,and Oncogene,while Nature Genetics,Hepatology,and Nature Reviews Disease Primers had the most citations.We extracted 2293 keywords from the publications,120 of which appeared more than ten times.The most frequent were HCC,telomerase and human telomerase reverse transcriptase(hTERT).Keywords such as mutational landscape,TERT promoter mutations,landscape,risk,and prognosis were among the most common issues in this field in the last three years and may be topics for research in the coming years.CONCLUSION Our bibliometric analysis provides a comprehensive overview of HCC/telomerase research and insights into promising upcoming research.

Value of endoscopic methylene blue and Lugol's iodine double staining and detection of GST-n and telomerase in the early diagnosis of esophageal carcinoma

AIM：To explore the expressions of GST-π and telomerase activity in esophageal carcinoma and premalignant lesions and to investigate the value of endoscopic methylene blue （MB） and Lugol＇s iodine double staining. METHODS： Seventy-two patients with esophagopathy were sprayed endoscopically with MB and Lugol＇s iodine in proper order and the areas stained blue and brown, and the area between the blue and brown stains were obtained. Depending on the pattern of mucosal staining, biopsy specimen was obtained. GST-π and telomerase activity in specimens were examined by immunohistochemistry and PCR-based silver staining telomeric repeat amplification protocol, respectively. RESULTS： After MB and Lugol＇s iodine staining, the area between both the colors was obtained in 64 of the 72 patients and the areas were stained blue and brown in all of the 72 patients. Association test of two simultaneous ordinal categorical data showed a correlation between the esophageal mucosal staining and the esophageal histology （P〈0.005）. The expression of GST-π and telomerase activity in esophageal carcinoma and premalignant lesions increased. The expression of GST-π and telomerase activity in dysplasia and carcinoma was significantly higher than that in normal epithelium （P〈0.005）. The expression in hyperplasia was slightly higher than that in normal epithelium. With the lesions progressing from low- to moderate- to high-grade dysplasia, the positive rate increased （P〈0.025）. Expression of GST-π was correlated with that of telomerase activity in dysplasia and carcinoma （φ= 0.4831, P〈0.005;φ= 0.3031, P〈0.025, respectively）; but there was no correlation between them in normal epithelium and hyperplasia. CONCLUSION： The expression of GST-π and telomerase may be an early event in the carcinogenesis of esophagus. They may play an induced and synergistic role with each other in the carcinogenesis of esophagus. Endoscopic MB and Lugol＇s iodine double staining and detection of GST-π and telomerase activity may contribute to the early diagnosis of esophageal carcinoma.

Telomerase Activity in Peripheral Blood Mononuclear Cells from Senile Patients with Pneumonia

To investigate the changes of the activity of telomerase in peripheral blood mononuclear cells （PBMCs） from senile patients with pneumonia, the telomerase activity was examined before and after the stimulation of phytohemagglutinin-M （PHA-M） in PBMCs from 10 control subjects （group A）, 12 non-senile patients with pneumonia （group B） and 9 senile patients with pneumonia （group C）. Also observed was the proliferative response of these PBMCs to PHA-M. The results showed that, both with or without the stimulation of PHA-M, the values of telomerase activity in PBMCs from group C patients （A values： pre-stimulation, 0.43±0.04; post-stimulation, 0. 63± 0. 03） were significantly lower than those in PBMCs from both group A patients （A values： prestimulation, 0. 65 ± 0. 05 ; post-stimulation, 1.26 ± 0. 13 ; P〈0. 001, respectively） and group B patients （A values： pre-stimulation, 0. 63±0. 03; post-stimulation, 0. 93± 0. 03; P〈0. 05, respectively）. The results of MTT test showed that the proliferative activity of PBMCs in group C patients （A value： 0. 35±0. 03） was also significantly lower than that in group A patients （A value： 0. 55±0. 04; P〈0. 05） and group B patients （A value= 0. 46±0.03; P〈0.05）. These results indicate that the telomerase activity decreases in senile patients with pneumonia, which may be one of the mechanisms for the weakened immune function in those patients.

Effects of Combined siRNA-TR and-TERT on Telomerase Activity and Growth of Bladder Transitional Cell Cancer BIU-87 Cells

The effects of combined RNA interference(RNAi) of human telomerase RNA(hTR) and human telomerase reverse transcriptase(hTERT) genes on telomerase activity in a bladder cancer cell line(BIU-87 cells) were investigated by using gene chip technology in vitro with an attempt to evaluate the role of RNAi in the gene therapy of bladder transitional cell cancer(BTCC).Three TR-specific double-stranded small interfering RNAs(siRNAs) and three TERT-specific double-stranded siRNAs were designed to target different regions of TR and TERT mRNA.The phTR-siRNA,phTERT-siRNA,and the combination of both plasmids phTR+phTERT-siRNA were transfected into BIU-87 cells.The expression of hTR and hTERT mRNA was detected by quantitative fluorescent reverse transcription-polymerase chain reaction,and a telomeric repeat amplification protocol was applied to detect telomerase activity.Growth inhibition of BIU-87 cells was measured by MTT assay.Gene chip analysis was performed to evaluate the effects of the combined RNAi of hTR+hTERT genes on telomerase activity and growth of BIU-87 cells in vitro.The results showed that the expression of hTERT and hTR mRNA was inhibited by pRNAT-hTERT-Ⅲ,pRNAT-hTR-Ⅲ,and pRNAT-hTR-Ⅲ+hTERT-Ⅲ in BIU-87 cells.The inhibition efficiency of pRNAT-hTERT-Ⅲ,pRNAT-hTR-Ⅲ,pRNAT-hTERT-Ⅲ+pRNAT-hTR-Ⅲ was 67% for TERT mRNA,41% for TR mRNA,57% for TR mRNA and 70% for TERT mRNA in BIU-87 cells respectively.The growth of BIU-87 cells was inhibited and telomerase activity was considerably decreased,especially in the cells treated with combined RNAi-hTR and-hTERT.Gene chip analysis revealed that 21 genes were down-regulated(ATM,BAX,BCL2,BCL2L1,BIRC5,CD44,CTNNB1,E2F1,JUN,MCAM,MTA1,MYC,NFKB1,NFKBIA,NME4,PNN,PNN,SERPINE1,THBS1,TNFRSF1A,and UCC1).The results indicated that hTR-siRNA and hTERT-siRNA,especially their combination,siRNA hTR+hTERT,specifically and effectively suppressed the expression of both hTR and hTERT mRNA and telomerase activity.Molecular biological mechanism by which combined siRNA-TR and-TERT inhibited telomerase activity and growth of BIU-87 cells in vitro may involve the down-regulation of the 21 genes.

Dynamic alteration of telomerase expression and its diagnostic significance in liver or peripheral blood for hepatocellular carcinoma

AIM： To investigate the dynamic alteration of telomerase expression during development of hepatocellular carcinoma （HCC） and its diagnostic implications in liver tissues or peripheral blood mononuclear cells for HCC. METHODS： Dynamic expressions of liver telomerase during malignant transformation of hepatocytes were observed in Sprague-Dawly （SD） rats fed with 0.05% of 2-fluoenyacetamide （2-FAA）. Total RNA and telomerase were extracted from rat or human liver tissues. The telomerase activities in livers and in circulating blood were detected by a telomeric repeat amplification protocol-enzyme-linked immunosorbent assay （TRAP- ELISA）, and its diagnostic value was investigated in patients with benign or malignant liver diseases. RESULTS： The hepatoma model displayed the dynamic expression of hepatic telomerase during HCC development. The telomerase activities were consistent with liver total RNA levels （r = 0.83, P 〈 0.01） at the stages of degeneration, precancerosis, and cancerization of hepatocytes. In HCC patients, the telomerase levels in HCC tissues were significantly higher than in their adjacent non-cancerous tissues, but liver total RNA levels were lower in the former than in the latter. Although the circulating telomerase of HCC patients was abnormally expressed among patients with chronic liver diseases, the telomerase activity was a non-specific marker for HCC diagnosis, because the incidence was 15.7% in normal control, 25% in chronic hepatitis, 45.9% in liver cirrhosis, and 85.2% in HCC, respectively when absorbance value of telomerase activity was more than 0.2. If the value was over 0.6, the incidence was 60% in HCC group and 0% in any of the others （P 〈 0.01） except in two cases with liver cirrhosis. However, the combination of circulating telomerase with serum alpha-fetoprotein level could increase the positive rate and the accuracy （92.6%, 125 of 135） of HCC diagnosis. CONCLUSION： The overexpression of telomerase is associated with HCC development, and its abnormality in liver tissues or in peripheral blood could be a useful marker for diagnosis and prognosis of HCC.

Fibroblast growth factor receptor 3 effects on proliferation and telomerase activity in sheep growth plate chondrocytes

Background： Fibroblast growth factor receptor 3 （FGFR3） inhibits growth-plate chondrocyte proliferation and limits bone elongation. Gain-of-function FGFR3 mutations cause dwarfism, reduced telomerase activity and shorter telomeres in growth plate chondroyctes suggesting that FGFR3 reduces proliferative capacity, inhibits telomerase, and enhances senescence. Thyroid hormone （1-3） plays a role in cellular maturation of growth plate chondrocytes and a known target of T3 is FGFR3. The present study addressed whether reduced FGFR3 expression enhanced telomerase activity, mRNA expression of telomerase reverse transcriptase （TERT） and RNA component of telomerase （TR）, and chondrocyte proliferation, and whether the stimulation of FGFR3 by T3 evoked the opposite response. Results： Sheep growth-plate proliferative zone chondrocytes were cultured and transfected with siRNA to reduce FGFR3 expression; FGFR3 siRNA reduced chondrocyte FGFR3 mRNA and protein resulting in greater proliferation and increased TERT mRNA expression and telomerase activity （p 〈 0.0.5）. Chondrocytes treated with T3 significantly enhanced FGFR3 mRNA and protein expression and reduced telomerase activity （p 〈 0.05）; TERT and TR were not significantly reduced. The action of T3 at the growth plate may be partially mediated through the FGFR3 pathway. Conclusions： The results suggest that FGFR3 inhibits chondrocyte proliferation and reducing telomerase activity indicating an important role for telomerase in capacity during bone elongation. by down-regulating TERT expression sustaining chondrocyte proliferative

Detection of telomerase activity in biopsy samples for predicting prognosis in cirrhotic patients with hepatocellular carcinoma after laparoscopic radiofrequency ablation therapy

Objective: To explore the role of telomerase activity detected in biopsy samples for evaluating the efficacy of lapa- roscopic radiofrequency ablation (RFA) therapy in patients with hepatocellular carcinoma (HCC) and liver cirrhosis. Methods: From August 2001 to October 2004, 34 cirrhotic patients with HCC were treated by laparoscopic RFA under general anesthe- sia. A total of 34 tumors, with a mean maximum tumor diameter of 4.0 ± 1.0 cm, were all located on the liver surface or adja- cent to the gallbladder. Laparoscopic ultrasound-guided core biopsy for liver lesions was performed before and immediately after RFA therapy. In these biopsy samples, telomerase activity was detected by the ELISA-based telomeric repeat amplifica- tion protocol (ELISA-TRAP) assay, and pathological examination was routinely performed. Results: Laparoscopic RFA was successfully performed in all the 34 patients. A complete tumor necrosis was achieved in all patients on the contrast-enhanced helical CT scanning one month after laparoscopic RFA. The positive rates of telomerase activity and histopathologic diagnosis in biopsy samples were 91.2% (31/34) and 100% (34/34) respectively before RFA, and 26.5% (9/34) and 0% respectively after RFA. During a median follow-up period of 35 months (range, 18–51 months), the rates of local tumor recurrence at the ablation sites in post-RFA telomerase-positive and negative patients were 88.9% (8/9) and 4% (1/25) respectively (P < 0.01), and the rates of distant recurrence within the livers were 0% (0/9) and 12% (3/25) respectively (P > 0.05). Conclusion: For cirrhotic patients with HCC treated by laparoscopic RFA, detection of telomerase activity in biopsy samples may be useful for evaluating the therapeutic efficacy of RFA and predicting postoperative local tumor recurrence.

BLOOD TELOMERASE ACTIVITY AND ITS CORRELATIVITY WITH NON-SMALL CELL LUNG CARCINOMA

Objective: To study the correlativity between blood telomerase activity and Non-small cell lung carcinoma (NSCLC) through relative quantitative analysis of telomerase activity. Methods: Thirty-eight NSCLC and 25 inpatients with benign lung disease were selected. Telomerase repeat amplification protocol was adopted. PCR products were assayed with ELISA. Results: (a) Blood telomerase activity during operation was higher than that before or after operation (P<0.01). (b) Blood telomerase activity after operation was higher in stage IIIa-IIIb than that in stage I-II (P<0.01). Blood telomerase activity before and during operation had no statistical difference between stage IIIa-IIIb and stage I-II (P>0.05). (c) Blood telomerase activity of adenocarcinoma during and after operation was higher than that before operation (P<0.01, P<0.05). Blood telomerase activity of squamous carcinoma during operation was higher than that before or after operation (P<0.01). (d) Blood telomerase activity after operation was higher in adenocarcinoma than that in squamous carcinoma (P<0.01). There was no statistical difference between that before and during operation (P>0.05). Conclusion: The qualitative assay of blood telomerase activity can be adopted as an assistant index for diagnosis of NSCLC. Postoperative blood telomerase activity of adenocarcinoma is higher than that of squamous carcinoma. It may be an evidence for the likelihood of adenocarcinoma to metastase through blood. Blood telomerase activity increases significantly during operation, suggesting that operation may cause more cancer cells entering into circulation.

CLINICAL SIGNIFICANCE OF TELOMERASE ACTIVITY AND PERIPHERAL VENOUS BLOOD CK-20 EXPRESSION IN BLADDER TRANSITIONAL CELL CARCINOMA

Objective: The relationship between peripheral blood CK-20 mRNA expression and tissue telomerase activity in bladder transitional cell carcinoma (TCCB) was investigated to evaluate the feasibility of their combined detection in early-stage diagnosis and prognosis estimation of TCCB. Methods: the blood CK-20 was detected by semi-nested RT-PCR and telomerase activity in tumor tissue was examined with silver-stained TRAP reaction. Results: the blood CK-20 expression and tissue telomerase activity in TCCB were 41% and 93% respectively. No statistical significance was detected among pathological grading and clinical staging (P>0.05). Positive correlation was shown between CK-20 expression and telomerase activity with the pathologic grade or clinical stage. Conclusion: combined use of blood CK-20 and tissue telomerase activity detections might be of great importance for clinical diagnosis, treatment and prognosis evaluation.

Study on neoplasia of hydatidiform mole by detecting telomerase reverse transcriptase mRNA expression in peripheral blood mononuclear cells

By setting up a real-time fluorescent quantitative RT-PCR assay to detect human telomerase reverse transcriptase （hTERT） mRNA in hydatidiform mole in peripheral blood mononuclear cells, to analyze the correlation between the expression level of hTERT mRNA and the prognosis of hydatidiform mole, and to evaluate the clinic value of quantitative determination of hTERT mRNA in the diagnosis of hydatidiform mole. Methods： A real-time fluorescent quantitative RT-PCR （FQ RT-PCR） assay based on TaqMan fluorescence methodology and the Light-Cycler system was used to quantify the full range of hTERT mRNA copy numbers in 30 samples of hydatidiform mole and the neoplasia of hydatidiform mole. The normalized hTERT （NhTERT） was standardized by quantifying the number of GAPDH transcripts as internal control and expressed as 100x （hTERT/GAPDH） ratio. Based on the prognosis of the hydatidiform mole, the patients were divided into two groups： the experimental group and the control group, to compare the telomerase reverse transcriptase mRNA expression in peripheral blood mononuclear cells. Results： hTERT mRNA was both expressed in the peripheral blood mononuclear cells and pathological tissues in the mole experimental group and the control group. In the mole experimental group, the values were 6.31±0.32 and 6.24±0.44, respectively, and there was no significant difference between them （P〉0.05）. But in the control group the values were 1.21±0.65 and 1.40±0.61, respectively, and there was no significant difference between them （P〉0.05） The values in experimental group was significantly higher than those in the control group （P〈0.01）. Conclusion： Quantitative determination of hTERT mRNA by FQ RT-PCR is a rapid and sensitive method, hTERT in peripheral blood mononuclear cells may have potential use as a biomarker for the early detection of the prognosis of the hydatidiform mole.

3-58 Telomerase Activity Inhibition Block DNA Damage Repair

Previous studies in malignant cells have shown that irradiation-induced upregulation of telomerase activity,not only protected damaged telomeres, but also contributed to DNA damage repair by chromosomal healing andincreased resistance to irradiation[1;2].To investigate the radiosensitizing mechanism of telomerase inhibition, the influence of telomerase inhibitor(MST-312) combined with X-ray irradiation on -H2AX foci were determined. As shown in Fig. 1(a), the combinedtreatment resulted in retention of -H2AX nuclear foci and significant decrease of DNA damage repair.

Inhibition of Telomerase with hTERT Antisense Increases Susceptibility of Leukemic Cells to CDDP-induced Apoptosis

Objective: To investigated the e?ect of inhibition of telomerase with hTERT antisense on leukemic cells (HL-60 and K562) to CDDP-induced apoptosis. Methods: Antisense phosphorothioate oligodeoxynucleotide (AS PS-ODN) was synthesized and puri?ed. Telomerase activity was detected by Telomerase PCR ELASA kit and cell apoptosis was observed by morphological method and determined by ?owcytometry. Results: AS PS-ODN could signi?cantly inhibit telomerase activity by down regulat- ing the hTERT expression, and increase the susceptibility of leukemic cells to CDDP-induced apoptosis. Conclusion: Inhibition of telomerase with hTERT antisense can increases the susceptibility of leukemic cells to CDDP-induced apoptosis.

Trichostatin A Induces Apoptosis by Inhibiting Telomerase Activity and Expression of Telomerase Reverse Transcriptase in HL-60 Cells

Aim To investigate the effects of trichostatin A （TSA） on telomerase activity and the expression of human telomerase reverse transcriptase （hTERT） during apoptosis in vitro and the mechanisms in HL-60 cells. Methods The proliferative activity of HL-60 cells was assessed by MTT assay. Cell apoptosis was analyzed by flow cytometry. Telomerase activity was examined by TRAP-ELISA. The expression of telomerase subunits was analyzed by RT-PCR. Results A time- and dose-dependent inhibition was detected in HL-60 cells treated with TSA. After treatment with 600 nmol· L^-1 TSA for 48 h, the apoptosis rate in HL-60 cells was 42. 6% and telomerase activity decreased 1.95 ± 0.25, 1.73 ± 0. 12, and 1.52 ± 0. 09 for 12, 24, and 48 h, respectively. The expression of hTERTmRNA decreased. No significant changes were observed in the expression of hTRmRNA and hTPI mRNA. Condusion TSA inhibits telomerase activity and induces apoptosis in HL-60 cells. The underlying mechanism may be related to the down-regulation of hTERT transcription.

Telomerase Activity in Human Renal Cell Carcinoma with Reference to Clinicopathologic Features

Objective: To study the telomerase activity in human renal cell carcinoma and to evaluate the correlation with the clinicobiologic features of the neogrowth.Methods: The telomerase activity was studied by means of a modified telomeric repeat amplification protocol (TRAP) in 32 renal cell carcinoma tissues, 32 normal renal tissues and 32 paracancer tissues and its correlation with the clinicopathologic features of the tumor was evaluated.Results: Telomerase activity was strongly positive in 17, positive in 12 and negative in 3 cases of renal cell carcinoma tissues, the total positive rate being 91%. Telomerase activity was weakly positive (6%) in only 2 out of 32 samples of normal renal cortex tissues and positive in 6 paracancer tissues (19%), the difference was conspicuous (P<0.01).Conclusion: The positive rate of telomerase activity was significantly higher in renal cell carcinoma tissues and might serve as a prognostic marker for estimating the biologic characteristics of renal cell carcinoma.

Expression of Telomerase Activity in Gastric Cancer Cells

Objective To study the relationship between telomerase activity and biological behavior in human gastric cancer cells and appraise the clinical significance of detecting telomerase activity.Methods The telomerase activity in 47 gastric cancer tissue samples , their matched normal tissues, 7 gastric ulcer and 2 gastric cancer cell lines was detected using a PCR-based non-radioisotopic telomeric repeat amplification protocol (TRAP) assay. Results None of the 47 samples from normal gastric tissues expressed telomerase activity. The 41 of 47 cases of gastric cancer presented telomerase activity with an 87.2 % positive rate (P < 0.001). 2/2 gastric cancer cell lines and 0/7 gastric ulcer line were also positive for telomerase activity. The activity of telomerase was associated with the pathological differentiation of gastric cancer. Conclusion Telomerase activity may be related to the biological behavior of gastric cancer and can help in assessing the malignant potential of gastric cancer. Telomerase activity will be a good diagnostic marker for the detection of gastric cancer.

基于CEEMDAN-QPSO-BLS模型的径流预测研究

准确的径流预测是水资源优化配置和高效利用的前提,是制定防洪减灾决策的基础,然而受到人类活动、环境、气候等因素的影响,径流序列呈现出非线性、非稳态、多尺度变化的特点,这为径流的精准预测增加了难度。为提高径流预测的精准度和可信度,结合自适应噪声完备集合经验模态分解(Complete Ensemble Empirical Mode Decomposition with Adaptive Noise,CEEMDAN)方法,量子粒子群优化算法(Quantum Particle Swarm Optimization,QPSO)、宽度学习系统(Broad Learning System,BLS)模型,提出了一种基于CEEMDAN-QPSO-BLS组合式的径流预测模型。该组合模型首先使用CEEMDAN方法对原始径流信号进行分解,得到若干相对平稳的本征模态分量。其次利用QPSO算法对BLS模型的特征层节点组数、增强层节点组数和组内节点数进行寻优,得到最优的宽度学习网络拓扑结构,进而使用最优的QPSOBLS对多个稳态分量进行预测,并对预测分量进行重构,从而获得更高的预测精度。以黄河流域小浪底水库的日径流值为实验数据,将EMD-QPSO-BLS、QPSO-BLS作为CEEMDAN-QPSO-BLS的对比模型,并采用纳什效率系数(NSE)、均方根误差(RMSE)、平均绝对误差(MAE)和平均绝对百分比误差(MAPE)作为模型预测可信度和精准度的评价指标。实验表明,在预见期4天内,与QPSO-BLS、EMD-QPSO-BLS模型相比,CEEMDAN-QPSO-BLS的预测精准度分别提高了79.87%、19.80%,可信度分别提高了131.2%、10.98%,径流预测精度的提高,可为防洪抗旱保护人民生命财产和可持续发展提供决策支持。

Effects of Artificially Designed shRNA of chTR on Telomerase Activity

[Objective] The study was to investigate the inhibitory effects of shRNA of chTR on telomerase activity in MDCC-MSB1 cells. [Method] The artificially designed and synthesized short hairpin RNA(shRNA) of chicken telomerase RNA(chTR) was used to construct the expression vector that was subsequently transfected to MDCC-MSB1 cells, then the telomerase activity of these cells measured by improved TRAP method. [Result] Compared to the CK group, the telomerase activities in the treatment cells showed no obvious decrease in 24 h after transfection, while decreased remarkably 48 h later, among which in the cells transfected by interference vector pSi-chTR-sh1 presented the most obvious inhibitory effects. [Conclusion] This vector could effectively inhibit the telomerase activities in MDCC-MSB1 cells.

Telomerase activity in gastric cancer and its clinical implications

AIM To study the telomerase expression in gastric carcinoma and its clinical implications. METHODS Telomerase activity was examined in gastric cancer and corresponding normal tissues using a modified TRAP (telomeric repeat amplification protocol) assay (TRAP eze) in tissue samples from 94 gastric carcinomas and 58 normal tissues, 12 gastric adenomas and 9 gastric ulcer lesions. RESULTS Telomerase activity was present in 81 of the 94 (86 2%) gastric cancer tissues, whereas no telomerase activity was detected in any normal tissues. The incidence of telomerase activity in gastric cancer tissues was unrelated to the tumor diameter, histological grade, tumor invasion in depth, lymph node metastasis and TNM stage. CONCLUSION Telomerase plays an important role in carcinogenesis and progression of gastric cancer, and it is suggested to be a useful tumor marker.

Effect of VEGF,P53 and telomerase on angiogenesis of gastric carcinoma tissue

Objective:To investigate the effect of vascular endothelial growth factor(VEGF),P53 and telomerase on angiogenesis in gastric carcinoma tissue.Methods:A total of 95 surgical resection samples of gastric cancer tissue after pathological diagnosis are collected to observe the VEGF,P53 and telomerase expression using immunohistochemical methods.Relationship between their expression and its influence on angiogenesis in gastric carcinoma tissue were analyzed.Results:Microvascular density(MVD)and the expression of VEGF,P53 and telomerase were positively correlated.Expression of VEGF and P53 protein were related to tumor type and lymph metastasis,and also a correlation was observed between P53 and VEGF.The telomerase expression had no correlation with VEGF,and P53.Conclusions:VEGF angiogenesis has a angiogenesis promoting effect on gastric cancer tissue development and plays an important role in tumor generation and metastasis.Mutant P53 promotes the tumor angiogenesis generation by adjusting VEGF.Telomerase has a certain role in promoting activity of angiogenesis through different way rather than P53.

Inhibitory Effects of Selenium on Telomerase Activity and hTERT Expression in Cadmium-transformed 16HBE Cells

To investigate the effects of sodium selenite on telomerase activity and expression of hTERT mRNA in cadmium-transformed 16HBE cells. Methods Telomerase activity and expression of genes were measured after cultured cadmium-transformed 16HBE cells were exposed to sodium selenite at different doses （0.625, 1.25, 2.50, 5.00 pmol/L） for 24 hours. Results Selenium decreased telomerase activity in cadmium-transformed 16HBE cells. There existed an obvious dose-effect relationship between the selenium concentration and these changes. The expression of hTERT and c-myc mRNA also decreased but the expression of madl mRNA increased after exposure to selenium for 24 hours. No difference was found in expression of hTRF1 and hTRF2 mRNA after incubated with sodium selenite for 24 hours, compared with control group. Conclusion Selenium inhibits telomerase activity by decreasing hTERT and c-myc mRNA expression and increasing madl mRNA expression in cadmium-transformed 16HBE cells and selenium concentration is significantly correlated with these changes.