Biomedical subjects

Teng-Xiang Ma

Publications and source records attributed to Teng-Xiang Ma.

5 recordsLinked to original sources

PubMed2006

Treatment with vector-expressed small hairpin RNAs against Ki67 RNA-induced cell growth inhibition and apoptosis in human renal carcinoma cells.

Short hairpin RNAs (shRNAs) transcribed by RNA polymerase III promoters can trigger sequence-selective gene silencing in mammalian cells. By virtue of their excellent function in knocking down expression of cancer-associated genes, shRNAs could be used as new therapeutic agents for cancer. As overexpression of Ki67 in renal cancer has been correlated to a more aggressive tumor phenotype, inhibition of Ki67 protein expression by means of shRNAs seems to be a promising approach for the therapy of renal cancer. In this study, we constructed an expression plasmid encoding shRNAs against the Ki67 gene, named pSilencerKi67, and transfected it into human renal carcinoma cells. The pSilencerKi67 was shown to significantly knock down the expression of the Ki67 gene in human renal carcinoma cells, resulting in inhibiting proliferation and inducing apoptotic cell death that can be maintained for at least 6 d. These findings offer the promise of using vector-based shRNAs against Ki67 in renal cancer gene therapy.

Apoptosis↗

PubMed2006

Inhibition of proliferation and induction of apoptosis in human renal carcinoma cells by anti-telomerase small interfering RNAs.

Telomerase is an attractive molecular target for cancer therapy because it is present in most malignant cells but is undetectable in most normal somatic cells. Human telomerase consists of two subunits, an RNA component (hTR) and a human telomerase reverse transcriptase component (hTERT). Small interfering RNA (siRNA), one kind of RNA interferences, has been demonstrated to be an effective method to inhibit target gene expression in human cells. We investigated the effects of siRNA targeting at both hTR and hTERT mRNA on the inhibition of telomerase activity in human renal carcinoma cells (HRCCs). The proliferation and apoptosis of HRCCs were examined. The treatment of HRCCs using hTR and hTERT siRNAs resulted in significant decrease of hTR mRNA, hTERT mRNA and hTERT protein. The siRNA can also inhibit the telomerase activity and the proliferation of HRCCs. Moreover, they can induce apoptotic cell death in a dose-dependent manner. From these findings, we propose that the inhibition of telomerase activity using siRNA targeting hTR and hTERT might be a rational approach in renal cancer therapy.

Apoptosis↗

PubMed2005

Knockdown of Ki-67 by small interfering RNA leads to inhibition of proliferation and induction of apoptosis in human renal carcinoma cells.

To investigate the effect of small-interfering RNA (siRNA) targeted against Ki-67, which is an attractive molecular target for cancer therapy, on inhibiting Ki-67 expression and cell proliferation in human renal carcinoma cells (HRCCs), siRNAs were used to inhibit the expression of Ki-67 in HRCCs. Ki-67 mRNA levels were detected by RT-PCR and in situ hybridization analysis. Ki-67 protein levels were detected by Western blot and immunocytochemistry analysis. TUNEL assay was used to measure the apoptosis of carcinoma cells. Results of RT-PCR and in situ hybridization demonstrated reduction of Ki-67 mRNA expression in Ki-67 siRNAs treated 786-0 cells. Similar reduction in Ki-67 protein measured by Western blot and immunocytochemistry was observed in cells transfected with Ki-67 siRNA. Ki-67-siRNA treatment of HRCCs resulted in specific inhibition of proliferation and increased apoptotic cell death. From these findings we conclude that inhibition of Ki-67 expression by siRNA may be a reasonable approach in renal cancer therapy.

Apoptosis↗

PubMed2004

[Generation of specific cytotoxicity T lymphocytes induced by tumor-derived heat shock protein 90-peptide complexes in vitro].

OBJECTIVE: To investigate the specific induction of cytotoxic lymphocyte (CTL) by tumor-derived heat shock protein 90-peptide complexes (HSP90-PC). METHODS: Heat shock protein 90-peptide complex (HSP90-PC) was isolated and purified by liquid chromatography after precipitation by 50% - 70% (NH4) 2SO4 saturation from 10 specimens of renal carcinoma resected from 10 patients aged 40 - 60 during operation. The component containing HSP90-PC was filtered and sterilized. The molecular weight and the identity of the purified HSP90-PC were confirmed by SDS-PAGE and Western blotting. 10 - 15 ml peripheral blood was extracted from these patients. T cells were amplified. Flow cytometry was used to detect the phenotype of dendritic cells (DCs). The DCs in the experimental group were cultured for 5 days and then HSP90-PC and tumor necrosis factor (TNF)-alpha was added into the culture. The HSP90-PC pulsed DCs were collected and co-cultured with auto-T cells for 72 hours. Flow cytometry was used to detect the content of CD8(+) T cells. The DC of the control group were mixed directly with auto-T cells and the content of CD8(+) T cells was examined by flow cytometry. RESULTS: The proliferation of T cells co-cultured with the HSP90-PC pulsed DCs was significantly remarkable and the content of CD8(+) CTLs was significantly more in comparison with the control DC (P < 0.01). CONCLUSION: HSP90-PC prepared from tumor tissues has strong immunogenicity and the DC sensitized thereby effectively induces the proliferation of CTL. Application of HSP90-PC provides a new approach in tumor immunotherapy.

Adult↗

PubMed2003

Androgen and prostatic stroma.

AIM: To investigate the effect of androgen on the proliferation, differentiation and regression of canine prostatic stromal cells in vivo and human stromal cells in vitro. METHODS: Twenty-two dogs, including 15 normal prostate dogs and 7 prostatic hyperplasia dogs, had their serum concentration of testosterone and estrodiol determined by radioimmunoassay before and after castration. The expression of androgen receptor (AR) and estrogen receptor (ER) in the prostate were analysed by immunohistochemistry and semi-quantitative RT-PCR before and after castration. Light microscopy, transmission electron microscopy and TUNEL assay were carried out successively before and after castration to evaluate the prostatic histomorphology. In vitro serum-free cell cultures from human prostatic stroma were established and exposed to dihydrotestosterone (DHT). The proliferation of the cell culture was detected by MTT assay. The expression of TGFbgr, bFGF, AR, and smooth muscle cell (SMC) specific proteins (myosin and/or smoothelin) were detected using immunohistochemistry and RT-PCR. The differentiation from fibroblasts to smooth muscle cells was deduced by measuring the expression of SMC specific proteins. RESULTS: Before castration, the serum concentrations of testosterone and estrodiol were not statistically different between normal and hyperplasia groups. Following castration, the serum concentration of testosterone decreased rapidly in 2 days, and the concentration of estrodiol had no significant change compared with the pre-castration data. In the prostate, AR was presented in both the epithelial and stromal cells and the AR mRNA level was higher in hyperplasia than in normal prostate tissues (P<0.05). While ER predominantly existed in the prostate stromal cells and the ER mRNA had no difference between the hyperplasia and the normal group. Within the early phase of castration (<d7), the expression of AR was increased rapidly. Then it gradually dropped to a lower level than that of the pre-castration by the end of d90. The expression of ER remained unchanged in the whole course. The prostatic stromal cells, including SMCs and fibroblasts, diminished and underwent serial pathological changes of atrophy and apoptosis after castration. The atrophic cells were filled with huge intracellular lipofuscin. The expression of SMC myosin declined after castration, coincident with the increase in TGFbgr mRNA level and decline in bFGF mRNA level. In vitro, DHT caused a weak increase in the proliferation and expression of SMC-specific proteins (P<0.05). However, DHT and bFGF together stimulated the proliferation of stromal cells significantly more than either agent alone (P<0.01). The combination of DHT and TGFbgr greatly enhanced the expression of SMC-specific proteins (P<0.01) more strongly than either alone (P<0.01). CONCLUSION: The whole prostate gland is an androgen-sensitive organ with both the epithelium and stroma under the control of androgen. Androgen may direct the proliferation, differentiation and regression of stromal cells by regulating the expression of TGFbgr, bFGF, AR and smooth muscle cell specific proteins.

Animals↗