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1.
Chinese Medical Journal ; (24): 3030-3034, 2013.
Article in English | WPRIM | ID: wpr-263531

ABSTRACT

<p><b>BACKGROUND</b>Cancer stem cells (CSCs) are the cause of cancer recurrence because they are resistant to conventional therapy and contribute to cancer growth and metastasis. Endocrinotherapy is the most common breast cancer therapy and acquired tamoxifen (TAM) resistance is the main reason for endocrinotherapy failure during such therapy. Although acquired resistance to endocrine treatment has been extensively studied, the underlying mechanisms are unclear. We hypothesized that breast CSCs played an important role in TAM-induced resistance during breast cancer therapy. Therefore, we investigated the biological characteristics of TAM-resistant (TAM-R) breast cancer cells.</p><p><b>METHODS</b>Mammosphere formation and tumorigenicity of wild-type (WT) and TAM-R MCF7 cells were tested by a mammosphere assay and mouse tumor xenografts respectively. Stem-cell markers (SOX-2, OCT-4, and CD133) and epithelial-mesenchymal transition (EMT) markers were tested by quantitative real-time (qRT)-PCR. Morphological observation was performed to characterize EMT.</p><p><b>RESULTS</b>After induction of TAM resistance, TAM-R MCF7 cells exhibited increased proliferation in the presence of TAM compared to that of WT MCF7 cells (P < 0.05), indicating enhanced TAM resistance of TAM-R MCF7 cells compared to that of WT MCF7 cells. TAM-R MCF7 cells showed enhanced mammosphere formation and tumorigenicity in nude mice compared to that of WT MCF7 cells (P < 0.01), demonstrating the elevated CSC properties of TAM-R MCF7 cells. Consistently, qRT-PCR revealed that TAM-R MCF7 cells expressed increased mRNA levels of stem cell markers including SOX-2, OCT-4, and CD133, compared to those of WT MCF7 cells (P < 0.05). Morphologically, TAM-R MCF7 cells showed a fibroblastic phenotype, but WT MCF7 cells were epithelial-like. After induction of TAM resistance, qRT-PCR indicated that MCF7 cells expressed increased mRNA levels of Snail, vimentin, and N-cadherin and decreased levels of E-cadherin, which are considered as EMT characteristics (P < 0.05).</p><p><b>CONCLUSION</b>TAM-R MCF7 cells possess CSC characteristics and may be responsible for TAM resistance during breast cancer therapy.</p>


Subject(s)
Animals , Female , Humans , Mice , Antineoplastic Agents, Hormonal , Pharmacology , Breast Neoplasms , Drug Therapy , Pathology , Drug Resistance, Neoplasm , Epithelial-Mesenchymal Transition , MCF-7 Cells , Neoplastic Stem Cells , Tamoxifen , Pharmacology
2.
Chinese Medical Journal ; (24): 3138-3145, 2013.
Article in English | WPRIM | ID: wpr-263511

ABSTRACT

<p><b>BACKGROUND</b>The effectiveness of chemoradiotherapy followed by surgery (CRTS) in patients with resectable esophageal carcinoma remains controversial. We performed a systematic review of the literature with meta-analysis.</p><p><b>METHODS</b>Electronic databases were used to identify published studies between January 1992 and April 2012. Pooled relative risk (RR) with 95% confidence interval (95% CI) was utilized to estimate the strength of the association between CRTS and surgery alone (SA) survival of the resectable esophageal carcinoma patients. Heterogeneity and publication bias were also assessed in the present study.</p><p><b>RESULTS</b>The final analysis of 2755 resectable esophageal carcinoma cases from 21 randomized controlled trials (RCTs) are presented. Compared to the SA group, the 1, 3- and 5-year survival rates were significantly higher in the CRTS group (all P < 0.05); the 3- and 5-year survival rates for the Eastern patients, Western patients, patients undergoing concurrent chemoradiotherapy, patients with squamous cell carcinoma, patients undergoing High-dose radiotherapy (≥ 40 Gy), and patients given either "cisplatin + Fluorouracil" or "cisplatin + paclitaxel" chemotherapy were significantly higher in the CRTS group (all P < 0.05). There were no statistical significances in the 3- and 5-year survival rates for patients undergoing sequential chemoradiotherapy or patients with adenocarcinoma between the two groups (all P > 0.05). Compared to the RCTS group, the surgery rate in the SA group was higher (P < 0.05), while the CRTS group had significantly higher radical resection rate, R0 resection rate and lower postoperative local recurrence rate (all P < 0.05). The differences in postoperative complication incidence, post-operative distant metastasis and postoperative mortality rate were not statistically significant between the two groups (all P > 0.05).</p><p><b>CONCLUSION</b>CRTS can significantly improve the survival and surgical conditions of patients with resectable esophageal carcinoma.</p>


Subject(s)
Humans , Chemoradiotherapy , Esophageal Neoplasms , Mortality , General Surgery , Therapeutics , Postoperative Complications , Epidemiology , Randomized Controlled Trials as Topic , Survival Rate
3.
Chinese Journal of Oncology ; (12): 645-651, 2012.
Article in Chinese | WPRIM | ID: wpr-307323

ABSTRACT

<p><b>OBJECTIVE</b>To study the demethylation effect of arsenic trioxide (As2O3) on ERα-negative human breast cancer MDA-MB-435s cells and its possible mechanisms, and to observe its treatment efficacy in combination with tamoxifen (TAM) after ERα re-expression.</p><p><b>METHODS</b>MTT assay was used to examine the inhibitory effect of As2O3 treatment alone or in combination with TAM on cell proliferation. A nude mouse xenograft model was used to further examine the treatment efficacy in vivo. MSP was used to detect the methylation status of ERα gene after treated with As2O3 in MDA-MB-435s cells and the transplanted tumor tissues. RT-PCR was used to detect the mRNA expression of DNMT1 and Erα. Western bolt was used to detect the DNMT1 and ERα protein expression. The diameter of xenograft tumors was measured weekly, and the tumor growth curve was drawn.</p><p><b>RESULTS</b>The level of proliferation of the MDA-MB-435s cells was significantly suppressed after treatment with different concentration of As2O3 alone or As2O3 combined with TAM, and the 4 µmol/L As2O3 + TAM treatment for 72 h showed the highest inhibition rate (62.6%). 1, 2, 4 µmol/L As2O3 had demethylation effect on MDA-MB-435s cells, and the DNMT1 mRNA and protein expression was inhibited and accompanied by ERα mRNA and protein re-expression. The unmethylation specific bands of ERα gene were enhanced after treated by As2O3 alone or As2O3 combined with TAM in the xenograft tumors. The expression of DNMT1 mRNA and protein was inhibited, and accompanied by ERα mRNA and protein re-expression. An significant decrease of volume and weight of the xenograft tumors in the As2O3 treated alone or combined with TAM groups was observed compared with those of the normal saline group or TAM alone group (P < 0.05), and the 4 mg/kg As2O3 + TAM group had the highest inhibition rate of tumor weight (79.5%) and volume (76.4%).</p><p><b>CONCLUSIONS</b>ERα can be re-expressed in ERα-negative breast cancer MDA-MB-435s cells after treated with As2O3 by inhibiting the DNMT1 activity. MDA-MB-435s cells are re-sensitized to endocrine therapy after ERα re-expression. As2O3 combined with TAM may provide a new therapeutic approach for patients with ERα-negative breast cancer in the clinic.</p>


Subject(s)
Animals , Female , Humans , Mice , Antineoplastic Agents , Pharmacology , Antineoplastic Agents, Hormonal , Antineoplastic Combined Chemotherapy Protocols , Pharmacology , Arsenicals , Pharmacology , Breast Neoplasms , Genetics , Metabolism , Pathology , Cell Line, Tumor , Cell Proliferation , DNA (Cytosine-5-)-Methyltransferase 1 , DNA (Cytosine-5-)-Methyltransferases , DNA Methylation , Dose-Response Relationship, Drug , Estrogen Receptor alpha , Genetics , Metabolism , Mice, Inbred BALB C , Mice, Nude , Oxides , Pharmacology , RNA, Messenger , Metabolism , Tamoxifen , Tumor Burden , Xenograft Model Antitumor Assays
4.
Chinese Medical Journal ; (24): 2708-2714, 2011.
Article in English | WPRIM | ID: wpr-292818

ABSTRACT

<p><b>BACKGROUND</b>The potential application of retinoic acid receptor activators, such as all trans-retinoic acid (ATRA), for treating various cancers have been studied both pre-clinically and clinically. Whether ATRA has an anticancer effect on human esophageal squamous cancer cell (ESCC) is still unknown. We have explored the anticancer effect of ATRA in ESCC, and in this study, the effects of ATRA on levels and patterns of expression of the vascular endothelial growth factor (VEGF) signal transduction pathway in transplantable tumor growth of the human ESCC cell line, EC9706, in nude mice.</p><p><b>METHODS</b>The animal model of the ESCC xenograft was made by subcutaneous implantation of tumor cells into nude mice. Reverse transcription-polymerase chain reaction (RT-PCR), Western blotting and immunohistochemical assays were used to detect the expression of the VEGF signal transduction pathway in ESCC xenograft tissues.</p><p><b>RESULTS</b>Compared to the control group, the tumor inhibition rates in the low dose ATRA, high dose ATRA, and 5-FU groups were 83.21%, 88.32%, 91.02%, respectively. The protein and mRNA levels of VEGF were down-regulated after being treated with ATRA and 5-FU compared to the control group (P < 0.05). The study also revealed that ATRA specifically down-regulated VEGF and the component of the VEGF signal transduction pathway of CD31, CD34, and CD105 (component of the TGF-β receptor) in ESCC xenograft tissues (P < 0.05).</p><p><b>CONCLUSIONS</b>ATRA can significantly inhibit tumor growth and has anticancer effects on transplantable tumor growth of human ESCC cell line EC9706 in nude mice. These findings indicate that ATRA specifically down regulated VEGF and the components of VEGF signal transduction, which may be an important mechanism responsible for the neoangiogenesis inhibition of ESCC cells.</p>


Subject(s)
Animals , Humans , Mice , Blotting, Western , Carcinoma, Squamous Cell , Drug Therapy , Metabolism , Cell Line, Tumor , Esophageal Neoplasms , Drug Therapy , Metabolism , Immunohistochemistry , Mice, Nude , Neovascularization, Pathologic , Drug Therapy , Metabolism , Real-Time Polymerase Chain Reaction , Tretinoin , Therapeutic Uses , Vascular Endothelial Growth Factor A , Metabolism , Xenograft Model Antitumor Assays
5.
Chinese Journal of Oncology ; (12): 363-366, 2011.
Article in Chinese | WPRIM | ID: wpr-303296

ABSTRACT

<p><b>OBJECTIVE</b>The aim of this study was to assess the TOP2A RNA expression and the relationship of TOP2A protein expression with metastasis-free interval in breast cancer patients.</p><p><b>METHODS</b>TOP2A expression was analyzed prior to surgery in 86 patients. The level of TOP2A gene amplification was analyzed by fluorescence in situ hybridization (FISH), its RNA expression level with RT-PCR, and their correlation with TOP2A protein expression was assessed by immunohistochemistry (IHC). The correlation between RNA expression level and metastasis-free interval in breast cancer patients was also analyzed.</p><p><b>RESULTS</b>Aberrations (amplification or deletion) of TOP2A copy number was observed in 25.6% (22/86) of the cases. TOP2A protein expression was detected in 66.3% (57/86) of the samples. There was a significant correlation between the TOP2A RNA expression and protein expression (P < 0.001). TOP2A gene expression was significantly associated with the metastasis-free interval in the breast cancer patients (P = 0.001). There was no significant correlation between TOP2A gene amplification and TOP2A protein expression (P = 0.211).</p><p><b>CONCLUSIONS</b>TOP2A RNA level is an objective and reliable prognostic indicator in breast cancer.</p>


Subject(s)
Female , Humans , Middle Aged , Antigens, Neoplasm , Genetics , Metabolism , Breast Neoplasms , Drug Therapy , Genetics , Metabolism , General Surgery , Carcinoma, Ductal, Breast , Drug Therapy , Genetics , Metabolism , General Surgery , Carcinoma, Intraductal, Noninfiltrating , Drug Therapy , Genetics , Metabolism , General Surgery , Carcinoma, Lobular , Drug Therapy , Genetics , Metabolism , General Surgery , Chemotherapy, Adjuvant , DNA Topoisomerases, Type II , Genetics , Metabolism , DNA-Binding Proteins , Genetics , Metabolism , Disease-Free Survival , Gene Amplification , Gene Deletion , Gene Expression Regulation, Neoplastic , Neoadjuvant Therapy , Poly-ADP-Ribose Binding Proteins , RNA , Metabolism , Remission Induction
6.
Chinese Journal of Oncology ; (12): 609-612, 2011.
Article in Chinese | WPRIM | ID: wpr-320160

ABSTRACT

<p><b>OBJECTIVE</b>To explore the correlation of IGF-1R expression with clinical features of esophageal squamous cell carcinoma (ESCC) and to investigate the effect of silencing IGF-1R by siRNA on the proliferation of esophageal cancer cell line EC9706 cells.</p><p><b>METHODS</b>Immunohistochemistry was used to detect the expresion of IGF-1R in 80 specimens of ESCC and 18 specimens of normal esophageal mucosa. IGF-1R siRNA was transfected into esophageal squamous cell carcinoma EC9706 cells, and the effect of RNAi was assessed by Western blot. The proliferation of EC9706 cells was determined by drawing growth curve, MTT assay and plate colony-forming assay.</p><p><b>RESULTS</b>The total and strong positive rates of IGF-1R expression were 86.3% and 51.3% in ESCC, and 61.1% and 11.1% in normal esophageal epithelium, respectively. The total and strong positive rates of IGF-1R expression in patients with lymph node metastasis were 94.4% and 74.1%, significantly higher than 69.2% and 3.9%, respectively, in those without lymph node metastasis (P<0.01). A significantly higher IGF-1R expression was associated with lower histological grade (P<0.05). The total and strong rates of IGF-1R expression in 39 patients of stages III and IV were 97.4% and 71.8% , significantly higher than the 75.6% and 31.7%, respectively, in 41 cases of stages I and II (P<0.01). IGF-1R RNAi significantly inhibited IGF-1R expression and the growth of EC9706 cells. The clone formation rate of RNAi-IGF-1R transfected cells was 19.1%, significantly lower than that of 52.3% in non-transfected cells and 49.0% in empty vector-transfected EC9706 cells (P<0.05).</p><p><b>CONCLUSIONS</b>The overexpression of IGF-1R is colerated with lymph node metastasis, differentiation and clinical stage. Down-regulation of IGF-1R can inhibit the proliferation of esophageal cancer EC9706 cells in vitro.</p>


Subject(s)
Aged , Female , Humans , Male , Middle Aged , Carcinoma, Squamous Cell , Genetics , Metabolism , Pathology , Cell Line, Tumor , Cell Proliferation , Down-Regulation , Esophageal Neoplasms , Genetics , Metabolism , Pathology , Gene Expression Regulation, Neoplastic , Lymphatic Metastasis , Neoplasm Grading , Neoplasm Staging , RNA Interference , RNA, Small Interfering , Genetics , Receptor, IGF Type 1 , Genetics , Metabolism , Transfection
7.
Chinese Medical Journal ; (24): 1524-1528, 2011.
Article in English | WPRIM | ID: wpr-353951

ABSTRACT

<p><b>BACKGROUND</b>Overexpression of breast cancer-specific gene 1 (SNCG) is associated with poor prognosis in advanced breast cancer patients. This study aimed to determine the effects of SNCG knockdown in breast cancer cells by using small hairpin RNA (shRNA).</p><p><b>METHODS</b>Four different SNCG shRNA oligonucleotides were designed and chemically synthesized to construct mammalian expression vectors. These vectors were then stably transfected into a breast cancer MCF-7 cell line to knockdown SNCG expression. After SNCG knockdown was confirmed, the stable cell lines were inoculated into nude mice. SNCG mRNA and protein expressions were analyzed by semi-quantitative reverse transcription-polymerase chain reaction (RT-PCR) and immunohistochemistry, respectively in both the stable cell lines and xenografts.</p><p><b>RESULTS</b>All four SNCG shRNA constructs significantly reduced SNCG mRNA and protein levels in MCF-7 cells, as compared to the unrelated sequence control shRNA and the liposome control mice (P < 0.05). SNCG-knockdown MCF-7 cells formed significantly smaller tumor masses than cells expressing the unrelated sequence control or the liposome control mice (P < 0.05).</p><p><b>CONCLUSION</b>SNCG shRNA effectively suppressed breast cancer cell formation in vivo and may be a useful clinical strategy to control breast cancer.</p>


Subject(s)
Animals , Female , Humans , Mice , Breast Neoplasms , Genetics , Therapeutics , Cell Line, Tumor , Gene Expression Regulation, Neoplastic , Genetics , Immunohistochemistry , Mice, Nude , RNA, Small Interfering , Genetics , Physiology , Reverse Transcriptase Polymerase Chain Reaction , Xenograft Model Antitumor Assays , gamma-Synuclein , Genetics , Metabolism
8.
Chinese Medical Journal ; (24): 4012-4017, 2011.
Article in English | WPRIM | ID: wpr-273934

ABSTRACT

<p><b>BACKGROUND</b>Esophageal cancer is the sixth most common cause of cancer-related death worldwide. Prior studies had demonstrated potential synergistic antitumor activity of gemcitabine in combination with cisplatin. Therefore, we studied the efficacy and tolerability of such combination for esophageal cancer.</p><p><b>METHODS</b>Between October 2003 and October 2006, thirty-eight patients with metastatic or recurrent advanced squamous cell carcinoma of the esophagus were enrolled. The median number of treatment cycles per patient was 4 (range 1 - 7). Gemcitabine was given at 1000 mg/m(2) over 30 minutes on days 1, 8 and cisplatin 40 mg/m2 was given on days 1, 2 in an every 21-day cycle.</p><p><b>RESULTS</b>The median follow-up for all 38 patients was 76 months (range 11 - 88 months). The overall response rate was 42.1% (95%CI, 25.5% - 56.5%). Median progression-free survival and median survival for all patients were 4.1 months (95%CI, 3.0 - 5.7 months) and 10 months (95%CI, 7 - 12 months), respectively. Patients with a response had significantly longer median survival compared with the patients without a response (11 months vs. 7.5 months, P = 0.0069). Overall survival at 1 year was 36.8%, at 2 years was 10.5%, and at 5 years was 5.3%. The most common grade 3 - 4 toxicity for all patients was leucopenia (44.7%).</p><p><b>CONCLUSIONS</b>This cisplatin-gemcitabine regimen was manageable and had significant efficacy in patients with esophageal squamous cell carcinoma. Patients with a response had improved survival time. Furthermore, a small number of the patients with metastatic esophageal cancer were still alive in 5 years with this regimen.</p>


Subject(s)
Adult , Aged , Female , Humans , Male , Middle Aged , Antineoplastic Combined Chemotherapy Protocols , Carcinoma, Squamous Cell , Drug Therapy , Mortality , Cisplatin , Therapeutic Uses , Deoxycytidine , Therapeutic Uses , Disease-Free Survival , Esophageal Neoplasms , Drug Therapy , Mortality
9.
Chinese Journal of Oncology ; (12): 663-666, 2010.
Article in Chinese | WPRIM | ID: wpr-293531

ABSTRACT

<p><b>OBJECTIVE</b>To investigate the impact of all-trans retinoic acid (ATRA) on chemosensitivity to esophageal squamous cell carcinoma EC9706 cells in vitro and its mechanism.</p><p><b>METHODS</b>EC9706 cells were routinely cultured as the control group. The experimental group was divided into three groups. The ATRA group with ATRA in final concentration of 1 µmol/L; the 5-Fu group with 5-Fu in final concentration of 50 mg/L; the combined treatment group with ATRA in final concentration of 1 µmol/L and 5-Fu 50 mg/L. The cell apoptosis was detected by terminal deoxynucleotidy transferase mediated dUTP nick end labelling (TUNEL). The cell cycle and apoptosis were detected by flow cytometry.</p><p><b>RESULTS</b>The results of TUNEL showed that in the combined treatment group appeared a large number of apoptotic cells, and their nuclei were stained brown, with a positive rate of 89.7%. There was a significant difference in the comparison with the ATRA group (38.3%) and 5-Fu group (40.3%) (P < 0.05). The flow cytometry showed that the ATRA + 5-Fu group had a significantly higher apoptosis rate (76.9% ± 2.7%) than that in the ATRA group (38.2% ± 2.6%) and 5-Fu group (45.2% ± 2.3%) (P < 0.05). The ratio of cells in G(1) phase increased in the ATRA + 5-Fu group (83.4% ± 3.0%), significantly higher than (48.2% ± 2.5%) in the ATRA group and (53.2% ± 2.6%) in the 5-Fu group (P < 0.05). The ratio of cells in S + G(2)/M phase was decreased in the ATRA + 5-Fu group, with a significant difference (P < 0.05) when compared with other groups. There was no significant difference between the ATRA group and 5-Fu group (P > 0.05) in the apoptosis rate and the proportion of cells at different phases.</p><p><b>CONCLUSION</b>ATRA can induce apoptosis of esophageal carcinoma EC9706 cells in vitro. The combination of ATRA and 5-Fu may enhance the chemotherapeutic efficacy.</p>


Subject(s)
Humans , Antimetabolites, Antineoplastic , Pharmacology , Antineoplastic Agents , Pharmacology , Apoptosis , Carcinoma, Squamous Cell , Pathology , Cell Cycle , Cell Line, Tumor , Drug Synergism , Esophageal Neoplasms , Pathology , Fluorouracil , Pharmacology , Tretinoin , Pharmacology
10.
Chinese Journal of Oncology ; (12): 892-896, 2010.
Article in Chinese | WPRIM | ID: wpr-293458

ABSTRACT

<p><b>OBJECTIVE</b>To investigate the mechanism of apoptosis of EC9706 tumor-bearing nude mice induced by all-trans retinoic acid (ATRA).</p><p><b>METHODS</b>Human esophageal carcinoma cell line EC9706 cells were inoculated into nude mice to establish the solid tumor model. The tumor models were divided into the following groups: ATRA group, fluorouracil group, the two-drugs combination group, and with an equal volume fraction of solvent as the control group. The nude mice were sacrificed after 10 days of medication. TUNEL staining was used to detect cell apoptosis. RT-PCR was used to detect the expression level of mRNA and immunohistochemistry was used to detect the expression level of protein of caspase-3 and survivin, the apoptosis-related genes in the tumor tissue.</p><p><b>RESULTS</b>The apoptosis rates of the ATRA group, 5-Fu group and ATRA + 5-Fu group were 44.3%, 39.7% and 91.0%, respectively. There was a significant difference in comparison with the control group (0.7%), and the ATRA group had no significant difference compared with that of the fluorouracil group (P > 0.05), but the apoptosis rate of the two-drugs combination group was significantly higher than that in the two single-drug groups (P < 0.05). The average gray value of caspase-3 protein expressed in the control group was 46.12 ± 0.33 and the relative expression of caspase-3 mRNA was 0.14 ± 0.03, both were significantly lower than that in the ATRA group, 5-Fu group and the two-drugs combination group (P < 0.05). The average gray value of survivin protein expressed in the control group was 96.07 ± 0.13 and the relative expression of survivin mRNA was 0.84 ± 0.04, both were significantly higher than those of other groups (P < 0.05). The ATRA group had no significant difference compared with the fluorouracil group (P > 0.05), but the two-drugs combination group was significantly different compared with the single-drug groups (P < 0.05).</p><p><b>CONCLUSION</b>Apoptosis in the EC9706 tumor cells in nude mice can be induced by ATRA. The mechanism may be related with down-regulation of the level of survivin gene expression and up-regulation of the level of caspase-3 gene expression.</p>


Subject(s)
Animals , Female , Humans , Male , Mice , Antimetabolites, Antineoplastic , Pharmacology , Antineoplastic Agents , Pharmacology , Apoptosis , Caspase 3 , Genetics , Metabolism , Cell Line, Tumor , Esophageal Neoplasms , Metabolism , Pathology , Fluorouracil , Pharmacology , Inhibitor of Apoptosis Proteins , Genetics , Metabolism , Mice, Nude , Neoplasm Transplantation , RNA, Messenger , Metabolism , Tretinoin , Pharmacology
11.
Chinese Journal of Pathology ; (12): 691-694, 2010.
Article in Chinese | WPRIM | ID: wpr-295151

ABSTRACT

<p><b>OBJECTIVE</b>To investigate the inhibitory effects of siRNA targeting BCSG1 gene expression in tumor transplants of human breast cancer cell line in nude mice.</p><p><b>METHODS</b>Four-pairs of small interfering RNA sequences of BCSG1 were chemically synthesized and inserted into the plasmid expression vectors, and were then transfected into human breast carcinoma cell line MCF7 by liposome method. Plasmid vector with unrelated sequence was used as the vector control. Cells transfected with 4 siRNA sequences, control vector and naive FCF7 cells were transplanted into the nude mice. The tumor inhibition was analysised. Immunohistochemical SP method and semi-quantitative RT-PCR were adopted to detect the BCSG1 mRNA and protein expression, respectively. Breast tissue samples of human infiltrating ductal carcinoma, ductal hyperplasia and fibroadenoma were also used as the controls.</p><p><b>RESULTS</b>The inhibition rates of tumor growth in four BCSG1-siRNA transfected groups were remarkably higher than those of the vector control group and naive MCF7 cells (P<0.01). Compared with that of the vector control and naïve MCF7 cell group, there was a significant decrease of BCSG-1 protein expression in the four experimental groups by immuno-histochemistry staining (P<0.01). In addition, BCSG1 mRNA expression in the four groups transfected with BCSG1-siRNA were significantly less than that of the control vector group, naive MCF7 cell control group and human breast IDC (P<0.01).</p><p><b>CONCLUSION</b>BCSG1-siRNA down-regulates the expression of BCSG1 and inhibits effectively growth of the transplaned human breast cancer cell line in nude mice.</p>


Subject(s)
Animals , Female , Humans , Mice , Breast Neoplasms , Metabolism , Pathology , Carcinoma, Ductal, Breast , Metabolism , Cell Line, Tumor , Fibroadenoma , Metabolism , Gene Expression Regulation, Neoplastic , Mice, Nude , Neoplasm Proteins , Genetics , Neoplasm Transplantation , RNA Interference , RNA, Messenger , Metabolism , RNA, Small Interfering , Genetics , Random Allocation , Transfection , Tumor Burden , gamma-Synuclein , Genetics
12.
Journal of Southern Medical University ; (12): 1552-1557, 2010.
Article in Chinese | WPRIM | ID: wpr-336144

ABSTRACT

<p><b>OBJECTIVE</b>To explore the expression of stathmin gene in esophageal squamous cell carcinoma (ESCC) and its correlation to oncogenesis of ESCC.</p><p><b>METHODS</b>Three ESCC cell lines, 75 ESCC samples, 25 tumor-adjacent samples and 30 normal esophageal mucosa samples were examined for the expression of stathmin mRNA and protein by in situ hybridization and immunohistochemistry, respectively. The correlations of stathmin expression to the clinicopathological features of the patients were analyzed.</p><p><b>RESULTS</b>Overexpression of stathmin mRNA and protein was found in 3 ESCC cell lines EC9706, Eca109 and EC-1, with the positive expression rates exceeding 80%. The positive rates of stathmin mRNA and protein in ESCC samples were 82.7% and 81.3%, respectively. There were significant differences in the relative contents of stathmin mRNA and protein among normal mucosa tissue, tumor-adjacent tissue and cancer tissue (chi2=19.204 and 25.03, respectively, P<0.01). In addition, a positive correlation was noted between stathmin mRNA and protein expressions in ESCC (r=0.413, P=0.000). The relative contents of stathmin mRNA and protein were significantly correlated to the differentiation degree, lymph node metastasis, invasive depth and TNM stage of ESCC (P<0.05).</p><p><b>CONCLUSIONS</b>The expression of stathmin mRNA and protein is upregulated in ESCC with correlation to the differentiation degree, lymph node metastasis, invasive depth and TNM stage of ESCC, suggesting the possible involvement of stathmin in the oncogenesis of ESCC. Combined detection of stathmin mRNA and protein may prove valuable for early diagnosis and prognosis of ESCC, and stathmin may serve as a potential molecular target for biotherapy of the tumor.</p>


Subject(s)
Adult , Aged , Female , Humans , Male , Middle Aged , Carcinoma, Squamous Cell , Metabolism , Pathology , Cell Line, Tumor , Esophageal Neoplasms , Metabolism , Pathology , Lymphatic Metastasis , Neoplasm Staging , Prognosis , Stathmin , Genetics , Metabolism
13.
Chinese Journal of Oncology ; (12): 169-172, 2010.
Article in Chinese | WPRIM | ID: wpr-260443

ABSTRACT

<p><b>OBJECTIVE</b>To explore the possibility of use of insulin as a potentiator of 5-Fu to human colon cancer cell lines HCT-8 and HT-29 and study its mechanism.</p><p><b>METHODS</b>MTT assay was used to examine the inhibition rate of cell growth after treatment with 5-Fu and insulin. Cell cycle was determined by flow cytometry.</p><p><b>RESULTS</b>Insulin showed an enhancing effect on the chemotherapeutic response of 5-Fu when insulin was applied at a dose of exceeding 0.8 mU/ml 0 approximately 8 h before 5-Fu. Within the range of from 0.8 mU/ml to 8 mU/ml, a higher concentration of insulin gave a higher proportion of inhibited cells. But when the insulin concentration exceeds 8 mU/ml, the proportion became stable as that of 8 mU/ml. Insulin increased the percentage of S phase cells and decreased the percentage of G(1) phase cells (P < 0.01). The percentage of S phase cells reached a peak when the cells were treated with insulin for 6 hours.</p><p><b>CONCLUSION</b>Insulin can enhance the anticancer toxicity of 5-Fu to human colon cancer cell lines HCT-8 and HT-29 cells. Insulin increases the percentage of S phase cells, which may be one of the main mechanisms of insulin-induced enhancement of anticancer response of cancer cells to 5-Fu chemotherapy.</p>


Subject(s)
Humans , Antimetabolites, Antineoplastic , Pharmacology , Cell Cycle , Cell Line, Tumor , Cell Proliferation , Colonic Neoplasms , Pathology , Dose-Response Relationship, Drug , Fluorouracil , Pharmacology , HT29 Cells , Insulin , Pharmacology , S Phase , Time Factors
14.
Journal of Southern Medical University ; (12): 2319-2320, 2009.
Article in Chinese | WPRIM | ID: wpr-325120

ABSTRACT

<p><b>OBJECTIVE</b>To evaluate the efficacy and safety of docetaxel (Taxotere) (DTX) and oxaliplatin (OXA) for treatment of recurrent epithelial ovarian cancer.</p><p><b>METHODS</b>Thirty-six patients with histologically confirmed recurrent epithelial ovarian cancer received chemotherapy with DTX and OXA. DTX at the dose of 75 mg/m(2) was administered on day 1 by intravenous infusion in 60 min, followed by OXA at 100 mg/m(2) given by a 2 h infusion. The chemotherapy cycles were repeated every 21 days, and the patients received at least 2 cycles.</p><p><b>RESULTS</b>All the patients were available for response evaluation, among whom 3 (8.3%) showed complete responses and 17 (47.2%) showed partial responses, with an overall response rate of 55.6%. The main adverse effects included hematological toxicities and peripheral neuropathy.</p><p><b>CONCLUSION</b>Combination of DTX and OXA produces good therapeutic effect with tolerable toxicity profile for treatment of recurrent epithelial ovarian cancer.</p>


Subject(s)
Adult , Aged , Female , Humans , Middle Aged , Antineoplastic Combined Chemotherapy Protocols , Therapeutic Uses , Cystadenoma, Mucinous , Drug Therapy , Cystadenoma, Serous , Drug Therapy , Neoplasm Recurrence, Local , Drug Therapy , Organoplatinum Compounds , Ovarian Neoplasms , Drug Therapy , Taxoids
15.
Journal of Southern Medical University ; (12): 1823-1826, 2009.
Article in Chinese | WPRIM | ID: wpr-336075

ABSTRACT

<p><b>OBJECTIVE</b>To investigate the effect of ginsenoside Rg3 on the apoptosis and survivin expression in human lung squamous cell carcinoma cell line SK-MES-1.</p><p><b>METHODS</b>SK-MES-1 cells were divided into Rg3 treatment group, blank control group and positive control (arsenic trioxide) group. The apoptotic rate of the cells in each group was determined using flow cytometry, and the expression of survivin protein and mRNA was detected by immunocytochemistry and RT-PCR, respectively.</p><p><b>RESULTS</b>A 48-h treatment with Ginsenoside Rg3 induced increased apoptotic rate of SK-MES-1 cells in a dose-dependent manner. Ginsenoside Rg3 significantly downregulated the expressions of survivin protein and mRNA as compared with the expression levels in the blank control group (P<0.05).</p><p><b>CONCLUSION</b>Ginsenoside Rg3 can induce the apoptosis of SK-MES-1 cells, the mechanism of which may involve inhibited survivin expression.</p>


Subject(s)
Humans , Apoptosis , Carcinoma, Squamous Cell , Metabolism , Pathology , Cell Line, Tumor , Down-Regulation , Ginsenosides , Pharmacology , Inhibitor of Apoptosis Proteins , Lung Neoplasms , Metabolism , Pathology , Microtubule-Associated Proteins , Genetics , Metabolism , RNA, Messenger , Genetics , Metabolism
16.
Chinese Journal of Oncology ; (12): 179-183, 2008.
Article in Chinese | WPRIM | ID: wpr-348138

ABSTRACT

<p><b>OBJECTIVE</b>To construct an eukaryotic expression vector of human stathmin gene and to assess its effect on esophageal cancer EC9706 cells.</p><p><b>METHODS</b>Stathmin cDNA coding sequence was amplified by RT-PCR from Eca109 cells and was cloned into pMD18-T vector. After identifying and sequencing, the correct inserting stathmin gene was sub-cloned into eukaryotic expression vector pEGFP-C2. EC9706 cells were transfected with this recombinant plasmid and control plasmid using Lipofectamine 2000, and the stable intergrant was selected with G418 medium. The expression of enhanced green fluorescent protein (EGFP) protein was detected by fluorescence microscopy and EGFP/stathmin fusion protein by Western blot assay in transfected EC9706 cells. The growth curve of the two stably transfected cells was protracted with cell counting. FACS was used to detect the cell cycle. The clone formation rate in plate and in nude mice was tested to investigate the tumorigenic characteristics of the two stably transfected cells in vitro and vivo.</p><p><b>RESULTS</b>A 450 bp coding sequence of stathmin cDNA was amplified by RT-PCR, which was cloned into pMD18-T vector. After identified with restriction enzyme the recombinant plasmid pMD18-T-stathmin containing reverse inserting sequence was constructed successfully. Then, the sub-clone pEGFP-stathmin was sequenced, confirming that the recombinant vector was right. The recombinant plasmid pEGFP-stathmin and pEGFP-C2 vector were transfected separately into EC9706 cells. After selecting with G418, the cells were transfected steadily. EGFP in EC9706 cells was observed after transfection by fluorescence microscopy. The expressed product was proved to be 46,000 EGFP/stathmin fusion protein by Western blot. Compared with those transfected with pEGFP-C2, the growth of cells transfected with pEGFP-stathmin became slow, the cells were swelled, the cell cycle was blocked at G2/M phase, the average clone formation rate decreased in vitro, and the tumorigenicity of inoculated cells in nude mice was decreased.</p><p><b>CONCLUSION</b>The recombinant eukaryotic expression vector pEGFP-stathmin has been constructed successfully. It expresses steadily in esophageal cancer cells and inhibits the proliferation and tumorigenicity of transfected cells.</p>


Subject(s)
Animals , Female , Humans , Mice , Cell Cycle , Cell Proliferation , Escherichia coli , Genetics , Esophageal Neoplasms , Metabolism , Pathology , Genetic Vectors , Mice, Inbred BALB C , Mice, Nude , Neoplasm Transplantation , Plasmids , Recombinant Fusion Proteins , Genetics , Metabolism , Stathmin , Genetics , Metabolism , Transfection
17.
Chinese Journal of Oncology ; (12): 937-939, 2008.
Article in Chinese | WPRIM | ID: wpr-255580

ABSTRACT

<p><b>OBJECTIVE</b>To investigate the efficacy and toxicity of nedaplatin combined with tegafur in the treatment for patients with advanced esophageal cancer.</p><p><b>METHODS</b>Among the 65 patients with advanced esophageal cancer, 27 had no history of prior chemotherapy and the other 38 had ever received postoperative adjuvant chemotherapy before. The median age of those cases was 58.0 years. Nedaplatin was given daily by intravenous infusion at a dose of 20 mg/m(2) for 2 hours and tegafur at a dose of 500 mg/m(2) for 8 hours on D1 approximately D5, every 21 days as a cycle.</p><p><b>RESULTS</b>193 cycles of chemotherapy were accomplished in the 65 patients, and 63 patients were evaluable for response evaluation. Of 27 patients with no prior history of chemotherapy, 6 achieved complete response and 16 partial response, with a response rate (CR + PR) of 81.5%. Among the 36 patients who had ever received postoperative adjuvant chemotherapy, 6 obtained complete response and 10 partial response with a response rate (CR + PR) of 44.4%. The overall median time to tumor progression in this series was 5.6 months. The overall median actuarial survival was 9.3 months, and the one-year survival rate was 24.9%. Nausea and vomiting were the major toxicities, but were mild and well tolerable. Grade 3 to 4 neutropenia was only observed in two patients (3.2%).</p><p><b>CONCLUSION</b>The regimen of nedaplatin combined with tegafur is effective and tolerable for the treatment of advanced esophageal cancer.</p>


Subject(s)
Adult , Aged , Female , Humans , Male , Middle Aged , Adenocarcinoma , Drug Therapy , Pathology , Antineoplastic Combined Chemotherapy Protocols , Therapeutic Uses , Carcinoma, Squamous Cell , Drug Therapy , Pathology , Esophageal Neoplasms , Drug Therapy , Pathology , Follow-Up Studies , Nausea , Neoplasm Staging , Neutropenia , Organoplatinum Compounds , Remission Induction , Survival Rate , Tegafur , Vomiting
18.
Chinese Journal of Oncology ; (12): 822-825, 2007.
Article in Chinese | WPRIM | ID: wpr-298503

ABSTRACT

<p><b>OBJECTIVE</b>To study the anti-tumor effects of all-trans retinoic acid (ATRA) and mechanisms of its action.</p><p><b>METHODS</b>Human esophageal carcinoma cell line EC9706 cells were treated with ATRA at different concentration. The proliferation inhibition was examined by MTT assay. Morphological examination, TUNEL method and flow cytometry were used to detect the apoptosis and changes of cell cycle. Immunohistochemical method was used to detect the expression of apoptosis-related genes caspase-3 and bcl-2. The semi-quantification of protein expression was analyzed by pathological image analysis.</p><p><b>RESULTS</b>ATRA inhibited the proliferation of EC9706 cells moderately. Apoptosis in EC9706 cells was induced by ATRA treatment. The morphology of EC9706 cells showed changes such as nuclear chromatin condensation and fragmentation. Sub-G1 peak was found by flow cytometry. The maximal apoptosis rate was 32.6%. The expression of caspase-3 gene was enhanced. The expression of bcl-2 gene was decreased. All these effects were presented in a dose-dependent and time-depend manner.</p><p><b>CONCLUSION</b>Apoptosis is one of the key mechanisms of ATRA action on EC9706 cells.</p>


Subject(s)
Humans , Antineoplastic Agents , Pharmacology , Apoptosis , Caspase 3 , Metabolism , Cell Cycle , Cell Line, Tumor , Cell Proliferation , Dose-Response Relationship, Drug , Esophageal Neoplasms , Metabolism , Pathology , Proto-Oncogene Proteins c-bcl-2 , Metabolism , Tretinoin , Pharmacology
19.
Chinese Journal of Oncology ; (12): 894-897, 2006.
Article in Chinese | WPRIM | ID: wpr-316272

ABSTRACT

<p><b>OBJECTIVE</b>To investigate the correlation between the lack of estrogen receptor (ER) gene expression and hypermethylation of ER gene, and detect whether re-expressed ER protein is activated.</p><p><b>METHODS</b>The methylation status of ER gene promoter in the ER-negative breast cancer cells was evaluated by methylation specific PCR (MSP) and genomic sequencing. The expression of ER and progesterone receptor (PR) mRNA as well as the production of ER protein were detected by RT-PCR and Western blot method, respectively. MTI assay was used to examine the function of re-expressed ER protein.</p><p><b>RESULTS</b>The ER gene promoter was highly methylated, while ER mRNA and ER protein were not expressed in the ER-negative breast cell line MDA-MB-231. The ER-negative breast cells treated with demethylating agent 5 -aza-2'-deoxycytidine (5-AZA-2'-deoxyC) restored the expression of ER mRNA and ER protein. Expression of the endogenous ER-responsive PR gene was activated and the methylation of ER gene was simultaneously decreased. After MDA-MB-231 was treated with 5-AZA-2'-deoxyC, the protein of ER was re-expressed and the growth of cells treated with tamoxifen were inhibited significantly (P < 0.05).</p><p><b>CONCLUSION</b>inactivation of ER gene has a close relationship with the abnormal methylation of ER gene promoter. 5-AZA-2'-deoxyC may effectively cause demethylation and restore functional expression of ER silenced by aberrant hypermethylation. The result may offer a new measure and theory for breast cancer patients with ER-negative expression to receive endocrine therapies.</p>


Subject(s)
Female , Humans , Antimetabolites, Antineoplastic , Pharmacology , Antineoplastic Agents, Hormonal , Pharmacology , Azacitidine , Pharmacology , Base Sequence , Blotting, Western , Breast Neoplasms , Genetics , Metabolism , Pathology , Cell Line, Tumor , Cell Proliferation , DNA Methylation , Estrogen Receptor alpha , Genetics , Gene Expression Regulation, Neoplastic , Genetics , Promoter Regions, Genetic , Genetics , RNA, Messenger , Genetics , Receptors, Progesterone , Genetics , Reverse Transcriptase Polymerase Chain Reaction , Selective Estrogen Receptor Modulators , Pharmacology , Tamoxifen , Pharmacology
20.
Chinese Journal of Oncology ; (12): 504-506, 2003.
Article in Chinese | WPRIM | ID: wpr-271092

ABSTRACT

<p><b>OBJECTIVE</b>To evaluate the response rate and adverse reactions of exemestane (a new aromatase inactivator) in the treatment of postmenopausal women with advanced breast cancer.</p><p><b>METHODS</b>One hundred and seventy-three patients with advanced breast cancer entered this study with two patients excluded because of postmenopausal time being less than one year. Therefore, 173 patients could be evaluated for adverse events and 171 patients could be evaluated for efficacy. Exemestane, 25 mg orally daily for 4 weeks as one cycle was given.</p><p><b>RESULTS</b>In the 171 patients evaluated for efficacy, 4 (2.3%) experienced a complete response (CR) and 40 (23.4%) a partial response (PR), with the overall response rate of 25.7%. Ninety patients (52.6%) had stable disease (SD), with 25 having SD for at least 24 weeks. The clinical benefit (CR + PR + SD > or = 24 weeks) was shown in 69 (40.4%) patients. Progressive disease (PD) was shown in 37 (21.6%) patients. The untreated patients had a higher objective response rate (33.8%) than the retreated ones (18.1%) with significant difference (P = 0.019 7). The response rates for soft-tissue, bone involvement and visceral metastasis were 32.8%, 23.9%, and 12.4% (P = 0.002). There was no significant difference in different ages, time of menopause, disease-free interval or receptor status (P > 0.05). Drug-related adverse events were gastric discomfort (17.9%), malaise (17.9%), nausea (13.9%), hot flushes (11.0%) and dysphoria (5.8%). Other side reactions and abnormal laboratory parameters were observed occasionally which were irrelevant.</p><p><b>CONCLUSION</b>Exemestane can be used to treat postmenopausal women with advanced breast cancer giving only mild adverse reactions which are well tolerated.</p>


Subject(s)
Adult , Aged , Female , Humans , Middle Aged , Androstadienes , Therapeutic Uses , Antineoplastic Agents , Therapeutic Uses , Aromatase Inhibitors , Breast Neoplasms , Drug Therapy , Enzyme Inhibitors , Therapeutic Uses , Postmenopause
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