miR-221 promotes proliferation of lung cancer A549 cells by down-regu-lating PTEN / 中国病理生理杂志

AIM:To explore the effect of microRNA-221 (miR-221) on the proliferation of lung cancer A549 cells, and to investigate its mechanism .METHODS: The A549 cells were transfected with miR-221 mimics by Lipo-fectamine 2000.The expression of miR-221 was detected by RT-qPCR.The expression of PTEN at mRNA and protein le-vels was detected by RT-qPCR and Western blot , respectively .The cell proliferation was examined by CCK-8 assay and colony formation assay.The 3'-UTR of PTEN was cloned into luciferase reporter vector and its enzymatic activity was detec-ted to verify whether miR-221 targeted to PTEN.RESULTS:The expression level of miR-221 in the A549 cells was sig-nificantly increased after transfection with miR-221 mimics as compared with negative control group and blank group ( P<0.01).The mRNA and protein levels of PTEN were significantly down-regulated compared with control group and blank group ( P <0.05 ) .In addition , miR-221 over-expression significantly promoted the proliferation of A 549 cells ( P <0.05).Moreover, miR-221 inhibited the enzymatic activity of luciferase reporter vector of PTEN.CONCLUSION:Over-expression of miR-221 significantly promotes the proliferation ability of human lung cancer A 549 cells by down-regulation of PTEN.

Somatostatin enhances growth inhibition by cisplatin in gallbladder cancer cells through inducing PTEN expression / 中华肝胆外科杂志

Objective To investigate the combined effects of somatostatin (SST) and cisplatin (DDP) on proliferation and apoptosis in gallbladder cancer cells,and to investigate the mechanism of the combined effects.Methods We performed immunohistochemistry to detect the PTEN expression in gallbladder cancer.We then investigated the combined effects of SST and DDP on cell proliferation in vitro with CCK-8 assay and analyzed the interaction between these two drugs using isobologram analysis.We also investigated the combined effects on cell proliferation in vivo using a xenograft nude mouse model.FITC-Annexin V/PI assay and TUNEL staining assay were performed to detect the proportion of apoptosis after combined treatment in vitro and in vivo.Reactive oxygen species and mitochondrial membrane potential were detected with DCFH-DA assay and JC-1 staining assay after the combined treatment.We finally detected the PTEN and p-AKT associated proteins using western blotting after the combined treatment.Results PTEN was abnormally decreased in gallbladder cancer tissues.PTEN expression was negatively correlated with cancer differentiation and was positively correlated with patients'survival time.DDP treatment decreased while combined treatment with SST induced PTEN expression and inhibited AKT activation by reversing resistance to DDP.Isolated SST or DDP treatment inhibited gallbladder cancer GBC-SD and SGC996 cell proliferation which was dose-dependence.These two drugs synergistically inhibited gallbladder cancer cell growth in vivo and in vitro.Isolated SST or DDP treatment induced cell apoptosis and combined treatment induced cell apoptosis the most.SST inhibited AKT activation but did not induce ROS.DDP induced ROS resulting in increased cell apoptosis.Either SST or DDP alone increased the levels of cytoplasmic cytochrome C protein and activated caspase-3.Conclusions SST enhanced growth inhibition by cisplatin in gallbladder cancer cells through inducing PTEN expression.This study provides the theoretical basis for further combined clinical chemotherapeutic applications.

Expression of MMP-1 and PTEN protein in the lesions of basal cell papilloma and its correlation with skin photoaging / 中国肿瘤临床

Objective:To investigate the expression of MMP-1 and PTEN protein in basal cell papilloma (BCP), as well as their correlation with skin photoaging. Methods:Immunohistochemistry technique via Elivison method was employed to measure the expres-sion of MMP-1 and PTEN protein in lesions from 50 cases of BCP on exposed areas, 50 cases on non-exposed areas, and 30 normal controls. We compared the differences among the three groups and analyzed the result. A total of 90 BCP cases on exposed areas were randomly divided into three groups. Titanium dioxide cream and placebo were respectively applied in the trial groups twice daily for 12 weeks, whereas the control group was non-administered. After 12 weeks, the MMP-1 in the lesions of the three groups was measured and compared. Results:The expression scores of MMP-1 on exposed areas were significantly higher than those in the control group (P0.05). The expression scores of PTEN protein on exposed areas and on non-exposed areas were significantly lower than that in control group (P<0.01). The expression scores of MMP-1 in the group that used titanium dioxide were evidently lower than those in control group after 12 weeks (P<0.05). Conclu-sion:MMP-1 is overexpressed in BCP on exposed areas. PTEN protein is underexpressed in BCP of exposed areas and non-exposed ar-eas. Skin photoaging is a possible cause of BCP on exposed areas.

p16INK4a, PTEN, E-cadherin, Bcl-2 and Ki-67 Expression in Prostate Cancer: Its Relationship with the Metastatic Potential and Known Prognostic Factors

BACKGROUND: At present, adequate prognostic markers for prostate cancer progression are still lacking, in spite of intensive investigation. Accordingly, our study examined the relationship between expression of candidate biomarkers and metastasis in prostate cancer patients. Correlation of molecular markers with prostate-specific antigen (PSA) level, Gleason sum score and tumor stage were also evaluated. METHODS: A total of 105 prostate tumor specimens and specimens from 19 cases of nodular hyperplasia were obtained through Yeungnam University Hospital from 2007 to 2008. Immunohistochemical analyses for p16INK4a, phosphatase and tensin homolog (PTEN), E-cadherin, Ki-67 and Bcl-2 were performed. RESULTS: Overexpression of Bcl-2 was significantly related to bone (p = 0.006) and nodal metastases (p = 0.017). Other biomarkers were not related to metastatic potential. There were statistically significant relationships between increased PSA level and loss of expression of PTEN (p = 0.019) and E-cadherin (p = 0.001). High Ki-67 index was significantly correlated with nodal metastasis (p = 0.029) as well as with loss of p16INK4a expression (p = 0.002) and high Gleason score (p = 0.011). CONCLUSIONS: High Gleason score, Bcl-2 overexpression and increased Ki-67 labeling have significant predictive value in assessing the potential for prostate cancer metastasis. In addition, a high Ki-67 index is related to high Gleason score and loss of p16INK4a expression.

Knock-down of miR-221 and miR-222 in the radiosensitization of breast cancer cells / 中华放射肿瘤学杂志

cells, the expression of PTEN was up-regulated while pAkt down-regulated. Conclusions AS-miR-221 and AS-miR-222 may enhance the radiosensitivity of MCF-7 breast cancer cells by up-regulating the expression of PTEN.

Clinical Significance of PTEN and Ki-67 Expression in Prostate Cancer

PURPOSE: Phosphatase and tensin homolog (PTEN) is a novel tumor suppressor gene located at chromosome 10q23. Ki-67 antigen is a human nuclear protein that is expressed in all active parts of the cell cycle. We evaluated the significance of PTEN and Ki-67 expression in prostate cancer and investigated the relation of this expression with clinico-pathological factors in prostate cancer. MATERIALS AND METHODS: Initially, we did two kinds of immunohistochemical staining for PTEN and Ki-67. Immunohistochemical staining was performed on 75 formalin-fixed paraffin-embedded cancer specimens. Staining on paraffin blocks from prostate carcinomas was compared with that for adjacent normal prostate. Stainings were considered positive if nuclear staining was seen. Positive stainings were analyzed with the patient's clinico-pathological findings. Statistical analysis was performed by using chi-square test with p0.05). PTEN expression was negatively correlated with lymph node or distant metastases (p<0.05). Ki-67 was positively correlated with the serum PSA level, the Gleason score, and metastases (p<0.05). CONCLUSIONS: PTEN and Ki-67 staining correlated well with Gleason score and PSA level in prostate cancer. These could be a possible predictor of prostatic neoplasms.

Expression of COX-2 and the relationship between COX-2 and PTEN in endometrial adenocarcinoma / 肿瘤研究与临床

Objective To study the expression and clinical significance of COX-2 and the relation- ship between COX-2 and PTEN in endometrial adenocarcinoma(EAC).Methods The expression of COX-2, PTEN protein was detected by SP-immunohistochemical method in EAC,endometrial intraepithelial neoplasia, corresponding normal endometrium.Results The positive rates of COX-2 protein increased from normal en- dometrium(13.33%) to endometrial intraepithelial neoplasia(50.00%) and adenocarcinoma(64.58 %)(P

Mutational and Loss of Heterozygosity Analysis of the p53 and PTEN Tumor Suppressor Genes in Breast Carcinoma

BACKGROUND: Although the genetic determinants of most sporadic breast cancers remain unknown, the understanding of the molecular and genetic events that contribute to breast carcinogenesis has been significantly advanced. We investigated the clinicopathologic significance of allelic imbalance or mutation of both p53 and PTEN tumor suppressor genes in sporadic breast carcinomas. METHODS: Genomic DNA from 62 breast carcinoma cases was extracted from paraffin blocks, and PCR was performed to determine loss of heterozygosity (LOH) for DNA markers around the p53 and PTEN genes and to amplify exons 5, 6, 7, and 8 of p53 and all 9 coding axons of PTEN. RESULTS: Somatic p53 mutations were detected in 6 (9.7%) of the 62 cases. LOH for DNA markers surrounding p53 was observed in 18 (29.0%) of the 62 cases. LOH for DNA markers surrounding PTEN was detected in 29 (46.8%) of the 62 cases. Only one case (1.6%) showed somatic PTEN mutations. Tumors with LOH on 17p or p53 mutation were large in size and negative for ER, had a high Ki-67 index, and exhibited p53 immunoreactivity (p<0.05). Tumors with LOH on 10q23 were associated with c-erbB-2 positivity (p=0.018). CONCLUSIONS: Our results indicate that LOH at 17p and/or p53 mutation is significantly associated with the aggressive pathologic parameters of breast cancer.

Expression of PTEN,CDK4 protein in endometrial carcinoma and its clinical significance / 重庆医科大学学报

Objective:To study the relationship between cyclin dependent kinase 4 (CDK4),PTEN protein expression and carcinogenisis,progression and recurrence of endometrial carcinoma.Methods:A specific and sensitive immunohistochemical S-P assay was used to detect the expression of PTEN and CDK4 in paraffin-embedded sections of 50 cases of endometrial carcinoma,12 atypical hyperplasia of endometrium and 10 normal endometrium.Results:1.The positive immunostainning rates of PTEN in endometrial carcinoma,atypical hyperplasia of endometrium and normal endometrium were 56.00%,91.00%,100.00%,respectively;and the difference was statistically significant between carcinoma and normal endometrium or atypical hyperplasia of endometrium(P1/2 muscle invasion cancer and in recurrence cases.Conclusion:The results suggest that the aberrant expressions of PTEN and CDK4 are closely related to the occurrence,development and recurrence of endometrial carcinoma.

PTEN expression in breast cancer and its correlation with the tumor angiogenesis / 医学研究生学报

Objective:To investigate the expression of PTEN(phosphatase and tensin hmmlogy deleted on ten) in the breast cancer and the relationship with the tumor angiogenesis.Methods:The expression of PTEN and MVD were detected by immunohistochemical SP method in paraffin section from 53 women with primary breast cancer and 10 subjects of hyperplasia of mammary glands.Results:The higher lever PTEN expression in 53 case with the rate 49.1 %(26/53),which was reduced compared with the expression in benign hyperplasia of mammary glands(P

Expression and clinical significance of PTEN in non-small cell lung cancer / 中国癌症杂志

Purpose:To study the expression and clinical significance of PTEN in non-small cell lung cancer. Methods:Immunohistochemical staining was used to determine the expression of PTEN in 10 cases of normal lung issues and 56 cases of non-small cell lung cancer. Results:The positive incidences of PTEN expression in NSCLC was 59% while positive expression was found in all normal lung issues. The expression of PTEN was correlated to degree of differention of cancer, lymph node metastasis and clinical stages. The PTEN negative group was seen to have the worst survival rate among all groups. Conclusions:The results suggest that PTEN gene plays an important role in carcinogenesis and progress of NSCLC. Expression of PTEN may be valuable in prognosis assessment of NSCLC.

Expression and correlation between Survivin and PTEN proteins in astrocytoma / 临床神经病学杂志

Objective To investigate the expressions and correlation between Survivin and PTEN proteins in astrocytoma.Methods The expressions of Survivin and PTEN proteins were examined by immunohistrochemistry in astrocytoma specimens from 65 patients with astrocytoma.Results The positive expression rate of Survivin in astrocytoma grade Ⅱ was significantly lower than that in grade Ⅲ and grade Ⅳ(all P