Intersectin 1: a molecular linker in the central nervous system / 神经科学通报·英文版

Down syndrome (DS) is the most common cause of cognitive impairment associated with a congenital chromosomal abnormality, trisomy of chromosome 21. Mental retardation and congenital heart defects are key features of DS. All DS individuals develop early-onset Alzheimer's disease-like neuropathology. Intersectin 1 gene is localized on human chromosome 21, the critical region of DS, and it has higher expression in the brain of DS patients than in normal individuals. So fully understanding functions of intersectin 1 is critical for revealing the pathogenesis of DS. Intersectin 1 protein has two isoforms: intersectin 1-L and intersectin 1-S. This review will focus on the distribution, expression characters and functions of intersectin 1 in the central nervous system.

Targeted down-regulation of p53 gene expression by individual antisense RNA in vitro / 中华病理学杂志

<p><b>OBJECTIVE</b>To investigate the effect of specific blockage of mutant p53 gene by individualized antisense RNA in vitro.</p><p><b>METHODS</b>Mutation status of p53 in human breast cancer cell lines was determined by immunocytochemical staining, PCR-SSCP and sequencing. Single strand antisense transcription system targeting specific p53 mutation site (mt-p53) was constructed, and corresponding antisense RNA was prepared. The hybridization of antisense RNA with its corresponding mt-p53 gene was confirmed by in-situ hybridization. Human breast cancer cells were transfected with antisense RNA by cationic liposome-mediated method. Time course of effects of antisense RNA was investigated by immunocytochemical staining and cell growth inhibiting assay. Expression of mt-p53 protein was examined by Western blot. Cell proliferation was evaluated by MTT assay and cell cycle distribution was determined by flow cytometry (FCM). Apoptosis was determined by TUNEL assay.</p><p><b>RESULTS</b>Mutation of p53 exon 8 was found in MDA-MB-231 cells and antisense transcription system (pGEM3zf (+/-) p53exon8) was then constructed successfully. In transfected MDA-MB-231 cells, hybridization signals were observed in cytoplasm. Fourth-eight hours after transfection, the antisense RNA (ASp53exon8'RNA) had a significant retarding effect on p53 related proliferation inhibition, along with a decrease of p53 protein expression.</p><p><b>CONCLUSIONS</b>ASp53exon8'RNA specifically blocks mt-p53 gene expression, resulting in an inhibition of MDA-MB-231 cell proliferation. Such an approach may be used as a therapeutic option against human malignancy.</p>

Study on gene control region of mitochondrial DNA in familial breast cancer / 中华医学遗传学杂志

<p><b>OBJECTIVE</b>To study on mutations in D-loop region which is gene control region of mitochondrial genome in patients with familial breast cancer.</p><p><b>METHODS</b>Twenty-three breast cancer patients came from twenty-one families of breast cancer, and eighteen healthy controls participated in the study. PCR amplification of D-loop region in mitochondrial DNA was performed and then the product was sequenced to analyze mutations.</p><p><b>RESULTS</b>One hundred and twenty-six mutations in D-loop region were found in twenty-three patients with familial breast cancer, and four mutations were new. In all of twenty-three patients, thirty-seven mutations were found in D310 which was hot spot of D-loop region in mitochondrial DNA. In these mutations, T>C in 310, TC insert in 311-312, CA deletion in 522-523 and C>G in 527 were multi-presentation mutations in patients with familial breast cancer. Mutations had no difference in the same family member of breast cancer family except that occurrence in the region of D310. In the same family, mutations in D310 of patients were different from controls.</p><p><b>CONCLUSION</b>Mutations in D310 of familial breast cancer patients may enhance their susceptibility to breast cancer.</p>

Circulating endothelial cells in the peripheral blood of advanced NSCLC patients / 中华肿瘤杂志

<p><b>OBJECTIVE</b>To investigate the changes and clinical value of circulating endothelial cells (CEC) in the peripheral blood of advanced NSCLC patient.</p><p><b>METHODS</b>Sixty-seven advanced NSCLC patients were randomly divided into either the treatment group with NP plus endostatin or control group with NP alone. Level of CEC and cytokeratin (CK) in the peripheral blood were measured by flow cytometry.</p><p><b>RESULTS</b>The response rate and benefit rate was 44.4%, 80.0% in the treatment group, and 27.3%, 50.0% in the control group, respectively (P = 0.176 and P = 0.012). Time to tumor progression (TTP) was 146.7 days in the treatment group and 91.1 days in the control group (P = 0.061). However, when the cut-off of TTP was defined as > 170 days, there was a significant difference between two groups (cut-off = 170, P = 0.034; cut-off = 180, P = 0.009). The number of CEC decreased by 0.29 +/- 0.47 in the treatment group and by 0.01 +/- 0.43 in the control group (P = 0.033). The correlation between CEC and CK was found to be positive either before (r = 0.381, P = 0.013) or after the treatment (r = 0.450, P = 0.004).</p><p><b>CONCLUSION</b>Chemotherapy combined with endostatin is superior to chemotherapy alone in the treatment of NSCLC. CEC, as a biomarker, may be useful in predicting the efficacy of the combined treatment.</p>

A quantitative immuno-fluorescence analysis of alpha-tubulin and gamma-tubulin proteins in precancerous lesion and carcinoma of the breast and their clinical significance / 中华肿瘤杂志

<p><b>OBJECTIVE</b>In order to explore the correlation between the centrosome aberration and oncogenesis of the breast carcinoma, the expression of alpha-tubulin and gamma-tubulin proteins in breast precancerous lesions, ductal carcinoma in situ (DCIS) and invasive ductal carcinomas (IDC) was investigated.</p><p><b>METHODS</b>Quantitative immunofluorescence analysis was performed for measuring centrosome proteins by FITC-labeled monoclonal anti-alpha and anti-gamma-tubulin antibodies in 90 cases with precancerous lesions, DCIS and IDC of the breast, respectively. Normal breast tissue from 30 cases were taken as control group.</p><p><b>RESULTS</b>The average of positive (FITC-labeled) cells were 3.2, 11.6, 14.8, 23.1 (alpha-tubulin) and 3.3, 10.7, 14.5, 24.5 (gamma-tubulin) in four groups, respectively. There were significant differences of alpha-tubulin or gamma-tubulin expression among those groups (P = 0.000), respectively. The highest expression quantity was in IDC group and the lowest was in normal breast tissue. Their expression was significantly associated with cellular proliferation and differentiation.</p><p><b>CONCLUSION</b>There is over-expression of the centrosome tubulin protein in the precancerous stage of the breast. The centrosome aberration may play an important role during the crucial early step of oncogenesis and it may promote the cellular cancerization or transformation into malignancy. Quantitative immuno-fluorescence analysis and immunohistochemistry can be complementary each other.</p>

Inhibitory effects of antisense TGF beta1 on in vitro and in vivo proliferation of human bladder cancer cells / 中华肿瘤杂志

<p><b>OBJECTIVE</b>To investigate the inhibitory effects of antisense TGF beta1 on proliferation of human bladder transitional cell carcinoma in vitro and in vivo.</p><p><b>METHODS</b>Human bladder carcinoma cell line EJ was transfected with pRevT beta-AS, a replication defective retroviral vector carried antisense TGF beta1 fragment. The growth of the transfected cells was observed in vitro and in vivo. TGF beta1 mRNA expression and protein expression were detected by RT-PCR and ELISA. The proliferative activity was evaluated by immunohistochemistry method. The ultrastructure of cells was observed by image analysis system and electron microscopy. Cell cycle was determined by flow cytometry.</p><p><b>RESULTS</b>The expression of TGF beta1 mRNA and protein in EJ cells was inhibited by pRevT beta-AS, G(1) to S transition was restrained in cell cycle and cell proliferation decreased in vitro. The tumorigenesis and growth of EJ cells and DNA heteroploidy were reduced by antisense TGF beta1 in vivo.</p><p><b>CONCLUSION</b>TGF beta1 plays a role in vitro proliferation and in vivo growth of bladder transitional cell carcinoma.</p>

Correlation of E2F-1 and Rb expression with papillomatosis and ductal carcinoma in situ of the breast / 中华肿瘤杂志

<p><b>OBJECTIVE</b>E2F-1 and Rb are involved in cell cycle regulation. This study was to illustrate the mechanism of transformation from benign papillomatosis to ductal carcinoma in situ (DCIS) of the breast in relation to E2F-1 and Rb expression.</p><p><b>METHODS</b>In situ hybridization (ISH) was used to determinate the expression of E2F-1 and Rb mRNA of mild papillomatosis (MP, n = 40), severe papillomatosis (SP, n = 40) and DCIS (n = 40). Immunohistochemistry (IHC) was used to examine the expression of E2F-1 and Rb protein.</p><p><b>RESULTS</b>The positive rate of E2F-1 mRNA expression in MP, SP and DCIS was 17.5%, 45.0% and 80.0%, and that of E2F-1 protein expression was 20.0%, 47.5% and 77.5%, respectively. There were significant differences among the three groups (P < 0.01), and between any two groups (P < 0.01). The positive rate of Rb mRNA expression in MP, SP and DCIS was 90.0%, 50.5% and 20.0%, and that of Rb protein expression was 85.0%, 52.5% and 22.5%, respectively, with statistically significant difference similar with that of E2F-1. With the progression of papillomatosis to DCIS, the expression of E2F-1 mRNA and protein increased, while that of Rb decreased. The protein expression by IHC was positively correlated with the mRNA expression by ISH. However, that of E2F-1 was negatively correlated with Rb.</p><p><b>CONCLUSION</b>E2F-1 and Rb might provide a valuable basis for screening high risk papillomatosis and new target of gene therapy for pre-cancerous lesions of the breast.</p>