Effects of angiotensin converting enzyme inhibitor, angiotensin II type I receptor blocker and their combination on postinfarcted ventricular remodeling in rats / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Transforming growth factor (TGF) beta(1)-Smads signal plays an important role in cardiac remodeling following myocardial infarction (MI). In addition, both angiotensin converting enzyme inhibitor (ACEI) and angiotensin II type I receptor blocker (ARB) can effectively prevent left ventricular remodeling. The current study focused on whether the combination of ACEI and ARB is more beneficial for preventing ventricular remodeling and whether Smad proteins mediate this beneficial effect.</p><p><b>METHODS</b>MI was induced by ligating the left anterior descending coronary artery in rats. Twenty-four hours after ligation, the survived rats were randomly divided into five groups and treated for 8 weeks: placebo group, ACEI group (benazepril 10 mg.kg(-1).d(-1)), ARB group (irbesartan 50 mg.kg(-1).d(-1)), ACEI + ARB group (benazepril 10 mg.kg(-1).d(-1) + irbesartan 50 mg.kg(-1).d(-1)) and control group (sham-operated rats). After 8 weeks, we examined the following indexes: the ratio of ventricular weight to body weight (VW/BW), left ventricular end diastolic dimension (LVDd), ejection fraction (EF), fractional shortening (FS), ratio of E-wave to A-wave velocity, collagen of noninfarcted zone, the mRNA expression of TGFbeta(1), Smad 2, and Smad 3 by RT-PCR in noninfarcted zone, the protein expression of Smad 2 and Smad 3 in noninfarcted zone by Western blot.</p><p><b>RESULTS</b>VW/BW significantly increased in the placebo groups compared with that in the control group (P < 0.01). This increase was limited in ACEI, ARB, and combined groups (P < 0.01 compared with placebo group). There was no significant difference among the three actively treated groups. Collagen was increased in placebo group (5.68 +/- 0.5)% compared with that in control group (P < 0.01). ACEI, ARB and combined treatment attenuated this increase of collagen [(4.3 +/- 0.5)%, (3.5 +/- 0.5)%, (3.2 +/- 0.4)%] in comparison with that in placebo group (P < 0.01 respectively). Combined treatment showed more significant effect on collagen deposition. EF and FS significantly decreased, LVDd and E/A significantly increased in placebo group compared with that in control group (P < 0.01 respectively). ACEI, ARB and combined treatment ameliorated these indexes (P < 0.01 compared with placebo group). The mRNA expression of TGFbeta(1), Smad 2, and Smad 3 (0.700 +/- 0.045, 0.959 +/- 0.037 and 0.850 +/- 0.051) increased in placebo group compared with that in control group (P < 0.01). ACEI, ARB and combined treatment normalized the increase (P < 0.01). Furthermore, ARB and combined treatment proved to be more effective in decreasing TGF beta(1) and Smad mRNA expression than ACEI treatment (P < 0.01). The expression of Smad 2 and Smad 3 protein increased in placebo group compared with that in control group (P < 0.01). ACEI, ARB and combined treatment normalized the increase (P < 0.01). Furthermore, ARB and combined treatment proved to be more effective than ACEI alone (P < 0.01).</p><p><b>CONCLUSIONS</b>TGFbeta(1)-Smads signal activation is correlated with ventricular remodeling following MI. ACEI and ARB treatment prevents ventricular remodeling by inhibiting expression of Smad 2 and Smad 3. ARB and combined treatment are more effective than ACEI alone.</p>

Expression of retinoic acid receptor-beta mRNA and p16, p53, Ki67 proteins in esophageal carcinoma and its precursor lesions / 中华肿瘤杂志

<p><b>OBJECTIVE</b>To study the expression of retinoic acid receptor-beta (RAR-beta) mRNA and p16, p53, Ki67 proteins in squamous-cell carcinoma of the esophagus and its precursor lesions in a high risk population.</p><p><b>METHODS</b>A total of 397 tissue specimens were collected from individuals with normal mucosa (NM, n = 25), mild dysplasia (MiD, n = 69), moderate dysplasia (MoD, n = 106), severe dysplasia (SD, n = 51), carcinoma in situ (CIS, n = 78), and squamous-cell carcinoma (SC, n = 68). Expression of RAR-beta mRNA was detected by in situ hybridization, and that of p16, p53 and Ki67 proteins by immunohistochemistry.</p><p><b>RESULTS</b>The frequencies of RAR-beta mRNA expression in NM, MiD, MoD, SD, CIS and SC were 96.0%, 89.9%, 67.9%, 68.6%, 62.8%, and 63.2%, respectively. The frequencies of p16 expression were 88.0%, 71.0%, 64.2%, 51.0%, 53.8% and 52.9%; those of p53 expression were 4.0%, 39.1%, 57.5%, 52.9%, 67.9% and 69.1%; those of Ki67 expression were 0, 40.6%, 61.3%, 58.8%, 59.0% and 75.0%, respectively.</p><p><b>CONCLUSION</b>There are no significant differences in four biomarkers expression between carcinoma of the esophagus and its precursor lesions.</p>

Diversity of invasiveness and matrix metalloproteinases expression profile of human gastric carcinoma xenografted in different tissue environments / 中华病理学杂志

<p><b>OBJECTIVE</b>To study the effect of tissue environment on the invasiveness of carcinoma cells and the implication of expression of matrix metalloproteinases.</p><p><b>METHODS</b>Tissue from a human gastric carcinoma was transplanted and passaged subcutaneously in nude mice. After the 3rd passage, the xenografts were also transplanted into the abdominal cavity of nude mice. The invasiveness of xenografts at the two locations were observed morphologically and the expressions of MMP-2, MMP-7, MMP-9, MMP-13, TM1-MMP, TM2-MMP and TM3-MMP were monitored by immunohistochemistry.</p><p><b>RESULTS</b>The subcutaneous xenografts of human gastric carcinoma in nude mice presented as expanding outgrowths with limited invasion. Except for MMP-7, the other 6 MMPs (MMP-2, MMP-9, MMP-13, TM1-MMP, TM2-MMP, TM3-MMP) were not expressed in the neoplastic cells nor in the tumor stroma. In contrast, the intra-peritoneal xenografts displayed an invasive growth pattern accompanied by more fibrous stroma. All MMPs examined were expressed in the tumor cells at the invasive fronts and in the adjacent stroma.</p><p><b>CONCLUSIONS</b>Invasiveness and expression of MMPs were obviously diverse in human gastric carcinoma cells when grafted at different anatomic locations in nude mice, thus indicating: (1) There exists a close interaction between tumor cells and surrounding stromal cells. The tissue environment may play a definitive role in the tumor phenotype. (2) The expression of MMPs is closely related to the growth pattern and the invasiveness of tumor cells. MMPs produced by the stroma cells at the invasion front may be linked to the invasiveness of neoplastic cells.</p>

Correlative study between expression of BRI gene and metastatic potential in human non-small cell lung cancer / 中华病理学杂志

<p><b>OBJECTIVE</b>To investigate the potential relationship between BRI gene expression and metastatic potential in human non-small cell lung cancer (NSCLC).</p><p><b>METHODS</b>Using semi-quantitative reverse-transcription polymerase chain reaction (RT-PCR) and Northern blot hybridization techniques, differential expression of the BRI gene in human lung adenocarcinoma cell lines AGZY-83-a and Anip-973 was investigated. Having a much higher metastatic potential, Anip-973 was isolated from AGZY-83-a parental cell line. In addition, the other 6 non-small cell lung cancer cell lines (SPC-A-1, A549, 95D, TKB-18, GLC-82, PAa) and 30 samples of lung cancer tissues with matched corresponding adjacent normal tissues were also analyzed.</p><p><b>RESULTS</b>There were significant differences in BRI gene expression between the two cell lines. BRI was preferentially expressed in Anip-973 cells compared to its parental cell line AGZY-83-a, and was also up-regulated in the other 6 lung cancer cell lines, correlating possibly with their metastatic potentials. BRI gene over-expression was observed in 30 lung cancer tissues compared with its corresponding adjacent normal tissues. A relative over-expression of BRI mRNA (tumor/normal >or= 2) was observed in 6 of 8 cancer samples with lymph node metastasis and 10 of 22(45.5%) samples without lymph node metastasis. Furthermore, two mRNA transcripts of BRI gene were observed: a 2.0 kb transcript which was mainly observed in normal lung tissues and a 1.6 kb transcript which was present as a dominant species in cancer tissues.</p><p><b>CONCLUSION</b>BRI mRNA expression is significantly up-regulated in NSCLC cell lines and clinical tumor samples. An alternatively spliced 1.6 kb mRNA is a major transcript of the gene in NSCLCs, suggesting that differential RNA processing and expression of BRI gene may play a role in the tumorigenesis and/or be related to the metastatic potential of human lung cancer.</p>