Intestinal mucosal barrier dysfunction after abdominal operation and its clinical significance / 南方医科大学学报

<p><b>OBJECTIVE</b>To investigate the plasma glutamine (Gln) level and relationships between the intestinal mucosal permeability and bacterial translocation and between bacterial translocation and systemic inflammatory response syndrome (SIRS) after abdominal operation.</p><p><b>METHODS</b>The peripheral blood was collected from 42 patients before and 2 and 7 days after elective abdominal operation. The plasma Gln concentration and lactulose/mannitol (L/M) ratio were measured and the whole blood bacterial DNA concentration was determined by polymerase chain reaction (PCR). The relationship between intestinal mucosal barrier dysfunction and the occurrence of postoperative SIRS was analyzed.</p><p><b>RESULTS</b>The plasma Gln level was significantly lowered (P<0.01) and L/M ratio increased (P<0.01) in these patients 2 and 7 days after the operation in comparison with the preoperative level. No bacterial DNA was detected before surgery, but PCR yielded positive results in 4 patients (9.5%, 4/42) at 2 days and in another patient at 7 days (2.4%, 1/42) after the operation. The 4 patients with positive PCR results 2 days after the operation showed significantly lower plasma Gln concentration (P<0.01) and higher L/M ratio (P<0.01) than those with negative results. SIRS occurred in 24 patients after surgery, whose plasma Gln level was significantly lower (P<0.01) and L/M ratio significantly higher (P<0.01) than that in the SIRS-free patients 2 days after the operation. Five of the 26 SIRS patients showed positive PCR results, while none of the 16 non-SIRS patients were positive, but this difference was not statistically significant (P>0.05).</p><p><b>CONCLUSION</b>Decreased plasma Gln and increased intestinal mucosal permeability are closely related to postoperative bacterial translocation and the intestinal mucosal barrier dysfunction, which may contribute to the occurrence of postoperative infection.</p>

Apoptosis resistance induced by leptin and its mechanism in breast cancer cells / 中华肿瘤杂志

<p><b>OBJECTIVE</b>To explore the apoptosis resistance induced by Leptin and its mechanism in breast cancer cells in vitro.</p><p><b>METHODS</b>The leptin-mediated reduction of docetaxel-induced apoptosis in human breast cancer T47D cells was evaluated by TransAM ELISA, MTT and caspase-9 assay. The leptin-promoted survivin expression was analyzed by Western-blot and RT-PCR. The reversing effect of STAT3 knockdown on leptin-induced survivin upregulation was measured by Western-blot and RT-PCR.</p><p><b>RESULTS</b>Leptin promoted T47D cells proliferation and the inhibitory rate was -63.6%. It reduced docetaxel-induced apoptosis in T47D cells by 31.9%. Leptin at different concentrations promoted survivin protein and mRNA expression in T47D cells. The expression of survivin mRNA was 4.6 fold compared with the T47D cells not treated with leptin(10 nmol/L). The expression of survivin mRNA in T47D cells was 0.55 +/- 0.15 fold after transfected with small interfering RNA (siRNA) of STAT3. The expression of survivin mRNA in STAT3 siRNA group and mock transfected group were 0.56 +/- 0.18 fold and 1.61 +/- 0.22 fold after treated by leptin, respectively. The survivin protein level of T47D mock transfected cells was increased after treated by leptin, but the protein level of T47D transfected with STAT3 siRNA cells were not changed significantly.</p><p><b>CONCLUSION</b>Leptin/STAT3 signaling is a novel pathway for up-regulation of survivin expression in breast cancer cells.</p>

Estrogen receptor alpha variant ERalpha46 mediates growth inhibition and apoptosis of human HT-29 colon adenocarcinoma cells in the presence of 17beta-oestradiol / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Estrogen is involved in suppression of colon cancer development and exerts its function via estrogen receptors alpha and beta (ERalpha, ERbeta). The recently identified ERalpha46 resulted from exon 1-deletion from the 66-kDa full length form of ERalpha66 is devoid of the transactivation domain AF-1, whose function remains largely unknown.</p><p><b>METHODS</b>In this study, we compared the expression of ERalpha46 mRNA in 32 normal colorectal tissues and their matched colorectal cancer tissues by real-time quantitative polymerase chain reaction (PCR). Human colon adenocarcinoma cell HT-29, that has low endogenous expression of ERalpha46, was transfected with ERalpha46-expression vector; methyl thiazolyl tetrazolium (MTT) assay, flow cytometry, DNA fragmentation and TUNEL staining were used to evaluate the proliferation and apoptosis status of the cells in the presence of 17beta-oestradiol.</p><p><b>RESULTS</b>Higher ERalpha46 mRNA levels were observed in normal colorectal tissues than in the corresponding cancer tissues. ERalpha46-transfected cells showed a significantly decreased growth rate than control cells and an accumulation of cells in the G(0/1) phase and a reduced proportion of cells in G(2)/M phase after exposed to 10(-8) mol/L 17beta-oestradiol. There were also more positive TUNEL stained cells in ERalpha46-transfected cells than the control cells in the presence of 17beta-oestradiol (P < 0.05).</p><p><b>CONCLUSIONS</b>These data suggest that ERalpha46 may be involved in the development and/or progression of colorectal cancer via mediating growth inhibition and apoptosis of cancer cells in the presence of 17beta-oestradiol.</p>

Protective effect of glutamine on intestinal barrier function in patients receiving chemotherapy / 中华胃肠外科杂志

<p><b>OBJECTIVE</b>To study the protective effect of glutamine (Gln) on intestinal permeability in patients receiving chemotherapy.</p><p><b>METHODS</b>Thirty-nine patients with gastrointestinal cancer after operation were randomly divided into Gln and control groups, and received oral administration of glutamine (30 g/d) for 7 days (n=22) or not (n=17). All patients received CF+ 5-FU chemotherapy for 5 days. Serum concentration of glutamine and urinary lactulose/mannitol (L/M) ratio were measured before and 1 day after chemotherapy.</p><p><b>RESULTS</b>After chemotherapy, the serum Gln concentration was significantly decreased to (535.42+/- 53.75) micromol/L in the control group and increased to (54.44+/- 81.26) micromol/L in the Gln group, and there was significant difference between the two groups (P< 0.01). Urine L/M ratio was significantly increased to (0.0453+/- 0.0078) in the control group and decreased to (0.0331+/- 0.0061) in the Gln group, and there was significant difference between the two groups after chemotherapy (P< 0.01).</p><p><b>CONCLUSION</b>Oral administration of glutamine granules can increase serum concentration of glutamine in chemotherapy patients with gastrointestinal cancer and can decrease intestinal permeability, maintain intestinal barrier.</p>

Screening and identification of phage-displayed polypeptides specifically binding to human gastric cancer with high metastatic potential to peritoneum / 中华肿瘤杂志

<p><b>OBJECTIVE</b>By means of phage-display technique, to screen polypeptides that specifically bind to human gastric cancer with high metastatic potential to peritoneum.</p><p><b>METHODS</b>Two human gastric cancer cell lines were used: GC9811-P with high metastatic potential to peritoneum and its wild type parental GC9811, to carry out subtractive screening with a phage display-12 peptide library.</p><p><b>RESULTS</b>After three rounds of screening, 40 phage clones bond to GC9811-P cells were randomly selected. When injected into the peritoneal cavity of nude mice, 6 of the 40 clones did not bind to mouse peritoneum as examined by immunohistochemical staining. They were considered to be capable of binding specifically to GC9811-P cells. Sequence analysis revealed two different exogenous peptides: TLNINRLILPRT and SMSI(X)SPYI(XXX).</p><p><b>CONCLUSION</b>Two peptides have been obtained that specifically bind to a gastric cancer cell variant GC9811-P, which easily disseminates to the peritoneum. Whether or not they could block GC9811-P metastasis to peritoneum in vivo remains to be determined.</p>

Rac subfamily expression and activity in gastrointestinal cancer cell lines / 中华肿瘤杂志

<p><b>OBJECTIVE</b>To investigate the significance of Rac subfamily members in the gastrointestinal carcinogenesis and progression.</p><p><b>METHODS</b>The mRNA expression of Rac1, Rac2 and Rac3 in 12 kinds of gastrointestinal cancer cell lines was examined by semi-quantitative RT-PCR. The activities of Rac1 protein in 5 kinds of gastric cancer cell lines were tested by pull-down assay.</p><p><b>RESULTS</b>Compared with the normal gastric mucosa and intestinal epithelial cell line, the mRNA expression of Rac1 and Rac3 was up-regulated in most of gastrointestinal cancer cell lines. The activities of Rac1 protein increased markedly in gastric cancer cell lines.</p><p><b>CONCLUSION</b>The increased mRNA expression of Rac1 and Rac3 in gastrointestinal cancer cell lines and the abnormal activation of Rac1 protein in gastric cancer cell lines might be correlated with the carcinogenesis of gastrointestinal cancer.</p>