Study of TLRs recognition in the immune response post tumor chemotherapy / 中国免疫学杂志

Toll like receptor ( TLRs) is a highly conserved transmembrane protein expressed in epithelial cells and immune cells,which is a kind of important receptor to identify the damage associated molecular patterns (DAMPs). TLRs and DAMP produced by tumor cells after chemotherapy combine to produce the corresponding biological effects via MyD88 dependent and independent path-ways. At present,the research application of TLRs identifying DAMP clinically is mainly focused on promoting the release of the DAMP and enhancing the expression of TLRs to strengthen the immune effect of chemotherapy drugs.

Oxidized low-density lipoprotein modulates differentiation of murine memory CD8T cell subpopulations / 南方医科大学学报

<p><b>OBJECTIVE</b>To investigate effect of oxidized low-density lipoprotein (ox-LDL) on memory CD8T cell subpopulation differentiation in mice with autoimmune diabetes.</p><p><b>METHODS</b>Cultured splenic CD8T cells from pre-diabetic NOD mice isolated with magnetic beads were treated with 30 µg/mL ox-LDL and 10 U/mL interleukin-2 (IL-2) for 24 h and the control cells were treated with IL-2 only. Flow cytometry was used to determine the percentage of splenic CD8IFN-γT cells, expressions of CD8, CD44 and CD62L on the T cells, and the activation of T cell factor-1 (TCF-1) and STAT-3. The CD127memory T cells were purified and transplanted into the pre-diabetic NOD mice via the tail vein, and the blood glucose was recorded weekly and survival time of the mice was monitored.</p><p><b>RESULTS</b>Treatment with ox-LDL significantly reduced islet β cell-specific cytotoxic CD8T cells as compared with the control group [(0.7∓0.03)% vs (2.7∓0.14)%, P<0.01]. The percentage of effector memory CD8T cells (Tem) in the total memory CD8T cells was reduced [(10.3∓0.71)% vs (30.3∓1.36)%, P<0.01] and that of stem cell-like memory T cells was significantly increased [(72.3∓3.8)% vs (55.1∓2.61)%, P<0.05] following ox-LDL treatment, which also resulted in significantly decreased activation of TCF-1 [(14.5∓0.82)% vs (34.2∓1.23)%, P<0.01] and pSTAT-3 [(3.3∓0.12)% vs (22.1∓1.1)%, P<0.01]. Transplantation of ox-LDL-treated memory T cells in pre-diabetic NOD mice obviously inhibited the increase of blood glucose and prolonged the survival time of the mice (P<0.05).</p><p><b>CONCLUSION</b>Ox-LDL decreases the activation of transcriptional factors TCF-1 and phosphorylation of STAT-3, inhibits the formation of effector memory CD8T cells with long-term cytotoxicity, but promote the generation of stem cell-like memory CD8T cells, which result in suppression of islet β cell-specific effector cytotoxic CD8T cell differentiation to lessen autoimmune injury to the islet β cells.</p>

Expression of metastasis associated 1 family member 2 (MTA2) in gastric cancer and its relationship with transcription factor Sp1 / 中华肿瘤杂志

<p><b>OBJECTIVE</b>To determine the expression patterns of metastasis associated 1 family member 2 (MTA2) in gastric cancer and non-cancerous gastric mucosa, and analyze its relationship with nuclear transcription factor Sp1 expression.</p><p><b>METHODS</b>Tissue samples and clinicopathological information from 83 gastric cancer patients, who underwent surgery, were collected from Shanghai Rui Jin Hospital. All samples included cancer tissue and non-cancerous mucosa which was 5 cm away from the tumor lesion. The expression of MTA2 and Sp1 were detected by immunohistochemistry (IHC) staining. The mRNA of MTA2 was also detected by reverse transcription-polymerase chain reaction (RT-PCR). SPSS software was used for statistical analysis.</p><p><b>RESULTS</b>The expression of MTA2 protein was significantly higher in primary lesions of the gastric cancer than that in non-cancerous mucosa by IHC (31.3% vs 12.0%, P < 0.01). MTA2 expression was closely related with tumor invasion or T staging (χ(2) = 5.677, P < 0.05). Yet, no significant relationship was observed between MTA2 expression and other clinicopathological parameters, including the age, sex, tumor differentiation, Lauren classification, lymph node metastasis, distant metastasis, as well as pathological staging. Furthermore, MTA2 expression was concomitant with Sp1 expression (r = 0.320, P < 0.05). Elevated MTA2 expression was observed in Sp1 positive cancer tissues (χ(2) = 9.565, P < 0.01). RT-PCR results also demonstrated that MTA2 mRNA was also highly expressed in the tissue samples with Sp1 expression.</p><p><b>CONCLUSIONS</b>MTA2 is highly expressed in the primary lesions of gastric cancer than that in adjacent non-cancerous tissues, and is closely related with tumor invasion. MTA2 expression is elevated in Sp1 positive gastric cancer.</p>

Impacts of Bevacizumab on vascular endothelial growth factor and Sp1 expression in gastric cancer xenografts / 中华胃肠外科杂志

<p><b>OBJECTIVE</b>To evaluate the effects of Bevacizumab on the tumor growth, proliferation and apoptosis of gastric cancer xenograft, and the impacts on the VEGF and Sp1 expression.</p><p><b>METHODS</b>Gastric cancer xenografts in nude mice were established using SGC-7901 gastric cancer cell line. The nude mice were randomly divided into two groups, Bevacizumab treatment group and PBS group. The tumor sizes were measured for tumor growth curve. The proliferation and angiogenesis were evaluated by immunohistochemistry (IHC) staining of Ki67 and CD34. TUNEL assay was used for apoptosis evaluation. The expression of VEGF and Sp1 in tumor cells were detected by IHC and Western blot.</p><p><b>RESULTS</b>Compared to the PBS group, the tumor growth decreased significantly (P<0.05), the proliferation of tumor cells and angiogenesis decreased, and apoptosis index increased significantly [(5.3 ± 1.8)% vs. (16.7 ± 6.7)%, P<0.01] in Bevacizumab group. The results of IHC and Western blot demonstrated that the expression of VEGF and the microvessel density (MVD) was decreased (4.0 ± 1.0 vs. 16.3 ± 1.5, P<0.001) in Bevacizumab treatment group. No obvious changes of Sp1 expression were observed in Bevacizumab treatment group.</p><p><b>CONCLUSIONS</b>Bevacizumab can inhibit the growth of gastric cancer xenografts in nude mice, decrease the VEGF expression and MVD. However, the compensatory up-regulation of transcription factor Sp1 is not affected by Bevacizumab.</p>