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Xu Y.-Y.,Binzhou Medical University | Jiang N.,Dalian Sixth Peoples Hospital | Liu T.-S.,Binzhou Medical University | Qu H.-Q.,Binzhou Medical University | Wang T.,Yantai University
Molecular Medicine Reports | Year: 2012

Cisplatin (cis-diamminedichloroplatinum, CDDP) is one of the most potent anticancer drugs. However, the therapeutic value of CDDP is greatly compromised by its dose-limiting nephrotoxicity. This study was performed to investigate whether reduced glutathione (GSH) was able to reduce the kidney injury induced by CDDP and whether it affected the anticancer activity of CDDP in vivo and in vitro. In in vivo experiments, mice were divided into five groups: control, CDDP only and three GSH treatment groups. Blood samples were collected 72 h after CDDP administration to determine the levels of blood urea nitrogen (BUN) and plasma creatinine (Cr). In addition, we examined antioxidative parameters, malondialdehyde (MDA) levels and histopathological changes in the kidney. In order to investigate whether GSH affected the anticancer activity of CDDP, we performed a sulforhodamine B (SRB) assay to determine the antiproliferative effect in three tumor cell lines of treatment with CDDP alone or combined with GSH and examined the cell morphology. The results revealed that GSH decreased the BUN and Cr levels in plasma, ameliorated the pathological changes induced by CDDP and enhanced the endogenous antioxidant capacities in all three GSH groups. Furthermore, GSH significantly inhibited the growth of the three tumor cell lines when combined with CDDP and did not affect the inhibitory effect of CDDP on the carcinoma cell proliferation. In addition, we found no differences among the three GSH groups. These findings suggest that GSH is able to attenuate the nephrotoxicity induced by CDDP, not only when administered prior to CDDP, but also when administered at the same time as or subsequent to CDDP administration, without affecting the anticancer activity of CDDP. Thus, the administration of GSH is a promising approach for attenuating the nephrotoxicity caused by CDDP. Source

Wang T.,Zhengzhou University | Wang T.,Deakin University | Shigdar S.,Deakin University | Shamaileh H.A.,Deakin University | And 11 more authors.
Cancer Letters | Year: 2016

As one of the life-threatening diseases involving multi-step genetic and epigenetic disorders, cancer has long been a dynamic research area for siRNA-based therapy as half of the current siRNA-based clinical trials are involved in oncology. However, despite consistent enthusiasm in the academic world, siRNA-based cancer treatment still faces obstacles and difficulties in clinical development. In this article, we discuss key challenges facing siRNA-based cancer treatment revealed from recent clinical and preclinical studies, including chemical modification, tumour penetration, endosomal escape, target selection and off-target effects. In addition, opportunities and avenues for translating siRNA technology from bench to oncologic clinics are explored. © 2016 Elsevier Ireland Ltd. Source

Mao J.-W.,Dalian Medical University | Huang Y.-S.,Dalian Sixth Peoples Hospital | Tang H.-Y.,Dalian Medical University | Bi J.,Dalian Medical University | And 2 more authors.
Gastroenterology Research and Practice | Year: 2014

The immunoregulation between dendritic cells (DCs) and regulatory T cells (T-regs) plays an important role in the pathogenesis of ulcerative colitis (UC). Recent research showed that Fms-like tyrosine kinase 3 (Flt3) and Flt3 ligand (Flt3L) were involved in the process of DCs regulating T-regs. The DSS-induced colitis model is widely used because of its simplicity and many similarities with human UC. In this study, we observe the disease activity index (DAI) and histological scoring, detect the amounts of DCs and T-regs and expression of Flt3/Flt3L, and investigate Flt3/Flt3L participating in the process of DCs regulating T-regs in DSS-induced colitis. Our findings suggest that the reduction of Flt3 and Flt3L expression may possibly induce colonic immunoregulatory imbalance between CD103+MHCII+DCs and CD4+CD25+FoxP3+T-regs in DSS-induced colitis. Flt3/Flt3L participates in the process of regulating DCS and T-regs in the pathogenesis of UC, at least, in the acute stage of this disease. © 2014 Jing-Wei Mao et al. Source

Tian F.,Liaoning Medical University | Wang L.,Dalian Sixth Peoples Hospital | Zhang Y.-J.,Liaoning Medical University
World Chinese Journal of Digestology | Year: 2011

AIM: To investigate whether celecoxib, a selective cyclooxygenase-2 (COX-2) inhibitor, protects from carbon tetrachloride (CCl4)-induced liver fibrosis in rats. METHODS: Fifty male SD rats were randomly divided into six groups. Group A (n = 10) was subcutaneously injected with 50% 1 mL/kg CCl4 olive oil solution, twice per week, to induce hepatic fibrosis and intragastrically given saline. Groups B (n = 10), C (n = 10) and D (n = 10) were also subjected to induction of hepatic fibrosis and intragastrically given celecoxib 15 mg/kg once daily from day 1, week 3, and week 5 after CCl4 injection. Group E (n = 5) was subcutaneously injected with equal volume of olive oil and intragastrically given the same dose of celecoxib, while group F (n = 5) was subcutaneously injected with equal volume of olive oil and intragastrically given saline. The treatment lasted for 8 weeks. At the end of the experiment, blood samples were collected to measure serum ALT, HA and LN levels, while hepatic tissue samples were taken to evaluate the degree of liver fibrosis by HE staining and to detect the expression of type I collagen, alpha SMA, COX-1, and COX-2 by immunohistochemistry. RESULTS: Compared to group F, significant hepatic fibrosis was observed in group A (P < 0.01). Compared to group A, liver fibrosis was significantly reduced (P < 0.01), serum ALT, HA and LN levels significantly decreased (100.4 U/L ± 8.7 U/L vs 287.8 U/L ± 9.6 U/L, 189.6 μg/L ± 83.0 μg/L vs 382.6 μg/L ± 136.0 μg/L, 71.4 μg/L ± 4.6 μg/L vs 108.7 μg/L ± 9.8 μg/L, all P < 0.01), and the areas positive for type I collagen, alpha SMA, and COX-2 were reduced (all P < 0.01). The above parameters showed significant differences among groups B, C and D (all P < 0.05). No significant differences were observed in the above parameters between groups E and F. COX-1-positive area showed no significant difference among each group. CONCLUSION: COX-2 plays an important role in liver fibrogenesis. Celecoxib can reduce or prevent liver fibrosis in a time-dependent manner probably by inhibiting hepatic stellate cell activation and inflammation. Source

Shigdar S.,Deakin University | Qian C.,Deakin University | Lv L.,Dalian Medical University | Pu C.,Dalian Sixth Peoples Hospital | And 6 more authors.
PLoS ONE | Year: 2013

EpCAM is expressed at low levels in a variety of normal human epithelial tissues, but is overexpressed in 70-90% of carcinomas. From a clinico-pathological point of view, this has both prognostic and therapeutic significance. EpCAM was first suggested as a therapeutic target for the treatment of epithelial cancers in the 1990s. However, following several immunotherapy trials, the results have been mixed. It has been suggested that this is due, at least in part, to an unknown level of EpCAM expression in the tumors being targeted. Thus, selection of patients who would benefit from EpCAM immunotherapy by determining EpCAM status in the tumor biopsies is currently undergoing vigorous evaluation. However, current EpCAM antibodies are not robust enough to be able to detect EpCAM expression in all pathological tissues. Here we report a newly developed EpCAM RNA aptamer, also known as a chemical antibody, which is not only specific but also more sensitive than current antibodies for the detection of EpCAM in formalin-fixed paraffin-embedded primary breast cancers. This new aptamer, together with our previously described aptamer, showed no non-specific staining or cross-reactivity with tissues that do not express EpCAM. They were able to reliably detect target proteins in breast cancer xenograft where an anti-EpCAM antibody (323/A3) showed limited or no reactivity. Our results demonstrated a more robust detection of EpCAM using RNA aptamers over antibodies in clinical samples with chromogenic staining. This shows the potential of aptamers in the future of histopathological diagnosis and as a tool to guide targeted immunotherapy. © 2013 Shigdar et al. Source

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