Liaoning Cancer Hospital and Institute
Liaoning Cancer Hospital and Institute
Peng Y.,Shenyang Pharmaceutical University |
Li J.,Shenyang Pharmaceutical University |
Fei Y.,Liaoning Cancer Hospital and Institute |
Dong J.,Liaoning Cancer Hospital and Institute |
Pan W.,Shenyang Pharmaceutical University
International Journal of Pharmaceutics | Year: 2013
Chitosan/glycerophosphate disodium (GP) thermosensitive hydrogels were prepared for the sustained delivery of venlafaxine hydrochloride (VH) and optimization of this formulation was mainly studied. Release mechanism was investigated by applying various mathematical models to the in vitro release profiles. Overall, drug release from the hydrogels showed best fit in first-order model and drug release mechanism was diffusion-controlled release. Optimization of VH chitosan/GP thermosensitive hydrogels was conducted by using a three-level three-factorial Box-Behnken experimental design to evaluate the effects of considered variables, the strength of the formulation, chitosan concentration and GP amount, on the selected responses: cumulative percentage drug release in 1 h, 24 h and the rate constant. It presented that higher strength and GP concentration resulted in higher initial release and rate constant, which supported the hypothesis that the kinetic gelation mechanism of this system was nucleation and growth. Drug release profiles illustrated that controlled drug delivery could be obtained over 24 h, which confirmed the validity of optimization. In vivo pharmacokinetic study was investigated and it demonstrated that compared with VH solution, chitosan/GP thermosensitive hydrogels had a better sustained delivery of VH. © 2012 Elsevier B.V. All rights reserved.
Sun T.,Jozef Stefan Institute |
Sun T.,Liaoning Cancer Hospital and Institute |
Turk V.,Jozef Stefan Institute |
Turk B.,Jozef Stefan Institute |
Kopitar-Jerala N.,Jozef Stefan Institute
Frontiers in Molecular Neuroscience | Year: 2012
Stefin B (cystatin B) is an endogenous inhibitor of cysteine proteinases localized in the nucleus and the cytosol. Loss-of-function mutations in the stefin B gene (CSTB) gene were reported in patients with Unverricht-Lundborg disease (EPM1). Our previous results showed that thymocytes isolated from stefin B-deficient mice are more sensitive to apoptosis induced by the protein kinase C inhibitor staurosporin (STS) than the wild-type control cells. We have also shown that the increased expression of stefin B in the nucleus of T98G astrocytoma cells delayed cell cycle progression through the S phase. In the present study we examined if the nuclear or cytosolic functions of stefin B are responsible for the accelerated induction of apoptosis observed in the cells from stefin B-deficient mice. We have shown that the overexpression of stefin B in the nucleus, but not in the cytosol of astrocytoma T98G cells, delayed caspase-3 and-7 activation. Pretreatment of cells with the pan-caspase inhibitor z-ValAla-Asp(OMe)-fluoromethylketone completely inhibited caspase activation, while treatment with the inhibitor of calpains- and papain-like cathepsins (2S,3S)-trans-epoxysuccinylleucylamido-3-methyl-butane ethyl ester did not prevent caspase activation. We concluded that the delay of caspase activation in T98G cells overexpressing stefin B in the nucleus is independent of cathepsin inhibition. © 2012 Sun, Turk, Turk and Kopitar?jerala.
Wang Y.,Liaoning Cancer Hospital and Institute |
Wang S.,Shenyang Environmental Protection Bureau of China |
Huang Z.-Q.,Liaoning Cancer Hospital and Institute |
Chou W.-P.,Liaoning Cancer Hospital and Institute
Surgeon | Year: 2014
In recent decades, laparoscopy assisted distal gastrectomy (LADG) has been introduced to treat early gastric cancer (EGC). This study evaluated the safety and efficacy of laparoscopy assisted and conventional open distal gastrectomy for EGC. Comprehensive searches of PubMed, EmBase, Cochrane Controlled Trials Register and Chinese Biomedical Database (CBM) were performed. Included literature was evaluated using the Newcastle-Ottawa Scale. Original data were extracted, pooled odds ratio (OR) and 95% confidence intervals (CI) were calculated using RevMan 5.0. Eight RCTs of 734 patients were included in the study. Compared to CODG, LADG increases the operation time (weighted mean difference [WMD]: 63.35; 95% confidence interval [CI]: 57.96, 68.74; P<. 0.01), reduces intraoperative blood loss (WMD: -127.95; 95% CI: -147.97, -107.93; P<. 0.01), decreases number of harvested lymph nodes (WMD: -4.21; 95% CI: -6.10, -2.31; P<. 0.01), forwards oral intake time (WMD:-0.43; 95% CI: -0.61, -0.24; P<. 0.01), and shortens hospital stay(WMD: -1.29; 95% CI: -1.76, -0.83; P<. 0.01). There is no significant difference in postoperative complications(OR: 0.70; 95% CI: 0.46, 1.06; P=0.09). All these findings indicate that LADG for EGC is feasible and safe. © 2013 Royal College of Surgeons of Edinburgh (Scottish charity number SC005317) and Royal College of Surgeons in Ireland.
Huang Z.,Liaoning Cancer Hospital and Institute
Chinese Journal of Tissue Engineering Research | Year: 2014
Background: Bmi-1 (B-cell-specific moloney murineleukemia virus insertion site), a colorectal cancer stem cell gene is of great significance in the regulation of telomere reverse transcriptase activity and transcriptional status as well as cell aging and carcinogenesis. Objective: To investigate the correlation between Bmi-1 expression and clinicopathological changes of colorectal cancer. Methods: The expression of Bmi-1 mRNA in carcinoma cells was detected in 50 cases of colorectal cancer using quantitative real-time PCR. The expression of Bmi-1 protein in cancer tissue was detected by hematoxylin-eosin staining and immunohistochemical staining SP method. Results and Conclusion: Sex, age, and tumor size showed no different effects on the expression of Bmi-1 mRNA. The expression of Bmi-1 protein showed no significant difference in patients who were different in sex, age, tumor size and Duke staging of tumor. The expressions of Bmi-1 mRNA and protein in patients with lymph node metastasis and depth of invasion deeper than the serosa were much higher than those in patients with no lymph node metastasis and depth of invasion shallower than the serosa (P < 0.05). The expression of Bmi-1 mRNA was much higher in patients with higher Duke staging cancer (P < 0.05). The expression of Bmi-1 mRNA and protein are closely related to different pathological features of colorectal cancer, such as metastasis, infiltration, and Duke staging.
Xing X.,Liaoning Cancer Hospital and Institute |
Gu X.,Liaoning Cancer Hospital and Institute |
Ma T.,Liaoning Cancer Hospital and Institute |
Ye H.,Liaoning Cancer Hospital and Institute
Tumor Biology | Year: 2015
Biglycan is an important component of the extracellular matrix, which belongs to the small leucine-rich proteoglycan family. Recent studies have shown that biglycan expression is elevated in many tumor tissues and implies poor prognosis, such as colon cancer. However, the molecular mechanism of biglycan in colon cancer has not been investigated. The present study aimed to investigate the effects of biglycan on vascular endothelial growth factor (VEGF) expression in colon cancer cells and on tumor angiogenesis in vivo. Biglycan overexpression vectors were constructed, and the stable biglycan overexpression in human colon cancer cell lines (HCT116 cells) was established by G418 screening. The stable cell clones were subsequently used to initiate tumor xenografts in nude mice. Our results showed that biglycan overexpression notably up-regulated the levels of VEGF in colon cancer cells, which was further confirmed by immunohistochemistry analysis in the xenograft colon tumors. Moreover, high levels of biglycan promoted angiogenesis and colon tumor growth, as evidenced by the increased cell viability, colon tumor size, and weight, as well as the CD34 expression. Additionally, we found that the extracellular signal-regulated kinase (ERK) signaling pathway was activated by biglycan in colon cancer cells. The ERK inhibitor PD98059 dramatically reversed the increased expression of VEGF induced by biglycan. Taken together, our results indicated that biglycan up-regulated VEGF expression in colon cancer cells and promoted tumor angiogenesis. Biglycan-mediated VEGF regulation may correlate with the activation of the ERK signaling pathway. Therefore, biglycan may be a promising target for anti-angiogenic therapy for cancer. © 2014, International Society of Oncology and BioMarkers (ISOBM).
Liang J.-W.,Liaoning Cancer Hospital and Institute |
Zhang J.-J.,Liaoning Cancer Hospital and Institute |
Zhang T.,Liaoning Cancer Hospital and Institute |
Zheng Z.-C.,Liaoning Cancer Hospital and Institute
Tumor Biology | Year: 2014
Human epidermal growth factor receptor 2 (HER2) plays an important role in the aggressiveness and progression of gastric cancer. With the publication of trial results, we conducted a meta-analysis to investigate its prognostic significance for patients with gastric cancer. PubMed, Ovid, Web of Science, and Cochrane databases were searched. Statistical analysis was carried out by STATA version 12.0 software. The Newcastle-Ottawa scale was used to assess the quality of evidence. Fifteen studies involving 5,290 patients met the inclusion criteria. The results showed that HER2 overexpression was significantly associated with patients' overall survival (HR=1.56, 95% confidence interval (CI) 1.05-2.07; Z=6.03; P=0.000). The results also suggested that HER2 overexpression was associated with Bormann type (odds ratio (OR)=1.76, 95% CI 1.19-2.59; Z=2.85; P=0.004), tumor differentiation (OR=3.14, 95% CI 1.91-5.17; Z=4.49; P=0.000), Lauren's classification (OR=6.25, 95% CI 4.29-9.10; Z=9.54; P=0.000), lymph node metastasis (OR=1.43, 95% CI 1.15-1.77; Z=3.23; P=0.001), venous invasion (OR=1.69, 95% CI 1.15-2.48; Z=2.67; P=0.008), and lymphovascular invasion (OR=1.57, 95% CI 1.21-2.04; Z=3.4; P=0.001). However, it had no correlation with tumor size, depth of invasion, and tumor stage. This study showed that HER2 overexpression had an unfavorable prognostic role for patients with gastric cancer. HER2-positive expression was associated with Bormann type, Lauren's classification, tumor differentiation, lymph node status, venous invasion, and lymphovascular invasion. © International Society of Oncology and BioMarkers (ISOBM) 2014.
Yang S.,Liaoning Medical University |
Chou W.-P.,Liaoning Cancer Hospital and Institute |
Pei L.,Liaoning Medical University
Experimental and Therapeutic Medicine | Year: 2013
Renal ischemia/reperfusion injury (IRI) is a major cause of acute renal failure. The aim of this study was to investigate whether propofol pretreatment in a rat model protects kidney tissue against IRI. Thirty-two Wistar rats were equally divided into four groups: a sham-operated group, untreated renal IRI group, and low-dose (5 mg/kg) and high-dose (10 mg/kg) propofol-treated groups which were treated with propofol prior to the induction of IRI. The rats were subjected to renal ischemia by bilateral clamping of the pedicles for 50 min, followed by reperfusion. The low-dose and high-dose propofol treatment groups were pretreated via femoral vein injection with a propofol suspension prior to the induction of ischemia/reperfusion. The untreated IRI group showed signifcantly higher serum creatinine (SCr), blood urea nitrogen (BUN), interleukin 6 (IL-6), IL-8, tumor necrosis factor-α (TNF-α), and malondialdehyde (MDA) levels compared with the sham-operated rats. Superoxide dismutase (SOD) levels were significantly reduced following IRI; however, they significantly increased following propofol administration. Bone morphogenetic protein 2 (BMP2) levels were significantly increased in the propofol-treated groups compared with the untreated IRI group. These results suggest that propofol reduces renal oxidative injury and facilitates repair following IRI. Propofol may play a protective role by regulating BMP2 expression in renal IRI.
Zhang R.,Liaoning Cancer Hospital and Institute |
Song C.,Liaoning Cancer Hospital and Institute
Tumor Biology | Year: 2014
CUB and sushi multiple domain protein 1 (CSMD1) is a candidate tumor suppressor gene. The three members of CSMD family have very similar structures, each consisting of 14 CUB domains separated from one another by a sushi domain, an additional uninterrupted array of sushi domains, a single transmembrane domain, and a short cytoplasmic tail. In this work, we aimed to study the protein and mRNA levels of the CSMD1, CSMD2, and CSMD3 and evaluate their prognostic importance in colorectal cancer. Reduced expressions of these three proteins were detected in colorectal cancer tissues by comparing matched normal tissues. Low CSMD2 expression was significantly associated with differentiation, lymphatic invasion, and tumor size. CSMD3 was associated with differentiation and lymphatic invasion. CSMD1 and CSMD2 expressions were associated with overall survival. This study offers convincing evidence for the first time that the three genes of CSMD family were downregulated in the patients with colorectal cancer and may be used as predictors of colorectal cancer. © International Society of Oncology and BioMarkers (ISOBM) 2014.
Xing X.-J.,Liaoning Cancer Hospital and Institute |
Xiao-Hu G.,Liaoning Cancer Hospital and Institute |
Ma T.-F.,Liaoning Cancer Hospital and Institute
Tumor Biology | Year: 2014
This meta-analysis aimed to identify the value of serum matrix metalloproteinase-7 (MMP-7) levels for the diagnosis of colorectal cancer (CRC). Through searching the following electronic databases: Cochrane Library (Issue 12, 2014), Web of Science (1945~2014), PubMed (1966~2014), CINAHL (1982~2014), EMBASE (1980~2014), and CBM (1982~2014), related articles were determined without any language restrictions. Stata statistical software (Version 12.0, Stata Corporation, College Station, TX, USA) was chosen to deal with statistical data. Standard mean difference (SMD) and its corresponding 95% confidence interval (95% CI) were calculated to clarify the correlation between serum MMP-7 levels and CRC. Seven clinical case–control studies which recruited 430 CRC patients and 357 healthy subjects were selected for statistical analysis. The main findings of our meta-analysis showed that the serum MMP-7 level in CRC patients was significantly higher than that in control subjects (SMD=2.15, 95% CI=1.46~2.84, P<0.001). Ethnicity-stratified analysis indicated a higher serum MMP-7 level in CRC patients than that of control subjects among the Asians and the Caucasians (Asians: SMD=2.83, 95% CI= 1.76~3.91, P<0.001; Caucasians: SMD=1.06, 95% CI= 0.46~1.66, P=0.001; respectively). The present meta-analysis indicated that the increased serum level of MMP-7 may be connected with the development of CRC; thus, serum levels of MMP-7 could be an independent biomarker for CRC patients. © International Society of Oncology and BioMarkers (ISOBM) 2014
Huang Z.,Liaoning Cancer Hospital and Institute |
Liu F.,Liaoning Cancer Hospital and Institute
Tumor Biology | Year: 2014
Pancreatic cancer is a highly malignant cancer with increasing incidence and mortality worldwide. Carbohydrate antigen 19-9 (CA19-9) has been widely reported to play a role in the diagnosis of pancreatic cancer patients. However, published data on this subject are inconclusive. There was no meta-analysis that has been previously performed to evaluate critically the diagnostic accuracy of CA19-9 for pancreatic cancer. Therefore, we performed a meta-analysis to evaluate the sensitivity and specificity of CA19-9 in the diagnosis of pancreatic cancer. We conducted a comprehensive search to identify studies in which the pooled sensitivity, specificity, diagnostic odds ratio (DOR), and summary receiver operating curves (SROC) could be determined. A total of 11 studies that included 2,316 individuals who fulfilled all of the inclusion criteria were considered for analysis. The summary estimates for serum CA19-9 in the diagnosis of pancreatic cancer in these studies were pooled sensitivity 0.80 (95 % confidence interval [CI] 0.77–0.82), specificity 0.80 (95 % CI 0.77–0.82), and DOR 14.79 (95 % CI 8.55–25.59), and the area under the curve was 0.87. Our meta-analysis showed that serum CA19-9 plays important role in the diagnosis of pancreatic cancer. © 2014, International Society of Oncology and BioMarkers (ISOBM).