Zhang Y.,Zhabei District Central Hospital |
Yang C.-Q.,Shanghai University |
Gao Y.,Shanghai University |
Wang C.E.,Shanghai University |
And 2 more authors.
Oncology Reports | Year: 2014
CXC chemokine receptor 7 (CXCR7) has been implicated in tumor development and metastasis in multiple malignancies. Yet, the function and molecular mechanisms of CXCR7 in human osteosarcoma (OS) are still unclear. The aim of the present study was to investigate the role of CXCR7 in human OS. The expression of CXCR7 was assessed by immunohistochemical assay using a tissue microarray procedure in 45 cases of OS tissues. A loss-of-function approach was used to observe the effects of lentiviral vector-mediated CXCR7 siRNA (Lv-siCXCR7) on biological behaviors including proliferative activities and invasive potential, as indicated by MTT and Transwell assays in OS (MG-63 and U-2 OS) cells. The results showed that the expression of CXCR7 protein in OS tissues was significantly increased compared to that in adjacent non-cancerous tissues (68.9 vs. 53.3%, P=0.033), and was correlated with the distant metastasis of the tumors (P=0.004). Knockdown of CXCR7 suppressed proliferation and invasion of OS cells through decreased expression of PI3K, AKT, β-arrestin, proliferating cell nuclear antigen (PCNA), and matrix metalloproteinase-9 (MMP-9). In addition, the tumor volume in U-2 OS subcutaneous tumor models treated with Lv-siCXCR7 was significantly smaller than the tumor volume in the negative control group (P<0.01). Collectively, our findings indicate that upregulation of CXCR7 expression is correlated with distant metastasis of OS, while knockdown of CXCR7 blocks the development of OS cells through inhibition of the PI3K/AKT and β-arrestin pathways, suggesting that CXCR7 may serve as a potential therapeutic target for the treatment of cancer.
Guan L.,Zhabei District Central Hospital |
Xu G.,Peking University
World Journal of Surgical Oncology | Year: 2016
Background: High-intensity focused ultrasound (HIFU) is a noninvasive therapy that makes entire coagulative necrosis of a tumor in deep tissue through the intact skin. There are many reports about the HIFU's efficacy in the treatment of patients with breast cancer, but randomized clinical trials are rare which emphasize on the systematic assessment of histological changes in the ablated tumor vascularities, while clinical trials utilizing bevacizumab and other anti-angiogenic drugs in breast cancer have not demonstrated overall survival benefit. The purpose of this study is to evaluate the damage effect of HIFU on breast cancer tissues and their vascularities. Methods: Randomized clinical trials and the modality of treat-and-resect protocols were adopted. The treated outcome of all patients was followed up in this study. The target lesions of 25 breast cancer patients treated by HIFU were observed after autopsy. One slide was used for hematoxylin-eosin (HE) staining, one slide was used for elastic fiber staining by Victoria blue and Ponceau's histochemical staining, and one slide was used for vascular endothelial cell immunohistochemical staining with biotinylated-ulex europaeus agglutinin I (UEAI); all three slides were observed under an optical microscopic. One additional slide was systematically observed by electron microscopy. Results: The average follow-up time was 12months; no local recurrence or a distant metastatic lesion was detected among treated patients. Histological examination of the HE slides indicated that HIFU caused coagulative necrosis in the tumor tissues and their vascularities: all feeder vessels less than 2mm in diameter in the insonated tumor were occluded, the vascular elasticity provided by fibrin was lost, the cells were disordered and delaminated, and UEAI staining of the target lesions was negative. Immediately after HIFU irradiation, the tumor capillary ultrastructure was destroyed, the capillary endothelium was disintegrated, the peritubular cells were cavitated, and the plasma membrane was incomplete. Conclusions: HIFU ablation can destroy all proliferating tumor cells and their growing vascularities simultaneously; this may break interdependent vicious cycle of tumor angiogenesis and neoplastic cell growth that results in infinite proliferation. While it cannot cause tumor resistance to HIFU ablation, it may be a new anti-angiogenic strategy that needs further clinical observation and exploration. Furthermore, the treatment indications of HIFU ablation were reviewed and discussed in this manuscript. © 2016 The Author(s).
Liu S.,Zhabei District Central Hospital |
Wu H.-J.,Shanghai University |
Zhang Z.-Q.,Shanghai JiaoTong University |
Chen Q.,Zhabei District Central Hospital |
And 3 more authors.
Cancer Biology and Therapy | Year: 2011
Cancer cachexia is characterized by progressive weight loss with the depletion of adipose tissue and skeletal muscle. Impaired fatty acid oxidation mainly resulting from the decrease of carnitine palmitoyltransferase I and II activities in the liver is an important factor that contributes to cancer cachexia. Although recent studies suggest a potential application of L-carnitine in treatment of cancer cachexia, the underlying mechanisms are unknown. In the present study, we aim to assess the effects of L-carnitine on the activity and expression of CPT I and II in the liver of cachectic cancer mice. Our results show that the inoculation of colon-26 adenocarcinoma cells into mice led to cancer cachexia characterized by notable decreases in food intake, gastrocnemius muscle and epididymus fat weight. In addition, the mRNA level and activity of liver carnitine palmitoyltransferase (CPT) I and II, and serum levels of free carnitine and acetylcarnitine were markedly decreased in cachectic mice, accompanied by marked increases in serum levels of tumor necrosis factor-alpha (TNFα) and interleukin-6 (IL-6). A continuous oral treatment with L-carnitine at 18 mg/kg per day increased dietary uptake, gastrocnemius muscle weight and epididymus fat weight, increased blood glucose and serum albumin levels, and decreased total cholesterol level in cancer cachectic mice, but did not affect tumor growth. These effects of L-carnitine on cancer cachexia mice were accompanied by the upregulation of mRNA level of CPT I and II and increased enzyme activity of CPT I in the liver, as well as the downregulation of serum TNFα and IL-6 levels. Moreover, free carnitine levels were negatively correlated with serum TNFα or IL-6 level. These results indicate that L-carnitine ameliorates cancer cachexia by regulating serum TNFα and IL-6 levels and modulating the expression and activity of CPT in the liver. © 2011 Landes Bioscience.
Wu H.-J.,Shanghai University |
Zhang Z.-Q.,U.S. Center for Disease Control and Prevention |
Yu B.,Shanghai University |
Liu S.,Zhabei District Central Hospital |
And 2 more authors.
Cellular Physiology and Biochemistry | Year: 2010
Background and Aims: Hepatic fibrosis is associated with elevated sinusoidal pressure, which can be transmitted to the hepatic stellate cells (HSCs) in the perisinusoidal space of Disse. Here, we sought to determine the effects of pressure on cellular growth and Src-dependent signaling pathways in the rat HSCs. Methods: Cultured rat HSCs were exposed to pressures (0 to 80 mmHg) by using a pressure-inducing apparatus. The proliferation of the cells was determined by a 5-bromo-2′-deoxy-uridine (BrdU) incorporation assay. Reverse transcription-PCR and Western-blot analysis were used to examine the mRNA and protein levels of representative molecules in Src-dependent signaling pathways. Results: Pressure at 10 to 20 mmHg applied to the HSCs over 1 h upregulated Brdu incorporation and expression of proliferating cell nuclear antigen (PCNA) and type I collagen, while a higher pressure of 40-80 mmHg did not have noticeable effect. The mRNA level of β 3 integrin was increased by 1-h application of 5 to 20 mmHg. Immunoblot with phospho-specific antibodies demonstrated the phosphorylation of Src (Tyr418), focal adhesion kinase (FAK) (Tyr397), Akt (Ser473) and extracellular signal-regulated kinases 1 and 2 (ERK1/2) (Thr421/Ser424) was increased in response to 10-mmHg pressure. Herbimycin A, an inhibitor of Src phosphorylation, attenuated the pressure-induced HSC proliferation and phosphorylation of above-mentioned signaling molecules. Conclusion: Our data demonstrated that pressure alone induced HSC proliferation involving the activation of Src-dependent signaling pathways. © 2010 S. Karger AG, Basel.
Wang Z.,Shanghai University |
Gan L.,Fudan University |
Nie W.,Shanghai University |
Geng Y.,Zhabei District Central Hospital
Genetic Testing and Molecular Biomarkers | Year: 2013
Background: The oxoguanine DNA glycosylase (OGG1) Ser326Cys polymorphism has been implicated in susceptibility to esophageal cancer. Several studies investigated the association of this polymorphism with esophageal cancer in different populations. However, the results were contradictory. A meta-analysis was conducted to assess the association between the OGG1 Ser326Cys polymorphism and esophageal cancer susceptibility. Methods: Databases, including PubMed, EMBASE, China National Knowledge Infrastructure (CNKI), and Weipu Database were searched to find relevant studies. Odds ratios (ORs) with 95% confidence intervals (CIs) were used to assess the strength of associations. A random-effects model was used. Results: Twelve studies involving 2363 cases and 3621 controls were included. Overall, a significant association between the OGG1 Ser326Cys polymorphism and esophageal cancer was observed for Cys/Cys versus Cys/Ser+Ser/Ser (OR=1.40; 95% CI 1.12-1.74; p=0.003; Pheterogeneity= 0.18). In the subgroup analysis by ethnicity, a significant association was found among Asians (OR=1.51; 95% CI 1.15-1.96; p=0.002; P heterogeneity=0.22), but not among Caucasians (OR=1.21; 95% CI 0.81-1.81; p=0.35; Pheterogeneity=0.21). In the subgroup analysis by pathologic type, we found that the Cys/Cys genotype was associated with increased esophageal squamous cell carcinoma risk (OR=1.86; 95% CI 1.36-2.53; p<0.0001; Pheterogeneity=0.73). Conclusions: This meta-analysis suggested that the OGG1 Ser326Cys polymorphism was a risk factor of esophageal cancer. © Mary Ann Liebert, Inc.
Zhang J.F.,Shanghai JiaoTong University |
Yao G.Y.,Shanghai JiaoTong University |
Wu Y.H.,Zhabei District Central Hospital
Genetics and Molecular Research | Year: 2012
The aim of this study was to identify related genes and the underlying molecular mechanisms in obese patients who show a series of clinical and metabolic abnormalities known as metabolic syndrome. We identified expression profiles through a coexpression network. In addition, a similarity matrix and expression modules were constructed based on domain and pathway enrichment analysis. The genes in module 1 were mainly involved in the metabolism of xenobiotics by cytochrome P450, aldosterone-regulated sodium reabsorption, and focal adhesion owing to the presence of aldo/ketoreductase, basic helix-loop-helix, von Willebrand factor, Frizzled-related domain, and other domains. The genes in module 3 may be involved in cell cycle (hsa04110) and DNA replication (hsa03030) pathways through mini-chromosome maintenance, serine/threonine protein kinase, the protein kinase domain, and other domains. We analyzed the published molecular mechanisms of obesity and found many genes and pathways that have not been given enough attention and require further confirmation. © FUNPEC-RP.
Man Y.,Zhabei District Central Hospital
Zhonghua yi xue za zhi | Year: 2011
To test the nickel-titanium (Ni-Ti) shape memory alloys of vertebral body reduction fixator with assisted distraction bar for the treatment of traumatic and osteoporotic vertebral body fracture. A Ni-Ti shape memory alloys of vertebral body reduction fixator with assisted distraction bar was implanted into the compressed fracture specimens through vertebral pedicle with the radiographic monitoring to reduce the collapsed endplate as well as distract the compressed vertebral fracture. Radiographic film and computed tomographic reconstruction technique were employed to evaluate the effects of reduction and distraction. A biomechanic test machine was used to measure the fatigue and the stability of deformation of fixation segments. Relying on the effect of temperature shape memory, such an assembly could basically reduce the collapsed endplate as well as distract the compressed vertebral fracture. And when unsatisfied results of reduction and distraction occurred, its super flexibility could provide additional distraction strength. A Ni-Ti shape memory alloys of vertebral body reduction fixator with assisted distraction bar may provide effective endplate reduction, restore the vertebral height and the immediate biomechanic spinal stability. So the above assembly is indicated for the treatment of traumatic and osteoporotic vertebral body fracture.
Zhang Y.,Zhabei District Central Hospital |
Tang Y.-J.,Zhabei District Central Hospital |
Man Y.,Zhabei District Central Hospital |
Pan F.,Zhabei District Central Hospital |
And 2 more authors.
International Journal of Immunopathology and Pharmacology | Year: 2013
Dysregulation of the Axl receptor tyrosine kinase (RTK) has been implicated in the development and progression of a variety of malignancies. Axl is known to activate strong anti-apoptotic signaling pathways that promote oncogenesis. However, the role of Axl plays in osteosarcoma (OS) remains elusive. The present study aimed to investigate the clinical significance and function of Axl in human OS. Forty cases of OS and corresponding adjacent non-cancerous tissues (ANCT) were collected. The expression of Axl was assessed using immunohistochemical assay through tissue microarray procedure. A loss-of-function experiment was performed to investigate the effects of small hairpin RNA (shRNA)-mediated knockdown of Axl on the expression of p-AKT, poly ADP-ribose polymerase (PARP) and Ki-67, the proliferative activities, indicated by MTT assay, and the apoptotic index in OS MG-63 cells. As a result, the expression of Axl was found in OS tissues with higher strong reactivity rate, compared with the ANCT (75.0% vs 20.0%, P=0.000), but it did not associate with the age, gender, tumor size, TNM staging and distant metastases (each P>0.05). Furthermore, knockdown of Axl inhibited the proliferative activities and induced apoptosis in MG-63 cells with decreased expression of p-AKT, and Ki-67 and increased expression of PARP. In conclusion, our findings suggest that Axl is highly expressed in most of the OS tissues compared with the ANCT, and knockdown of Axl inhibits proliferation and induces apoptosis of OS cells possibly through downregulation of the AKT pathway, suggesting that our findings may provide new insights into the potential therapeutic target for cancer. Copyright © by BIOLIFE, s.a.s.
Zhang Y.,Zhabei District Central Hospital
European journal of histochemistry : EJH | Year: 2013
As a metastasis suppressor, KiSS1 has been implicated in numerous human cancers. However, recent studies have demonstrated that KiSS1 promotes tumor growth and metastasis in breast cancer, and it is unclear about the expression and function of KiSS1 in human osteosarcoma (OS). The aim of the present study was to investigate the role and molecular mechanisms of KiSS1 in human OS. The expression of KiSS1 was assessed by immunohistochemical assay using a tissue microarray procedure in forty cases of OS tissues. A gain-of-function approach was used to observe the effects of lentiviral vector-mediated overexpression of KiSS1 (Lv-KiSS1) on the biological behaviors including proliferative activities and invasive potential of OS MG-63 cells, indicated by MTT and Transwell assays, respectively. The results showed that the expression of KiSS1 protein in OS tissues was significantly lowered compared to that in adjacent non-cancerous tissues (ANCT) (42.5% vs 70.0%, P=0.023), and had negative correlation with distant metastases of the tumor (P=0.019). Overexpression of KiSS1 inhibited proliferation and invasion of OS cells with the decreased expression of p38 MAPK and matrix metalloproteinase-9 (MMP-9). Taken together, our findings indicate that the decreased expression of KiSS1 is correlated with distant metastasis of OS, and KiSS1 may function as a tumor suppressor in OS cells through inhibition of the MAPK pathway, suggesting that KiSS1 may serve as a potential therapeutic target for the treatment of cancer.
Shi H.-T.,Zhabei District Central Hospital
Journal of Leukemia and Lymphoma | Year: 2010
Objective: To evaluate the efficacy and side effects of standard-dose of dexamethasone and low-dose dexamethasone combined with thalidomide in treatment of multiple myeloma. Methods: Thirtynine patients with multiple myeloma were randomly divided into 2 groups, who were treated with chemotherapy of thalidomide (200 mg/d) plus dexamethasone (40 mg d1-4d/28 days in standard-dose group and 20 mg d1-4d/28 days in low-dose group), for a total of 4 courses. The efficacy, survival time and adverse events were compared between the two groups. Results: Complete remission rate, partial remission rate and overall response rate of the standard-dose group were 26.3%, 35% and 75%, respectively; and those of the low-dose group were 15.8%, 36.8% and 68.4%, respectively. No statistical difference between the two groups (P >0.05) was observed. Lung infections, blood pressure elevation, blood glucose elevation, shingles and other adverse reactions in the standard-dose group were statistically higher than those in the low-dose group (P <0.05). Conclusion: Efficacy on multiple myeloma of standard-dose and low-dose dexamethasone are similar, but adverse reactions are significantly increased.