Chenghao Shao

Changhai Hospital, Shanghai, Shanghai, Shanghai Shi, China

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Publications (15)38 Total impact

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    ABSTRACT: Pancreatic ductal adenocarcinoma (PDAC) ranks fourth on the list of cancer-related causes of death. Deregulation or dysfunction of miRNAs contribute to cancer development. In this study, we found that low miR-545 level and high RIG-I protein in PDAC tissues were both correlated with low survival rate. MiR-545 up-regulation inhibited PDAC cell lines growth and vice versa. 3'UTR of RIG-I was targeted by miR-545. Thus we concluded that low miR-545 levels in PDAC promote tumor cells growth, and this is associated with reduced survival in PDAC patients. MiR-545 exerts its effects by directly targeting RIG-1..
    FEBS letters. 10/2014;
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    ABSTRACT: Mesenchymal stem cells (MSCs) represent a new tool for delivery of therapeutic agents to cancer sites due to their strong tropism toward tumors. Interleukin-15 (IL-15) has demonstrated a potent anti-tumor activity in various animal models as well as clinical trials. However, because of its short half-life, effective therapeutic effects usually require a high dose which often results in undesired side effects, thus new strategies for overcoming this disadvantage are needed. In this study, human MSCs were isolated from umbilical cord blood as delivery vehicles, and transduced with lentivirus vector expressing murine IL-15 (MSC-IL-15). In vitro assays of lymphocyte activation and proliferation demonstrated that IL-15 produced by MSCs was biofunctional. In syngeneic mice bearing Pan02 pancreatic tumors, systemic administration of MSC-IL-15 significantly inhibited tumor growth and prolonged the survival of tumor-bearing mice, which were associated with tumor cell apoptosis, and NK and T cell accumulation. Furthermore, we confirmed that MSC- IL-15 could migrate toward tumor and secreted IL-15 in tumor specific sites. Depletion of NK and CD8+ T cells abolished the anti-tumor activity of MSC-IL-15, suggesting that NK and CD8+ T cells play a key role for MSC-IL-15 -mediated effect. Interestingly, cured mice after MSC-IL-15 treatment were resistant to Pan02 pancreatic tumor rechallenge, and adoptive transfer of lymphocytes from cured mice also could reject Pan02 tumor inoculation in naïve mice, indicating that MSC-IL-15 induced tumor-specific T-cell immune memory response. Overall, these data supported that MSCs producing IL-15 might represent an innovative strategy for therapy of pancreatic tumor.
    Molecular Cancer Therapeutics 06/2014; · 5.60 Impact Factor
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    ABSTRACT: Hepatocellular carcinoma (HCC) is one of the most lethal and prevalent cancers in human population. The 6-fluoro-3-formylchromone (FCC) has been shown to have anti-tumor activity against various tumor cells. However, the effects of FCC on HCC cell lines have not yet been reported. This study aims to research the effects of FCC on HCC and advance the understanding of the molecular mechanism. HCC cell line SMMC-7721 was treated with FCC at various concentrations (0, 2, 5, 10, and 20 mug/ml) for 24, 48 and 72 h, respectively. The proliferations of SMMC-7721 cells were measured by MTT assays. After cultured 24 hours, cell cycle distribution and apoptosis were determined by flow cytometry. However, the expression levels of PCNA, Bax and Bcl-2 were measured by western blotting after 48 hours. FCC displayed a dose- and time-dependent inhibition of the SMMC-7721 cell proliferations in vitro. It also induced apoptosis with 45.4% and caused cell accumulation in G0/G1 phase with 21.5%. PCNA and Bcl-2 expression was significantly suppressed by FCC in a dose-dependent manner (P < 0.05), while Bax expression was increased. FCC could significantly inhibit HCC cell growth in vitro through cell cycle arrest and inducing apoptosis by suppressing PCNA expression and modulating the Bax/Bcl-2 ratio.
    BMC Gastroenterology 04/2014; 14(1):62. · 2.11 Impact Factor
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    ABSTRACT: The aim of this study was to investigate the role of miR-208 in the invasion and metastasis of pancreatic cancer cells and the underlying molecular mechanism. miR-208 mimic, miR-208 inhibitor and NC were transfected into pancreatic cancer cell line Bxpc3 using liposome. Transwell invasion and scratch assays were used to test cell migratory and invasive abilities. Western blotting and quantitative PCR methods were used to detect E-cadherin, fibronectin and vimentin protein and mRNA expression in pancreatic cancer cell line BxPC3 after transfection by miR-208 mimic, miR-208 inhibitor and NC. Transwell invasion and scratch assays showed that after overexpressing miR-208, pancreatic cancer cell line BxPC3 exhibited enhanced in vitro migratory and invasive abilities, while after downregulating miR-208 expression, cell migratory and invasive abilities were decreased. Western blotting and quantitative PCR showed that after overexpressing miR-208, expression of E-cadherin, an epithelial cell marker, was decreased and expression of fibronectin and vimentin, interstitial cell markers, was increased in pancreatic cancer cell line BxPC3; however, after inhibiting miR-208, increased E-cadherin expression and decreased fibronectin and vimentin expression were observed in pancreatic cancer cell line BxPC3. After overexpressing miR-208, p-AKT and p-GSK-3β expression was altered by activating AKT/GSK-3β/snail signaling pathway. miR-208 induces epithelial to mesenchymal transition of pancreatic cancer cell line BxPC3 by activating AKT/GSK-3β/snail signaling pathway and thereby promotes cell metastasis and invasion.
    Cell biochemistry and biophysics 03/2014; · 3.34 Impact Factor
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    ABSTRACT: Background/Aims: En bloc resection of a tumor located in the uncinate process of the pancreas is a challenging problem. The aim of this study was to analyze outcomes of modified Miwa's augmented regional pancreatoduodenectomy for patients with pancreatic cancer in the uncinate process involving the root of the mesentery. Methodology: We analyzed by summarizing the 48 cases of ductal adenocarcinoma in the uncinate process of the pancreas during January 2004 to December 2010 with Miwa's augmented regional pancreatoduodenectomy in our hospital and examined the clinical effect and safety of this procedure. Results: We performed extended pancreaticoduodenectomy combined with isolation of full-length superior mesentery artery (SMA) for 48 patients. Sixteen of the forty-eight patients were combined with PV/SMV resection and reconstruction. There was no operative death and 20 cases developed complications, including mild to severe diarrhea in 17 cases. During follow-up survey among all patients of 6 to 45 months (median 20 months), 9 died of liver metastasis, 10 died of local recurrence, and 5 died of non-tumor causes. The 1-, 2- and 3-year accumulated survival rates were 69.1%, 35.1% and 20.2%, respectively. Conclusions: Full-length SMA isolation and involved mesentery resection with extended pancreaticoduodenectomy is safe and effective.
    Hepato-gastroenterology 12/2012; 60(122). · 0.77 Impact Factor
  • The American surgeon 11/2012; 78(11):459-62. · 0.92 Impact Factor
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    Cancer Science 10/2012; 103(10):Octobercover. · 3.48 Impact Factor
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    ABSTRACT: Background/Aims: Pancreatic body and tail carcinoma (PBTC) is an aggressive disease with a low resectability rate. Celiac axis infiltration usually contraindicates resection. Extended distal pancreatectomy with combined en bloc celiac axis resection (DP-CAR, also named Appleby operation) was described as a new concept for the curative treatment of these tumors. The aim of this study was to analyze the results of DP-CAR in PBTC. Methodology: Analyze by summarizing the 24 cases of PBTC during October 2005 to August 2010 in the pancreatic surgery of our hospital and analyzing the clinical manifestations, surgical processing, pathological effects and survival rate of the patients. Results: The postoperative mortality rate was 0%, despite a high morbidity rate (54%). Preoperative intractable abdominal and/or back pain in all the patients was completely alleviated immediately after surgery. During the follow-up survey among all the patients of 2 to 37 months (with an average follow-up survey of 12.67 months), no patient was still alive, with the median survival of 9.25 months. Estimated overall 1- and 3-year survival rates were 46% and 4%, respectively. Conclusions: DP-CAR offers a high resectability rate without increasing the mortality rate given skilled surgical technique.
    Hepato-gastroenterology 07/2012; 60(121). · 0.77 Impact Factor
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    ABSTRACT: Cancer cells can metastasize throughout the body by various mechanisms, including the lymphatic system, resulting in tumor-induced lymphangiogenesis that can profoundly affect patient survival. The aim of the present study was to examine the role of lymphangiogenesis in the metastasis of pancreatic cancer to the peripheral nerve plexus. Immunohistochemistry was performed to analyze specimens obtained from 70 ductal adenocarcinoma patients. The markers used included lymphangiogenic factor vascular endothelial growth factor (VEGF)-C, the lymphatic-specific marker D2-40, and cytokeratin 19, an independent prognostic factor for pancreatic tumors. The relationship between survival rate and invasion of both the lymphatic vessels and peripancreatic nerve plexus (PNP) was evaluated, with clearly elevated lymphatic vessel density (LVD) in tissues adjacent to the cancer tissues. In fact, LVD levels were higher in adjacent tissues than in localized cancer tissues, and lymphatic vessel invasion into tissues adjacent to the tumor was significantly correlated with both PNP invasion (P = 0.005) and lymph node metastasis (P = 0.010). Correspondingly, LVD in tissues adjacent to the tumor was correlated with both invasion of lymphatic vessels surrounding the tumor (P = 0.024) and VEGF-C expression (P = 0.031); in addition, VEGF-C expression was correlated with invasion of lymphatic vessels around the tumor (P = 0.004). Survival rates were significantly lower in patients in whom there was peritumor lymphatic vessel invasion (P < 0.001), extrapancreatic nerve plexus invasion (P = 0.001), and/or lymph node metastasis (P < 0.001). Based on these results, lymphatic invasion associated with adjacent tumor growth likely contributes to the development of metastatic tumors that invade the PNP.
    Cancer Science 06/2012; 103(10):1756-63. · 3.48 Impact Factor
  • The American surgeon 03/2012; 78(3):E178-80. · 0.92 Impact Factor
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    ABSTRACT: Diabetes mellitus (DM) has been reported to be associated with an increased risk of several types of cancers. However, its relationship with cholangiocarcinoma (CC), which includes intrahepatic cholangiocarcinoma (ICC) and extrahepatic cholangiocarcinoma (ECC), remains unclear. We conducted a meta-analysis to assess the association between diabetes and the risk of CC (including ICC and ECC). We identified studies by a literature search of Medline (from 1 January 1966) and Embase (from 1 January 1974), through 30 November 2010, and by searching the reference lists of pertinent articles. Summary relative risks (RRs) with corresponding 95% confidence intervals (CIs) were calculated with a random-effects model. A total of 15 articles (10 case-control and five cohort studies) were included in this study. The number of reports on DM and risk of specific cancer were as follows: CC (n=5), ECC (n=9), and ICC (n=9). Compared with those without diabetes, individuals with diabetes had an increased risk of CC (summary RRs, 1.60; 95% CI, 1.38-1.87; P=0.992 for heterogeneity), ECC (summary RRs, 1.63; 95% CIs, 1.29-2.05; P=0.005 for heterogeneity), and ICC (summary RRs, 1.97; 95% CIs, 1.57-2.46; P=0.025 for heterogeneity). The funnel plot revealed no evidence for publication bias concerning diabetes and the risk of CC (including ICC and ECC). These findings strongly support the positive link between DM and the increased risk of CC (including ICC and ECC).
    European journal of cancer prevention: the official journal of the European Cancer Prevention Organisation (ECP) 08/2011; 21(1):24-31. · 2.21 Impact Factor
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    ABSTRACT: MicroRNAs (miRNAs), which regulate gene expression by partial complementarity to the 3' untranslated region of their target genes, have been implicated in cancer initiation and progression. However, the molecular mechanism underlying the regulation of miRNA expression during pancreatic tumorigenesis has not been extensively reported. In this study, we first compared the miRNA expression in human pancreatic cancers and adjacent normal tissues by miRNA array and identified 12 differentially expressed miRNAs. miR-132, which is downregulated in tumors, was further studied in greater detail. Decreased expression of miR-132 was confirmed in 16 of 20 pancreatic carcinomas (P < 0.0001), compared with their respective benign tissues by TaqMan miRNA assays. miR-132 expression was remarkably influenced by promoter methylation in PANC1 and SW1990 cells. Promoter hypermethylation was observed in tumor samples but not in the normal counterparts, and the expression of miR-132 negatively correlated with its methylation status (P = 0.013). miR-132 was transcribed by RNA polymerase II, and Sp1 played a major role in miR-132 transcription. The expression of Sp1 correlated with that of miR-132 in tissues. Moreover, cancerous tissues showed significantly lower Sp1-binding affinity to the miR-132 promoter, relative to non-tumor samples. Proliferation and colony formation of pancreatic cancer cells were suppressed in cells transfected with miR-132 mimics and enhanced in cells transfected with miR-132 inhibitor by negatively regulating the Akt-signaling pathway. Our present findings illustrate the mechanism driving miR-132 downregulation and the important role of miR-132 in pancreatic cancer development.
    Carcinogenesis 06/2011; 32(8):1183-9. · 5.64 Impact Factor
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    ABSTRACT: MicroRNAs (miRNAs) have emerged as important regulators in the development of pancreatic cancer and may be a valuable therapeutic application. DPC4/Smad4 is a critical tumor suppressor involved in the progression of pancreatic cancer, but few studies have been conducted to determine its relationship with miRNAs. In this study, we identify miR-421 as a potential regulator of DPC4/Smad4. We find that in human clinical specimens of pancreatic cancer miR-421 is aberrantly upregulated while DPC4/Smad4 is strongly repressed, and their levels of expression are inversely correlated. Moreover, ectopic expression of miR-421 significantly decreases DPC4/Smad4 protein level in pancreatic cancer cell lines and simultaneously promotes cell proliferation and colony formation in vitro. Our findings identify miR-421 as a potent regulator of DPC4/Smad4, which may provide a novel therapeutic strategy for treatment of DPC4/Smad4-driven pancreatic cancer.
    Biochemical and Biophysical Research Communications 02/2011; 406(4):552-7. · 2.28 Impact Factor
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    ABSTRACT: Both deregulation of tumor-suppressor genes and misexpression of microRNAs (miRNAs) have been implicated in the development of pancreatic cancer, but their relationship during this process remains less clear. Here, we report that the expression of miR-483-3p is strongly enhanced in pancreatic cancer tissues compared to side normal tissues using a miRNA-array differential analysis. Furthermore, DPC4/Smad4 is identified as a target of miR-483-3p and their expression levels are inversely correlated in human clinical specimens. Ectopic expression of miR-483-3p significantly represses DPC4/Smad4 protein levels in pancreatic cancer cell lines, and simultaneously promotes cell proliferation and colony formation in vitro. Our findings identify miR-483-3p as a potent regulator of DPC4/Smad4, which may provide a novel therapeutic strategy for the treatment of DPC4/Smad4-driven pancreatic cancer.
    FEBS letters 01/2011; 585(1):207-13. · 3.54 Impact Factor
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    ABSTRACT: Develop a swine model of secondary infection in severe acute pancreatitis (SAP). Twenty-seven female swine were divided into 3 groups (1-3). In the first experiment, a SAP model was developed by retrograde injection of sodium taurocholate and trypsin into the pancreatic duct. In the second experiment, the SAP model was used to develop a secondary infection model. In groups 1 to 3, 10⁸/mL or 10⁴/mL Escherichia coli or saline were respectively used to inoculate necrotic areas of the pancreas using computed tomographic guidance. Biochemical, histopathological, and imaging analyses were used to characterize disease presentation. The survival rate was 85.2% (23/27) during the course of the 9-day experiment. The secondary infection rates in groups 1 to 3 were 100% (8/8), 37.5% (3/8), and 14.3% (1/7), respectively. In group 1, the infection rate was significantly higher in comparison to the other 2 groups (χ²=4.66 and 8.14, respectively, and both P<0.05). The biochemical and histopathological parameters and computed tomographic images indicated successful development of the SAP secondary infection model. The swine model of SAP secondary infection was successfully developed using a 2-step method, which could serve as a platform for SAP studies that need complex experimental manipulations for longer time spans, especially for imaging research.
    Pancreas 10/2010; 40(1):114-9. · 2.95 Impact Factor