Investigating the effect of Icaritin on hepatocellular carcinoma based on network pharmacology.

Hepatocellular carcinoma is one of the cancers that kill people in the global population. Icaritin, a small molecule drug approved by NMPA, has demonstrated potential anti-HCC effects. However, its underlying molecular mechanisms remain unclear. We employed a multi-omics approach in this study, including pharmaco-omics and proteomics, to look into the Icaritin's possible molecular targets and workings in the therapy of HCC. Through pharmaco-omics analysis, we identified ten putative target genes of Icaritin, including FYN. The relationship between Icaritin and these target genes, particularly FYN, was further validated through in vitro and in vivo experiments. The outcomes revealed that Icaritin may exert its anti-HCC effects through modulating the FYN gene, highlighting the importance of multi-omics approaches in drug discovery research. This research gives valuable insights regarding the therapeutic potential of Icaritin against HCC and its possible molecular mechanisms.

Cryptotanshinone induces cell cycle arrest and apoptosis through the JAK2/STAT3 and PI3K/Akt/NFκB pathways in cholangiocarcinoma cells.

BACKGROUND: Cholangiocarcinoma (CCA) is the most common biliary tract malignancy in the world with high resistance to current chemotherapies and extremely poor prognosis. The main objective of this study was to investigate the inhibitory effects of cryptotanshinone (CTS), a natural compound isolated from Salvia miltiorrhiza Bunge, on CCA both in vitro and in vivo and to explore the underlying mechanisms of CTS-induced apoptosis and cell cycle arrest. METHODS: The anti-tumor activity of CTS on HCCC-9810 and RBE cells was assessed by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-tetrazolium bromide (MTT) assay and colony forming assays. Cell cycle changes were detected by flow cytometric analysis. Apoptosis was detected by annexin V/propidium iodide double staining and Hoechst 33342 staining assays. The efficacy of CTS in vivo was evaluated using a HCCC-9810 xenograft model in athymic nude mice. The expression of key proteins involved in cell apoptosis and signaling pathway in vitro was analyzed by Western blot analysis. RESULTS: CTS induced potent growth inhibition, S-phase arrest, apoptosis, and colony-forming inhibition in HCCC-9810 and RBE cells in a dose-dependent manner. Intraperitoneal injection of CTS (0, 10, or 25 mg/kg) for 4 weeks significantly inhibited the growth of HCCC-9810 xenografts in athymic nude mice. CTS treatment induced S-phase arrest with a decrease of cyclin A1 and an increase of cyclin D1 protein level. Bcl-2 expression was downregulated remarkably, while Bax expression was increased after apoptosis occurred. Additionally, the activation of JAK2/STAT3 and PI3K/Akt/NFκB was significantly inhibited in CTS-treated CCA cells. CONCLUSION: CTS induced CCA cell apoptosis by suppressing both the JAK2/STAT3 and PI3K/Akt/NFκB signaling pathways and altering the expression of Bcl-2/Bax family, which was regulated by these two signaling pathways. CTS may serve as a potential therapeutic agent for CCA.

MiR-31 regulates the cisplatin resistance by targeting Src in gallbladder cancer.

BACKGROUND: Gallbladder cancer (GBC) is a malignant tumor highly resistant to chemotherapy. MicroRNAs (miRNAs) are found extensively involved in modulation of carcinogenesis and chemoresistance. This study aimed to investigate cisplatin (DDP)-susceptibility regulated by expression of the miRNAs and underlying pathways in GBC. RESULTS: The microRNA-31 (miR-31) was selected by microarray due to the biggest fold change between DDP-resistant and parental cells. Ectopic overexpression of miR-31 decreased cell proliferation, viability and invasion capacity, but promoted apoptosis in DDP-resistant cells and in xenograft tumor models. Cell apoptosis and DDP-chemosensitivity was remarkably increased by knockdown of Src proto-oncogene (Src) expression, which was subsequently reversed by rescue of Src expression in miR-31-expressing cells. METHODS: The microarray was used to select the candidate miRNA in two DDP-resistant GBC cell lines. The effect of regulated expression of the miRNA on cell migration, invasion, proliferation and apoptosis was examined by wound healing, transwell assays, CCK-8 assays, colony formation and flow cytometry assays, respectively. Xenograft tumor models were used to validate the function of the downstream target. CONCLUSION: Our results demonstrated that miR-31reduced significantly in GBC cells rendering resistance to cisplatin, and upregulated expression of miR-31 augmented chemosensitivity, presenting a therapeutic potential to overcome drug resistance in GBC.

Upregulated LASP-1 correlates with a malignant phenotype and its potential therapeutic role in human cholangiocarcinoma.

LIM and SH3 protein 1 (LASP-1) is demonstrated to play a key role in occurrence and development of tumors. However, the expression and function of LASP-1 in cholangiocarcinoma (CCA) remain largely unexplored. This study aimed to investigate the effect of regulated LASP-1 expression on migration, invasion, proliferation, and apoptosis of CCA cells and on tumorigenesis in vivo, and to examine clinico-oncological correlates of LASP-1 expression. Expression of LASP-1 by immunohistochemistry was evaluated in CCA tissue samples. HCCC-9810 and RBE cells were transfected with the LASP-1 small interfering RNA (siRNA), and the effect of knocking down LASP-1 gene expression on cell migration, invasion, proliferation, and apoptosis were examined by wound healing, transwell assays, CCK-8 assays, colony formation, and flow cytometry assays, respectively. Xenograft tumor model was used to validate the effect of downregulated LASP-1 in vivo. Our results demonstrated that LASP-1 was over-expressed in CCA tissues, positively correlating with larger tumors, poor histological differentiation, lymph node metastasis, advanced TNM stage, and poor prognosis in CCA patients (P < 0.05). Downregulation of LASP-1 in HCCC-9810 and RBE cell lines significantly increased cell apoptosis and suppressed cell migration, invasion, and proliferation in vitro and tumorigenesis in vivo. Our results indicate that LASP-1 may essentially involve in the metastasis and growth of CCA and clinical significance of LASP-1 may reside in function as a biomarker to predict prognosis and as a promising therapeutic strategy for CCA patients by the inhibition of LASP-1 expression.

Radiological Imaging for Assessing the Respectability of Hilar Cholangiocarcinoma: A Systematic Review and Meta-Analysis.

Hilar cholangiocarcinoma (HCC) remains one of the most difficult tumors to stage and treat. The aim of the study was to assess the diagnostic efficiency of computed tomography (CT), magnetic resonance imaging (MRI), and positron emission tomography/computer tomography (PET/CT) in evaluating the resectability of HCC. A systematic search was performed of the PubMed, EMBASE, and Cochrane databases. Sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and diagnostic accuracy were calculated for individual studies and pooled data as well as test for heterogeneity and public bias. Our data showed that CT had the highest pooled sensitivity at 95% (95% CI: 91-97), whereas PET/CT had the highest pooled specificity at 81% (95% CI: 69-90). The area under the curve (AUC) of CT, MRI, and PET/CT was 0.9269, 0.9194, and 0.9218, respectively. In conclusion, CT is the most frequently used imaging modality to assess HCC resectability with a good sensitivity and specificity. MRI was generally comparable with that of CT and can be used as an alternative imaging technique. PET/CT appears to be the best technique in detecting lymph node and distant metastasis in HCC but has no clear role in helping to evaluate issues of local resectability.

Comparison of postoperative complications between internal and external pancreatic duct stenting during pancreaticoduodenectomy: a meta-analysis.

BACKGROUND: Two types of pancreatic duct stents are used to improve postoperative outcomes of pancreatic anastomosis. The aim of this meta-analysis was to evaluate and compare the postoperative outcomes of patients with internal or external stenting during pancreaticoduodenectomy (PD). METHODS: We searched PubMed, EMBASE, the Cochrane Library and Web of Science databases until the end of December, 2014. Studies comparing outcomes of external vs. internal stent placement in PD were eligible for inclusion. Included literature was extracted and assessed by two independent reviewers. RESULTS: Seven articles were identified for inclusion: three randomized controlled trials (RCTs) and four observational clinical studies (OCS). The meta-analyses revealed that use of external stents had advantage on reducing the incidences of pancreatic fistula (PF) in total [odds ratio (OR) =0.69; 95% confidence interval (CI), 0.48-0.99; P=0.04], PF in soft pancreas (OR =0.30; 95% CI, 0.16-0.56; P=0.0002) and delayed gastric emptying (DGE) (OR =0.58; 95% CI, 0.38-0.89; P=0.01) compared with internal stents. There were no significant differences in other postoperative outcomes between two stenting methods, including postoperative morbidity (OR =0.93; 95% CI, 0.39-2.23; P=0.88), overall mortality (OR =0.70; 95% CI, 0.22-2.25; P=0.55), and intra-abdominal collections (OR =0.67; 95% CI, 0.26-1.71; P=0.40). CONCLUSIONS: Based upon this meta-analysis, the use of external pancreatic stents might have potential benefit in reducing the incidence of PF and DGE. Due to the limited number of original studies, more RCTs are needed to further support our result and clarify the issue.

Does the reporting of randomized clinical trials published in Chinese pediatrics journals improve after the CONSORT Statement is adopted?

BACKGROUND: There is no systematic assessment whether the quality of reporting has been improved since the CONSORT Statement was introduced into China in 1997. The aim of this study is to determine whether the use of the CONSORT Statement is associated with improved quality of reporting of RCTs published in Chinese pediatrics journals. METHODS: Six core Chinese pediatrics journals that included Journal of Clinical Pediatrics, Chinese Journal of Contemporary Pediatrics, Chinese Journal of Practical Pediatrics, Chinese Journal of Evidence-based Pediatrics, Chinese Journal of Pediatrics, and Chinese Journal of Pediatric Surgery were searched from inception through Dec. 2010. The CONSORT checklists were used to assess the quality of reporting. Data was collected using a standardized form. Analyses were performed using SPSS 15.0 software. RESULTS: A total of 619 RCTs were included. The quality of reporting has improved significantly in aspects such as introduction, recruitment, baseline data, and ancillary analyses (p<0.05), but not in several important methodological components, including sample size calculation (0.63% vs.1.08%), randomization sequence generation (3.18% vs. 7.58%), allocation concealment (0% vs. 1.08%), and blinding (0% vs. 0.87%). CONCLUSIONS: The quality of reporting of RCTs has not significantly improved since the CONSORT Statement was introduced into China. The reporting remains poor, and often inadequate for assessment of the rigor of studies. Chinese pediatrics journals should reinforce the use of the CONSORT Statement in the reporting of trials.