Linquan Wu

Overexpressed targeting protein for Xklp2 (TPX2) serves as a promising prognostic marker and therapeutic target for gastric cancer.

ABSTRACT The targeting protein for Xenopus kinesin-like protein 2 (TPX2) is a putative oncogene in different human cancers. This study assessed TPX2 expression in gastric cancer tissue samples and then determined the effects of TPX2 knockdown on the regulation of gastric cancer cell malignant behaviors in vitro. Tissue samples from 115 gastric cancer patients were analyzed for TPX2 expression. The effects of TPX2 siRNA on gastric cancer cells were assessed in vitro, including cell viability, cell cycle distribution, apoptosis, migration, and invasion. The data showed that TPX2 was overexpressed in gastric cancer tissues compared to that in the adjacent normal epithelia. Moreover, TPX2 overexpression was associated with a poor overall survival and was an independent prognostic predictor of gastric cancer. In addition, the in vitro study further confirmed the ex vivo data, i.e., knockdown of TPX2 expression reduced gastric cancer cell viability but induced apoptosis and arrested cells at the G2/M phase of the cell cycle. Knockdown of TPX2 expression also inhibited the tumor cell migration and invasion capacity in vitro. At the gene level, knockdown of TPX2 expression upregulated the levels of cyclin B1, cdk4, p53, Bax, caspase-3, and E-cadherin, but downregulated the levels of cyclin D1, cdk2, N-cadherin, slug, matrix metalloprotease (MMP)-2, and MMP-9, suggesting that knockdown of TPX2 expression suppressed tumor cell epithelial–mesenchymal transition (EMT). This study demonstrated that detection of TPX2 overexpression could serve as a prognostic marker and therapeutic target for gastric cancer.

Overexpression of non‑SMC condensin I complex subunit G serves as a promising prognostic marker and therapeutic target for hepatocellular carcinoma

The non-SMC condensin I complex subunit G (NCAPG) that organizes the coiling topology of individual chromatids, represents an overexpressed antigen in various types of cancer, and also contributes to restructuring chromatin into rod-shaped mitotic chromosomes and ensuring the segregation of sister chromatid during cell division. In this study, we investigated the association between NCAPG expression and the biological behavior of hepatocellular carcinoma (HCC) to further explore the potential of NCAPG as a therapeutic target. The expression of NCAPG was detected in human HCC cell lines and tumor samples. The effects of NCAPG on the cell cycle, apoptosis and metastasis were investigated by various assays. NCAPG was found to be overexpressed in HCC compared with the adjacent normal tissue (P<0.001), and high levels of NCAPG expression were found to significantly correlate with recurrence, the time of recurrence, metastasis, differentiation and TNM stage. Furthermore, an elevated expression of NCAPG was associated with a poor overall survival (P<0.05). In addition, in vitro experiments further confirmed the ex vivo data; i.e., the knockdown of NCAPG expression reduced HCC cell viability, but induced apoptosis and arrested the cells at the S phase of the cell cycle. The knockdown of NCAPG expression also inhibited tumor cell migration and the cell invasive capacity in vitro. At the protein level, the knockdown of NCAPG expression upregulated Bax, cleaved caspase-3 and E-cadherin, but downregulated cyclin A1, CDK2, Bcl-2, N-cadherin and HOXB9 expression, suggesting that the knockdown of NCAPG expression suppressed tumor cell epithelial-mesenchymal transition. On the whole, this study demonstrates that NCAPG plays an important role in the development and progression of HCC, and that it may be a novel therapeutic target for patients with HCC.

The diagnostic value of assays for circulating tumor cells in hepatocellular carcinoma: A meta-analysis

Purpose: Circulating tumor cells (CTCs) are considered potential biomarkers for the detection of hepatocellular carcinoma (HCC). Many studies have attempted to explore this role, but the results are variable. We conducted the first comprehensive meta-analysis to evaluate the diagnostic value of CTC assay for HCC patients. Additional prognostic value was also assessed. Experimental design: All articles included in our study were assessed using QUADAS guidelines after a literature search. Using bivariate generalized linear mixed model and random-effects model, effect measures such as pooled sensitivity/specificity, positive likelihood ratios/negative likelihood ratios (NLRs), diagnostic odds ratios, hazard ratios (HRs), risk ratios, and corresponding 95% confidence intervals (95% CIs) were calculated. We used receiver operating characteristic curves and area under the curve (AUC) to summarize overall test performance. Heterogeneity, publication bias, subgroup, and sensitivity analyses were also performed. Results: A total of 2256 subjects including 998 HCC patients in 20 studies were recruited in this meta-analysis. Although the overall diagnostic accuracy of the CTC assay was high (AUC 0.93, 95% CI: [0.90–0.95]), there was a high probability of error rate (NLR 0.33, 95% CI: [0.23, 0.48]). The results were more robust when nonmagnetic-activated isolation was used, compared with magnetic-activated isolation subgroup (NLR: 0.18 vs. 0.41; z = 2.118, P = .034). CTCs positivity was significantly associated with relapse-free survival (HR 2.417, 95% CI: [1.421–3.250]; P < .001), overall survival (HR 3.59, 95% CI: [1.984–6.495]; P < .001), and some clinical characteristics. Conclusion: CTC assay is not recommended as an independent HCC diagnostic tool, but is associated with poor clinicopathologic characteristics of HCC patients and could indicate poor prognosis.

Laparoscopic Transcystic Common Bile Duct Exploration: Advantages over Laparoscopic Choledochotomy

Purpose The ideal treatment for choledocholithiasis should be simple, readily available, reliable, minimally invasive and cost-effective for patients. We performed this study to compare the benefits and drawbacks of different laparoscopic approaches (transcystic and choledochotomy) for removal of common bile duct stones. Methods A systematic search was implemented for relevant literature using Cochrane, PubMed, Ovid Medline, EMBASE and Wanfang databases. Both the fixed-effects and random-effects models were used to calculate the odds ratio (OR) or the mean difference (MD) with 95% confidence interval (CI) for this study. Results The meta-analysis included 18 trials involving 2,782 patients. There were no statistically significant differences between laparoscopic choledochotomy for common bile duct exploration (LCCBDE) (n = 1,222) and laparoscopic transcystic common bile duct exploration (LTCBDE) (n = 1,560) regarding stone clearance (OR 0.73, 95% CI 0.50–1.07; P = 0.11), conversion to other procedures (OR 0.62, 95% CI 0.21–1.79; P = 0.38), total morbidity (OR 1.65, 95% CI 0.92–2.96; P = 0.09), operative time (MD 12.34, 95% CI −0.10–24.78; P = 0.05), and blood loss (MD 1.95, 95% CI −9.56–13.46; P = 0.74). However, the LTCBDE group showed significantly better results for biliary morbidity (OR 4.25, 95% CI 2.30–7.85; P<0.001), hospital stay (MD 2.52, 95% CI 1.29–3.75; P<0.001), and hospital expenses (MD 0.30, 95% CI 0.23–0.37; P<0.001) than the LCCBDE group. Conclusions LTCBDE is safer than LCCBDE, and is the ideal treatment for common bile duct stones.

Inhibitory effect of humanized anti-VEGFR-2 ScFv-As2O3-stealth nanoparticles conjugate on growth of human hepatocellular carcinoma: in vitro and in vivo studies

OBJECTIVE To investigate the inhibitory effect of humanized anti-VEGFR-2 ScFv-As2O3-stealth nanoparticles conjugate on growth of human hepatocellular carcinoma both in vitro and in vivo, which may be a potential agents with sensitivity and targeting ability for human hepatocellular cancer. METHODS Humanized anti-VEGFR-2 ScFv-As2O3-stealth nanoparticles conjugate was previously constructed using ribosome display technology and antibody conjugate technology. In this combined in vitro and in vivo study, the inhibitory effects of anti-VEGFR-2 ScFv-As2O3-stealth nanoparticles conjugate on tumor growth, invasion, and metastasis was observed with human liver carcinoma cell line Bel7402 and normal cell L02 by MTT assay, Tanswell assay, Hochest33258 staining, and DNA ladder analysis. The anticancer activity and distribution of anti-VEGFR-2 ScFv-As2O3-stealth nanoparticles was then verified in a mouse model of Bel7402 xenografts. RESULTS Anti-VEGFR-2 ScFv-As2O3-stealth nanoparticles significantly inhibited the proliferation of Bel7402 in the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay while had almost no effects on L02 cells. And the apoptosis inducing effects were proved by Hochest33258 staining and DNA ladder analysis. Transwell assay found that the drug also inhibited the metastasis ability of tumor cells. Furthermore, anti-VEGFR-2 ScFv-As2O3-stealth nanoparticles significantly delayed the growth of Bel7402 xenografts after administration (92.9%), followed by As2O3-stealth nanoparticles, anti-VEGFR-2 ScFv, and As2O3 (61.4%, 58.8%, 20.5%, P<0.05). The concentration of As2O3 in anti-VEGFR-2 ScFv-As2O3-stealth nanoparticles group was more selectively. CONCLUSIONS Anti-VEGFR-2 ScFv-As2O3-stealth nanoparticles is a potent and selective anti-hepatocellular carcinoma agent which could inhibit the growth of liver cancer as a targeting agent both in vitro and in vivo and also significantly inhibit angiogenesis.

miR‑29a suppresses the growth and metastasis of hepatocellular carcinoma through IFITM3

The interferon-induced transmembrane protein 3 (IFITM3, also called 1-8U) gene represents dysregulated expression in various tumors and is involved in tumorigenesis and progression. However, the role of IFITM3 and its underlying mechanism in hepatocellular carcinoma (HCC) are still far from elucidated. MicroRNAs (miRNAs), a class of endogenous (approximately 22 nucleotides) small noncoding RNAs, can post-transcriptionally regulate gene expression by repressing protein translation or silencing the expression of target genes that play critical roles in various cancers. miR-29a was identified as being aberrantly expressed in a significant proportion of HCC. However, the correlation between IFITM3 and miR-29a has not been reported to date. In this study, we investigated the expression of IFITM3 in HCC and its effect on the biological behavior of HCC cells as well as the association between IFITM3 and miR-29a. We determined that IFITM3 was upregulated and miR-29a downregulated in HCC tissues and that they were associated with HCC tumor size, tumor multifocal, and venous invasion. The expression of IFITM3 in HCC tissues was negatively correlated with miR-29a expression. Additionally, IFITM3 overexpression and miR-29a nonoverexpression were related to poor prognosis of HCC patients. Knockdown of IFITM3 inhibited migration, invasion, proliferation and promoted apoptosis of HCC cells, which are consistent with the effects of upregulated miR-29a. Additionally, after upregulation of IFITM3, the invasion, migration and proliferation abilities of HL-7702 cells were increased, but the apoptosis rate was decreased. Furthermore, using a Dual-Luciferase reporter gene assay, we identified IFITM3 as a new functional target gene of miR-29a. In conclusion, our findings demonstrated that the migration, invasion, proliferation and apoptosis features of HCC cells could be regulated by miR-29a via IFITM3. Thus, the present study indicated that miR-29a and IFITM3 play critical roles in the development and progression of HCC, revealing that miR-29a and IFITM3 may be novel potential therapeutic targets for patients with HCC.

IFITM3 promotes hepatocellular carcinoma invasion and metastasis by regulating MMP9 through p38/MAPK signaling

Interferon‐induced transmembrane protein 3 (IFITM3) has been shown to be overexpressed in multiple cancers. However, the role of IFITM3 in metastasis of hepatocellular carcinoma (HCC) is still poorly understood. In this study, we showed that IFITM3 was frequently overexpressed in HCC tissues compared with adjacent nontumor tissues. Overexpression of IFITM3 was significantly correlated with tumor metastasis and poor prognosis in HCC. Knockdown of IFITM3 dramatically decreased MMP9 expression and inhibited the invasion and metastasis of HCC in vitro and in vivo. Moreover, the upregulation of MMP9 rescued the decreased migration and invasion induced by the knockdown of IFITM3, whereas the knockdown of MMP9 decreased IFITM3‐enhanced HCC migration and invasion. Mechanistically, we found that IFITM3 regulates MMP9 expression through the p38/MAPK pathway. Taken together, we identified a novel IFITM3–p38/MAPK–MMP9 regulatory circuitry, the dysfunction of which drives invasive and metastatic character in HCC.

Rare anatomic variation of the right hepatic artery and accessory right hepatic artery supplying hepatocellular carcinoma: A case report and literature review

Introduction: Each hepatic artery is functionally essential for providing blood supply to the liver, and so are variant arteries. Variant arteries, including the accessory right hepatic artery (ARHA) and replaced right hepatic artery (RRHA) are commonly described in the literature. However, they usually occur independently. Here, we report an extremely rare case that involved both an ARHA and an RRHA arising from the gastroduodenal artery (GDA) and superior mesenteric artery (SMA), respectively. To date, this situation has never been reported in the literature. They were preoperatively identified during magnetic resonance imaging (MRI) examination in a 69-year-old male patient with hepatocellular carcinoma. And they were further verified by following conventional angiography for transcatheter arterial chemoembolization (TACE) for the patient. In addition, the patients tumor was primarily supplied by these 2 variant arteries. After the successful TACE procedure, the patient had a well postoperative recovery. Conclusions: By analyzing this case and performing a systematic review of the literature, the important clinical implications of the ARHA and RRHA will be investigated and discussed. Main lessons learned from this case thorough understanding of the normal anatomy of the hepatic artery and its anatomic variation is crucial for surgeons and interventional radiologists; preoperative computed tomography, MRI, and intraoperative angiography play an important role in detecting the variant hepatic artery; identifying these anomalous hepatic arteries before operation can effectively avoid unintentional injury during surgery, such as massive hemorrhage or hepatic infarction.