Zhiqian Hu

miR-374a promotes cell proliferation, migration and invasion by targeting SRCIN1 in gastric cancer

MicroRNAs (miRNAs) play a prominent role in gastric cancer (GC) initiation and progression. In this study, we found that miR‐374a expression was up‐regulated in human GC cell lines and tissues. Inhibition of miR‐374a suppressed GC cell proliferation, migration and invasion in vitro and slowed tumor growth in vivo. SRC kinase signaling inhibitor 1 (SRCIN1) was identified as a direct target of miR‐374a. Silencing of SRCIN1 significantly enhanced cell proliferation, migration and invasion, whereas SRCIN1 reintroduction partially abrogated the oncogenic effects of miR‐374a. Taken together, these findings suggest that miR‐374a functions as a candidate oncogene in GC by directly targeting SRCIN1. miR‐374a may therefore be useful as a promising therapeutic target for malignant GC.

Systematic Review and Meta-Analysis of Somatostatin Analogues in the Prevention of Postoperative Complication after Pancreaticoduodenectomy

Background: The use of somatostatin analogues (SAs) following pancreaticoduodenectomy (PD) is controversial. Method: Literature databases were searched systematically for relevant articles. A meta-analysis of all randomized controlled trials (RCTs) evaluating prophylactic SAs in PD was performed. Results: Fifteen RCTs involving 1,352 patients were included. There was a towards reduced incidences of pancreatic fistulas (p = 0.26), clinically significant pancreatic fistulas (p = 0.08), and bleeding (p = 0.05) in prophylactic SAs group. In subgroup analyses, prophylactic somatostatin significantly reduced the incidence of pancreatic fistulas (p = 0.02), with a nonsignificant trend toward reduced incidence of clinically significantly pancreatic fistulas (p = 0.06). Pasireotide significantly reduced the incidence of clinically significantly pancreatic fistulas (p = 0.03). Octreotide had no influence on the incidence of pancreatic fistulas. Conclusion: The current best evidence suggests prophylactic treatment with somatostatin or pasireotide has a potential role in reducing the incidence of pancreatic fistulas, while octreotide had no influence on the incidence of pancreatic fistulas. High-quality RCTs assessing the role of somatostatin and pasireotide are required for further verification.

Emodin enhances cisplatin-induced cytotoxicity in human bladder cancer cells through ROS elevation and MRP1 downregulation.

BackgroundChemoresistance is one of the most leading causes for tumor progression and recurrence of bladder cancer. Reactive oxygen species (ROS) plays a key role in the chemosensitivity of cancer cells. In the present study, emodin (1,3,8-trihydroxy-6-methylanthraquinone) was applied as a ROS generator in combination with cisplatin in T24 and J82 human bladder cancer cells.MethodsCell viability and apoptosis rate of different treatment groups were detected by 3-(4,5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide (MTT) and flow cytometry (FCM). The expression of transporters was measured at both the transcription and translation levels using PCR and western blotting. In vitro findings were confirmed by in vivo experiments using tumor-bearing mice. The expression of multidrug resistance-associated protein 1 (MRP1) in tumour tissue was measured using immunohistochemistry and side effects of the emodin/cisplatin co-treatment were investigated by histological examination.ResultsEmodin increased the cellular ROS level and effectively enhanced the cisplatin-induced cytotoxicity of T24 and J82 human bladder cancer cells through decreasing glutathione-cisplatin (GSH-cisplatin) conjugates. It blocked the chemoresistance of T24 and J82 cells to cisplatin through suppressing the expression of MRP1. This effect was specific in T24 and J82 cells but not in HCV-29 normal bladder epithelial cells. Consistent with in vitro experiments, emodin/cisplatin co-treatment increased the cell apoptosis and repressed the MRP1 expression in xenograft tumors, and without obvious systemic toxicity.ConclusionsThis study revealed that emodin could increase the cisplatin-induced cytotoxicity against T24 and J82 cells via elevating the cellular ROS level and downregulating MRP1 expression. We suggest that emodin could serve as an effective adjuvant agent for the cisplatin-based chemotherapy of bladder cancer.

Proteomic identification of tumor biomarkers associated with primary gallbladder cancer

AIM To identify potential biomarkers of primary gallbladder cancer (PGC). METHODS Fresh PGC, cholecystitis and normal gallbladder tissue specimens collected from 10 patients, respectively, were subjected to comparative proteomic analysis. The proteomic patterns of PGC were compared with those of cholecystitis and normal gallbladder tissues using two-dimensional gel electrophoresis (2-DE). The differentially expressed proteins were then identified using a MALDI-TOF mass spectrometer (MS) and database searches. To further validate these proteins, 20 samples of PGC tissues and normal tumor-adjacent tissues were collected for Western blot, quantitative real-time PCR, and immunohistochemical staining assay. RESULTS Seven differentially expressed protein spots were detected by 2-ED analysis by comparing the average maps of PGC, cholecystitis and normal gallbladder tissues. Six of the seven differentially expressed proteins were identified using MALDI-TOF MS, with three overexpressed and three underexpressed in PGC tissue. Protein levels of annexin A4 (ANXA4) were significantly elevated, and heat shock protein 90-beta (Hsp90β) and dynein cytoplasmic 1 heavy chain 1 (Dync1h1) were decreased in PGC tissues relative to the normal tumor-adjacent tissues as shown by Western blot analysis. However, levels of actin, aortic smooth muscle and gamma-actin were unchanged. In addition, the mRNA levels of all 5 proteins showed similar changes to those of the protein levels (P < 0.01). Further validation by immunohistochemical analysis showed the upregulated expression of ANXA4 and decreased expression of Hsp90β and Dync1h1 in the cytoplasm of PGC tissues relative to the normal tumor-adjacent tissues. CONCLUSION Three proteins are identified as potential biomarkers of PGC using proteomic analysis. The functions of these proteins in the carcinogenesis of PGC remain to be studied.

TROP2 promotes proliferation, migration and metastasis of gallbladder cancer cells by regulating PI3K/AKT pathway and inducing EMT

The human trophoblast cell surface antigen 2 (TROP2) is overexpressed in many cancers. However, its effect on proliferation, migration and metastasis of gallbladder cancer remains unclear. In this study, we found that TROP2 was highly expressed in gallbladder cancer. Overexpression of TROP2 was associated with poor prognosis. Knockdown of TROP2 in gallbladder cancer cell lines strongly inhibited the cell proliferation, clone formation, invasion and migration in vitro, while TROP2 overexpression had opposite effects. In addition, knockdown of TROP2 increased the expression of total PTEN, p-PTEN and PDK-1 but reduced p-AKT via PI3K/AKT pathway. TROP2 downregulation also inhibited vimentin and increased E-cadherin expression during epithelial-mesenchymal transition (EMT). Moreover, gallbladder cancer cells with TROP2 knockdown formed smaller xenografted tumors in vivo. In consistent with in vitro results, TROP2 inhibition decreased Akt phosphorylation, increased PTEN expression and postponed EMT of gallbladder cancer cells in vivo. In conclusion, we revealed that TROP2 promoted the proliferation, migration and metastasis of gallbladder cancer cells by regulating PI3K/AKT pathway and inducing EMT. TROP2 could serve as a potential prognostic biomarker and therapeutic target for the clinical management of gallbladder cancer.

Single Incision versus Conventional Multiport Laparoscopic Appendectomy: A Systematic Review and Meta-Analysis of Randomized Controlled Trials

Background: The efficacy of single incision laparoscopic appendectomy (SILA) in comparison with conventional multiport laparoscopic appendectomy (CMLA) has not been conclusively determined. Methods: A systematic literature review (Medline, EMBASE, Science Citation Index, and Cochrane Central Register of Controlled Trials) was performed. Meta-analyses of randomized controlled trials (RCTs) comparing SILA with CMLA were carried out by RevMan 5.0 software. Results: Eleven RCTs comparing SILA and CMLA were included. Overall, 1,216 patients were operated on: 611 cases by SILA versus 605 cases by CMLA. Compared with CMLA, SILA was associated with increased procedural difficulty, prolonged procedural duration, shorter length of hospital stay, earlier return to normal activity and better cosmesis. There were no significant differences in postoperative pain scores and complication rates between SILA and CMLA. Conclusion: The current best evidence shows SILA holds the promise of improving postoperative recovery and cosmetic result with equal efficacy and safety, whereas it is associated with higher surgical difficulty with longer surgical time when compared with CMLA.

HIF-1α activates hypoxia-induced BCL-9 expression in human colorectal cancer cells

B-cell CLL/lymphoma 9 protein (BCL-9), a multi-functional co-factor in Wnt signaling, induced carcinogenesis as well as promoting tumor progression, metastasis and chemo-resistance in colorectal cancer (CRC). However, the mechanisms for increased BCL-9 expression in CRC were not well understood. Here, we report that hypoxia, a hallmark of solid tumors, induced BCL-9 mRNA expression in human CRC cells. Analysis of BCL-9 promoter revealed two functional hypoxia-responsive elements (HRE-B and HRE-C) that can be specifically bound with and be transactivated by hypoxia inducible factors (HIF) -1α but not HIF-2α. Consistently, ectopic expression of HIF-1α but not HIF-2α transcriptionally induced BCL-9 expression levels in cells. Knockdown of endogenous HIF-1α but not HIF-2α by siRNA largely abolished the induction of HIF by hypoxia. Furthermore, there was a strong association of HIF-1α expression with BCL-9 expression in human CRC specimens. In summary, results from this study demonstrated that hypoxia induced BCL-9 expression in human CRC cells mainly through HIF-1α, which could be an important underlying mechanism for increased BCL-9 expression in CRC.

Retrograde vs Conventional Dissection Technique in Pancreaticoduodenectomy A Pilot Study

IMPORTANCE A retrograde dissection technique of pancreaticoduodenectomy in a caudocranial direction has been described recently. OBSERVATIONS Fifteen consecutive patients who underwent retrograde pancreaticoduodenectomy were compared with 15 consecutive patients operated on through a conventional approach. The mean (SD) intraoperative blood loss was 407 (202) mL in the retrograde group compared with 423 (253) mL in the conventional group (P = .84). The mean (SD) operative duration was 255 (57) minutes in the retrograde group compared with 264 (54) minutes in the conventional group (P = .66). The overall morbidity was 7 of 15 patients (47%) in the retrograde group and 6 of 15 (40%) in the conventional group (P > .99). Neither group had a positive resection margin or a perioperative death. CONCLUSIONS AND RELEVANCE The retrograde dissection technique had no significant difference in perioperative outcomes compared with the conventional dissection technique and could serve as an alternative dissection approach in pancreaticoduodenectomy.

The influence of marital status on survival of gallbladder cancer patients: a population-based study

Marital status has been found to be a prognostic factor for survival in various cancers, but its role in gallbladder cancer (GBC) has not been fully studied. In this study, we used the Surveillance, Epidemiology, and End Results Program (SEER)-registered database to analyze the survival of GBC patients with different marital status. A total of 6,627 GBC patients were selected from SEER database from 2004 to 2013. The age, race, grade, histologic type, AJCC stage, SEER stage and marital status were identified as independent prognostic factors. Married GBC patients had a higher 5-year cancer-specific survival (CSS) than that of unmarried ones (20.1% v.s. 17.8%, P < 0.05). Subgroup analyses showed that widowed patients had 14.0% less of 5-year CSS compared to married ones of stage I (55.9% v.s. 41.9%, P < 0.05), 14.7% of stage II (15.6% v.s. 10.9%, P < 0.05), and 1.5% of stage III + IV (2.9% v.s. 1.4%, P < 0.05). In addition, single is an independent prognostic factor at stage III + IV (HR = 1.225, 95%CI 1.054–1.423, P = 0.008). These results indicated that widowed patients were at a high risk of cancer-specific mortality and marriage can be a protective prognostic factor in CSS.

Age-specific impact on the survival of gastric cancer patients with distant metastasis: an analysis of SEER database

The age-specific impact on the survival of gastric cancer patients with distant metastasis is still unclear. In this study, we identified 11, 299 gastric cancer patients with distant metastasis between 2004 and 2013 from Surveillance, Epidemiology, and End Results population-based dataset. Patients were divided into young (≤60) and elderly groups (>60). Kaplan-Meier methods and multivariable Cox regression were used for the analysis of long-term survival outcomes and risk factors. There were significant differences between the two groups in terms of race, primary site, grade, histologic type, surgery, marital status and clinical T stage (P<0.05). The 1- and 3-year cancer specific survival rates were 29.0% and 6.2% in young group and 22.8% and 4.8% in elderly group in both univariate (X2=116.430, P<0.001) and multivariate analysis (P<0.001). Young patients had significantly better 1- and 3-year cancer specific survival than elderly patients in each T stage. Age was further validated as an independent survival factor in all T stages (T1, T2, T3, T4 and TX, P<0.05). In conclusion, age was an independent prognostic factor for gastric cancer patients with distant metastasis.