Xiaoming Shuai

Sericin/Dextran Injectable Hydrogel as an Optically Trackable Drug Delivery System for Malignant Melanoma Treatment

Severe side effects of cancer chemotherapy prompt developing better drug delivery systems. Injectable hydrogels are an effective site-target system. For most of injectable hydrogels, once delivered in vivo, some properties including drug release and degradation, which are critical to chemotherapeutic effects and safety, are challenging to monitor. Developing a drug delivery system for effective cancer therapy with in vivo real-time noninvasive trackability is highly desired. Although fluorescence dyes are used for imaging hydrogels, the cytotoxicity limits their applications. By using sericin, a natural photoluminescent protein from silk, we successfully synthesized a hydrazone cross-linked sericin/dextran injectable hydrogel. This hydrogel is biodegradable and biocompatible. It achieves efficient drug loading and controlled release of both macromolecular and small molecular drugs. Notably, sericins photoluminescence from this hydrogel is directly and stably correlated with its degradation, enabling long-term in vivo imaging and real-time monitoring of the remaining drug. The hydrogel loaded with Doxorubicin significantly suppresses tumor growth. Together, the work demonstrates the efficacy of this drug delivery system, and the in vivo effectiveness of this sericin-based optical monitoring strategy, providing a potential approach for improving hydrogel design toward optimal efficiency and safety of chemotherapies, which may be widely applicable to other drug delivery systems.

HMGB1 recruits myeloid derived suppressor cells to promote peritoneal dissemination of colon cancer after resection

Peritoneal metastasis of colorectal cancer is a major clinical issue and results in poor prognosis for patients after surgical resection. Here, we found that abdominal surgery trauma induced high release of high-mobility group box 1 (HMGB1) in the peritoneal cavity of mice. Recombinant HMGB1 injected in the peritoneal cavity recruited abundant myeloid derived suppressor cells (MDSCs) after the surgical trauma. HMGB1 Box-A and gemcitabine reduced the recruitment of MDSCs in the peritoneal cavity after the operation and ameliorated the peritoneal metastasis burden of colon cancer in mouse model. These results showed that abdominal surgery trauma leads to a large amount of HMGB1 released in the peritoneal cavity which recruits numerous MDSCs to promote peritoneal metastasis of colon cancer after curative surgery.

Inhibition enhancer of zeste homologue 2 promotes senescence and apoptosis induced by doxorubicin in p53 mutant gastric cancer cells

Enhancer of zeste homologue 2 (EZH2) is crucially involved in epigenetic silencing by acting as a histone methyltransferase. Although EZH2 is overexpressed in many cancers and is involved in malignant cell proliferation and invasion, the role of EZH2 in senescence induced by DNA damage has up to now remained largely unknown. In this study, we sought to explore the outcome of EZH2 depletion along with exposure of doxorubicin (DOX), and related mechanisms, in gastric cancer cells.

Inhibiting Enhancer of Zeste Homolog 2 Promotes Cellular Senescence in Gastric Cancer Cells SGC-7901 by Activation of p21 and p16

Cellular senescence, which can be defined as a stress response preventing the propagation of cells that have accumulated potentially oncogenic alterations, is invariably associated with a permanent cell cycle arrest. Enhancer of zeste homolog 2 (EZH2) as a member of polycomb group proteins and its targets include cell cycle regulatory proteins, which govern cell cycle progression and cellular senescence. In this study, we report that EZH2 depletion promotes the senescent state in human gastric cancer cells SGC-7901. We found that EZH2 functionally suppressed the senescent state in human gastric cancer cells SGC-7901. EZH2 depletion inhibited cell proliferation, arrested cellular cycle, restored features of a cellular senescence phenotype, and promoted doxorubicin-induced senescence. To prove that EZH2 expression contributes substantially to the change of key cell cycle regulators, we showed that p21 and p16 were activated to a certain extent upon EZH2 depletion and activation of p21 was in a p53-independent manner. Taken together, our data suggest that EZH2 depletion promotes the progression of senescence by mediating the activation of tumor suppressor genes p21 and p16, and could serve as a potential epigenetic target for gastric cancer therapy.

The comprehensive summary of surgical versus non-surgical treatment for obesity: a systematic review and meta-analysis of randomized controlled trials

Background Bariatric surgery has emerged as a competitive strategy for obese patients. However, its comparative efficacy against non-surgical treatments remains ill-defined, especially among nonseverely obese crowds. Therefore, we implemented a systematic review and meta-analysis in order for an academic addition to current literatures. Methods Literatures were retrieved from databases of PubMed, Web of Science, EMBASE and Cochrane Library. Randomized trials comparing surgical with non-surgical therapies for obesity were included. A Revised Jadads Scale and Risk of Bias Summary were employed for methodological assessment. Subgroups analysis, sensitivity analysis and publication bias assessment were respectively performed in order to find out the source of heterogeneity, detect the outcome stability and potential publication bias. Results 25 randomized trials were eligibly included, totally comprising of 1194 participants. Both groups displayed well comparability concerning baseline parameters (P > 0.05). The pooled results of primary endpoints (weight loss and diabetic remission) revealed a significant advantage among surgical patients rather than those receiving non-surgical treatments (P < 0.05). Furthermore, except for certain cardiovascular indicators, bariatric surgery was superior to conventional arms in terms of metabolic secondary parameters (P < 0.05). Additionally, the pooled outcomes were confirmed to be stable by sensitivity analysis. Although Eggers test (P < 0.01) and Beggs test (P<0.05) had reported the presence of publication bias among included studies, “Trim-and-Fill” method verified that the pooled outcomes remained stable. Conclusion Bariatric surgery is a better therapeutic option for weight loss, irrespective of follow-up duration, surgical techniques and obesity levels.

The Safety and Efficiency of Surgery with Colonic Stents in Left-Sided Malignant Colonic Obstruction: A Meta-Analysis

Objective. This meta-analysis is aimed at assessing the safety and efficiency of colonic self-expanding metallic stents (SEMS) used as a bridge to surgery in the management of left-sided malignant colonic obstruction (LMCO). Methods. A systematic search was conducted in PubMed, Web of Knowledge, OVID, Google Scholar, CNKI, and WANGFANG for relevant randomized trials comparing colonic stenting used as a bridge in semielective surgery versus emergency surgery from January 2001 to September 2013. Result. Five published studies were included in this systematic review, including 273 patients (140 male/133 female). 136 patients received semielective surgery after SEMS installation while 137 patients underwent emergency surgery without SEMS. SEMS intervention resulted in significantly lower overall colostomy rate (41.9% versus 56.2%, P = 0.02), surgical site infection rate (10.2% versus 19.7%, P = 0.03), and overall complication rate (29.2% versus 60.5%, P = 0.05). There was no statistic difference for the rate of primary anastomosis, anastomotic leak and operation-related mortality between two groups. Conclusions. semielective surgery with SEMS as a bridge for proper patients of LMCO can lower the overall rate for colostomy, surgical site infection, and complications.

miR-219-5p plays a tumor suppressive role in colon cancer by targeting oncogene Sall4

Sall4 is a novel oncogene found upregulated in several malignancies including colon cancer. However, its upstream regulatory miRNA is still undefined. miR-219-5p is regarded as a tumor-related miRNA in cancer research. Nevertheless, its actual role of whether inhibiting or promoting tumorigenesis is unclear in colon cancer. Potential interaction between Sall4 and miR-219-5p is predicted by TargetScan. CCK-8 test was used for evaluation of cell proliferation and cell survival rates. Western blot analysis and real-time PCR were applied for detection of target molecules. Luciferase assay was a direct confirmation of mutual interaction. Wound healing assay and transwell assay were conducted for cell migration and invasion tests. Flow cytometry was used for cell apoptosis analysis. Tissue specimens and cell lines were explored for miR-219-5p inhibition on colon cancer proliferation, migration, invasion, apoptosis and drug resistance by targeting Sall4. The results show that miR-219-5p inhibited carcinogenesis of colon cancer by targeting oncogene Sall4.

Two-dimensional versus three-dimensional laparoscopy in surgical efficacy: a systematic review and meta-analysis

Background Laparoscopy is a revolutionary technique in modern surgery. However, the comparative efficacy between two-dimensional laparoscopy and three-dimensional laparoscopy remains in uncertainty. Therefore we performed this systematic review and meta-analysis in order to seek for answers. Methods Databases of PubMed, Web of Science, EMBASE and Cochrane Library were carefully screened. Clinical trials comparing two-dimensional versus three-dimensional laparoscopy were included for pooled analysis. Observational and randomized trials were methodologically appraised by Newcastle-Ottawa Scale and Revised Jadads Scale respectively. Subgroup analyses were additionally conducted to clarify the potential confounding elements. Outcome stability was examined by sensitivity analysis, and publication bias was analyzed by Beggs test and Eggers test. Results 21 trials were screened out from the preliminary 3126 records. All included studies were high-quality in methodology, except for Bilgen 2013 and Ruan 2015. Three-dimensional laparoscopy was superior to two-dimensional laparoscopy in terms of surgical time (P < 0.00001), blood loss (P = 0.01), perioperative complications (P = 0.04) and hospital stay (P = 0.03). Additionally, both techniques demonstrated comparable results of secondary endpoints, including drainage volume (P = 0.74), drainage time (P = 0.26), numbers of retrieved lymphnodes (P = 0.85), hospital expenses (P = 0.49), anastomosis time in prostatectomy (P=0.15) and 6-month continence rate (P = 0.61). The pooled outcomes of primary endopoints were verified to be stable by sensitivity analysis. Although Beggs test (P = 0.215) and Eggers test (P = 0.003) revealed that there was publication bias across included studies, Trim-and-Fill method confirmed that the results remained stable. Conclusion Three-dimensional laparoscopy is a preferably surgical option against two-dimensional laparoscopy due to its better surgical efficacy.

Role of IL-17 and TGF-β in peritoneal adhesion formation after surgical trauma

Peritoneal adhesions are fibrous tissues formed after surgery. Both cytokines and transforming growth factors (TGFs) are involved in this process. The objective of this study was to investigate the cross talk between these entities. Peritoneal drainage fluid after surgery from patients and rodent models was examined by enzyme‐linked immunosorbent assay and fluorescence‐activated cell sorter. Data showed that the concentrations of interferon (IFN)‐γ and interleukin (IL)‐17 reached their peaks 6–12 hours after surgery, whereas TGF‐β1 concentrations showed two postoperative peak time points at 2 and 72–96 hours. By neutralizing IFN‐γ, IL‐17 6–12 hours, and TGF‐β1 72–96 hours after surgery, the degree of adhesion reduced significantly. However, neutralizing TGF‐β1 2 hours after surgery did not affect adhesion formation. Furthermore, in vitro studies showed that compared with the fibroblasts that were directly stimulated with TGF‐β1, the prestimulation of IL‐17 promoted plasminogen activator inhibitor‐1 production while inhibiting tissue‐type plasminogen activator production. Moreover, additional stimulation with IFN‐γ enhanced this effect. Together, these data indicate that IL‐17 may promote adhesion formation by increasing the reaction of fibroblasts against TGF‐β1. Blocking IL‐17 might have a therapeutic potential in preventing adhesion formation after surgery.

Oncogenic protein SALL4 and ZNF217 as prognostic indicators in solid cancers: a meta‑analysis of individual studies

Background SALL4 and ZNF217 have been widely acknowledged as pivotal effectors stimulating embryonic immortalization as well as oncogenicity. Nevertheless, their prognostic worthiness towards solid tumors remains obscure. Hence we performed this comprehensive meta-analysis aiming to unveil the survival significance of both aberrantly expressed proteins. Results Overall we included 22 eligible entries comprising of 3093 participants. Over-expression of SALL4 and ZNF217 were negatively correlated with clinical prognosis of 3-year, 5-year, 10-year and disease-free survival in solid malignancies, irrespective of cancer types, source regions, mean-age and sex predominance. Results of sensitivity analysis additionally verified the stability of the pooled outcomes. No publication bias was observed on the basis of Eggers test and Beggs test. Methods Studies were eventually included via database searching and rigorous eligibility appraisal. Data extraction and methodological assessment were implemented under a standard manner. Review Manager 5.3 and STATA 12.0 were utilized as statistical platforms following the recommendations by Cochrane Collaboration protocols. Conclusions Aberrant amplification of SALL4 and ZNF217 serve as unfavorable predictors of survival expectancy among cancer sufferers, revealing great potential as targeted spots in future therapeutics.