Long non-coding RNA antisense non-coding RNA in the INK4 locus (ANRIL) has been reported to promote tumorigenesis via regulating microRNA (miR)-99a in gastric cancer cells. However, the role of each component involved in it is still not well understood. This study aimed to verify the role of ANRIL in gastric cancer as well as the underlying mechanisms. ANRIL levels in clinical gastric cancer tissues and cell lines were tested by qPCR. Effects of ANRIL silence on cell viability, migration and invasion, apoptosis, and miR-99a expression in MKN-45 and SGC-7901 cells were measured using CCK-8, Transwell assay, flow cytometry, and qPCR assays, respectively. Then, effects of miR-99a inhibition on ANRIL-silenced cells were evaluated. B-lymphoma Mo-MLV insertion region 1 (BMI1) expression, after abnormal expression of ANRIL and miR-99a, was determined. Finally, expression of key proteins in the apoptotic, Notch, and mTOR pathways was assessed. ANRIL level was elevated in gastric cancer tissues and cell lines. Knockdown of ANRIL suppressed cell viability, migration, and invasion, and increased apoptosis through up-regulating miR-99a. Furthermore, ANRIL silence down-regulated BMI1 via up-regulating miR-99a. BMI1 silence down-regulated Bcl-2 and key kinases in the Notch and mTOR pathways and up-regulated p16 and cleaved caspases. We verified the tumor suppressive effects of ANRIL knockdown in gastric cancer cells via crosstalk with miR-99a. Together, we provided a novel regulatory mechanism for ANRIL in gastric cancer, in which ANRIL silence down-regulated BMI1 via miR-99a, along with activation of the apoptotic pathway and inhibition of the Notch and mTOR pathways.

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Knockdown of long non-coding RNA ANRIL inhibits tumorigenesis in human gastric cancer cells via microRNA-99a-mediated down-regulation of BMI1

The limitations of traditional two-dimensional (2D) cultures and animal testing, when it comes to precisely foreseeing the toxicity and clinical effectiveness of potential drug candidates, have resulted in a notable increase in the rate of failure during the process of drug discovery and development. Three-dimensional (3D) in-vitro models have arisen as substitute platforms with the capacity to accurately depict in-vivo conditions and increasing the predictivity of clinical effects and toxicity of drug candidates. It has been found that 3D models can accurately represent complex tissue structure of human body and can be used for a wide range of disease modeling purposes. Recently, substantial progress in biomedicine, materials and engineering have been made to fabricate various 3D in-vitro models, which have been exhibited better disease progression predictivity and drug effects than convention models, suggesting a promising direction in pharmaceutics. This comprehensive review highlights the recent developments in 3D in-vitro tissue models for preclinical applications including drug screening and disease modeling targeting multiple organs and tissues, like liver, bone, gastrointestinal tract, kidney, heart, brain, and cartilage. We discuss current strategies for fabricating 3D models for specific organs with their strengths and pitfalls. We expand future considerations for establishing a physiologically-relevant microenvironment for growing 3D models and also provide readers with a perspective on intellectual property, industry, and regulatory landscape. 

A comprehensive review on 3D tissue models: Biofabrication technologies and preclinical applications

Background: Although haemorrhage is a major cause of morbidity and mortality in liver surgery, there is very little available guidance on its management. Methods: The aim of this study was to identify current practice in the UK in this regard. An online survey was created and hepatobiliary (HPB) specialists who were members of a specialist society and others who were known practitioners were invited by e-mail to complete the survey anonymously. Results: Fifty-one percent responded (n = 36/70), and most of these respondents worked at large HPB centres (>100 liver resections/year; n = 24, 66%). Not all questionnaires were fully completed by the individual surgeons. Thirty-eight percent of the surgeons routinely used Pringle's manoeuvre. Most surgeons used ligation of the inflow vessels (n = 16, 44%) and stapled the outflow vessels (n = 15, 42%). The Cavitron ultrasonic surgical aspirator (CUSA; 54%, 13/24) was preferred for parenchymal transection. The majority routinely used haemostatic adjuncts (n = 22, 62%), whilst 33% (n = 12) used them occasionally. Twenty-three (64%) felt manufactured haemostatic adjuncts played a major role in maintaining haemostasis and 19 preferred fibrin-based products. Conclusion: The Pringle manoeuvre is a popular technique amongst specialist UK liver surgeons and the CUSA is used by nearly half of the surgeons. Despite the absence of definitive evidence for their benefit, manufactured haemostatic adjuncts are still widely used, especially the fibrin-based adjuncts.

Methods of haemostasis during liver resection--a UK national survey.

Introduction Endoscopic thyroidectomy (ET) has become a well-established surgical technique that is mainly performed for benign thyroid lesions. Several endoscopic approaches are available, such as transaxillary, unilateral axillo-breast approach (UABA), modified anterior chest wall approach (MACWA), bilateral axillo-breast approach, and most recently the transoral approach and the robotic-assisted techniques. There is no recommended approach, because each approach has its own positive and negative attributes. We, herein, compare between UABA and MACWA in terms of surgical and cosmetic outcomes. Methods This prospective study was conducted from April 2016 to August 2017. Forty patients with unilateral benign thyroid lesions were selected. Of them, 20 patients underwent ET using UABA, and 20 patients underwent ET using MACWA. Gas insufflation was implemented for all patients. Clinicopathologic data, surgical outcomes, and cosmetic outcomes in both groups were analyzed. Results There was no significant difference between both groups in the clinicopathologic characteristics. The mean surgical time was significantly longer in the UABA group compared with the chest wall group (147.3 vs. 124.3 min). The postoperative pain scores were relatively lower in the UABA group compared with the MACWA group. We reported a higher rate of persistent paresthesia, neck contracture with swallowing discomfort, and hypertrophic scars in the MACWA group. Cosmetic satisfaction scores for patients who underwent UABA were higher than for those who underwent MACWA. Conclusions Both approaches were similar in terms of safety, feasibility, and operative complications. Even though the surgical time was longer, patients who underwent the UABA reported relatively less postoperative pain, superior cosmetic results, scar perception, and patient satisfaction compared with MACWA.

Endoscopic Thyroidectomy Using the Unilateral Axillo-breast Approach Versus the Modified Anterior Chest Wall Approach: A Prospective Comparative Study.

PURPOSE Laparoscopic total gastrectomy for advanced proximal gastric carcinoma is a complex and challenging procedure, limited to a few expert centers. This study analyzed the short- and long-term outcomes of laparoscopic total gastrectomy for advanced proximal gastric carcinoma compared with open gastrectomy. METHODS From January 2008 to January 2015, 61 patients underwent laparoscopic total gastrectomy for advanced proximal gastric carcinoma. They were matched and compared to 61 patients who underwent a conventional open operation. Short-term operative and postoperative outcomes as well as long-term outcomes, including overall survival and disease-free survival rates, were assessed. RESULTS Patients were well matched for several preoperative factors. Overall postoperative 30-day complication rates were significantly higher for the open group. No significant difference was seen in 5-year overall survival and 5-year disease-free survival between the open and laparoscopic groups. The same result was seen in subgroup analyses of TNM stage. CONCLUSION This study shows the feasibility of laparoscopic total gastrectomy for advanced proximal gastric carcinoma compared to open resection in regard to both short- and long-term outcomes. Laparoscopic surgery offers many advantages commonly attributed to laparoscopy and is well suited for proximal gastric carcinoma when performed by experienced surgeons.

Laparoscopic versus open total gastrectomy for advanced proximal gastric carcinoma: a matched pair analysis.

CIP2A is highly expressed in a variety of malignancies. We determined the expression and clinical significance of CIP2A in patients with advanced gastric cancer. CIP2A protein was expressed in 25 of 37 cancer tissue specimens. There was no correlation between CIP2A and PGP, GST-π, Topo-II, and LRP expression. Survival analysis showed significant differences between the survival rate of the CIP2A protein-positive and -negative groups (χ(2)=4.509, P=0.034), but the degree of positive expression was unrelated to survival time (χ(2)=4.639, P=0.098). CIP2A expression may have no prospective value for optimizing chemotherapy regimens, but it can be an indicator for patient prognosis.

Relationship between CIP2A expression, and prognosis and MDR-related proteins in patients with advanced gastric cancer.

The existing in vitro models for antitumor drug screening have significant limitations. Many compounds that inhibit two-dimensional (2D) cultured cells do not exhibit the same pharmacological effects in vivo, thereby wasting human and material resources and time during drug development. Therefore, it is crucial to develop new models. Three-dimensional (3D) bioprinting technology has greater advantages in constructing human tissues than sandwich culture and organoid construction. We used 3D bioprinting technology to construct a 3D multicellular model of SW480 cells, tumor-associated macrophages, and endothelial cells. The biological activities of the model were evaluated by immunofluorescence, hematoxylin and eosin staining of frozen pathological sections, and transcriptome sequencing. Compared with 3D bioprinted single-cell model (3D printing-S), 3D bioprinted multicellular models (3D printing-M) showed significantly improved expression of tumor-related genes, including hub genes IL1B, FCGR2A, FCGR3A, CYBB, SPI1, CCL2, ITGAM, and ITGB2. Antitumor drug screening experiment showed that the IC50 values of 5-FU, oxaliplatin, and irinotecan in 3D printing-S group/2D culture group were 31.13 μM/12.79 μM, 26.79 μM/0.80 μM, and 16.73 μM/10.45 μM, respectively. Compared with the 3D printing-S group, 3D printing-M group was significantly more resistant to chemotherapy.

Study on drug screening multicellular model for colorectal cancer constructed by three-dimensional bioprinting technology

Background/aims Liver resection is the most effective treatment for selected patients with primary or metastatic hepatic tumor and many liver resection techniques have tried to minimize blood loss. The objective of the present study was to examine whether TissueLink dissection sealer (DS) was superior to clamp-crushing (CC) technique for liver transection or not. Methodology MEDLINE, Pubmed, Ovid and Cochrane Library electronic databases were used to search for studies without language and time period restrictions. Results Four clinical trials with 276 patients were involved. We evaluated intraoperative blood loss, postoperative morbidity, postoperative biliary leakage, transfusion rate, operation time,hospital stay duration, postoperative mortality,transection time, blood loss in liver transection and pertran section area, transection speed, AST and TBIL and found no statistical differences between the DS and CC groups. Sensitive analysis showed transection time was longer in the former group. In addition, there was no apparent publication bias concerning intraoperative blood loss. Conclusions In summary, we could not draw a firm conclusion that DS is superior to CC in liver resection of transection and the advantage of TissueLink dissecting sealer should be evaluated

Is the TissueLink dissecting sealer a better liver resection device than clamp-crushing? A meta-analysis and system review.

Dysregulated circWHSC1 has been shown to play potential roles in diverse cancer types, including ovarian cancer, endometrial cancer and hepatocellular carcinoma (HCC). The objective of this study was to investigate its expression, underlying role and regulatory mechanism in non-small-cell lung cancer (NSCLC). The expression of circWHSC1 was determined by real-time PCR. After knockdown of circWHSC1 expression in NSCLC cells, the proliferation, migration, and invasion were detected using CCK-8, colony formation, and Transwell assays, and the effects of circWHSC1 on NSCLC tumorigenesis in vivo was also investigated. With the help of luciferase reporter and pull-down assays, we further explored the downstream mechanism of circWHSC1 in NSCLC cells. CircWHSC1 was highly expressed in NSCLC tissues and cell lines. The inhibition of circWHSC1 suppressed the malignant properties of NSCLC cells, as evidenced by the reduction of proliferation, migration and invasion. CircWHSC1 sponged miR-590-5p and functioned as an oncogene in NSCLC by increasing sex determining region Y-boxprotein 5 (SOX5) expression. CircWHSC1 may contribute to the oncogenicity of NSCLC via the regulation of miR-590-5p/SOX5 axis, which might be a novel therapeutic target in NSCLC.

CircWHSC1 serves as a prognostic biomarker and promotes malignant progression of non-small-cell lung cancer via miR-590-5p/SOX5 axis.

CDK2 and CDK4 targeted liensinine inhibits the growth of bladder cancer T24 cells.

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