Long Non-Coding RNA (lncRNA) 91H Confers Tamoxifen Resistance in ER+ Breast Cancer Cells through Inhibiting mTOR Signaling Pathway.

OBJECTIVE: Estrogen receptor-positive (ER+) breast cancers are the most often diagnosed subtype of breast tumors, in which the development of tamoxifen resistance remains a major impediment. The effect of long non-coding RNA (lncRNA) on therapy resistance is beginning to emerge. The lncRNA 91H, a recently identified lncRNA involved in tumorigenesis, is also overexpressed in breast cancer. The purpose of this study was to explore the role of 91H in the biological function and tamoxifen resistance of ER+ breast cancer cells. METHODS: MCF-7 and T47D cells were transfected for 91H silence. CCK-8 assay was performed to examine cell viability and drug sensitivity. Cell cycle and apoptosis were analyzed using flow cytometry. Cell migration capacity was determined by wound healing assay. The protein level was analyzed by Western blotting. RESULTS: MCF-7 and T47D cells with 91H knockdown exhibited lower capacities of cell proliferation and migration. In addition, knockdown of 91H resulted in significantly increased sensitivity to tamoxifen and a higher ratio of apoptosis induced by tamoxifen. Furthermore, the protein level of p-mTOR was notably inhibited through downregulating 91H expression. And the mTOR inhibitor together with tamoxifen presented synergistic effect on the inhibition of cell viability. CONCLUSION: Our study highlights that 91H might serve as a potential target for ER+ breast cancer patients who have acquired tamoxifen resistance.

Carbohydrates based stimulus responsive nanocarriers for cancer-targeted chemotherapy: a review of current practices.

INTRODUCTION: Many nanocarriers have been developed to react physicochemically to exterior stimuli like ultrasonic, light, heat, and magnetic fields, along with various internal stimuli including pH, hypoxia, enzyme, and redox potential. Nanocarriers are capable to respond various stimuli within the cancer cells to enable on-demand drug delivery, activation of bioactive compounds, controlled drug release, and targeting ligands, as well as size, charge, and conformation conversion, enabling sensing and signaling, overcoming multidrug resistance, accurate diagnosis, and precision therapy. AREAS COVERED: Carbohydrates are ubiquitous biomolecules with a high proclivity for supramolecular network formation. Numerous carbohydrate-based nanomaterials have been used in biological solicitations and stimuli-based responses. Particular emphasis has been placed on the utilization of carbohydrate-based NPs and nanogels in various fields including imaging, drug administration, and tissue engineering. Because the assembly process is irreversible, carbohydrate-based systems are excellent ingredients for the development of stimulus-responsive nanocarriers for cancer-targeted chemotherapy. This review aims to summarise current research on carbohydrate-based nanomaterials, with an emphasis on stimuli-sensitive nanocarriers for cancer-targeted chemotherapy. EXPERT OPINION: Carbohydrates-based stimulus-responsive nanomaterials have been proved highly efficient for targeted delivery of anticancer drugs, thus leading to effective chemotherapy with minimum off-target effects.

Metastasis-associated protein 1 (MTA1) in gastric cancer tissues is positively associated with poorer prognosis.

BACKGROUND: The present study examined the clinical significance of metastasis-associated protein 1 (MTA1) in the progression and patient survival of gastric cancer. METHODS: Paraffin-embedded resected tissues of gastric cancer mucosa (n = 436) and adjacent normal mucosa (n = 92) were assessed immunohistochemically for MTA1 protein, and scored according to the percentage of cells positively stained for MTA1 combined with stain intensity. Associations between MTA1 staining scores and clinicopathological factors, including survival time, were evaluated. RESULTS: The staining scores for MTA1 were significantly higher in gastric cancer tissues than in matched normal tissues. MTA1 scores positively correlated with tumor size, depth of invasion, presence of lymph node metastasis, lymphatic involvement, venous invasion, distal metastasis, and advanced clinical staging. Patients with high MTA1 scores in gastric cancer tissues had a significantly lower five-year survival rate compared with patients with low MTA1 scores. The multivariate analysis indicated that MTA1 protein levels in resected gastric cancer tissues, as reflected by immunohistochemical staining, are an independent prognostic index of gastric carcinoma (P < 0.01). CONCLUSION: MTA1 immunopositivity was significantly associated with progression of gastric cancer, and may be helpful in gastric cancer prognosis.

The effect of continuous jejunal interposition on gastrointestinal hormones after distal gastrectomy.

The objective of our study was to determine the effect of continuous jejunal interposition on gastrointestinal hormones after distal gastrectomy, and lay a foundation for surgical management.Distal subtotal gastrectomy experimental model were established on 24 adult Beagle dogs. Digestive tract reconstruction of the dogs was randomly divided into continuous jejunal interposition group, Billroth II anastomosis group and isolated jejunum interposition group. The content of serum gastrin, plasma motilin and cholecystokinin after different digestive tract reconstructions was detected and compared by enzyme-linked immunosorbent assay. In the dogs which received continuous jejunal interposition, postoperative serum gastrin level was significantly lower than before surgery either in fasting or postprandial state (all p<0.05). The serum gastrin level of continuous jejunal interposition group was significantly higher than the other groups in postprandial state (all p<0.05), and was significantly higher than Billroth II -type anastomosis group in fasting state (p<0.05). Furthermore, the postoperative plasma motilin and cholecystokinin levels were significantly higher than before surgery either in fasting or postprandial in dogs received continuous jejunal interposition (all p<0.05). The postoperative plasma motilin level of continuous jejunal interposition group was significantly higher than the other groups in postprandial state (all p<0.05), and was significantly higher than Billroth II -type anastomosis group in fasting state (p<0.05). However, the postoperative cholecystokinin level of continuous jejunal interposition group was significantly lower than the other groups (all p <0.05).Continuous jejunal interposition after distal gastrectomy could maintain the postoperative plasma motilin and serum gastrin in a relatively high level, while cholecystokinin in a low level.

[Laparoscopic versus open wedge resection for gastrointestinal stromal tumors of the stomach: a clinical controlled study].

OBJECTIVE: To compare the surgical outcomes between laparoscopic and open wedge resection for gastrointestinal stromal tumors of the stomach. METHODS: Clinical data of 18 cases undergoing laparoscopic wedge resection from June 2000 to August 2009 at the Zhejiang Provincial People's Hospital were compared with 30 patients treated by open surgery. The perioperative parameters and prognosis data of the two groups were compared. RESULTS: Compared to the open group, laparoscopic group was found with longer operative time, less blood loss, less requirement of postoperative analgesia, earlier resumption of oral intake, earlier return of first flatus, and shorter postoperative hospital stay(all P<0.05). There were no postoperative deaths in both groups. Postoperative complication rate was significantly lower in the laparoscopic group(5.5% vs. 33.3%, P<0.05). The postoperative recurrence rates were 11.8%(2/17) and 10.7%(3/28); the 5-year survival rates were 78% and 63%, respectively, and the difference was not statistically significant(P>0.05). CONCLUSION: Laparoscopic wedge resection is a feasible treatment option for GISTs of the stomach.