Expression and Clinical Significance of Ki67 and SOX2 in Colorectal Cancer.

The purpose of the paper is to explore the expression levels and clinical significance of Ki67 and sex-determining region Y-box 2 (SOX2) in colorectal cancer. From January 2013 to December 2016, 176 patients with colorectal cancer who were pathologically diagnosed after surgery in the Department of General Surgery in Xiamen Chinese Medical Hospital are included in this study. The pathological parameters, including gender, age, pathological stage, depth of tumor invasion, lymph node metastasis, and distant metastasis, are recorded. Immunohistochemistry is used to detect the correlation between Ki67 and Sox2 protein expression and clinicopathological parameters in colorectal cancer. Immunohistochemistry shows that in each stage of colorectal cancer, the positive rate of SOX2 is higher than that of Ki67, and the sensitivity of SOX2 is relatively high. Moreover, the levels of Ki67 and SOX2 in the cancerous tissues are not related to gender, age, lymph node metastasis and distant metastasis (p > 0.05).

Lipidated Methotrexate Microbubbles: A Promising Rheumatoid Arthritis Theranostic Medicine Manipulated via Ultrasonic Irradiation.

De novo designed lipidated methotrexate was synthesized and self-assembled into microbubbles for targeted rheumatoid arthritis theranostic treatment. Controlled lipidatedmethotrexate delivery was achieved by ultrasound-targetedmicrobubble destruction technique. Methotrexate was dissociated inflammatory microenvironment of synovial cavity, owing to representive low pH and enriched leucocyte esterase. We first manipulated methotrexate controlled release with RAW 264.7 cell line in vitro and further verified with rheumatoid arthritis rabbits in vivo. Results showed that lipidated methotrexate microbubbles precisely affected infection focus and significantly enhanced rheumatoid arthritis curative effect comparing with dissociative methotrexate. This study indicates that lipidated methotrexate microbubbles might be considered as a promising rheumatoid arthritis theranostics medicine.

Correction: NLRP6 targeting suppresses gastric tumorigenesis via P14ARF-Mdm2-P53-dependent cellular senescence.

[This corrects the article DOI: 10.18632/oncotarget.22876.].

Comparing a Right- Versus Left-Side Approach in Laparoscopy-Assisted D2 Radical Gastrectomies in Overweight Patients with Gastric Cancer: A Retrospective Case-Controlled Study.

BACKGROUND: The safety and efficacy of the surgical path used in laparoscopy-assisted radical gastrectomies (LARGs) is still unknown in obese patients. This study aimed to compare the value of a right-side (R-LARG) versus a left-side (L-LARG) approach in LARGs in overweight patients (defined as a body mass index (BMI) ≥ 25 kg/m2). METHODS: 213 patients with gastric cancer were divided into 2 groups: an overweight group and a normal-weight group (BMI < 25 kg/m2). Clinical characteristics and perioperative outcomes were compared in the 2 groups. RESULTS: In the overweight group, patients who underwent R-LARG had a shorter operating time (204 ± 15 vs. 248 ± 21 min), less intraoperative blood loss (66 ± 8 vs. 78 ± 7 ml), less painkiller usage (2.0 ± 0.2 vs. 2.5 ± 0.3 days), shorter time to mobility (2.1 ± 0.3 vs. 2.7 ± 0.5 days), faster recovery of peristalsis (3.4 ± 0.3 vs. 4.1 ± 0.5 days) and more lymph node dissection per patient (37 ± 4 vs. 31 ± 2) compared with the patients who underwent L-LARG. No statistically significant differences in postoperative complications (11.9% vs. 10.8%), postoperative hospital stays or hospitalization expenses were found between the groups. In the normal-weight group, perioperative outcomes were similar between the R-LARG and L-LARG groups. CONCLUSION: R-LARG has obvious advantages in overweight patients with gastric cancer.

Overexpression of COUP­TFII suppresses proliferation and metastasis of human gastric cancer cells.

The abnormal expression of the chicken ovalbumin upstream promoter transcription factor 2 (COUP­TFII) is associated with numerous forms of cancer, including gastric, prostate, colon and lung cancer. However, previous studies investigating the association between COUP­TFII expression and the occurrence, recurrence, invasion and metastasis of gastric cancer are limited in number. In the present study, it was revealed that the expression of COUP­TFII is significantly reduced in gastric carcinoma tissues compared with normal gastric mucosa cells (GES­1). In addition, the expression of COUP­TFII was also reduced in gastric cancer cell lines compared with GES­1 cells. Furthermore, it was revealed that ectopic expression of COUP­TFII was able to suppress the proliferation, migration and invasion of gastric cells, as well as inhibit hepatic metastasis, in vivo. In addition, it was demonstrated that COUP­TFII knockdown was able to promote the proliferation, migration and invasion of GES­1 cells in vitro. Furthermore, database analysis suggested that COUP­TFII expression in patients with gastric cancer is correlated with clinical stage classification and increased expression levels of COUP­TFII improved overall survival rates in patients with gastric cancer. The results of the present study suggest that COUP­TFII functions as a significant regulatory suppressor of gastric cancer growth and metastasis, and suggests that COUP­TFII may serve as a novel diagnostic and prognostic biomarker for gastric cancer metastasis.

LRP6 targeting suppresses gastric tumorigenesis via P14ARF-Mdm2-P53-dependent cellular senescence.

NLRP6, a member of the Nod-like receptor family, protects against chemically induced intestinal injury and colitis-associated colon cancer. However, the cellular mechanisms involved in this NLRP6-mediated protection remain unclear. Here, we show that NLRP6 was down-regulated in approximately 75% of primary gastric cancer cases and exhibited significant associations with advanced clinical-stage lymph node metastasis and poor overall survival. Functional studies established that ectopic overexpression or down-regulation of NLRP6 inhibited cancer cell proliferation by inducing cell cycle arrest at the G1 phase via P21 and Cyclin D1 both in vitro and in vivo. Activation of the P14ARF-P53 pathway played a crucial role in the observed cellular senescence. We further demonstrated that ectopic overexpression of NLRP6 combined with inactivation of NF-κB(p65) and Mdm2 activates P14ARF-P53 to promote the senescence of gastric cancer cells. These findings indicate that NLRP6 functions as a negative regulator of gastric cancer and offer a potential new option for preventing gastric cancer.

miR-411-5p inhibits proliferation and metastasis of breast cancer cell via targeting GRB2.

miR-411-5p (previously called miR-411) is severely involved in human diseases, however, the relationship between miR-411-5p and breast cancer has not been investigated thoroughly. Here, we found that the expression of miR-411-5p was downregulated in breast cancer tissues compared with their matched adjacent non-neoplastic tissues. In addition, the expression of miR-411-5p was also lower in breast cancer cell lines in contrast with MCF-10A. Moreover, we investigated the target and mechanism of miR-411-5p in breast cancer using mimic and inhibitor, and demonstrated the involvement of GRB2 and Ras activation. Ectopic expression of miR-411-5p suppressed the breast cancer cell proliferation, migration and invasion while low expression of miR-411-5p exhibited the opposite effect. Furthermore, GRB2 was demonstrated to be significantly overexpressed in breast cancer tissues compared with normal tissues, and low expression of GRB2 had a longer overall survival compared with high expression of GRB2 in breast cancer. In general, our study shed light on the miR-411-5p related mechanism in the progression of breast cancer and, miR-411-5p/GRB2/Ras axis is potential to be molecular target for breast cancer therapy.