lncRNA BANCR promotes the colorectal cancer metastasis through accelerating exosomes-mediated M2 macrophage polarization via regulating RhoA/ROCK signaling.

Cancer cells-derived exosomal lncRNAs could modulate the tumorigenesis of colorectal cancer (CRC) via modulating macrophage M2 polarization. However, the clarified mechanism and function of lncRNA BANCR in CRC remains unclear. Exosomes were identified by TEM, NTA, western blot and fluorescent staining. M2 macrophages were identified by CD206 and CD163 expressions using by flow cytometry and RT-qPCR. In addition, the relation between IGF2BP2 and BANCR or RhoA were explored by RIP assay. The malignant behaviors of CRC cells were examined by CCK-8, EdU and transwell assays. Histopathological changes in mice were observed by H&E staining. Silencing of BANCR notably inhibited the proliferation, migration and invasion of CRC cells. SW620 and HCT-15 cells-derived exosomal BANCR positively regulated the macrophage M2 polarization. In addition, exosomal BANCR remarkably enhanced the promoting roles mediated by M2 macrophages on proliferation and invasion in CRC cells. Meanwhile, exosomal BANCR promoted the M2 macrophage polarization via activation of RhoA/Rock pathway by recruiting IGF2BP2. Inhibition of RhoA/Rock pathway reversed exosomal BANCR-mediated macrophages M2 polarization and CRC malignant behaviors in SW620 and HCT-15 cells. Exosomal lncRNA BANCR derived from SW620 and HCT-15 cells promoted the metastasis of CRC via inducing the polarization of M2 macrophages. Thus, BANCR might be a new target for the treatment of CRC.

Optimization of Transforming Growth Factor-ß1 siRNA Loaded Chitosan-Tripolyphosphate Nanoparticles for the Treatment of Colorectal Cancer Hepatic Metastasis in a Mouse Model.

Metastatic liver disease is the most frequent complication of colorectal cancer (CRC), and the development of liver-targeted nanoparticles for drug delivery is a promising therapeutic approach. However, to improve the efficacy of passive drug delivery, its release rate at the sites of liver metastases should be maximized while minimizing drug uptake in nontargeted cells. Herein, we report the development and use of tripolyphosphate (TPP) modified chitosan (CS) nanoparticles loaded with small interfering RNA (siRNA) directed against transforming growth factor ß1 (TGF-ß1), which promotes tumorigenesis in advanced CRC. The nanoparticles efficiently inhibited CRC hepatic metastasis in an animal model. Particles of 300 nm in size and zeta potential at 20 mV showed a more striking liver-targeting effect. A weight ratio of CS/TPP of 8:1 for particles with TGF- ß1 siRNA loaded at a concentration of 20 µM at pH 7.5 showed good pH-responsive drug release when exposed to a CRC homogenate at pH 6.5. In vivo, CS-TPP/TGF- ß1 siRNA nanoparticles significantly reduced the volume and number of CRC metastatic foci. This was accompanied by the downregulation of TGF- ß1 expression in the tumor microenvironment, inhibition of tumor associated macrophage formation, and improvement of the immune microenvironment. These results indicate that it is possible to achieve effective passive liver targeting by optimizing the processing parameters. The design of nanoparticles carrying siRNA against overexpressed oncogenes provides an excellent platform for the development of an efficient liver cancer therapy.

Simultaneous idiopathic segmental infarction of the great omentum with spontaneous splenic rupture: a rare association.

Idiopathic segmental infraction of the greater omentum (ISIGO) is a rare cause of acute abdomen. One of the main symptoms is right-side abdominal pain, while its etiology is still unclear. Until now, ISIGO simultaneously with spontaneous splenic rupture (SSR) has not been reported. Here, we presented a case of a 35-year old man, who was admitted with an acute abdomen, and the clinical diagnosis was ISIGO with SSR. He had a significant previous medical history of the vein thrombosis of lower limbs. Partial omental resection and splenectomy were performed, and the postoperative recovery of the patient was excellent. We also highlighted several possible theories to explain the etiology of the ISIGO, and emphasized that surgical methods, including laparoscopic surgery and laparotomy, are still the best way to treat the ISIGO at the emergency condition.

Prognostic role of YB-1 expression in breast cancer: a meta-analysis.

OBJECTIVE: In published studies, Y-box binding protein-1 (YB-1) correlated with the prognosis of patients with breast cancer (BC), but the specific role of YB-1 is still unclear. Our study aimed to evaluate the prognostic value of YB-1 in BC patients using meta-analysis based on the published studies. METHODS: We searched the relevant literatures deadline for June 2014 in databases, including PubMed, Embase, Medline and Cochrane library, and finally 8 studies were included in our study. Our study contained 1094 BC patients with 398 YB-1 positive and 696 YB-1 negative. RESULTS: Our results showed that YB-1 abnormal expression did not correlated with the lymph node status [OR = 1.258, 95% CI = 0.895-1.769, P = 0.186], high histological grade [OR = 2.709, 95% CI = 0.861-8.530, P = 0.089], histological type [OR = 0.837, 95% CI = 0.526-1.331, P = 0.452], P53 status [OR = 2.006, 95% CI 0.686-5.865, P = 0.203] and PR [OR = 0.607, 95% CI = 0.347-1.061, P = 0.080] in BC patients. But YB-1 over-expression was associated with other unfavorable factors: ER negativity [OR = 0.604, 95% CI = 0.388-0.941, P = 0.026], HER2 positivity [OR = 3.841, 95% CI = 2.637-5.594, P = 0.000], and high tumorous T stage [OR = 2.169, 95% CI = 1.295-3.632, P = 0.003]. In addition, our data suggested that high YB-1 expression had an adverse impact on 5-year OS [RR = 2.767, 95% CI = 2.054-3.727, P = 0.000] in BC patients. CONCLUSIONS: Our findings implied that YB-1 might a novel biomarker to predict the prognosis of BC, and could be a potential direction for developing diagnostic and therapeutic approaches in BC.

Prognostic significance of Beclin-1 expression in colorectal cancer: a meta-analysis.

OBJECTIVE: Beclin-1 has recently been observed as an essential marker of autophagy in several cancers. However, the prognostic role of Beclin-1 in colorectal neoplasia remains controversial. Our study aimed to evaluate the potential association between Beclin-1 expression and the outcome of colorectal cancer patients. MATERIALS AND METHODS: All related studies were systematically searched in Pubmed, Embase, Springer and Chinese National Knowledge Infrastructure databases (CNKI), and then a meta-analysis was performed to determine the association of Beclin-1 expression with clinical outcomes. Finally, a total of 6 articles were included in our analysis. RESULTS: Our data showed that high Beclin-1 expression in patients with CRC was associated with poor prognosis in terms of tumor distant metastasis (OR=2.090, 95%CI=1.061-4.119, p=0.033) and overall survival (RR=1.422, 95%CI=1.032-1.959, p=0.031). However, we did not found any correlation between Beclin-1 over-expression and tumor differentiation (OR=1.711, 95%CI=0.920-3.183, p=0.090). In addition, there was no evidence of publication bias as suggested by Egger's tests for tumor distant metastasis (p=1.000), differentiation (p=1.000) and OS (p=0.308). CONCLUSIONS: Our present meta-analysis indicated that elevated Beclin-1 expression iss associated with tumor metastasis and a poor prognosis in patients with CRC. Beclin-1 might serve as an efficient prognostic indicator in CRC, and could be a new molecular target in CRC therapy.