Overexpression of microRNA-29b inhibits epithelial-mesenchymal transition and angiogenesis of colorectal cancer through the ETV4/ERK/EGFR axis.

BACKGROUND: Recent studies have reported the involvement of microRNA-29 (miR-29) family members in human cancers through their ability to regulate cellular functions. The present study investigated biological function of miR-29b in colorectal cancer (CRC). METHODS: CRC tissues and adjacent normal tissues were collected and the expression of ETV4 and miR-29b in the tissues were identified. The relationship between ETV4 and miR-29b or ETV4 expression and the EGFR promoter was identified using dual-luciferase reporter gene and CHIP assays. The proliferation, invasion, migration, and apoptosis of CRC HCT116 cells were assayed using MTT assay, Scratch test, Transwell assay, and flow cytometry, respectively. Also, expression of epithelial-mesenchymal transition (EMT) markers, angiogenic factors, and vasculogenic mimicry formation were evaluated using RT-qPCR and Western blot. RESULTS: ETV4 was upregulated, while miR-29b expression was decreased in CRC tissues. ETV4 was identified as a target gene of miR-29b, which in turn inactivated the ERK signaling pathway by targeting ETV4 and inhibiting EGFR transcription. Transfection with miR-29b mimic, siRNA-ETV4, or ERK signaling pathway inhibitor U0126 increased expression of E-cadherin and TSP-1, and CRC cell apoptosis, yet reduced expression of ERK1/2, MMP-2, MMP-9, Vimentin, and VEGF, as well as inhibiting EMT, angiogenesis, and CRC cell migration and invasion. The EMT, angiogenesis and cancer progression induced by miR-29b inhibitor were reversed by siRNA-mediated ETV4 silencing. CONCLUSIONS: miR-29b suppresses angiogenesis and EMT in CRC via the ETV4/ERK/EGFR axis.

Gemcitabine plus concurrent irreversible electroporation vs gemcitabine alone for locally advanced pancreatic cancer.

BACKGROUND: Locally advanced pancreatic cancer (LAPC) is a common malignant digestive system tumor that ranks as the fourth leading cause of cancer-related death in the world. The prognosis of LAPC is poor even after standard treatment. Irreversible electroporation (IRE) is a novel ablative strategy for LAPC. Several studies have confirmed the safety of IRE. To date, no prospective studies have been performed to investigate the therapeutic efficacy of conventional gemcitabine (GEM) plus concurrent IRE. AIM: To compare the therapeutic efficacy between conventional GEM plus concurrent IRE and GEM alone for LAPC. METHODS: From February 2016 to September 2017, a total of 68 LAPC patients were treated with GEM plus concurrent IRE n = 33) or GEM alone n = 35). Overall survival (OS), progression free survival (PFS), and procedure-related complications were compared between the two groups. Multivariate analyses were performed to identify any prognostic factors. RESULTS: There were no treatment-related deaths. The technical success rate of IRE ablation was 100%. The GEM + IRE group had a significantly longer OS from the time of diagnosis of LAPC (19.8 mo vs 9.3 mo, P < 0.0001) than the GEM alone group. The GEM + IRE group had a significantly longer PFS (8.3 mo vs 4.7 mo, P < 0.0001) than the GEM alone group. Tumor volume less than 37 cm3 and GEM plus concurrent IRE were identified as significant favorable factors for both the OS and PFS. CONCLUSION: Gemcitabine plus concurrent IRE is an effective treatment for patients with LAPC.

Versatile RBC-derived vesicles as nanoparticle vector of photosensitizers for photodynamic therapy.

Various nanocarriers for photosensitizers have been developed to solve the problems of limiting the clinical utility of photodynamic therapy (PDT); however, to date, no carriers capable of supplying oxygen have been reported. We reported the development of a novel system composed of red blood cell (RBC)-derived vesicles (RDVs) generated by osmotic stress and demonstrated the capacity of RDVs for encapsulating and delivering external cargo into targeted cells due to the cellular uptake of RDVs. In this study, protoporphyrin IX (PpIX)-encapsulated RDVs (PpIX@RDVs) were prepared by the hypotonic incorporation of PpIX into RDVs in an aqueous environment, characterized, and utilized for PDT of cancer. PpIX@RDVs were rapidly uptaken by tumor cells via endocytosis in vitro, and the highly phototoxic effect of PpIX@RDVs was demonstrated upon irradiation. Superoxide anion (O(2)˙) and singlet oxygen ((1)O(2)) were involved in PpIX@RDV-induced cell apoptosis and necrosis. Finally, we demonstrated that RDVs with an oxygen supply capacity have potential as versatile delivery vehicles for efficient PDT.

Pancreatic head cryosurgery: safety and efficiency in vivo--a pilot study.

OBJECTIVES: Pancreatic cancer is the fourth leading cause of cancer-related death. Cryosurgery has emerged as a promising new technique for treatment. Although 80% of pancreatic cancers are located in the pancreatic head, no research has been conducted on the safety and efficacy of cryosurgery for these tumors. METHODS: Two groups of Tibetan miniature pigs (n = 4 per group) underwent cryosurgery to the pancreatic head with either the deep freezing protocol (100% argon output) or shallow freezing protocol (10% argon output), and compared to sham-operated pigs. RESULTS: Serum inflammatory factors and amylase increased during the 5 days after cryoablation in both groups but acute pancreatitis did not occur. Adhesions were observed between the pancreatic head and adjacent organs, and only minor trauma was caused to the stomach, duodenum, small intestine, and liver. Ice balls with a radius of 0.5 cm beyond the tumor edge were sufficient to cause complete necrosis of the pancreatic tissue, and decreased the degree of cold injury to surrounding tissues. CONCLUSIONS: Shallow freezing protocol seemed to be safer than, and just as effective as, the deep freezing protocol. This preliminary study suggests that cryosurgery could potentially be an effective treatment of cancer of the pancreatic head.

Comparison of dual- and triple-freeze protocols for hepatic cryoablation in a Tibet pig model.

The purpose of this study was to compare a dual-freeze protocol with a triple-freeze protocol for hepatic cryoablation in a porcine model. Eighteen cryoablations were performed over an exposed operation field in nine normal porcine livers, using dual- (10-5-10-5) and triple-freeze (5-5-5-5-10-5) protocols. Changes in the temperature of the cryoprobes and the diameter of the iceballs were recorded during the ablation, and pathological changes in the cryozones (zones of tissue destruction) were assessed seven days after the procedure. Use of two and three freeze-thaw cycles produced iceballs of different diameters. Seven days after cryosurgery, the triple-freeze protocol was associated with a larger zone of complete necrosis than the dual-freeze protocol, although the two protocols produced cryozones and cryolesions of similar length, and in both cases the cryozones contained five areas of destruction. With the same freezing time (20 min), the triple-freeze protocol may be a more powerful liver ablation method than the dual-freeze protocol.

Comparison of dual- and triple-freeze protocols for pulmonary cryoablation in a Tibet pig model.

The purpose of this study was to compare a dual-freeze protocol with a triple-freeze protocol for pulmonary cryoablation in a porcine lung model. Five dual- (10-5-10-5) and five triple-freeze (5-5-5-5-10-5) cryoablations were performed on an exposed operation field in normal porcine lung. Changes in the temperature of the cryoprobes and the diameter of the iceballs were measured during the ablation and pathologic changes in the cryozones (zones of tissue destruction) were reviewed 7 days after the procedure. The diameter of the iceball surface differed between the two protocols. Pathologically, the triple-freeze protocol was associated with a longer complete necrosis zone than the dual-freeze protocol, though the two protocols produced cryolesions and cryozones of similar length, and in both cases there were five areas of tissue destruction. With the same duration of freezing (20 min), the triple-freeze protocol may be better for pulmonary cryoablation than the dual-freeze protocol.