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Background: Rapamycin is an attractive approach for the treatment and prevention of HCC recurrence after liver transplantation. However, the objective response rates of rapamycin achieved with single-agent therapy were modest, supporting that rapamycin resistance is a frequently observed characteristic of many cancers. Some studies have been devoted to understanding the mechanisms of rapamycin resistance, however, the mechanisms are cell-type-dependent and studies on rapamycin resistance in HCC are extremely limited. Methodology/Principal Findings: The anti-tumor sensitivity of rapamycin was modest in vitro and in vivo. In both human and rat HCC cells, rapamycin up-regulated the expression and phosphorylation of PDGFRb in a time and dose-dependent manner as assessed by RT-PCR and western blot analysis. Using siRNA mediated knockdown of PDGFRb, we confirmed that subsequent activation of AKT and ERK was PDGFRb-dependent and compromised the anti-tumor activity of rapamycin. Then, blockade of this PDGFRb-dependent feedback loop by sorafenib enhanced the anti-tumor sensitivity of rapamycin in vitro and in an immunocompetent orthotopic rat model of HCC. Conclusions: Activation of PI3K/AKT and MAPK pathway through a PDGFRβ-dependent feedback loop compromises the anti-tumor activity of rapamycin in HCC, and blockade of this feedback loop by sorafenib is an attractive approach to improve the anti-tumor effect of rapamycin, particularly in preventing or treating HCC recurrence after liver transplantation. [ABSTRACT FROM AUTHOR]

Objective: The objective was to evaluate the clinical value of submucosal tunneling endoscopic resection (STER) for the treatment of submucosal tumors (SMTs) originating from the muscular propria (MP) in the rectum. Patients and Methods: The clinicopathological data of 12 cases with rectal SMTs originating from the MP layer performed STER in our center from January 2012 to June 2014 were analyzed retrospectively. Results: Three males and nine females (M/F, 1/3) were studied in this series. The median age of the patients was 53.5 (range, 41-84) years. The tumors located 5-10 cm from the anal verge. En bloc STER was performed successfully in all of the 12 cases. The median size of resected specimens was 1.4 cm (range 1.0-3.0 cm). The median procedure time was 49.5 min (range 40-70 min). Three patients developed low fever after the operation and were all recovered after receiving intravenous antibiotics. One of these three cases developed mucosa perforation, which was closed immediately with metal clips. One patient developed subcutaneous emphysema in one lower limb, which disappeared with conservative treatments 2 weeks after the STER procedure. The median hospital stays were 3.1 (range 2-8) days. Postoperative pathological outcomes revealed schwannoma in 3 cases, leiomyoma in 2 cases, stromal tumor in 5 cases, and proliferation of collagen fibers nodular degeneration in 2 cases. No lesion residual or recurrence was found during postoperative follow-up of 4-33 months. Conclusion: STER is a feasible, safe, and effective method for treating SMTs originating from the MP layer in the rectum. [ABSTRACT FROM AUTHOR]

Endoscopic resection of colonic submucosal tumors (SMTs) is challenging and carries a high risk of perforation. In this prospective pilot study we aimed to evaluate the feasibility, safety, and efficacy of endoscopic full-thickness resection of colonic SMTs. The study enrolled 19 consecutive patients with colonic SMTs 3cmin size or smaller. In 18 of the 19 patients full-thickness resection was carried out endoscopically with the entire tumor capsule intact. In 16 of these18 patients, fullthickness resection was carried out and the colonic wall defect closed all endoscopically; in the other 2 patients, laparoscopic closure was needed. Two cases of local peritonitis were managed with conservative treatment. No deaths occurred within 30 days, and no recurrence was detected after a median of 18 months' follow-up. Endoscopic full-thickness resection is a novel method enabling resection of colonic SMTs. The colonic wall mucosal defect can be closed endoscopically in the majority of cases. It appears to be a safe and effective endoscopic technique for managing these tumors, which traditionally are managed by colonic resection. [ABSTRACT FROM AUTHOR]