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Islet transplantation is a potential treatment option for certain patients with type 1 diabetes; however, it still faces barriers to widespread use, including the lack of tools to monitor islet grafts post-transplantation. This study investigates whether labeling neonatal porcine islets (NPI) with polyvinylpyrrolidone-coated superparamagnetic iron oxide nanoparticles (PVP-SPIO) affects their function, and whether this nanoparticle can be utilized to monitor NPI xenografts with magnetic resonance imaging (MRI) in a mouse model. In vitro, PVP-SPIO-labeled NPI in an agarose gel was visualized clearly by MRI. PVP-SPIO-labeled islets were then transplanted under the kidney capsules of immunodeficient nondiabetic and diabetic mice. All diabetic mice that received transplantation of PVP-SPIO-labeled islets reached normoglycemia. Grafts appeared as hypo-intense areas on MRI and were distinguishable from the surrounding tissues. Following injection of spleen cells from immunocompetent mice, normoglycemic recipient mice became diabetic and islet grafts showed an increase in volume, accompanied by a mixed signal on MRI. Overall, this study demonstrates that PVP-SPIO did not affect the function of NPI that PVP-SPIO-labeled islets were easily seen on MRI, and changes in MRI signals following rejection suggest a potential use of PVP-SPIO-labeled islets to monitor graft viability.

Drug-resistance to gemcitabine chemotherapy in pancreatic cancer is still an unsolved problem. Combinations of other chemotherapy drugs with gemcitabine have been shown to increase the efficacy of gemcitabine-based treatment. In this study, the effect of berbamine on the antitumor activity of gemcitabine was evaluated in human pancreatic cancer cell lines Bxpc-3 and Panc-1, and the underlying mechanisms were explored. Our results demonstrated that berbamine exhibited a time- and dose-dependent inhibitory effect in the pancreatic cancer cell lines. Berbamine enhanced gemcitabine-induced cell growth inhibition and apoptosis in these cells. Combined treatment of berbamine and gemcitabine resulted in down-regulation of anti-apoptotic proteins (Bcl-2, Bcl-xL) and up-regulation of pro-apoptotic proteins (Bax, Bid). More importantly, berbamine treatment in combination with gemcitabine activated the transforming growth factor-β/Smad (TGF-β/Smad) signaling pathway, as a result of a decrease in Smad7 and an increase in transforming growth factor-β receptor II (TβRII) expression. Changes in downstream targets of Smad7, such as up-regulation of p21 and down-regulation of c-Myc and Cyclin D1 were also observed. Therefore, berbamine could enhance the antitumor activity of gemcitabine by inhibiting cell growth and inducing apoptosis, possibly through the regulation of the expression of apoptosis-related proteins and the activation of TGF-β/Smad signaling pathway. Our study indicates that berbamine may be a promising candidate to be used in combination with gemcitabine for pancreatic cancer treatment.

Islets can be visualized on MRI by labeling with superparamagnetic contrast agent during the transplantation procedure. However, whether the signal intensity reflects the cell number and cellular viability has not been determined. We used a self-synthesized novel superparamagnetic contrast agent –polyvinylpyrrolidone-coated superparamagnetic iron oxide nanoparticles (PVP-SPIO) – to label β-TC-6 cells (a mouse insulinoma cell line) or primary islets with commercial Feridex as a control. The labeling efficiency of two agents was compared by Prussian blue staining, intracellular iron content determination and MR scanning. Cells were exposed to hypoxia, high-glucose or exogenous H2O2 stimulation before/after PVP-SPIO labeling. Normal and injured cells were also transplanted into renal subcapsule. A clinically used 3.0 T MR scan was performed in vitro and 24 h post-transplantation to investigate the correlation between cellular viability and signal. Our PVP-SPIO displayed superior biocompatibility and magnetic properties. All of the cells could be labeled at 100 µg/ml iron concentration after 24 h incubation. At 100 µg/ml iron concentration, 1 × 105β cells labeled with PVP-SPIO could already be visualized in vitro by MRI, less than the detection threshold of Feridex. There existed a linear correlation between the number of labeled cells and R2 value on the T2-weighted images. The signal intensity and the intracellular iron content declined along with the decreased viability of labeled cells. There was also a significant difference in signal intensity between injured and normal labeled cells after transplantation. From these results, we concluded that PVP-SPIO possessed superior cell labeling efficiency, and β cells could be labeled without compromising viability and function. The signal intensity on MRI might be a useful predictor to evaluate the number and the viability of PVP-SPIO-labeled cells. Copyright © 2012 John Wiley & Sons, Ltd.

A series of buta-1,3-dienes have been directly synthesized via a convenient palladium-catalyzed homodehydrogenation coupling reaction of aromatic alkenes under mild conditions. The homocoupling reaction enables a rapid synthesis of multisubstituted butadiene which shows typical aggregation-induced emission enhancement (AIEE) characteristics because it is practically not emissive in solution but emits blue fluorescence in aggregates.

Aim: To evaluate the feasibility and safety of ultrasound-guided radiofrequency ablation (RFA) of hepatic tumors in high-risk areas (in caudate lobe, adjacent to the hilum, capsular surface, gallbladder or diaphragm) in comparison with those in low-risk areas. Methods: A total of 526 patients with hepatic tumor treated with ultrasound-guided cool-tip RFA between October 2001 and October 2008 were included. The patients were divided into two groups according to the tumor location: group I (high-risk areas, 163 patients); group II (low-risk areas, 363 patients). The two groups had similar baseline characteristics. Repeated RFA was adopted if complete ablation (CA) was not achieved. Results: In group I, 20 cases had tumors close to the hilum, 11 in the caudate, 79 adjacent to the capsule, 24 near the gallbladder and 29 cases against the diaphragm. The percentage of patients with primary hepatic tumors in group I was higher than that in group 2 (80.4% vs 56.2%, P

Background In Appleby's operation, the adequate flow of proper hepatic artery (PHA) from pancreaticoduodenal arcades was considered to be important in the previous reported pancreatic cancer cases. Insufficient blood flow of PHA was considered as the contraindication for Appleby's operation. Methods We herein reported a 20 cm in diameter pancreatic sarcomatoid carcinoma involving celiac axis (CA), which was treated by extended Appleby's operation without proper hepatic arterial flow. The extended Appleby's operation for pancreatic cancer involving CA and/or common hepatic artery (CHA) was firstly applied to the current case according to the 43 previous reported cases in English literature from a Medline search. In the extended Appleby's operation, the resection scope included total pancreas, total stomach, spleen, and CA; the anterior and posterior pancreaticoduodenal arcades were removed in whipple's procedure, which was previously thought to be the contraindication for Applyby's operation. Results Proper hepatic arterial flow from superior mesenteric artery (SMA) was totally lost; No liver failure happened postoperatively. Conclusions The extended Appleby's procedure without blood flow of PHA might be feasible and offered a new approach to resection of pancreatic cancer involving CA and/or CHA; the involvement of pancreatic head might not be the contraindication for Appleby's operation. J. Surg. Oncol. 2007;96:442–446. © 2007 Wiley-Liss, Inc.

Background and Objectives Current preoperative N staging does not offer an accurate estimation of lymph node involvement. We establish a new scoring system for predicting N stages to guide a rational lymphadenectomy for gastric cancer. Methods Variables correlated with N stages were selected by multivariate stepwise logistic regression analysis. Variables granted the different scores according to the odds ratio (OR). Receiver operating characteristic (ROC) analysis was used to generate scoring ranges from N0 to N3. The agreement between predicted N staging and actual pN classification was analyzed using kappa statistics. Results Tumor size, depth of invasion, and histological types were selected to establish the scoring system. Scores 0–4, 5–7, 8–9, and 10–13 were postulated to predict N0-3, respectively. The predicted N stage has good agreement with the actual pN classifications. The negative predictive values for N0-3 were 87.0, 86.4, 90.4, and 90.2%; the positive predictive values were 74.7, 62.8, 57.3, and 69.6%, respectively. The accuracy is 82% for N0-1, and 83.7% for N2-3. Conclusions The new scoring system can predict the N stage of gastric cancer. With its good negative predictive value, it is possible to minimize the potential hazards of applying a more extensive lymph node dissection than necessary. J. Surg. Oncol. 2006;93:534–540. © 2006 Wiley-Liss, Inc.

TR6/DcR3/M68 is a soluble receptor that belongs to the TNF receptor family. It is expressed in malignant cells of several tumor types and has been postulated to help tumor cells to gain survival advantage by inhibiting apoptosis and by interfering with immune surveillance. In our study, we assessed for the first time serum TR6 in tumor patients to explore its diagnostic and prognostic value. We examined serum TR6 levels with ELISA in 146 tumor patients, 19 patients with acute infection, 5 patients with liver cirrhosis and 29 healthy individuals. TR6 expression in tumor mass was studied with immunohistochemistry. TR6 gene copy number in tumor tissues was evaluated by real time PCR. Ninety-seven point nine percent (47 of 48 cases) of healthy individuals and patients with acute infection were serum TR6-negative. In contrast, 56.2% (82 of 146 cases) of the tumor patients were serum TR6-positive. Almost all serum TR6-positive individuals (98.8%, 82 out of 83 cases) had malignancy, excluding the cases of liver cirrhosis. In gastric carcinomas, serum TR6 levels were closely correlated with tumor differentiation status and TNM classification. Tumor mass was the source of serum TR6 because its levels decreased drastically after curative tumor resection. TR6 gene amplification occurred in about half of liver carcinomas, but not in gastric or pancreatic carcinomas, indicating plural mechanisms of TR6 upregulation. Our study demonstrated that serum TR6 should be considered as a novel parameter for the diagnosis, treatment and prognosis of malignancies.