Background: Exosome is a novel secretory pathway for HSPs, which induce antitumor responses. Results: Anticancer drugs caused release of HSP-bearing exosomes by HepG2 cells and elicited efficient NK cell antitumor responses. Conclusion: Exosomes derived from hepatocellular carcinoma cell-resistant anticancer drug-treated HepG2 cells conferred superior immunogenicity in inducing HSP-specific NK cell responses. Significance: Exosomes provided a clue for finding an efficient vaccine for HCC immunotherapy.
We report the evolution of superconductivity in an FeSe thin flake with systematically regulated carrier concentrations by the liquid-gating technique. With electron doping tuned by the gate voltage, high-temperature superconductivity with an onset at 48 K can be achieved in an FeSe thin flake with T_{c} less than 10 K. This is the first time such high temperature superconductivity in FeSe is achieved without either an epitaxial interface or external pressure, and it definitely proves that the simple electron-doping process is able to induce high-temperature superconductivity with T_{c}^{onset} as high as 48 K in bulk FeSe. Intriguingly, our data also indicate that the superconductivity is suddenly changed from a low-T_{c} phase to a high-T_{c} phase with a Lifshitz transition at a certain carrier concentration. These results help to build a unified picture to understand the high-temperature superconductivity among all FeSe-derived superconductors and shed light on the further pursuit of a higher T_{c} in these materials.
In a semimetal, both electrons and holes contribute to the density of states at the Fermi level. The small band overlaps and multiband effects engender novel electronic properties. We show that a moderate hydrostatic pressure effectively suppresses the band gap in the elemental semiconductor black phosphorus. An electronic topological transition takes place at approximately 1.2 GPa, above which black phosphorus evolves into a semimetal state that is characterized by a colossal positive magnetoresistance and a nonlinear field dependence of Hall resistivity. The Shubnikov-de Haas oscillations detected in magnetic field reveal the complex Fermi surface topology of the semimetallic phase. In particular, we find a nontrivial Berry phase in one Fermi surface that emerges in the semimetal state, as evidence of a Dirac-like dispersion. The observed semimetallic behavior greatly enriches the material property of black phosphorus and sets the stage for the exploration of novel electronic states in this material.
Purpose: MET signaling has been suggested a potential role in hepatocellular carcinoma (HCC) and associated with prometastasis during antiangiogenesis therapy. We investigated the potential association between MET expression and therapeutic response to sorafenib in patients with HCC. Antitumor effects of cabozantinib, a dual inhibitor of MET and VEGFR2, were examined in cultured HCC cells as well as in vivo models.Experimental Design: Total MET and phosphorylated MET (p-MET) were measured in 29 resected HCC specimens, and correlated with response to sorafenib as postoperative adjuvant therapy. In the second set of experiments using cultured HCC cells, and mouse xenograft and metastatic models, effects of cabozantinib were examined.Results: High level of p-MET in resected HCC specimens was associated with resistance to adjuvant sorafenib therapy. In cultured HCC cells that expressed p-MET, cabozantinib inhibited the activity of MET and its downstream effectors, leading to G 1 -phase arrest. Cabozantinib inhibited tumor growth in p-METpositive and p-MET-negative HCC by decreasing angiogenesis, inhibiting proliferation, and promoting apoptosis, but it exhibited more profound efficacy in p-MET-positive HCC xenografts. Cabozantinib blocked the hepatocyte growth factor (HGF)-stimulated MET pathway and inhibited the migration and invasion of the HCC cells. Notably, cabozantinib reduced the number of metastatic lesions in the lung and liver in the experimental metastatic mouse model.Conclusions: Patients with HCC with high level of p-MET are associated with resistance to adjuvant sorafenib treatment. The dual blockade of VEGFR2 and MET by cabozantinib has significant antitumor activities in HCC, and the activation of MET in HCC may be a promising efficacy-predicting biomarker.
The optimal surgical strategy for treatment of patients with synchronous colorectal liver metastases (SCLRM) remains controversial. We conducted a systematic review and metaanalysis of all observational studies to define the safety and efficacy of simultaneous versus delayed resection of the colon and liver. A search for all major databases and relevant journals from inception to April 2012 without restriction on languages or regions was performed. Outcome measures were the primary parameters of postoperative survival, complication, and mortality, as well as other parameters of blood loss, operative time, and length of hospitalization. The test of heterogeneity was performed with the Q statistic. A total of 2,880 patients were included in the meta-analysis. Long-term oncological pooled estimates of overall survival (hazard ratio [HR]: 0.96; 95% confidence interval [CI]: 0.81-1.14; P 5 0.64; I 2 5 0) and recurrence-free survival (HR: 1.04; 95% CI: 0.76-1.43; P 5 0.79; I 2 5 53%) all showed similar outcomes for both simultaneous and delayed resections. A lower incidence of postoperative complication was attributed to the simultaneous group as opposed to that in the delayed group (modified relative ratio [RR] 5 0.77; 95% CI: 0.67-0.89; P 5 0.0002; I 2 5 10%), whereas in terms of mortality within the postoperative 60 days no statistical difference was detected (RR 5 1.12; 95% CI: 0.61-2.08; P 5 0.71; I 2 5 32%). Finally, selection criteria were recommended for SCRLM patients suitable for a simultaneous resection. Conclusion: Simultaneous resection is as efficient as a delayed procedure for long-term survival. There is evidence that in SCRLM patients simultaneous resection is an acceptable and safe option with carefully selected conditions. Due to the inherent limitations of the present study, future randomized controlled trials will be useful to confirm this conclusion. (HEPATOLOGY 2013;57:2346-2357 C olorectal cancer (CRC) remains the second leading cause of cancer-related death in Western Europe and North America, and there are more than 940,000 new cases annually and nearly 500,000 deaths each year worldwide. [1][2][3] Up to 50% of patients with CRC might have liver metastases during the course of the disease, and 15% to 20% have synchronous colorectal liver metastases (SCRLM) at the time of diagnosis, whereas an additional 20% to 25% develop metachronous hepatic tumors. [4][5][6][7] The presence of liver metastases has an important influence on patient prognosis, and the median survival is 2.3 to 21.3 months for patients in whom the cancer is nonresected. 3,5,[8][9][10] Furthermore, liver resection has been accepted as the only treatment offering the chance for a cure and long-term survival, with 5-year survival rates of 25% to 60% and 10-year survival rates of 22% to 26% reported in the literature. [11][12][13][14][15][16][17][18][19] However, optimal timing of liver surgery for synchronous metastases remains controversial and continues to evolve. 20 Previously, most series reporting on the surgical management ...
We measure the magnetotransport properties of the three-dimensional Dirac semimetal Cd_{3}As_{2} single crystal under magnetic fields up to 36 T. Shubnikov-de Haas (SdH) oscillations are clearly resolved and the n=1 Landau level is reached. A detailed analysis on the intercept of the Landau index plot reveals a significant dependence of the SdH phase factor on the orientation of the applied magnetic field. When the magnetic field is applied in the [001] direction, i.e., along the fourfold screw axis of the tetragonal crystal structure, a nontrivial π Berry phase, as predicted for the Dirac fermions, is observed. However, in a magnetic field tilted away from the [001] direction, the π Berry phase is evidently reduced, and a considerable enhancement of the effective mass is also revealed. Our observations demonstrate that the Dirac dispersion in Cd_{3}As_{2} is effectively modified in a tilted magnetic field, whereas the preserved π Berry phase in a magnetic field along the [001] direction can be related to the realization of the Weyl fermions. The sudden change of the SdH phase also indicates a possible topological phase transition induced by the symmetry-breaking effect.
In summary, lncRNA UCA1 was an independent prognostic biomarker of disease-free survival in gastric cancer patients and acted as an oncogene to regulate the malignant proliferation and resistance to adriamycin in gastric cancer cells. UCA1 might provide a new potential therapeutic target and stratagem for gastric cancer.
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