Complete response to FOLFOX4 therapy in a patient with advanced urothelial cancer: a case report

No standard has been established for salvage therapy in gemcitabine refractory advanced urothelial cancer. We report the complete response to FOLFOX4 therapy of a metastatic urothelial cancer patient, for whom adjuvant gemcitabine plus cisplatin combination chemotherapy had failed. A 54-year-old male patient with urothelial cancer (transitional cell carcinoma) in the right kidney underwent three rounds of adjuvant gemcitabine-cisplatin chemotherapy after extensive radical nephrectomy. However, he had new liver, lung metastases and synchronous two separate primary colon cancer. The lung metastasis lesion was confirmed as a metastatic urothelial cancer via percutaneous transthoracic needle biopsy (PTNB). Liver and lung metastasis lesions disappeared after the 4th cycle of FOLFOX4 chemotherapy. In addition, colon cancer also disappeared after the 8th cycle of FOLFOX4 chemotherapy. The patient was still showing a complete response after 4 months. Clinical trials using the FOLFOX regimen as salvage therapy for gemcitabine-refractory advanced urothelial cancer are warranted

Wafer-scale graphene/ferroelectric hybrid devices for low-voltage electronics

Preparing graphene and its derivatives on functional substrates may open enormous opportunities for exploring the intrinsic electronic properties and new functionalities of graphene. However, efforts in replacing SiO$_{2}$ have been greatly hampered by a very low sample yield of the exfoliation and related transferring methods. Here, we report a new route in exploring new graphene physics and functionalities by transferring large-scale chemical vapor deposition single-layer and bilayer graphene to functional substrates. Using ferroelectric Pb(Zr$_{0.3}$Ti$_{0.7}$)O$_{3}$ (PZT), we demonstrate ultra-low voltage operation of graphene field effect transistors within $\pm1$ V with maximum doping exceeding $10^{13}\,\mathrm{cm^{-2}}$ and on-off ratios larger than 10 times. After polarizing PZT, switching of graphene field effect transistors are characterized by pronounced resistance hysteresis, suitable for ultra-fast non-volatile electronics.Comment: 4 pages, 3 figures; EPL 2011; In pres

Curative Effects of Thiacremonone against Acetaminophen-Induced Acute Hepatic Failure via Inhibition of Proinflammatory Cytokines Production and Infiltration of Cytotoxic Immune Cells and Kupffer Cells

High doses of acetaminophen (APAP; N-acetyl-p-aminophenol) cause severe hepatotoxicity after metabolic activation by cytochrome P450 2E1. This study was undertaken to examine the preventive effects of thiacremonone, a compound extracted from garlic, on APAP-induced acute hepatic failure in male C57BL/6J. Mice received with 500 mg/kg APAP after a 7-day pretreatment with thiacremonone (10–50 mg/kg). Thiacremonone inhibited the APAP-induced serum ALT and AST levels in a dose-dependent manner, and markedly reduced the restricted area of necrosis and inflammation by administration of APAP. Thiacremonone also inhibited the APAP-induced depletion of intracellular GSH, induction of nitric oxide, and lipid peroxidation as well as expression of P450 2E1. After APAP injection, the numbers of Kupffer cells, natural killer cells, and cytotoxic T cells were elevated, but the elevated cell numbers in the liver were reduced in thiacremonone pretreated mice. The expression levels of I-309, M-CSF, MIG, MIP-1α, MIP-1β, IL-7, and IL-17 were increased by APAP treatment, which were inhibited in thiacremonone pretreated mice. These data indicate that thiacremonone could be a useful agent for the treatment of drug-induced hepatic failure and that the reduction of cytotoxic immune cells as well as proinflammatory cytokine production may be critical for the prevention of APAP-induced acute liver toxicity

Ellagic acid regulates Wnt/?-catenin signaling pathway and CDK8 in HCT 116 and HT 29 colon cancer cells

Colorectal cancer is one of the leading causes of death worldwide. Wnt/?-catenin signalling pathway plays a central role in normal cellular responses, making it a potent target in cancer therapy. Study was taken to assess whether ellagic acid modulates Wnt/?-catenin pathway and CDK8 activity in colon cancer cells. Effect of ellagic acid on viability of colon cancer cell lines (HT 29 and HCT 116), were assessed by MTT assay and its influence on CDK8, ?-catenin, p-?-catenin, axin1 and 2, survivin, c-Myc and cyclin D1 expressions were determined by western blotting. The levels of survivin, c-Myc and cyclin D1 were also analysed following siCDK8 transfection. Ellagic acid caused significant decrease in viability of HT 29 and HCT 116 cells. Expression of CDK 8, ?-catenin, survivin, c-Myc and cyclin D1were markedly reduced on exposure to ellagic acid. Significant up-regulation in the expression of p-?-catenin, axin1 and 2 were observed. siCDK8 transfection resulted in marked reduction in the expression of survivin, c-Myc and cyclin D1. Ellagic acid was able to effectively reduce cell viability and modulate expressions of Wnt/?-catenin signalling cascade proteins and down regulate the activity and expression of CDK8 in HT 29 and HCT 116 cells

Weight loss, insulin resistance, and study design confound results in a meta-analysis of animal models of fatty liver

The classical drug development pipeline necessitates studies using animal models of human disease to gauge future efficacy in humans, however there is a low conversion rate from success in animals to humans. Non-alcoholic fatty liver disease (NAFLD) is a complex chronic disease without any established therapies and a major field of animal research. We performed a meta-analysis with meta-regression of 603 interventional rodent studies (10,364 animals) in NAFLD to assess which variables influenced treatment response. Weight loss and alleviation of insulin resistance were consistently associated with improvement in NAFLD. Multiple drug classes that do not affect weight in humans caused weight loss in animals. Other study design variables, such as age of animals and dietary composition, influenced the magnitude of treatment effect. Publication bias may have increased effect estimates by 37-79%. These findings help to explain the challenge of reproducibility and translation within the field of metabolism