A hepatoprotective Lindera obtusiloba extract suppresses growth and attenuates insulin like growth factor-1 receptor signaling and NF-kappaB activity in human liver cancer cell lines

<p>Abstract</p> <p>Background</p> <p>In traditional Chinese and Korean medicine, an aqueous extract derived from wood and bark of the Japanese spice bush <it>Lindera obtusiloba </it>(<it>L.obtusiloba</it>) is applied to treat inflammations and chronic liver diseases including hepatocellular carcinoma. We previously demonstrated anti-fibrotic effects of <it>L.obtusiloba </it>extract in hepatic stellate cells. Thus, we here consequently examine anti-neoplastic effects of <it>L.obtusiloba </it>extract on human hepatocellular carcinoma (HCC) cell lines and the signaling pathways involved.</p> <p>Methods</p> <p>Four human HCC cell lines representing diverse stages of differentiation were treated with <it>L.obtusiloba </it>extract, standardized according to its known suppressive effects on proliferation and TGF-β-expression. Beside measurement of proliferation, invasion and apoptosis, effects on signal transduction and NF-κB-activity were determined.</p> <p>Results</p> <p><it>L.obtusiloba </it>extract inhibited proliferation and induced apoptosis in all HCC cell lines and provoked a reduced basal and IGF-1-induced activation of the IGF-1R signaling cascade and a reduced transcriptional NF-κB-activity, particularly in the poorly differentiated SK-Hep1 cells. Pointing to anti-angiogenic effects, <it>L.obtusiloba </it>extract attenuated the basal and IGF-1-induced expression of hypoxia inducible factor-1α, vascular endothelial growth factor, peroxisome proliferator-activated receptor-γ, cyclooxygenase-2 and inducible nitric oxide synthase.</p> <p>Conclusions</p> <p>The traditional application of the extract is confirmed by our experimental data. Due to its potential to inhibit critical receptor tyrosine kinases involved in HCC progression via the IGF-1 signaling pathway and NF-κB, the standardized <it>L.obtusiloba </it>extract should be further analysed for its active compounds and explored as (complementary) treatment option for HCC.</p

Thermosensitive nanohydrogel of 5-fluorouracil for head and neck cancer: preparation, characterization and cytotoxicity assay

Chintan Dalwadi, Gayatri Patel Department of Pharmaceutics and Pharmaceutical Technology, Ramanbhai Patel College of Pharmacy, Charotar University of Science and Technology, Changa, Gujarat, India Abstract: Systemic chemotherapy has been shown to produce side effects. A small fraction of the drug reaches the tumor site; other healthy organs or normal tissues get affected or damaged due to the nonspecific action of these cytotoxic agents. Furthermore, due to their short period of activity, repeat injections are often required, which can lead to the exacerbation of side effects and inconvenience. To overcome these obstacles, in this study, we developed controlled and targeted intratumoral injection. Hydrogel was prepared by physical cross-linking method; however, nanohydrogel was prepared using tip probe-sonicator method. Our results revealed that biodegradable and thermosensitive 5-fluorouracil-loaded methylcellulose nanohydrogel synthesized by physical cross-linking method may be a beneficial approach in targeting the therapeutic agent to the tumor site. Keywords: biodegradable, intra tumor, targeted drug deliver

Feasibility study concerning the use of reasoning technique in semantic reasoners

Inference engine plays an important role in knowledge-based system, where it is used to perform reasoning when queries are entered. There is a need to incorporate a semantic reasoner in the engine, in order for it to perform reasoning. With the growth of Semantic Web and increasing number of ontology implemented recently, several semantic reasoner have been design and implemented to cater the need of the current ontology-based systems. Since there are various numbers of available semantic reasoners in the market for general knowledge-based system or ontology-based system, developers are required to choose an appropriate reasoner that met the system requirements when developing the engine. This paper will review six different ontology reasoners, which have been widely applied previously in ontology based system. By studying the strength and weaknesses of the techniques and algorithms implemented, developer able to select an appropriate reasoner that will work efficiently according to system requirements