Pomegranate extract inhibits EMT in clear cell renal cell carcinoma in a NF-κB and JNK dependent manner.

Objective:Clear cell renal cell carcinoma (ccRCC) is the most common subtype of renal cell carcinoma (RCC) and is characterized by biallelic inactivation of the von Hippel-Lindau (VHL) tumor suppressor gene. One effect of VHL inactivation is hypoxia inducible factor alpha (HIFα)-independent constitutive activation of nuclear factor kappa B (NF-κB) and c-jun N-terminal kinase (JNK). Both NF-κB and JNK drive ccRCC growth and epithelial to mesenchymal transition (EMT). The purpose of this study was to determine the biochemical effects of pomegranate juice extracts (PE) on RCC cell lines. Methods:The pre-clinical effects of PE on NF-κB, JNK, and the EMT phenotype were assayed, including its effect on proliferation, anchorage-independent growth, and invasion of pVHL-deficient RCCs. Results:PE inhibits the NF-κB and JNK pathways and consequently inhibits the EMT phenotype of pVHL-deficient ccRCCs. The effects of PE are concentration-dependent and affect not only biochemical markers of EMT (i.e., cadherin expression) but also functional manifestations of EMT, such as invasion. These effects are manifested within days of exposure to PE when diluted 2000-fold. Highly dilute concentrations of PE (106 dilution), which do not impact these pathways in the short term, were found to have NF-κB and JNK inhibitory effects and ability to reverse the EMT phenotype following prolonged exposure. Conclusion:These findings suggest that PE may mediate inhibition growth of pVHL-deficient ccRCCs and raises the possibility of its use as a dietary adjunct to managing patients with active surveillance for small, localized, incidentally identified renal tumors so as to avoid more invasive procedures such as nephrectomy

Method for Assessing the Fidelity of Optical Diffraction Tomography Reconstruction Methods

We use a spatial light modulator in a diffraction tomographic system to assess the accuracy of different refractive index reconstruction algorithms. Optical phase conjugation principles through complex media, allows us to quantify the error for different refractive index reconstruction algorithms without access to the ground truth. To our knowledge, this is the first assessment technique that uses structured illumination experimentally to test the accuracy of different reconstruction schemes.Comment: 11 PAGES, 6 FIGURE

Magnetic Stability, Fermi Surface Topology, and Spin-Correlated Dielectric Response in Monolayer 1T-CrTe2

We have carried out density-functional theory (DFT) calculations to study the magnetic stability of both ferromagnetic (FM) and anti-ferromagnetic (AFM) states in monolayer 1T-CrTe2. Our results show that the AFM order is lower in energy and thus is the ground state. By tuning the lattice parameters, the AFM order can transition to the FM order, in good agreement with experimental observation. We observe a commensurate SDW alongside the previously predicted CDW, and attribute the AFM order to the SDW. This results in distinct hole and electron Fermi pockets and a pronounced optical anisotropy, suggesting quasi-one-dimensional behavior in this material

A Solution for the problems caused by Eichornia crassipes in the Ampara District

Eichornia crassipes (Japan Jabara/Japan Japarli/Aathu Valai/Water hyacinth) is a nonnative invasive freshwater plant to Sri Lanka, which blocks the drainage and irrigation cannels. During heavy rainy season Eichornia crassipes plants block the flow of rivers and by spreading over the paddy fields cause floods frequently, destroy the aesthetic value of the water bodies and obstructs the fishing activities. Due to very rapid growth and spread rate, farmers and local authorities need to spent significant amount of money to remove these plants and need large dumping areas for disposing of these plants. A study was conducted to prepare compost using Eichornia crassipes as the main resource material along with paddy straw and cow dung. Multiple layers of these materials were mixed at 3rd and 6th weeks and the moisture content was maintained at 50 - 60%. In the 10th week, compost was ready and it was sieved. The return percentage of compost from the input was 65. The moisture percentage of the produced compost was 50.3 and the volatile solid percentage was 22.8. The compost contained 39.5 % carbon, the pH was 8.1 and 73.5 % of the produced compost was sieved through 4 mm sieve. The total production cost was Rs 4.40 kg-I and it had very good demand and the selling price was Rs. 13.00 kg-

Tumor Growth Rate Approximation-Assisted Estimation

From tumor to tumor, there is a great variation in the proportion of cancer cells growing and making daughter cells that ultimately metastasize. The differential growth within a single tumor, however, has not been studied extensively and this may be helpful in predicting the aggressiveness of a particular cancer type. The estimation problem of tumor growth rates from several populations is studied. The baseline growth rate estimator is based on a family of interacting particle system models which generalize the linear birth process as models of tumor growth. These interacting models incorporate the spatial structure of the tumor in such a way that growth slows down in a crowded system. Approximation-assisted estimation strategy is proposed when initial values of rates are known from the previous study. Some alternative estimators are suggested and the relative dominance picture of the proposed estimator to the benchmark estimator is investigated. An over-riding theme of this article is that the suggested estimation method extends its traditional counterpart to non-normal populations and to more realistic cases

Adaptive changes of glioblastoma cells following exposure to hypoxic (1% oxygen) tumour microenvironment.

Glioblastoma multiforme is the most aggressive and malignant primary brain tumour, with a median survival rate of between 15 to 17 months. Heterogeneous regions occur in glioblastoma as a result of oxygen gradients which ranges from 0.1% to 10% in vivo. Emerging evidence suggests that tumour hypoxia leads to increased aggressiveness and chemo/radio resistance. Yet, few in vitro studies have been performed in hypoxia. Using three glioblastoma cell-lines (U87, U251, and SNB19), the adaptation of glioblastoma cells in a 1% (hypoxia) and 20% (normoxia) oxygen microenvironment on proliferation, metabolism, migration, neurosphere formation, CD133 and VEGF expression was investigated. Compared to cells maintained in normoxia (20% oxygen), glioblastoma cells adapted to 1% oxygen tension by reducing proliferation and enhancing metabolism. Both migratory tendency and neurosphere formation ability were greatly limited. In addition, hypoxic-mediated gene upregulation (CD133 and VEGF) was reversed when cells were removed from the hypoxic environment. Collectively, our results reveal that hypoxia plays a pivotal role in changing the behaviour of glioblastoma cells. We have also shown that genetic modulation can be reversed, supporting the concept of reversibility. Thus, understanding the degree of oxygen gradient in glioblastoma will be crucial in personalising treatment for glioblastoma patients

Frondoside A suppressive effects on lung cancer survival, tumor growth, angiogenesis, invasion, and metastasis

A major challenge for oncologists and pharmacologists is to develop less toxic drugs that will improve the survival of lung cancer patients. Frondoside A is a triterpenoid glycoside isolated from the sea cucumber, Cucumaria frondosa and was shown to be a highly safe compound. We investigated the impact of Frondoside A on survival, migration and invasion in vitro, and on tumor growth, metastasis and angiogenesis in vivo alone and in combination with cisplatin. Frondoside A caused concentration-dependent reduction in viability of LNM35, A549, NCI-H460-Luc2, MDA-MB-435, MCF-7, and HepG2 over 24 hours through a caspase 3/7-dependent cell death pathway. The IC50 concentrations (producing half-maximal inhibition) at 24 h were between 1.7 and 2.5 mu M of Frondoside A. In addition, Frondoside A induced a time- and concentration-dependent inhibition of cell migration, invasion and angiogenesis in vitro. Frondoside A (0.01 and 1 mg/kg/day i.p. for 25 days) significantly decreased the growth, the angiogenesis and lymph node metastasis of LNM35 tumor xenografts in athymic mice, without obvious toxic side-effects. Frondoside A (0.1-0.5 mu M) also significantly prevented basal and bFGF induced angiogenesis in the CAM angiogenesis assay. Moreover, Frondoside A enhanced the inhibition of lung tumor growth induced by the chemotherapeutic agent cisplatin. These findings identify Frondoside A as a promising novel therapeutic agent for lung cancer