A centrosome clustering protein, KIFC1, predicts aggressive disease course in serous ovarian adenocarcinomas

Background Amplified centrosomes are widely recognized as a hallmark of cancer. Although supernumerary centrosomes would be expected to compromise cell viability by yielding multipolar spindles that results in death-inducing aneuploidy, cancer cells suppress multipolarity by clustering their extra centrosomes. Thus, cancer cells, with the aid of clustering mechanisms, maintain pseudobipolar spindle phenotypes that are associated with low-grade aneuploidy, an edge to their survival. KIFC1, a nonessential minus end-directed motor of the kinesin-14 family, is a centrosome clustering molecule, essential for viability of extra centrosome-bearing cancer cells. Given that ovarian cancers robustly display amplified centrosomes, we examined the overexpression of KIFC1 in human ovarian tumors. Results We found that in clinical epithelial ovarian cancer (EOC) samples, an expression level of KIFC1 was significantly higher when compared to normal tissues. KIFC1 expression also increased with tumor grade. Our In silico analyses showed that higher KIFC1 expression was associated with poor overall survival (OS) in serous ovarian adenocarcinoma (SOC) patients suggesting that an aggressive disease course in ovarian adenocarcinoma patients can be attributed to high KIFC1 levels. Also, gene expression levels of KIFC1 in high-grade serous ovarian carcinoma (HGSOC) highly correlated with expression of genes driving centrosome amplification (CA), as examined in publically-available databases. The pathway analysis results indicated that the genes overexpressed in KIFC1 high group were associated with processes like regulation of the cell cycle and cell proliferation. In addition, when we performed gene set enrichment analysis (GSEA) for identifying the gene ontologies associated to KIFC1 high group, we found that the first 100 genes enriched in KIFC1 high group were from centrosome components, mitotic cell cycle, and microtubule-based processes. Results from in vitro experiments on well-established in vitro models of HGSOC (OVSAHO, KURAMOCHI), OVCAR3 and SKOV3) revealed that they display robust centrosome amplification and expression levels of KIFC1 was directly associated (inversely correlated) to the status of multipolar mitosis. This association of KIFC1 and centrosome amplification with HGSOC might be able to explain the increased aggressiveness in this disease. Conclusion These findings compellingly underscore that KIFC1 can be a biomarker that predicts an aggressive disease course in ovarian adenocarcinomas

Expression of glycolytic enzymes in ovarian cancers and evaluation of the glycolytic pathway as a strategy for ovarian cancer treatment

Table S2. Spearman correlation of the expression of four glycolytic enzymes in a cohort of 380 ovarian cancers. Spearman rho correlation values (top value) along with the respective adjusted P value (bottom value) of statistically significant correlations thresholded at FDR P < 0.01 are summarised. (DOCX 21 kb

Hemoglobin level predicts outcome for vulvar cancer patients independent of GLUT-1 and CA-IX expression in tumor tissue

Intratumoral hypoxia has been associated with poor prognosis in several solid tumors. The aim of this study was to determine whether the hypoxia-associated markers glucose transporter (GLUT)-1 and carbonic anhydrase (CA)-IX expression and preoperative hemoglobin (Hb) levels correlate with presence of inguinofemoral or distant metastases, and disease-free survival (DSS) in vulvar squamous cell carcinoma (SCC) patients. Vulvar SCC (n = 103) were reviewed for histopathological characteristics by an expert gynecopathologist and stained for GLUT-1 and CA-IX. Clinical data and preoperative Hb levels were obtained from medical records. No significant correlations were observed between GLUT-1 or CA-IX expression patterns and preoperative Hb levels, presence of inguinofemoral or distant metastases and DSS. However, anemic patients (Hb < 11.2 g/dL) had significantly more inguinofemoral metastases and lower Hb level was an independent prognostic factor for a worse DSS (p < 0.001). The number of comorbidic conditions was inversely correlated with preoperative Hb level. Preoperative Hb levels are associated with poor DSS for vulvar SCC patients, whereas tumor hypoxia reflected by GLUT-1 and CA-IX expression does not have a predictive value. Because preoperative Hb levels inversely correlated with the number of comorbidic conditions and not with GLUT-1 or CA-IX expression, it is most likely that preoperative Hb levels represent overall physical condition

Amplified centrosomes and mitotic index display poor concordance between patient tumors and cultured cancer cells

Centrosome aberrations (CA) and abnormal mitoses are considered beacons of malignancy. Cancer cell doubling times in patient tumors are longer than in cultures, but differences in CA between tumors and cultured cells are uncharacterized. We compare mitoses and CA in patient tumors, xenografts, and tumor cell lines. We find that mitoses are rare in patient tumors compared with xenografts and cell lines. Contrastingly, CA is more extensive in patient tumors and xenografts (~35–50% cells) than cell lines (~5–15%), although CA declines in patient-derived tumor cells over time. Intratumoral hypoxia may explain elevated CA in vivo because exposure of cultured cells to hypoxia or mimicking hypoxia pharmacologically or genetically increases CA, and HIF-1α and hypoxic gene signature expression correlate with CA and centrosomal gene signature expression in breast tumors. These results highlight the importance of utilizing low-passage-number patient-derived cell lines in studying CA to more faithfully recapitulate in vivo cellular phenotypes

Modulation of Cytochrome P450 Metabolism and Transport across Intestinal Epithelial Barrier by Ginger Biophenolics

Natural and complementary therapies in conjunction with mainstream cancer care are steadily gaining popularity. Ginger extract (GE) confers significant health-promoting benefits owing to complex additive and/or synergistic interactions between its bioactive constituents. Recently, we showed that preservation of natural ‘‘milieu’’ confers superior anticancer activity on GE over its constituent phytochemicals, 6-gingerol (6G), 8-gingerol (8G), 10-gingerol (10G) and 6-shogaol (6S), through enterohepatic recirculation. Here we further evaluate and compare the effects of GE and its major bioactive constituents on cytochrome P450 (CYP) enzyme activity in human liver microsomes by monitoring metabolites of CYPspecific substrates using LC/MS/MS detection methods. Our data demonstrate that individual gingerols are potent inhibitors of CYP isozymes, whereas GE exhibits a much higher half-maximal inhibition value, indicating no possible herb-drug interactions. However, GE’s inhibition of CYP1A2 and CYP2C8 reflects additive interactions among the constituents. In addition, studies performed to evaluate transporter-mediated intestinal efflux using Caco-2 cells revealed that GE and its phenolics are not substrates of P-glycoprotein (Pgp). Intriguingly, however, 10G and 6S were not detected in the receiver compartment, indicating possible biotransformation across the Caco-2 monolayer. These data strengthen the notion that an interplay of complex interactions among ginger phytochemicals when fed as whole extract dictates its bioactivity highlighting the importance of consuming whole foods over single agents. Our study substantiates the need for an indepth analysis of hepatic biotransformation events and distribution profiles of GE and its active phenolics for the design of safe regimens

Adsorption Of Silver From Aqueous Solution Onto Pre-treated Bentonite Clay: Complete Batch System Evaluation

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)In this work, thermally modified bentonite clay (Verde-lodo) was used for batch adsorption of silver from aqueous solution. The adsorption rate was evaluated by a kinetics study based on the following models: pseudo-first order, pseudo-second order, intra-particle diffusion, Mass Transfer in External Film and Boyd model. Among these models, the Mass Transfer in External Film model presented better agreements between experimental and calculated data, revealing that the process is mainly controlled by external transport. The equilibrium isotherms were obtained at four different temperatures (283, 293, 313 and 333 K) and were adjusted by three equilibrium models: Langmuir, Freundlich and Dubinin-Radushkevich. According to the correlation coefficient and Relative Standard Deviation, Langmuir model has presented the best adjustment results. The maximum adsorption capacities verified for Verdelodo clay at 283 K and 293 K were 61.48 mg g(-1) and 55.55 mg g(-1), respectively. Furthermore, the increasing trend of adsorption capacity for higher equilibrium temperatures indicates an exothermic behaviour for this process. This fact was also verified by the evaluation of thermodynamic parameters, which has concluded that the process is spontaneous and governed by physical adsorption. In order to bring scientific advances related to silver recovery from wastewater, batch desorption essays were performed using different eluents. Among the components, nitric acid presented a high desorption capacity and was selected for future experiments. The characterization techniques of regenerated clay revealed that the desorption process do not significantly affect the thermal stability and chemical and crystalline structure of Verde-lodo clay. However, some deformities were verified on the adsorbent's surface by the Scanning Electron Microscopy. (C) 2015 Elsevier Ltd. All rights reserved.11211121121Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)FAPESP [2013/00732-1]CNPq [300986/2013-0, 470615/2013-3

Biosorption of silver by Macrophyte Salvinia Cucullata

Silver removal from aqueous solutions by macrophyte Salvinia cucullata was investigated in static and dynamic system. The macrophyte Salvinia cucullata showed high potential for removing silver in previous tests using three different macrophytes. Batch experiments were performed at a constant temperature, adjusting solution pH in contact with Salvinia cucullata. Pseudo-first order, pseudo-second order and intra- particle diffusion models were used to analyze the kinetic curves. Equilibrium data were analyzed using Langmuir and Freundlich models. Adsorption essays at fixed bed were also carried out according to a study of outflow based on results from mass transfer zone (MTZ). The single-component essays showed that silver ions have affinity to macrophyte adsorptive sites. The maximum adsorption capacity increased significantly in the dynamic system of fixed bed compared to static batch38109114sem informação4th International Conference on Industrial Biotechnology (IBIC2014)2014-06-08Rome, ITALYsem informaçã

Removal And Recovery Of Silver By Dynamic Adsorption On Bentonite Clay Using A Fixed-bed Column System

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Several studies have focused on the removal and recovery of precious metal ions from industrial wastewater due to their environmental and economic importance. Adsorption on bentonite clays has been shown to possess a high removal potential for several metal ions. We herein investigated the dynamic adsorption of silver using a fixed-bed column and a calcined bentonite clay called Verde-lodo as an adsorbent. A fluid dynamic study was performed to evaluate the adsorption system's metal-ion removal capacity (q(u) and q(t)), the mass transfer zone and the percentage of total removal according to different effluent's flow. Adsorption-desorption cycles were carried out using nitric acid as an eluent to evaluate the useful lifetime of the column. The breakthrough curves were fitted to the Bohart-Adams model (quasichemical). Moreover, the zeta potential was analyzed to explain the difference between the removal capacity obtained for the static and dynamic systems.33291103Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)FAPESP [Proc. 2013/00732-1