A Regulator Role for the ATP-Binding Cassette Subfamily C Member 6 Transporter in HepG2 Cells: Effect on the Dynamics of Cell-Cell and Cell-Matrix Interactions

There is growing evidence that various ATP-binding cassette (ABC) transporters contribute to the growth and development of tumors, but relatively little is known about how the ABC transporter family behaves in hepatocellular carcinoma (HCC), one of the most common cancers worldwide. Cellular model studies have shown that ABCC6, which belongs to the ABC subfamily C (ABCC), plays a role in the cytoskeleton rearrangement and migration of HepG2 hepatocarcinoma cells, thus highlighting its role in cancer biology. Deep knowledge on the molecular mechanisms underlying the observed results could provide therapeutic insights into the tumors in which ABCC6 is modulated. In this study, differential expression levels of mRNA transcripts between ABCC6-silenced HepG2 and control groups were measured, and subsequently, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were performed. Real-Time PCR and Western blot analyses confirmed bioinformatics; functional studies support the molecular mechanisms underlying the observed effects. The results provide valuable information on the dysregulation of fundamental cellular processes, such as the focal adhesion pathway, which allowed us to obtain detailed information on the active role that the down-regulation of ABCC6 could play in the biology of liver tumors, as it is involved not only in cell migration but also in cell adhesion and invasion

Inventory management strategies for the Calabrian hospitals system

This paper addresses some inventory management problems arising in the Italian health care system. We aim at defining inventory management strategies for the hospitals located in Calabria, a Region in the South of Italy. We present some classical inventory management formulations together with the description of a new model, devised to take into account some peculiarities of the case under study. An extensive testing phase is carried out on real data. Numerical results show that the use of the presented mathematical models can be valuable in the decision making process

SVM-Based Multiple Instance Classification via DC Optimization

A multiple instance learning problem consists of categorizing objects, each represented as a set (bag) of points. Unlike the supervised classification paradigm, where each point of the training set is labeled, the labels are only associated with bags, while the labels of the points inside the bags are unknown. We focus on the binary classification case, where the objective is to discriminate between positive and negative bags using a separating surface. Adopting a support vector machine setting at the training level, the problem of minimizing the classification-error function can be formulated as a nonconvex nonsmooth unconstrained program. We propose a difference-of-convex (DC) decomposition of the nonconvex function, which we face using an appropriate nonsmooth DC algorithm. Some of the numerical results on benchmark data sets are reported

Models and Policies for Service Industries via Revenue Management

Dottorato di Ricerca in: Ricerca Operativa, XXIV Ciclo, a.a. 2008-2011Università della Calabri

Gene Expression Reprogramming by Citrate Supplementation Reduces HepG2 Cell Migration and Invasion

Citrate, which is obtained from oxaloacetate and acetyl-CoA by citrate synthase in mitochondria, plays a key role in both normal and cancer cell metabolism. In this work, we investigated the effect of 10 mM extracellular citrate supplementation on HepG2 cells. Gene expression reprogramming was evaluated by whole transcriptome analysis using gene set enrichment analysis (GSEA). The transcriptomic data were validated through analyzing changes in the mRNA levels of selected genes by qRT-PCR. Citrate-treated cells exhibited the statistically significant dysregulation of 3551 genes; 851 genes were upregulated and 822 genes were downregulated. GSEA identified 40 pathways affected by differentially expressed mRNAs. The most affected biological processes were related to lipid and RNA metabolism. Several genes of the cytochrome P450 family were upregulated in treated cells compared to controls, including the CYP3A5 gene, a tumor suppressor in hepatocellular carcinoma (HCC) that plays an important protective role in HCC metastasis. The citrate-induced dysregulation of cytochromes could both improve the effectiveness of chemotherapeutics used in combination and reduce the aggressiveness of tumors by diminishing cell migration and invasion

On solving the Lagrangian dual of integer programs via an incremental approach

Incremental algorithms, Convex minimization, Finite min-max, Lagrangian relaxation, Nonsmooth optimization, Bundle methods,