A multi-omics integrative approach unravels novel genes and pathways associated with senescence escape after targeted therapy in NRAS mutant melanoma.

Therapy Induced Senescence (TIS) leads to sustained growth arrest of cancer cells. The associated cytostasis has been shown to be reversible and cells escaping senescence further enhance the aggressiveness of cancers. Chemicals specifically targeting senescent cells, so-called senolytics, constitute a promising avenue for improved cancer treatment in combination with targeted therapies.

Expanding the Disease Network of Glioblastoma Multiforme via Topological Analysis.

Glioblastoma multiforme (GBM), a grade IV glioma, is a challenging disease for patients and clinicians, with an extremely poor prognosis. These tumours manifest a high molecular heterogeneity, with limited therapeutic options for patients. Since GBM is a rare disease, sufficient statistically strong evidence is often not available to explore the roles of lesser-known GBM proteins.

Construction and contextualization approaches for protein-protein interaction networks.

Protein-protein interaction network (PPIN) analysis is a widely used method to study the contextual role of proteins of interest, to predict novel disease genes, disease or functional modules, and to identify novel drug targets. PPIN-based analysis uses both generic and context-specific networks. Multiple contextualization methodologies have been described, such as shortest-path algorithms, neighborhood-based methods, and diffusion/propagation algorithms.

Topological network measures for drug repositioning.

Drug repositioning has received increased attention since the past decade as several blockbuster drugs have come out of repositioning. Computational approaches are significantly contributing to these efforts, of which, network-based methods play a key role. Various structural (topological) network measures have thereby contributed to uncovering unintuitive functional relationships and repositioning candidates in drug-disease and other networks.

Modulation of in vitro phagocytic uptake and immunogenicity potential of modified Herceptin-conjugated PLGA-PEG nanoparticles for drug delivery.

There is an increasing interest in engineered nanoparticle (NP) conjugates for targeted and controlled drug delivery. However, the practical applications of these NP delivery vehicles remain constrained because of their reactivity with the body's immune system defenses resulting in undesirable off-target effects. In this study, poly(D,L lactide-co-glycolide) (PLGA)-b-polyethylene glycol (PEG) NPs conjugated to different quantities of the commercial antibody Herceptin meant to target HER2-positive breast cancer cells were studied for their immune cell uptake and immunogenic properties (using murine macrophages and human dendritic cells).

Herceptin conjugated PLGA-PHis-PEG pH sensitive nanoparticles for targeted and controlled drug delivery.

A dual functional nano-scaled drug carrier, comprising of a targeting ligand and pH sensitivity, has been made in order to increase the specificity and efficacy of the drug delivery system. The nanoparticles are made of a tri-block copolymer, poly(d,l lactide-co-glycolide) (PLGA)-b-poly(l-histidine) (PHis)-b-polyethylene glycol (PEG), via nano-precipitation. To provide the nanoparticle feature of endolysosomal escape and pH sensitivity, poly(l-histidine) was chosen as a proton sponge polymer.