Therapies targeting oncogenic drivers rapidly induce compensatory adaptive responses that blunt drug effectiveness, contributing to therapeutic resistance. Adaptive responses are characteristic of robust cell signaling networks, and thus there is increasing interest in drug combinations that co-target the driver and the adaptive response. An alternative approach to co-inhibiting oncogenic and a...

UNLABELLED Invasion and metastasis increase after the inhibition of VEGF signaling in some preclinical tumor models. In the present study we asked whether selective VEGF inhibition is sufficient to increase invasion and metastasis and whether selective c-Met inhibition is sufficient to block this effect. Treatment of pancreatic neuroendocrine tumors in RIP-Tag2 mice with a neutralizing anti-VEG...

Background: Advanced papillary thyroid cancer (PTC) and anaplastic (ATC) are the leading causes of endocrine death. Mutations in MAP kinase (MAPK) pathway common PTC ATC. Recently, combination dabrafenib (BRAFi) trametinib (MEKi) was approved for treatment BRAF-mutant However, combined BRAF/ MEK inhibition is rarely curative ATC patients has had limited responses PTC. Here, we identify an induc...

Introduction: Recent studies have shown that astrocytes play major roles in normal and disease condition of the central nervous system including multiple sclerosis (MS). Molecular target therapy studies in MS have revealed that connexin-43 (Cx43) and Aquaporin-4 (AQP4) contents of astrocytes undergo expression alteration. Fluoxetine had some effects in MS patients unrelated to its known antidep...

Inhibition of Sonic hedgehog (Shh) signaling is of great clinical interest. Here we exploit Hedgehog acyltransferase (Hhat)-mediated Shh palmitoylation, a modification critical for Shh signaling, as a new target for Shh pathway inhibition. A target-oriented high-throughput screen was used to identify small-molecule inhibitors of Hhat. In cells, these Hhat inhibitors specifically block Shh palmi...

conclusions all plants could inhibit mushroom tyrosinase, but more investigations on human tyrosinase and clinical studies are needed. results the hydroalcoholic extract of p. alkekengi showed the most tyrosinase inhibitory effect with ic50 of 0.09 mg/ml vs. 0.38, 0.38 and 2.82 mg/ml of b. persicum, a. rosea and m. vulgare, respectively. m. vulgare exhibited uncompetitive inhibition and other p...

Caspase-3, one of the dominant effectors caspases, is activated in almost every model of apoptosis with various signaling pathways. Hence, inhibition of caspase-3 has become an attractive target in the treatment of neurodegenerative diseases. Caspase-3 inhibitory activities of some 1,2-benzisothiazol-3-one derivatives were modeled by quantitative structure–activity relationship (QSAR) using ste...

The inhibitory surround signal in retinal ganglion cells is usually attributed to lateral horizontal cell signaling in the outer plexiform layer (OPL). However, recent evidence suggests that lateral inhibition at the inner plexiform layer (IPL) also contributes to the ganglion cell receptive field surround. Although amacrine cell input to ganglion cells mediates a component of this lateral inhi...

The effects of selective phosphoinositide 3-kinase (PI3K) and AKT inhibitors were compared in human tumor cell lines in which the pathway is dysregulated. Both caused inhibition of AKT, relief of feedback inhibition of receptor tyrosine kinases, and growth arrest. However, only the PI3K inhibitors caused rapid induction of cell death. In seeking a mechanism for this phenomenon, we found that PI...

Since the incidence of cancer is increasing worldwide, there an urgent need for more successful therapies. Here, we focused on a literature review regarding lymphoma and deregulated pathways that are hallmarks development. Among others, PI3K/AKT, NF-ĸB JAK/STAT most common ones. These signaling crucial numerous cellular processes possible deregulation can mainly lead to uncontrolled cell divisi...