Current Pharmaceutical Design - Volume 16, Issue 35, 2010

Angiogenesis has been described as one of the hallmarks of cancer, playing an essential role in tumor growth, invasion and metastasis. Antiangiogenic therapy was initially perceived as a “magic bullet” that could eventually be used for the treatment of any type of cancer. For this reason inhibition of angiogenesis has become a major challenge in the development of new anticancer agents, with a countless number Read More

In eukaryotes, genes consist in coding sequences (exons) interspersed with non-coding ones (introns). The regulation of alternative inclusion/exclusion of exons, or part of exons, during the maturation of the pre-mRNA into mRNA (alternative splicing) allows a dramatic increase of the protein versus the gene repertoire. In a number of cases, alternative splicing decision generates proteins with distinct, sometimes o Read More

Historically, oxidative stress was recognized to contribute to cancer development uniquely by induction of genomic instability. However, recent research has provided multiple evidence that reactive oxygen species and other free radicals, such as nitric oxide, often produced at elevated levels within tumor tissue, may function as signaling molecules that initiate and/or modulate the different regulatory pathways involved i Read More

Vascular smooth muscle cells (VSMC) respond to arterial wall injury by intimal proliferation and play a key role in atherogenesis by proliferating and migrating excessively in response to repeated injury, such as hypertension and atherosclerosis. In contrast, fully differentiated, quiescent VSMC allow arterial vasodilatation and vasoconstriction. Exaggerated and uncontrolled VSMC proliferation appears therefore to be a common Read More

Chemokines are key players in the attraction and activation of leukocytes and are thus implicated in the recruitment of immune cells at sites of infection and/or inflammation. They exert their action by binding to seven-transmembrane G protein-coupled receptors. The chemokine stromal cell-derived factor-1 (SDF-1)/CXCL12 represents the single natural ligand for the chemokine receptor CXCR4. CXCL12 possesses angioge Read More

Angiogenesis is associated with tumor development and malignancy and is a validated target for cancer treatment. Preclinical and clinical evidence substantiates the feasibility of combining angiogenesis inhibitors with conventional anticancer therapy. This review discusses recent progress in combining antiangiogenic drugs, mainly acting on the VEGF/VEGFR pathway, with chemotherapy and other conventional therapies. Strat Read More

Angiogenesis has been described as one of the hallmarks of cancer, playing an essential role in tumor growth, invasion, and metastasis. Antiangiogenic therapy was initially perceived as a “magic bullet” that could eventually be used for the treatment of any type of cancer. For this reason inhibition of angiogenesis has become a major challenge in the development of new anticancer agents, with a countless number Read More

Recent developments in high-content screening (HCS) technologies make it an attractive alternative for anti-angiogenic drug discovery. HCS integrates high-throughput methodologies with automated multicolor fluorescence microscopy to collect quantitative morphological and molecular data from complex biological systems. Organotypic systems based on primary vascular cells model many facets of angiogenesis. The ad Read More

Human Pim1 (proviral integration site for Moloney murine leukemia virus) kinase is a 313-amino acid serine-threonine kinase that possesses several biological functions in cell survival, proliferation and differentiation, and its overexpression has been observed in a number of human cancers. Indeed, this kinase is a proto-oncogene that has been implicated in early transformation and tumor progression, especially in hematopoi Read More