Vascular endothelial growth factor in the management of hepatocellular carcinoma

Abstract

The consumption of antidepressants, especially selective serotonine reuptake inhibitors (SSRI) has been increasing. Because a large fraction of the population is exposed, even a small excess of risk with respect to cancer should be considered. We carried out a record linkage study in Finland utilizing nationwide databases of reimbursed medication and cancer. The study population included all antidepressant drug (AD) users in Finland who had purchased at least 1 prescription between 1998 and 2005, and who had no cancer diagnosis at the date of first purchase. A control population without AD usage (matched by age and sex) was also included. Data consisted of 418,588 pairs of individuals that cumulated 3.3 million person‐years with an average of 4.0 years of follow‐up. 19,365 cancer cases were observed. The most frequent cancers were breast, prostate, lung, colon, and brain cancer. In general, only few associations between the utilization of AD and cancer could be detected. Over four years exposure to AD showed a weak association with increased colon and breast cancer incidence, which could have been caused by bias. As conclusion, no clear evidence of neither beneficial nor harmful association between usage of antidepressant and cancer was found.

Systemic Delivery of a miR34a Mimic as a Potential Therapeutic for Liver Cancer

“…Interestingly, VEGF expression has been reported to be highest in cirrhotic regions of the liver which surround HCC tumors in human patients (39), and agents are currently being designed to target both tumor and surrounding liver tissue as both appear critical in tumor formation and propagation (40,38). Administering a single injection of MRX34 inhibited mRNA expression of MAPKAPK2, NFATC3, and MAPK1, which all function within the VEGF pathway (41). The ability to diminish angiogenesis via the VEGF pathway is a likely contributor to the efficacy observed in our mouse models of HCC.…”

Systemic therapy for advanced hepatocellular carcinoma: an update

“…There are three main subtypes of VEGF receptors: VEGFR-1, VEGFR-2, and VEGFR-3 (27). Binding of ligand to one of these receptors results in dimerization and auto phosphorylation of the intracellular tyrosine sites.…”

“…These phosphorylated tyrosine regions then serve as docking sites for a variety of signal transduction proteins. The role of VEGF1 signaling has not been completely established but the most current supported theory is that VEGF1 activation plays a major role in the modulation of VEGF2 (27). Research has also shown that VEGF1 positive cells, which are derived from the bone marrow, might play a substantial role in different types of tumor progression (28).…”

“…Through the phosphorylation of its tyrosine sites, VEGF2 can activate phospholipase C (PLC)-γ, and further downstream protein kinase C. Activated protein kinase C can induce MAPK signaling, which results in endothelial cell proliferation. In addition, VEGF2 induces angiogenesis by means of RAS homolog gene family-guanosine triphosphatase (Rho-GTPase) activation and influences the secretion of proteins like endothelial Von Willebrand Factor, thus increasing endothelial vascular permeability (27)(28)(29)(30). VEGF3 on the other hand is thought to play a role in lymphangiogenesis through the activation of protein kinase C and the RAS pathway (27,28).…”

“…In addition, VEGF2 induces angiogenesis by means of RAS homolog gene family-guanosine triphosphatase (Rho-GTPase) activation and influences the secretion of proteins like endothelial Von Willebrand Factor, thus increasing endothelial vascular permeability (27)(28)(29)(30). VEGF3 on the other hand is thought to play a role in lymphangiogenesis through the activation of protein kinase C and the RAS pathway (27,28). Due to HCC being a highly vascularized tumor, VEGF signaling increases tumor cell growth and proliferation.…”