Anti-Tumor Activity of a Novel HS-Mimetic-Vascular Endothelial Growth Factor Binding Small Molecule

The angiogenic process is controlled by variety of factors of which the vascular endothelial growth factor (VEGF) pathway plays a major role. A series of heparan sulfate mimetic small molecules targeting VEGF/VEGFR pathway has been synthesized. Among them, compound 8 (2-butyl-5-chloro-3-(4-nitro-benzyl)-3H-imidazole-4-carbaldehyde) was identified as a significant binding molecule for the heparin-binding domain of VEGF, determined by high-throughput-surface plasmon resonance assay. The data predicted strong binding of compound 8 with VEGF which may prevent the binding of VEGF to its receptor. We compared the structure of compound 8 with heparan sulfate (HS), which have in common the functional ionic groups such as sulfate, nitro and carbaldehyde that can be located in similar positions of the disaccharide structure of HS. Molecular docking studies predicted that compound 8 binds at the heparin binding domain of VEGF through strong hydrogen bonding with Lys-30 and Gln-20 amino acid residues, and consistent with the prediction, compound 8 inhibited binding of VEGF to immobilized heparin. In vitro studies showed that compound 8 inhibits the VEGF-induced proliferation migration and tube formation of mouse vascular endothelial cells, and finally the invasion of a murine osteosarcoma cell line (LM8G7) which secrets high levels of VEGF. In vivo, these effects produce significant decrease of tumor burden in an experimental model of liver metastasis. Collectively, these data indicate that compound 8 may prevent tumor growth through a direct effect on tumor cell proliferation and by inhibition of endothelial cell migration and angiogenesis mediated by VEGF. In conclusion, compound 8 may normalize the tumor vasculature and microenvironment in tumors probably by inhibiting the binding of VEGF to its receptor

E-endocrinology: An update

Internet, from a long time, has opened up a myriad resource of knowledge and applications for academicians, researchers and clinicians alike in all health care professions across the globe. Basic endocrinologists are exploring through bench-top protocols to understand endocrine system and to design therapeutic interventions. Clinicians are required to continuously look for new developments relating to investigation, diagnosis and therapeutic options in their everyday practice for better quality of life of patients. All these require managing a large body of information. Now, these innovative technologies have opened up newer avenues for endocrinologists. As internet is serving the backbone for modern technologies, it is of utmost necessity to use and refine internet applications for future endocrinologists. Increasingly, easy access to internet has dramatically reduced barriers in sharing information among basic and clinical endocrinologists. Considering the growing scope for endocrinologists in the use of internet, it is necessary to understand internet as a source of information and backbone of modern applications. This review illustrates the expanding roles of the internet for endocrinologists and provides a ready-to-use compilation of useful academic, research, clinical resources, and is expected to introduce, stimulate and guide endocrinologists into the realm of WWW

Endocrinological cancers and the internet

Endocrine cancers are some of the commonest forms of cancer getting mention as early as in old papyruses of Egypt. Our current knowledge about this cluster of cancer has grown immensely with improved survival rates. In the era of specialization and super specialization, we started peeking into these conditions more elaborately and beyond microscopically. The growing awareness demanded categorization of information into disease basics like molecular pathology of initiation and progression; advanced diagnostics; new therapeutic options; patient awareness and involvement in clinical trials. Recent advances in genomics and hereditary counseling have delineated pre-disease forecasting possibilities. With advanced diagnostics and therapeutic modalities, we saw an increase in cancer survivors demanding extra care and moral support. Throughout these developments, we went through a boost in global information communications, the main thrust being the Internet. Networking of computers globally generated a platform that created a ripple of knowledge far and wide. The purpose of this review is to investigate how the Internet is supporting the growth and development of the field of endocrine cancer, and present and future scope of the Internet as a tool for professionals involved in this area. The information furnished here were collected from cited references as well as all websites mentioned in the tables