The serum and glucocorticoid inducible protein kinase (SGK) family members share similar structure, substrate specificity and function with AKT and signal downstream of the phosphatidylinositol 3-kinase (PI3K) signalling pathway. They regulate a range of fundamental cellular processes such as cell proliferation and survival, thereby playing an important role in cancer development. This perspective intends to give an overview on the involvement of SGKs (particularly SGK3) in cancer progression, and compares the actions of SGK3 and AKT in cell cycle regulation, oncogenic signalling, and the potential as a therapeutic target for cancer.
Telemedicine is starting to play an important role in the health field in India. In this case report we describe the successful use of telementoring to remove a parathyroid tumor in a patient with residual hyperparathyroidism after two previous unsuccessful attempts in tumor excision. A 21-yr-old patient crippled with advanced hyperparathyroidism was taken up for third-time exploration at Amrita Institute of Medical Sciences (AIMS), Kochi, with guidance from the Sanjay Gandhi Postgraduate Institute of Medical Sciences (SGPGIMS), Lucknow, using telemedicine technology. These two centers are located 2,500 km apart, and telementoring from the more experienced endocrine surgeons at SGPGIMS resulted in successful tumor localization and removal. For this session both the institutions were provided with a dedicated 512 Kbps very small aperture terminal (VSAT) link and two-way video-audio connectivity. Even though two previous explorations were unsuccessful, with the help of telemedicine technology the same surgeon was successful in locating and removing the tumor. The video and audio quality was of good enough quality for the expert at SGPGIMS to guide the team at AIMS satisfactorily. The patient benefited since he did not have to travel to a far-off specialized center for surgery. This case report testifies to the usefulness of telemedicine in the field of surgery, especially in developing countries, which have few medical experts in certain specialized areas.
The serum and glucocorticoid-regulated kinase (SGK) family has been implicated in the regulation of many cellular processes downstream of the PI3K pathway. It plays a crucial role in PI3K-mediated tumorigenesis, making it a potential therapeutic target for cancer. SGK family consists of three isoforms (SGK1, SGK2, and SGK3), which have high sequence homology in the kinase domain and similar substrate specificity with the AKT family. In order to identify novel compounds capable of inhibiting SGK3 activity, a high-throughput screening campaign against 50,400 small molecules was conducted using a fluorescence-based kinase assay that has a Z' factor above 0.5. It identified 15 hits (including nitrogen-containing aromatic, flavone, hydrazone, and naphthalene derivatives) with IC values in the low micromolar to sub-micromolar range. Four compounds with a similar scaffold (i.e., a hydrazone core) were selected for structural modification and 18 derivatives were synthesized. Molecular modeling was then used to investigate the structure-activity relationship (SAR) and potential protein-ligand interactions. As a result, a series of SGK inhibitors that are active against both SGK1 and SGK3 were developed and important functional groups that control their inhibitory activity identified.
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