Identification of Potential Biomarkers for Cancer Cachexia and Anti-Fn14 Therapy.

Background: Developing therapies for cancer cachexia has not been successful to date, in part due to the challenges of achieving robust quantitative measures as a readout of patient treatment. Hence, identifying biomarkers to assess the outcomes of treatments for cancer cachexia is of great interest and important for accelerating future clinical trials.

Methods: We established a novel xenograft model for cancer cachexia with a cachectic human PC3* cell line, which was responsive to anti-Fn14 mAb treatment.

Bim Deletion Reduces Functional Deficits Following Ischemic Stroke in Association with Modulation of Apoptosis and Inflammation.

Cellular apoptosis is a key pathological mechanism contributing to neuronal death following ischemic stroke. The pro-apoptotic Bcl-2 family protein, Bim, is an important regulator of apoptosis. In this study we investigated the effect of Bim expression on post-stroke functional outcomes, brain injury and inflammatory mechanisms.

Discovery, synthesis and exploration of N-benzylsulfonyl-2-phenylazepanes as inhibitors of Bim expression in a mouse embryonic fibroblast model.

Chronic activation of beta-adrenergic receptors by the sympathetic nervous system results in the apoptosis of cardiomyocytes. Due to the inability of cardiomyocytes to regenerate, this can result in heart failure. Upregulation of the pro-apoptotic protein Bim has been implicated as the cause of cardiomyocyte apoptosis.

Generation of reporter cell lines for factors inducing muscle wasting in cancer cachexia.

Rapidly identifying cachexia-inducing factors that directly induce muscle wasting is an existing challenge. We developed two reporter cell lines that allow swift detection of such factors in blood from patients. C2C12 myoblasts were used for the establishment of reporter cells.

Bcl-2 family proteins, beyond the veil.

Apoptosis is an important part of both health and disease and is often regulated by the BCL-2 family of proteins. These proteins are either pro- or anti-apoptotic, existing in a delicate balance during homeostasis. They are best known for their role in regulating the activation of caspases and the execution of a cell in response to a variety of stimuli.