Oncogenic STAT Transcription Factors as Targets for Cancer Therapy: Innovative Strategies and Clinical Translation.

Despite advances in our understanding of molecular aspects of oncogenesis, cancer remains a leading cause of death. The malignant behavior of a cancer cell is driven by the inappropriate activation of transcription factors. In particular, signal transducers and activators of transcription (STATs), which regulate many critical cellular processes such as proliferation, apoptosis, and differentiation, are frequently activated inappropriately in a wide spectrum of human cancers. Multiple signaling pathways converge on the STATs, highlighting their importance in the development and progression of oncogenic diseases. STAT3 and STAT5 are two members of the STAT protein family that are the most frequently activated in cancers and can drive cancer pathogenesis directly. The development of inhibitors targeting STAT3 and STAT5 has been the subject of intense investigations in the last decade, although effective treatment options remain limited. In this review, we investigate the specific roles of STAT3 and STAT5 in normal physiology and cancer biology, discuss the opportunities and challenges in pharmacologically targeting STAT proteins and their upstream activators, and offer insights into novel therapeutic strategies to identify STAT inhibitors as cancer therapeutics.

Two Cases of Anterior Shoulder Dislocation and Fracture Secondary to Generalized Tonic-Clonic Seizure.

Dislocation of the glenohumeral joint secondary to generalized tonic-clonic seizures is well documented in the medical literature, with posterior dislocation being most commonly described. Still, these occurrences tend to be rare and affect a minority of patients, and fractures associated with dislocations after seizures are even less common. As such, the management of these injuries tends to be quite varied, and there is a paucity of documented cases in the literature. Here, we would like to present two rare cases of anterior shoulder dislocation secondary to seizures, with one patient also sustaining a fracture of the proximal humerus. We would also like to discuss the management and outcomes that have been achieved, since these cases tend to occur in a small number of epileptic patients.