ABSTRACT
The success of immunotherapy in the treatment of patients with advanced melanoma has paved the way for unprecedented successes in the treatment of many other malignancies. We present a case of extensively metastatic oral mucosal melanoma that responded successfully to combined immune checkpoint blockade with ipilimumab and nivolumab but developed multiple immune-related adverse events, including myocarditis, a rare event associated with immunotherapy of elderly melanoma patients. Though the acute myocarditis was managed successfully, the patient succumbed to sudden cardiac death. This case highlights the fact, that autoimmune carditis must be considered when working up the sudden onset of shortness of breath in patients on immune checkpoint blockade. After controlling the acute myocarditis with high-dose steroids, which should be tapered over 6 weeks, further cardiology care is needed, and a defibrillator might have to be implanted. Understanding the pathophysiology of immune-related adverse events could make cancer immunotherapy both more effective and safer.
Subject(s)
Antineoplastic Agents, Immunological/adverse effects , Heart Arrest/etiology , Ipilimumab/adverse effects , Nivolumab/adverse effects , Aged , Fatal Outcome , Humans , Male , Melanoma/drug therapyABSTRACT
Metformin has long been the drug of choice for treating patients with type 2 diabetes. Because of its effectiveness, safety profile, and affordability, it is used by millions of people worldwide. Emerging evidence indicates that metformin might also have antineoplastic effects in both diabetic and nondiabetic individuals. This article reviews studies that examine the potential mechanisms of action underlying the anticancer properties of metformin and discusses the possible use of this antidiabetic biguanide in the chemoprevention and treatment of head and neck cancer.
Subject(s)
Antineoplastic Agents/therapeutic use , Diabetes Mellitus, Type 2/drug therapy , Head and Neck Neoplasms/drug therapy , Hypoglycemic Agents/therapeutic use , Metformin/therapeutic use , Antineoplastic Agents/pharmacology , Dentistry , Head and Neck Neoplasms/prevention & control , HumansABSTRACT
When cellular contractile forces are central to pathophysiology, these forces comprise a logical target of therapy. Nevertheless, existing high-throughput screens are limited to upstream signalling intermediates with poorly defined relationships to such a physiological endpoint. Using cellular force as the target, here we report a new screening technology and demonstrate its applications using human airway smooth muscle cells in the context of asthma and Schlemm's canal endothelial cells in the context of glaucoma. This approach identified several drug candidates for both asthma and glaucoma. We attained rates of 1000 compounds per screening day, thus establishing a force-based cellular platform for high-throughput drug discovery.
