No abstract

Histone deacetylase inhibitors (HDACi) are promising therapeutics for cancer. HDACi alter the epigenetic state of tumors and provide a unique approach to treat cancer. Although studies with HDACi have shown promise in some cancers, variable efficacy and off-target effects have limited their use. To overcome some of the challenges of traditional HDACi, we sought to use a tumor-specific dendrimer scaffold to deliver HDACi directly to cancer cells. Here we report the design and evaluation of tumor-specific dendrimer–HDACi conjugates. The HDACi was conjugated to the dendrimer using an ester linkage through its hydroxamic acid group, inactivating the HDACi until it is released from the dendrimer. Using a cancer cell model, we demonstrate the functionality of the tumor-specific dendrimer–HDACi conjugates. Furthermore, we demonstrate that unlike traditional HDACi, dendrimer–HDACi conjugates do not affect tumor-associated macrophages, a recently recognized mechanism through which drug resistance emerges. We anticipate that this new class of cell-specific epigenetic therapeutics will have tremendous potential in the treatment of cancer.

No abstract

With the advent of the COVID-19 pandemic in the United States, resources have been reallocated and elective cases have been deferred to minimize the spread of the disease, altering the workflow of cardiac catheterization laboratories across the country. This has in turn affected the training experience of cardiology fellows, including diminished procedure numbers and a narrow breadth of cases as they approach the end of their training before joining independent practice. It has also taken a toll on the emotional well-being of fellows as they see their colleagues, loved ones, patients or even themselves struggling with COVID-19, with some succumbing to it. The aim of this opinion piece is to focus attention on the impact of the COVID-19 pandemic on fellows and their training, challenges faced as they transition to practicing in the real world in the near future and share the lessons learned thus far. We believe that this is an important contribution and would be of interest not only to cardiology fellows-in-training and cardiologists but also trainees in other procedural specialties.

Takotsubo Cardiomyopathy (TCM) is an increasing recognized form of acute reversible left ventricular systolic dysfunction not related to obstructive coronary disease. The exact physiology of this disorder is not yet known, however multiple agents have been hypothesized to have a link to this condition. Most commonly, TCM has been hypothesized as being triggered by a catecholamine surge after an inciting event. New evidence now suggests certain medications as a link to the disease. We describe a unique case of TCM in a woman after taking Treximet (naproxen and sumatriptan) as abortive therapy for a migraine.