Methionine S-adenosyltransferase 2A (MAT2A) is the catalytic subunit for synthesis of S-adenosylmethionine (SAM), the principal methyl donor in many biological processes. MAT2A is up-regulated in many cancers, including liver cancer and colorectal cancer (CRC) and is a potentially important drug target. We developed a family of fluorinated N,N-dialkylaminostilbene agents, called FIDAS agents, that inhibit the proliferation of CRC cells in vitro and in vivo. Using a biotinylated FIDAS analog, we identified the catalytic subunit of MAT2A as the direct and exclusive binding target of these FIDAS agents. MAT2B, an associated regulatory subunit of MAT2A, binds indirectly to FIDAS agents through its association with MAT2A. FIDAS agents inhibited MAT2A activity in SAM synthesis, and depletion of MAT2A by shRNAs inhibited CRC cell growth. A novel FIDAS agent delivered orally repressed CRC xenografts in athymic nude mice. These findings suggest that FIDAS analogs targeting MAT2A represent a family of novel and potentially useful agents for cancer treatment.

A new in vitro enzymatic pathway for the generation of molecular hydrogen from glucose has been demonstrated. The reaction is based on the oxidation of glucose by Thermoplasma acidophilum glucose dehydrogenase with the concomitant oxidation of NADPH by Pyrococcus furiosus hydrogenase. Stoichiometric yields of hydrogen were produced from glucose with the continuous recycling of cofactor. This simple system may provide a method for the biological production of hydrogen from renewable sources. In addition, the other product of this reaction, gluconic acid, is a high-value chemical commodity.

Necrotizing fasciitis is a rare, aggressive, soft-tissue infection that results in necrosis of skin, subcutaneous tissue, and fascia. It spreads rapidly and may progress to sepsis, multi-organ failure, and death. Predisposing conditions include diabetes, chronic alcoholism, advanced age, vascular disease, and immunosuppression and many cases are preceded by an injury or invasive procedure. Necrotizing soft-tissue infection of the breast is uncommon, with only a few reported cases in the literature. We present a 53-year-old diabetic woman who presented to the emergency room with several weeks of worsening breast and shoulder pain, swelling, and erythema. Upon formal evaluation by the surgical service, a necrotizing soft-tissue infection was suspected, and the patient was scheduled for emergent, surgical debridement. Because of the aggressive nature and high mortality of this disease, immediate surgical intervention, coupled with antibiotic therapy and physiologic support, is necessary to prevent complications and death.

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