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Acute pancreatitis is a leading cause of hospitalization within the United States, stemming from a variety of potential causes including druginduced pancreatitis. Although a host of potential drugs have been implicated, cases of acute pancreatitis have been described with use of canagliflozin and dapagliflozin, sodium-glucose cotransporter 2 (SGLT-2) inhibitors. Notably, another SGLT-2 inhibitor, empagliflozin, has not been previously identified as having an association with pancreatitis. Here we report a case of a 52-year-old female who presented with epigastric pain and elevated lipase after initiation of empagliflozin one-month prior. We review the case and provide an in-depth clinical review of drug-induced pancreatitis with discussion of potential mechanisms. Given the efficacy and rapid adoption of SGLT-2 inhibitors in clinical practice, it is pivotal for providers to have high index of suspicion and perform a careful drug history if adverse events such as drug-induced pancreatitis occur. [ABSTRACT FROM AUTHOR]

Keratins that are overexpressed selectively in human carcinomas may offer diagnostic and prognostic utility. In this study, we show that high expression of keratin-17 (K17) predicts poor outcome in patients with cervical cancer, at early or late stages of disease, surpassing in accuracy either tumor staging or loss of p27KIP1 as a negative prognostic marker in this setting. We investigated the mechanistic basis for the biologic impact of K17 through loss- and gain-of-function experiments in human cervix, breast, and pancreatic cancer cells. Specifically, we determined that K17 functions as an oncoprotein by regulating the subcellular localization and degradation of p27KIP1. We found that K17 was released from intermediate filaments and translocated into the nucleus via a nuclear localization signal (NLS), specific among keratins, where it bound p27KIP1 during G1 phase of the cell cycle. p27KIP1 lacks a nuclear export signal (NES) and requires an adaptor for CRM1 binding for nuclear export. In K17, we defined and validated a leucine-rich NES that mediated CRM1 binding for export. Cervical cancer cells expressing K17 mutations in its NLS or NES signals exhibited an increase in levels of nuclear p27KIP1, whereas cells expressing wild-type K17 exhibited a depletion in total endogenous p27KIP1. In clinical specimens of cervical cancer, we confirmed that the expressions of K17 and p27KIP1 were inversely correlated, both across tumors and within individual tumors. Overall, our findings establish that K17 functions specially among keratins as an oncoprotein by controlling the ability of p27KIP1 to influence cervical cancer pathogenesis. [ABSTRACT FROM AUTHOR]