Race and ethnicity define disparate clinical outcomes in chronic rhinosinusitis.

Background: Chronic rhinosinusitis (CRS) is a common upper airways inflammatory disease requiring multidisciplinary care.

Objective: To evaluate if African Americans (AA), Latinxs, and nonLatinx White (White) patients have different chronic rhinosinusitis outcomes and to identify associated factors impacting these outcomes.

Methods: We conducted a large prospective cohort study of CRS patients who were evaluated and followed for several clinical variables at the initial encounter and after continuous management of CRS for a mean of 40 months.

Review of poly (ADP-ribose) polymerase (PARP) mechanisms of action and rationale for targeting in cancer and other diseases.

Poly (ADP-ribose) polymerases (PARPs) are a family of related enzymes that share the ability to catalyze the transfer of ADP-ribose to target proteins. PARPs play an important role in various cellular processes, including modulation of chromatin structure, transcription, replication, recombination, and DNA repair. The role of PARP proteins in DNA repair is of particular interest, in view of the finding that certain tumors defective in homologous recombination mechanisms, may rely on PARP-mediated DNA repair for survival, and are sensitive to its inhibition.

Catalase abrogates β-lapachone-induced PARP1 hyperactivation-directed programmed necrosis in NQO1-positive breast cancers.

Improving patient outcome by personalized therapy involves a thorough understanding of an agent's mechanism of action. β-Lapachone (clinical forms, Arq501/Arq761) has been developed to exploit dramatic cancer-specific elevations in the phase II detoxifying enzyme NAD(P)H:quinone oxidoreductase (NQO1). NQO1 is dramatically elevated in solid cancers, including primary and metastatic [e.

An NQO1 substrate with potent antitumor activity that selectively kills by PARP1-induced programmed necrosis.

Agents, such as β-lapachone, that target the redox enzyme, NAD(P)H:quinone oxidoreductase 1 (NQO1), to induce programmed necrosis in solid tumors have shown great promise, but more potent tumor-selective compounds are needed. Here, we report that deoxynyboquinone kills a wide spectrum of cancer cells in an NQO1-dependent manner with greater potency than β-lapachone. Deoxynyboquinone lethality relies on NQO1-dependent futile redox cycling that consumes oxygen and generates extensive reactive oxygen species (ROS).