Comprehensive Reentry Policy for Student Registered Nurse Anesthetists With Substance Use Disorder.

Substance use disorder (SUD) is a common problem in anesthesia. Although there are SUD policies in place for practicing anesthetists, there were no known studies before this inquiry discussing reentry policies specific to the student registered nurse anesthetist (SRNA). The purpose of this research was to describe key stakeholders' knowledge and perspectives surrounding policies for reentry into academic programs in Illinois for SRNAs with SUD and to create a comprehensive structured policy template for SRNAs with SUD.

2-Methoxy antimycin reveals a unique mechanism for Bcl-x(L) inhibition.

Overexpression of Bcl-x(L) in multiple cancers correlates with resistance to chemotherapy and radiation therapy, and provides a rationale for development of small-molecule Bcl-x(L) inhibitors. Based on knockout studies, nonneoplastic cells also require Bcl-x(L) survival functions, particularly when challenged with cytotoxic agents. We analyze the selective cytotoxicity of one Bcl-x(L) inhibitor, 2-methoxy antimycin A, toward cells with excess exogenous Bcl-x(L) in isogenic cell line pairs.

Cancer chemotherapy and drug metabolism.

Drug-metabolizing enzymes and drug transporters are key determinants of the pharmacokinetics and pharmacodynamics of many antineoplastic agents. Metabolism and transport influence the cytotoxic effects of antineoplastic agents in target tumor cells and normal host tissues. This article summarizes several state-of-the-art approaches to enhancing the effectiveness and safety of cancer therapy based on recent developments in our understanding of antineoplastic drug metabolism and transport.

Sustained P450 expression and prodrug activation in bolus cyclophosphamide-treated cultured tumor cells. Impact of prodrug schedule on P450 gene-directed enzyme prodrug therapy.

Cytochrome P450-based gene therapy can substantially increase the sensitivity of tumor cells to P450-activated cancer chemotherapeutic prodrugs such as cyclophosphamide (CPA) without increasing host toxicity. While the role of 4-OH-CPA, the primary active metabolite of CPA, in eliciting tumor cell death is well established, the effect of 4-OH-CPA exposure on the capacity of P450-expressing tumor cells for continued metabolism and activation of CPA has not been investigated. The present study addresses this question and characterizes the impact of CPA dose and treatment schedule on the ability of P450-expressing tumor cells to sustain prodrug activation over time.

Enhanced bystander cytotoxicity of P450 gene-directed enzyme prodrug therapy by expression of the antiapoptotic factor p35.

Cytochrome P450 gene-directed enzyme prodrug therapy substantially augments intratumoral activation of anticancer prodrugs, such as cyclophosphamide (CPA), leading to a strong increase in antitumor effect without a corresponding increase in host toxicity. Attempts to additionally increase tumor cell kill by enhancing the intrinsic chemosensitivity of P450-expressing tumor cells by chemical means (depletion of cellular glutathione) or by coexpression of proapoptotic factors was shown to result in the desired increase in chemosensitivity, but with a decrease in net production of bystander cytotoxic drug metabolites because of accelerated death of the prodrug-activating tumor cells. Moreover, tumor cell P450 activity declined during the course of apoptosis induced by P450-activated CPA, limiting the potential of the tumor cell for continued production of activated drug metabolites.