RESUMEN
BACKGROUND AND OBJECTIVES: Amidst increasing opioid-related overdoses in the USA, opioid use disorder (OUD) treatment has seen few novel treatments emerge. High-potency synthetic opioids (HPSOs) have altered clinical approaches, prompting evaluation of existing medications for opioid use disorder (MOUD) and interest in slow-release oral morphine (SROM) as another therapeutic option. Here we survey addiction specialists on the influence of HPSOs on clinical practice, views on current MOUD regulations, and openness to novel therapies such as SROM. METHODS: Anonymous, online survey conducted at a national conference of addiction specialists (N = 91). Pearson χ2 tests and Fisher's exact tests to compare respondent characteristics. RESULTS: Approximately 89% of respondents (N = 91) acknowledge that HPSOs shifted addiction treatment in recent years, with 86% modifying their MOUD prescribing accordingly. Moreover, 84% report having patients who could benefit from other full opioid agonists beyond methadone for OUD management. Many report off-label prescribing of full agonist opioids other than methadone for withdrawal symptoms or initiating MOUD. Eighty percent reported being in favor of incorporating SROM as a third-line monotherapy for OUD. DISCUSSION AND CONCLUSION: This sample of addiction specialists supports innovative alternatives for MOUD in the USA to combat the challenges posed by fentanyl and related HPSOs. Future work should further addiction specialists' opinions on barriers to OUD treatment and exploration of these international strategies in the USA. SCIENTIFIC SIGNIFICANCE: This appears to be the first study exploring addiction specialists' perspectives on regulatory barriers to OUD treatment and their willingness to uptake internationally adopted strategies such as SROM.
RESUMEN
Multipotent adipose-derived stem cells (ASCs) are increasingly used for regenerative purposes such as soft tissue reconstruction following mastectomy; however, the ability of tumors to commandeer ASC functions to advance tumor progression is not well understood. Through the integration of physical sciences and oncology approaches we investigated the capability of tumor-derived chemical and mechanical cues to enhance ASC-mediated contributions to tumor stroma formation. Our results indicate that soluble factors from breast cancer cells inhibit adipogenic differentiation while increasing proliferation, proangiogenic factor secretion, and myofibroblastic differentiation of ASCs. This altered ASC phenotype led to varied extracellular matrix (ECM) deposition and contraction thereby enhancing tissue stiffness, a characteristic feature of breast tumors. Increased stiffness, in turn, facilitated changes in ASC behavior similar to those observed with tumor-derived chemical cues. Orthotopic mouse studies further confirmed the pathological relevance of ASCs in tumor progression and stiffness in vivo. In summary, altered ASC behavior can promote tumorigenesis and, thus, their implementation for regenerative therapy should be carefully considered in patients previously treated for cancer.