Browsing by Author "Baldi, Robert"

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    Complementary Approaches for Military Women with Chronic Pelvic Pain: A Randomized Trial.
    (Journal of integrative and complementary medicine, 2022-10) Crisp, Carol D; Baldi, Robert; Fuller, Matthew; Abreu, Eduardo; Nackley, Andrea G
    Introduction: Active duty (AD) women suffer with chronic pelvic pain (CPP) while providers tackle diagnoses and treatments to keep them functional without contributing to the opioid epidemic. The purpose of this randomized trial was to determine the effectiveness of noninvasive, self-explanatory mindfulness-based stress reduction (MBSR) or self-paced healthy lifestyle (HL) interventions on CPP in AD women. Methods: A 6-week, interventional prospective study with AD women aged 21-55 years at Mountain Home (MTHM), Idaho, was conducted. Women were randomly assigned to MBSR (N = 21) or HL (N = 20) interventions. The primary outcome was pain perception. The secondary outcomes were depression and circulating cytokine levels. Results: Women in the MBSR group exhibited reduced pain interference (p < 0.01) and depression (p < 0.05) alongside decreased interleukin (IL)-4 (p < 0.05), IL-6 (p < 0.05), eotaxin (p < 0.05), monocyte chemoattractant protein-1 (p = 0.06), and interleukin-1 receptor antagonist (IL-1ra) (p < 0.01) and increased vascular endothelial growth factor (p < 0.05). Women in the HL group did not have changes in pain; however, they did exhibit reduced depression (p < 0.05) alongside decreased granulocyte-macrophage colony-stimulating factor (p < 0.05) and increased tumor necrosis factor alpha (p < 0.05), stromal cell-derived factor-1 (p < 0.01), and IL-1ra (p < 0.01). Conclusions: AD women receiving MBSR or HL had reduced depression scores and altered circulating cytokine levels; however, only those receiving MBSR had reduced pain perception. Findings support MBSR as an effective and viable behavioral treatment for AD women suffering from CPP and provide premise for larger randomized controlled studies. Clinical Trial Registration: MOCHI-An RCT of mindfulness as a treatment for CPP in AD Women NCT04104542 (September 26, 2019).
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    Inhibition of estrogen signaling in myeloid cells increases tumor immunity in melanoma.
    (The Journal of clinical investigation, 2021-12) Chakraborty, Binita; Byemerwa, Jovita; Shepherd, Jonathan; Haines, Corinne N; Baldi, Robert; Gong, Weida; Liu, Wen; Mukherjee, Debarati; Artham, Sandeep; Lim, Felicia; Bae, Yeeun; Brueckner, Olivia; Tavares, Kendall; Wardell, Suzanne E; Hanks, Brent A; Perou, Charles M; Chang, Ching-Yi; McDonnell, Donald P
    Immune checkpoint blockade (ICB) therapies have significantly prolonged patient survival across multiple tumor types, particularly in melanoma. Interestingly, sex-specific differences in response to ICB have been observed, with males receiving a greater benefit from ICB than females, although the mechanism or mechanisms underlying this difference are unknown. Mining published transcriptomic data sets, we determined that the response to ICBs is influenced by the functionality of intratumoral macrophages. This puts into context our observation that estrogens (E2) working through the estrogen receptor α (ERα) stimulated melanoma growth in murine models by skewing macrophage polarization toward an immune-suppressive state that promoted CD8+ T cell dysfunction and exhaustion and ICB resistance. This activity was not evident in mice harboring macrophage-specific depletion of ERα, confirming a direct role for estrogen signaling within myeloid cells in establishing an immunosuppressed state. Inhibition of ERα using fulvestrant, a selective estrogen receptor downregulator (SERD), decreased tumor growth, stimulated adaptive immunity, and increased the antitumor efficacy of ICBs. Further, a gene signature that determines ER activity in macrophages predicted survival in patients with melanoma treated with ICB. These results highlight the importance of E2/ER signaling as a regulator of intratumoral macrophage polarization, an activity that can be therapeutically targeted to reverse immune suppression and increase ICB efficacy.