Converting an immunosuppressive melanoma microenvironment into one that favors the induction of antitumor immunity is indispensable for effective cancer immunotherapy. In the current study we demonstrate that oat-derived β-(1-3)-(1-4)-glucan of 200 kDa molecular size (BG34-200) previously shown to mediate direct interaction with macrophages could alter the immune signature within melanoma microenvironment. Systemic administration of BG34-200 resulted in reversion of tolerant melanoma microenvironment to an immunogenic one that allows M1-type activation of macrophages, the induction of pro-inflammatory cytokines/chemokines including IFN-γ, TNF-α, CXCL9, and CXCL10, and enhanced IRF1 and PD-L1 expression. In turn, BG34-200 induced a superior antitumor response against primary and lung metastatic B16F10 melanoma compared to untreated controls. The enhanced tumor destruction was accompanied with significantly increased tumor infiltration of CD4 and CD8 T cells as well as elevated IFN-γ in the tumor sites. Systemic administration of BG34-200 also provoked systemic activation of tumor draining lymph node T cells that recognize antigens naturally expressing in melanoma (gp100/PMEL). Mechanistic studies using CD11b-knockout (KO), CD11 c-DTR transgenic mice and nude mice revealed that macrophages, DCs, T cells and NK cells were all required for the BG34-200-induced therapeutic benefit. Studies using IFN-γ-KO transgenic mice showed that IFN-γ was essential for the BG34-200-elicited antitumor response. Beyond melanoma, the therapeutic efficacy of BG34-200 and its immune stimulating activity were demonstrated in a mouse model of osteosarcoma. Together, BG34-200 is highly effective in modulating antitumor immunity. Our data support the potential therapeutic use of this novel immune modulator in the treatment of metastatic melanoma.
BACKGROUND The objective of this study was to determine whether health care disparities exist in management of Graves’ disease. METHODS Patients treated for Graves’ disease from 1999 to 2009 were divided into medical and surgical treatment groups. A comparative analysis of age, sex, race, health insurance, and income was completed. Address and/or zip code were geocoded and median income was determined from census data. RESULTS A total of 634 patients were treated for Graves’ disease; 535 (84%) medically and 99 (16%) surgically. Mean age (40 ± 15 vs 43 ± 11 y), percentage of women (84% vs 91%), and racial distribution were similar in the 2 groups (P > .05). In the surgical group, median income was lower ($31,530 vs $34,404; P = .07) and 52% of patients were uninsured compared with 30% of patients treated medically (P < .0001). CONCLUSIONS A disproportionate number of uninsured patients underwent thyroidectomy for Graves’ disease. Social and economic factors may have a role in determining definitive therapy for Graves’ disease.
Objective: To evaluate the ability of sperm DNA fragmentation index (DFI) and high DNA stainability (HDS) to influence the chance of achieving pregnancy in couples undergoing intracytoplasmic sperm injection (ICSI) cycles. Design: A retrospective study evaluating couples who underwent an ICSI cycle between 2009 and 2018. Setting: Reproductive center. Patient(s): Consecutive couples who underwent an ICSI cycle and had a semen analysis with subsequent DFI and HDS testing, evaluated using Sperm Chromatin Structure Assay. Intervention(s): Measurement of DFI and HDS prior to ICSI cycle. Main Outcome Measure(s): To determine whether DFI or HDS of sperm was predictive of the number of ICSI cycles until the first clinical intrauterine pregnancy. Result(s): A total of 550 couples who underwent 1,050 ICSI cycles were analyzed. Of those, a total of 330 couples achieved pregnancy.As expected, in couples who achieved pregnancy, females were younger and underwent fewer cycles. Importantly, the DFI and HDS were similar between couples who achieved pregnancy (DFI% 12.9; HDS% 9.3) and couples who did not (DFI% 12.2; HDS% 9.1). A multivariable-adjusted analysis evaluating female age at the first cycle was associated negatively with pregnancy. Conclusion(s):Neither DFI nor HDS at baseline influenced the chances of a couple to achieve pregnancy after ICSI. Increased female age and couples who underwent more ICSI cycles were associated with lower chances of achieving pregnancy. (Fertil Steril Rep Ò 2020;1: 233-8. Ó2020 by American Society for Reproductive Medicine.
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