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.
Pancreatic surgeons will see an increasing number of patients with Roux-en-Y anatomy who will require evaluation and resection for periampullary diseases. For PD after RYGB, we recommend remnant gastrectomy with reconstruction using the BP limb.
A patient was referred at 21 weeks' gestation for unexplained fetal lung hyperechogenicity and ascites. Amniocentesis was normal. Fetal lung biopsy was consistent with the clinical diagnosis of cystic adenomatoid malformation of the lungs. However, autopsy of the stillborn infant demonstrated a cartilaginous bar, causing total laryngeal obstruction. The distinctive ultrasonographic appearance is presented.
Case ReportA 37-year-old man had multiple subcutaneous lumps on the torso and all extremities. These first became noticeable after puberty and had slowly increased in size and number over the years. They were variable in size, ranging from several millimeters to several centimeters. The lumps were firm, partially mobile, and smooth on palpation. The larger ones had a bosselated surface. Some were mildly tender on compression. Sonographic assessment of several of the larger lumps was requested before cosmetic surgery. The lumps were imaged with a high-resolution L12-5 linear array transducer on an HDI 5000 machine (Philips Medical Systems, Bothell, WA). These all had a similar appearance on sonography. The lumps were well defined and located in the subcutaneous layer. They had a predominantly hyperechoic appearance, which clearly distinguished them from the adjacent hypoechoic adipose tissue (Figure 1). Small, patchy hypoechoic areas were noted within the larger masses. No posterior acoustic enhancement was seen. The larger masses showed sparse internal vascularity on color Doppler imaging. Excisional biopsy of 16 lumps showed the typical features of angiolipomas, with a mixture of adipocytes and a variable amount of angiomatous tissue.
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