Anti-HMGB1 polyclonal antibody

The superiority of distinct anesthesia methods for geriatric hip fracture surgery remains unclear. We evaluated high mobility group box-1 (HMGB1) and interleukin-6 (IL-6) with three different anesthesia methods in elderly patients undergoing hip fracture surgery. Routine blood test findings, postoperative morbidity, and mortality were assessed as secondary outcome. In total, 176 patients were randomized into desflurane (n= 60), propofol (n= 58), or spinal groups (n= 58) that received desflurane-based balanced anesthesia, propofol-based total intravenous anesthesia (TIVA), or spinal anesthesia, respectively. The spinal group required less intraoperative vasopressors (p< 0.001) and fluids (p= 0.006). No significant differences in HMGB1 (p(groupxtime)= 0.863) or IL-6 (p(groupxtime)= 0.575) levels were noted at baseline, postoperative day (POD) 1, or POD2. Hemoglobin, albumin, creatinine, total lymphocyte count, potassium, troponin T, and C-reactive protein were comparable among groups at all time-points. No significant differences in postoperative hospital stay, intensive care unit (ICU) stay, and ventilator use among groups were observed. Postoperative pulmonary, cardiac, and neurologic complications; and in-hospital, 30-day, and 90-day mortality were not significantly different among groups (p= 0.974). In conclusion, HMGB1 and IL-6, and all secondary outcomes, were not significantly different between desflurane anesthesia, propofol TIVA, and spinal anesthesia.

Vascularization is a common pathology for many solid tumors, and therefore anti-angiogenic strategies are being investigated as a therapeutic target for treatment. Numerous studies are also being conducted regarding the effects of oncolytic viruses, including Imlygic(TM), an FDA approved oncolytic herpes simplex virus-1 (oHSV) for the treatment of highly vascularized tumors such as Kaposi sarcoma (NCT04065152), and brain tumors. To our knowledge, the effects of combining oncolytic HSV with angiogenesis inhibition on endothelial cell activation has not been previously described. Here, we tested the effects of Rapid Antiangiogenesis Mediated By Oncolytic Virus (RAMBO), an oHSV which expresses a potent anti-angiogenic gene Vasculostatin on endothelial cell activation in heavily vascularized solid tumors. oHSV treatment induces endothelial cell activation, which inhibits virus propagation and oncolysis in adjacent tumor cells in vitro. Consistently, this was also observed in intravital imaging of intracranial tumor-bearing mice in vivo where infected tumor endothelial cells could efficiently clear the virus without cell lysis. Quantitative real-time PCR (Q-PCR), leukocyte adhesion assay, and fluorescent microscopy imaging data, however, revealed that RAMBO virus significantly decreased expression of endothelial cell activation markers and leukocyte adhesion, which in turn increased virus replication and cytotoxicity in endothelial cells. In vivo RAMBO treatment of subcutaneously implanted sarcoma tumors significantly reduced tumor growth in mice bearing sarcoma compared to rHSVQ. In addition, histological analysis of RAMBO-treated tumor tissues revealed large areas of necrosis and a statistically significant reduction in microvessel density (MVD). This study provides strong preclinical evidence of the therapeutic benefit for the use of RAMBO virus as a treatment option for highly vascularized tumors.