Rabbit Anti-Human CXCL10 Polyclonal Antibody

Balanophora polyandraGriff. (B. polyandra) is a folk medicine used as an antipyretic, antidote, haemostatic, dressing and haematic tonic, for the treatment of gonorrhea, syphilis, wounds, and the bleeding of the alimentary tract by the local people in China. This study was designed to investigate the effects ofB. polyandraon dextran sulfate sodium (DSS)-treated colitis micein vivoand lipopolysaccharide (LPS)-induced RAW 264.7 macrophagesin vitro. Mice were induced withB. polyandratotal extract (BPE, 250 and 1000 mg kg(-1)) andB. polyandrapolysaccharides (BPP, 100 and 400 mg kg(-1)) for 22 days and treated with 3.5% DSS in their drinking water for the last 7 days and the LPS-induced RAW264.7 macrophages were treated with BPE (100 mu g ml(-1)) and BPP (100 mu g ml(-1)). Mice treated with DSS developed severe mucosal colitis, with a marked distortion and crypt loss of colonic surface epithelium and a colonic shortening.B. polyandrasignificantly inhibited colonic shortening and reduced the severity of colitis in the colon and lowered the colonic inflammation score (p< 0.05) and decreased the expression of interleukin (IL)-1 beta, tumor necrosis factor (TNF-alpha), inducible nitric oxide synthase (iNOS), and anti-serum amyloid A3 (SAA3) as well as the pro-inflammatory chemokine C-X-C motif chemokine 10 (CXCL10).B. polyandraalso significantly suppressed the activation of nucleotide-binding domain like receptor protein 3 (NLRP3) inflammasome and the nuclear factor kB (NF-kappa B). These results suggest that dietary intake ofB. polyandraameliorates colitis. Such activities ofB. polyandrain humans remain to be investigated.

Purpose: Preclinical studies suggest PARP inhibition (PARPi) induces immunostimulatory micromilieu in ovarian cancer thus complementing activity of immune checkpoint blockade. We conducted a phase II trial of PARPi olaparib and anti-PD-L1 durvalumab and collected paired fresh core biopsies and blood samples to test this hypothesis. Patients and Methods: In a single-center, proof-of-concept phase II study, we enrolled women aged >= 18 with recurrent ovarian cancer. All patients were immune checkpoint inhibitor-naive and had measurable disease per RECISTv1.1, ECOG performance status 0-2, and adequate organ and marrow function. Patients received olaparib 300 mg twice daily and durvalumab 1,500 mg intravenously every 4 weeks until disease progression, unacceptable toxicity, or withdrawal of consent. Primary endpoint was overall response rate (ORR). Secondary objectives were safety and progression-free survival (PFS). Translational objectives included biomarker evaluation for relationships with clinical response and immunomodulatory effects by treatment. Results: Thirty-five patients with ovarian cancer [median, four prior therapies (IQR, 2-5.5), predominantly platinum-resistant (86%), BRCA wild-type (77%)] received at least one full cycle of treatment. ORR was 14% [5/35; 95% confidence interval (CI), 4.8%30.3%]. Disease control rate (PR+SD) was 71% (25/35; 95% CI, 53.7%-85.4%). Treatment enhanced IFNg and CXCL9/CXCL10 expression, systemic IFN gamma/TNF alpha production, and tumor-infiltrating lymphocytes, indicating an immunostimulatory environment. Increased IFN gamma production was associated with improved PFS [HR, 0.37 (95% CI, 0.16-0.87), P = 0.023], while elevated VEGFR3 levels were associated with worse PFS (HR, 3.22 (95% CI, 1.23-8.40), P = 0.017]. Conclusions: The PARPi and anti-PD-L1 combination showed modest clinical activity in recurrent ovarian cancer. Our correlative study results suggest immunomodulatory effects by olaparib/durvalumab in patients and indicate that VEGF/VEGFR pathway blockade would be necessary for improved efficacy of the combination.