ABSTRACT
Although therapies of cancer are advancing, it remains challenging for therapeutics to reach the sites of metastasis, which accounts for majority of cancer associated death. In this study, we have developed a strategy that guides an anti-programmed cell death-ligand 1 (aPDL1) antibody to accumulate in metastatic lesions to promote anti-tumour immune responses. Briefly, we have developed a combination in which Vadimezan disrupts tumour blood vessels of tumour metastases and facilitates the recruitment and activation of adoptively transferred aPDL1-conjugated platelets. In situ activated platelets generate aPDL1-decorated platelet-derived microparticles (PMP) that diffuse within the tumour and elicit immune responses. The proposed combination increases 10-fold aPDL1 antibody accumulation in lung metastases as compared to the intravenous administration of the antibody and enhances the magnitude of immune responses leading to improved antitumour effects.
Subject(s)
Antineoplastic Agents/pharmacology , B7-H1 Antigen/antagonists & inhibitors , Blood Platelets/metabolism , Neoplasms/blood supply , Neoplasms/drug therapy , Xanthones/pharmacology , Animals , B7-H1 Antigen/immunology , Cell Line, Tumor , Female , Lung Neoplasms/drug therapy , Lung Neoplasms/pathology , Lung Neoplasms/secondary , Mice , Mice, Inbred BALB C , Mice, Inbred C57BL , Neoplasm Metastasis/drug therapy , Neoplasm Metastasis/pathology , Neoplasms/immunology , Neoplasms/pathology , Platelet Activation/drug effects , Platelet TransfusionABSTRACT
BACKGROUND: Limited outcome data exist regarding the survival of microvascular free flaps for head and neck reconstruction in children. The objectives of this study were to perform a systematic review of the literature and meta-analysis comparing the survival of the most commonly used free flaps used for head and neck reconstruction in children. METHODS: A systematic search of PubMed, Embase, and Scopus was conducted using various keywords up to January 1, 2015. Meta-analysis was used to compare the survival of the most commonly used free flaps. The primary predictor variable was free flap type. The primary outcome variable was flap failure. The pooled relative risk (RR) with 95% confidence intervals (CIs) was estimated using a Mantel-Haenszel, fixed-effects model. RESULTS: The authors reviewed 25,303 abstracts. Five studies met inclusion criteria. A total of 646 children received a total of 694 free flaps. The pooled survival rate among all free flaps was 96.4%. The fibula free flap (fibula) and subscapular system free flaps (scapula) were the most commonly used flaps. There was no difference in survival when comparing the scapula (RRâ=â0.59, 95% CI: 0.26, 1.56, Pâ=â0.29), or fibula (RRâ=â1.91, 95% CI: 0.55, 6.65, Pâ=â0.31) to other free flaps, or when comparing the scapula to the fibula (RRâ=â2.29; 95% CI: 0.40, 13.08, Pâ=â0.35). CONCLUSIONS: Free tissue transfer is highly successful in children. Although data are limited, there appears to be no difference in survival among various free flaps used for head and neck reconstruction in children.
