ABSTRACT
Cytoreduction and heated intraperitoneal chemotherapy (CS/HIPEC) is increasingly utilized as a treatment strategy for patients with peritoneal metastases from various primary tumor sites. For this heterogenous procedure, related to patient characteristics, patient selection, and the extent of surgical completeness of cytoreduction, high level evidence (ex: multiple randomized controlled trials) is not available to support efficacy. This review of the available literature supporting application of the procedure, focusing on colorectal cancer, provides a summary of current evidence for patient selection and treatment algorithms based on patient presentation.
Subject(s)
Adenocarcinoma/therapy , Antineoplastic Combined Chemotherapy Protocols/administration & dosage , Colorectal Neoplasms/therapy , Cytoreduction Surgical Procedures/methods , Hyperthermia, Induced/methods , Peritoneal Neoplasms/therapy , Adenocarcinoma/secondary , Algorithms , Colorectal Neoplasms/pathology , Evidence-Based Medicine , Humans , Infusions, Parenteral , Patient Selection , Peritoneal Neoplasms/secondaryABSTRACT
T-cell trafficking at vascular sites has emerged as a key step in antitumour immunity. Chemokines are credited with guiding the multistep recruitment of CD8(+) T cells across tumour vessels. However, the multiplicity of chemokines within tumours has obscured the contributions of individual chemokine receptor/chemokine pairs to this process. Moreover, recent studies have challenged whether T cells require chemokine receptor signalling at effector sites. Here we investigate the hierarchy of chemokine receptor requirements during T-cell trafficking to murine and human melanoma. These studies reveal a non-redundant role for Gαi-coupled CXCR3 in stabilizing intravascular adhesion and extravasation of adoptively transferred CD8(+) effectors that is indispensable for therapeutic efficacy. In contrast, functional CCR2 and CCR5 on CD8(+) effectors fail to support trafficking despite the presence of intratumoral cognate chemokines. Taken together, these studies identify CXCR3-mediated trafficking at the tumour vascular interface as a critical checkpoint to effective T-cell-based cancer immunotherapy.
Subject(s)
Neoplasms/blood supply , Receptors, CXCR3/metabolism , Signal Transduction/physiology , Adoptive Transfer , Animals , CD8-Positive T-Lymphocytes/physiology , Cell Movement , Female , Gene Expression Regulation , Melanoma/metabolism , Melanoma, Experimental/genetics , Melanoma, Experimental/metabolism , Mice , Mice, Knockout , Mice, Transgenic , Ovalbumin/genetics , Ovalbumin/metabolism , Receptors, CCR2/genetics , Receptors, CCR2/metabolism , Receptors, CCR5/genetics , Receptors, CCR5/metabolism , Receptors, CXCR3/geneticsABSTRACT
BACKGROUND: The American Society of Peritoneal Surface Malignancies (ASPSM) is a consortium of cancer centers performing cytoreductive surgery with hyperthermic intraperitoneal chemotherapy (HIPEC). This is a position paper from the ASPSM on the standardization of the delivery of HIPEC. METHODS: A survey was conducted of all cancer centers performing HIPEC in the United States. We attempted to obtain consensus by the modified method of Delphi on seven key HIPEC parameters: (1) method, (2) inflow temperature, (3) perfusate volume, (4) drug, (5) dosage, (6) timing of drug delivery, and (7) total perfusion time. Statistical analysis was performed using nonparametric tests. RESULTS: Response rates for ASPSM members (n = 45) and non-ASPSM members (n = 24) were 89 and 33 %, respectively. Of the responders from ASPSM members, 95 % agreed with implementing the proposal. Majority of the surgical oncologists favored the closed method of delivery with a standardized dual dose of mitomycin for a 90-min chemoperfusion for patients undergoing cytoreductive surgery for peritoneal carcinomatosis of colorectal origin. CONCLUSIONS: This recommendation on a standardized delivery of HIPEC in patients with colorectal cancer represents an important first step in enhancing research in this field. Studies directed at maximizing the efficacy of each of the seven key elements will need to follow.
Subject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Colorectal Neoplasms/therapy , Consensus , Hyperthermia, Induced , Peritoneal Neoplasms/therapy , Practice Guidelines as Topic/standards , Chemotherapy, Cancer, Regional Perfusion , Combined Modality Therapy , Humans , Societies, ScientificABSTRACT
Human neuroblastoma is one of the most common solid tumors in infants and children and represents about 10% of all childhood cancers. Nearly 70% of the patients present with disseminated disease and the long-term prognosis remains poor for this group despite advances in diagnosis and therapy. In this study, we discovered that an endogenous opioid peptide, [Met5]-enkephalin, inhibited the growth of human neuroblastoma SK-N-SH in vitro; in view of this pentapeptide's action it has been termed opioid growth factor (OGF). OGF was found to be constitutively expressed and tonically capable of suppressing cell replication, and its effects were opioid receptor mediated. Growth inhibition was dose-related, reversible, not cytotoxic, and independent of serum. Immunocytochemical studies detected both OGF and its related receptor, zeta, in the cytoplasm of log-phase cells. Pharmacological binding assays revealed specific and saturable binding with a one-site model of kinetics; this high-affinity opioid receptor was identified as zeta. These data suggest that a native opioid peptide, OGF, interacts with a novel opioid receptor, zeta, to arrest the growth of human neuroblastoma.
