Regional muramyl tripeptide phosphatidylethanolamine administration enhances hepatic immune function and tumor surveillance Journal Article

  

Authors:	Karpoff, H. M.; Jarnagin, W.; Delman, K.; Fong, Y.
Article Title:	Regional muramyl tripeptide phosphatidylethanolamine administration enhances hepatic immune function and tumor surveillance
Abstract:	Background. Immune status of the liver may affect growth of liver metastases. We analyzed the ability of muramyl tripeptide phosphatidylethanolamine (MTP-PE), an immunomodulatory bacterial cell wall analog, to stimulate Kupffer cells (KCs) and protect against tumor growth, with or without an immunosuppressive partial hepatectomy (PH). Impact of MTP-PE's route of administration on KC function was assessed. Methods. Buffalo rats (n = 7 to 12/group) were treated with saline, 40 μg MTP-PE intraportally (portal) or intravenously (IV) and challenged with 5 x 105 hepatoma cells, and tumors counted on day 21. To assess MTP-PE's impact on KC stimulation in animals undergoing PH, a known stimulant of tumor cell growth, groups were treated with saline or MTP-PE and challenged with tumor and underwent 30% PH. KCs were harvested and analyzed for superoxide production. Statistical analysis was performed with Mann-Whitney U test or chi-square test. Results. MTP-PE-treated animals had fewer tumor nodules than control animals (19 vs 184, P < .005). MTP-PE-portal animals had fewer nodules than MTP-PE-IV (2 vs 36, P < .05). MTP-PE treatment before PH resulted in fewer tumor nodules compared with control animals (192 vs 276, P < .05). MTP-PE administration increased macrophage superoxide production (20.6 ± 2 vs 11.9 ± 1.1 nmol/106 cells, P <. 005). Conclusions. MTP-PE improved KC function and decreased growth of microscopic tumor cells. MTP-PE's effects persist after an immunosuppressive hepatectomy. Portal administration was the most effective. MTP-PE administration may be useful as a neoadjuvant therapy for patients undergoing resection of liver malignancies.
Keywords:	controlled study; drug efficacy; liver function; nonhuman; cancer adjuvant therapy; animals; cell division; immune system; animal experiment; animal model; drug effect; liver; liver tumor; rat; liver resection; hepatectomy; kupffer cell; immunomodulation; rats; cancer epidemiology; acetylmuramyl-alanyl-isoglutamine; phosphatidylethanolamines; tumor growth; adjuvants, immunologic; cell stimulation; superoxides; infusions, intravenous; liposomes; drug carriers; n acetylmuramylalanyl dextro isoglutaminylalanyl dipalmitoylphosphatidylethanolamine; liver neoplasms, experimental; kupffer cells; male; priority journal; article; rats, inbred buf; portal system
Journal Title:	Surgery
Volume:	128
Issue:	2
ISSN:	0039-6060
Publisher:	Elsevier Inc.
Date Published:	2000-08-01
Start Page:	213
End Page:	218
Language:	English
DOI:	10.1067/msy.2000.107420
PUBMED:	10922994
PROVIDER:	scopus
DOI/URL:	http://www.scopus.com/inward/record.url?eid=2-s2.0-0033869511&partnerID=40&md5=626469db888217cf78de15154ef55865
Notes:	Export Date: 18 November 2015 -- Source: Scopus

https://synapse.mskcc.org/synapse/works/has_related_data_chk/84781