Abstract
BackgroundHuman xenograft models, resulting from orthotopic transplantation (implantation into the anatomically correct site) of histologically intact tissue into animals, are important for investigating local tumor growth, vascular and lymphatic invasion at the primary tumor site and metastasis.Methodology/Principal FindingsWe used surgical orthotopic transplantation to establish a nude mouse model of primary hepatic lymphoma (PHL), HLBL-0102. We performed orthotopic transfer of the HLBL-0102 tumor for 42 generations and characterized the tumor cells. The maintenance of PHL characteristics were supported by immunohistochemical and cytogenetic analysis. We also report the antitumor effect of Cantide, an antisense phosphorothioate oligonucleotide against hTERT, on the growth of HLBL-0102 tumors. We showed a significant, dose-dependent inhibition of tumor weight and serum LDH activity in the orthotopically transplanted animals by Cantide. Importantly, survival was prolonged in Cantide-treated HLBL-0102 tumor-bearing mice when compared to mock-treated mice.Conclusions/SignificanceOur study provided the basis for the development of a clinical trial protocol to treat PHL.
Highlights
The relevance of preclinical, animal models of cancer depends on how closely the xenografts mimic the histological, biochemical and metastatic patterns of the original tumor
A surgical specimen was obtained from the tumor mass in the left lobe of the liver of a patient diagnosed with hepatic primary lymphoma by Ann Arbor classification of IEA
Immunohistochemical analysis demonstrated that the tumor cells were positive for B cell lymphoma markers, CD20 and CD79a
Summary
The relevance of preclinical, animal models of cancer depends on how closely the xenografts mimic the histological, biochemical and metastatic patterns of the original tumor. Orthotopic implantation has been performed with tumor cells [4] as well as histologically intact tissue [5,6,7,8,9], it has been shown that the biologic behavior of natural tumors is more closely reproduced with transplantation of histologically-intact tissue These data suggest that human xenografts, resulting from orthotopic transplantation (implantation into the anatomically correct site) of histologically intact tissue into animals, provide an important model system to investigate local tumor growth, vascular and lymphatic invasion at the primary tumor site and metastasis. Human xenograft models, resulting from orthotopic transplantation (implantation into the anatomically correct site) of histologically intact tissue into animals, are important for investigating local tumor growth, vascular and lymphatic invasion at the primary tumor site and metastasis
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