Subject(s)
BK Virus , Kidney Transplantation , Myocardial Infarction/virology , Opportunistic Infections/virology , Polyomavirus Infections , Tumor Virus Infections , Vascular Diseases/virology , BK Virus/isolation & purification , BK Virus/pathogenicity , BK Virus/physiology , Edema/virology , Endothelium/pathology , Endothelium/ultrastructure , Fatal Outcome , Humans , Kidney/pathology , Male , Middle Aged , Muscle Weakness/pathology , Muscle Weakness/virology , Muscle, Skeletal/pathology , Opportunistic Infections/pathology , Polyomavirus Infections/pathology , Polyomavirus Infections/virology , Tumor Virus Infections/pathology , Tumor Virus Infections/virology , Vascular Diseases/pathologyABSTRACT
Lymphomatoid papulosis is part of a spectrum of CD30+ cutaneous lymphoproliferative disorders characterized by spontaneous tumor regression. The mechanism(s) of regression is unknown. In a recent study, a selective increase in CD30 ligand expression in regressing lesions of lymphomatoid papulosis and cutaneous CD30+ anaplastic large cell lymphoma was shown, suggesting that activation of the CD30 signaling pathway may be responsible for tumor regression, whereas no difference in Fas/Fas ligand expression was found between regressing and nonregressing lesions. Therefore we tested the effects of CD30 and Fas activation on three CD30+ cutaneous lymphoma cell lines (Mac-1, Mac-2 A, JK) derived from nonregressing tumors of two patients who had progressed from lymphomatoid papulosis to systemic anaplastic large cell lymphoma. To evaluate the effects of CD30 signaling, the cell lines were incubated with a CD30 agonistic antibody, HeFi-1. Proliferative responses, mitogen-activated protein kinase, and nuclear factor kappa B activities were determined with and without CD30 activation. Mac-1 and Mac-2 A showed increased proliferative responses to incubation with CD30 activating antibody, HeFi-1. Inhibition of the mitogen-activated protein kinase activity caused growth inhibition of the Mac-1, Mac-2 A, and JK cell lines. Activation of the Fas pathway induced apoptosis in all three cell lines. Taken together, these findings suggest that resistance to CD30-mediated growth inhibition provides a possible mechanism for escape of cutaneous anaplastic large cell lymphoma from tumor regression. Mitogen-activated protein kinase inhibitors are potential therapeutic agents for the treatment of advanced cutaneous anaplastic large cell lymphoma. J Invest Dermatol 115:1034-1040, 2000
Subject(s)
Ki-1 Antigen/physiology , Lymphoma/pathology , Skin Neoplasms/pathology , fas Receptor/physiology , Cell Division/immunology , Disease Progression , Humans , Immunohistochemistry , Mitogen-Activated Protein Kinases/physiology , NF-kappa B/physiology , Signal Transduction , Tumor Cells, CulturedABSTRACT
To develop a model for the biology and treatment of CD30+ anaplastic large cell lymphoma (ALCL), we transplanted leukemic tumor cells from a 22-month-old girl with multiple relapsed ALCL. Tumor cells were inoculated intraperitoneally into a 4-week-old SCID/bg mouse and produced a disseminated tumor within 8 weeks; this tumor was serially transplanted by subcutaneous injections to other mice. Morphology, immunohistochemistry, and molecular genetics which demonstrated the NPM-ALK fusion protein, resulting from the t(2;5)(p23;q35), confirmed the identity of the xenograft with the original tumor. The tumor produced transcripts for interleukin-1alpha, tumor necrosis factor-alpha, and interferon-gamma which could explain the patient's B-symptoms. Treatment of mice with monoclonal antibody (HeFi-1) which activates CD30 antigen administered on day 1 after tumor transplantation prevented tumor growth. Treatment with HeFi-1 after tumors had reached a 0.2 cm(3) volume caused tumor growth arrest and prevention of tumor dissemination. We conclude that transplantation of CD30+ ALCL to SCID/bg mice may provide a valuable model for the study of the biology and design of treatment modalities for CD30+ ALCL.
