[Abstract unavailable

Tumor-associated macrophages (TAMs) are frequently found in glioblastomas and a high degree of macrophage infiltration is associated with a poor prognosis for glioblastoma patients. However, it is unclear whether TAMs in glioblastomas promote tumor growth. In this study, we found that folate receptor beta (FR beta) was expressed on macrophages in human glioblastomas and a rat C6 glioma implanted subcutaneously in nude mice. To target FR beta-expressing TAMs, we produced a recombinant immunotoxin consisting of immunoglobulin heavy and light chain Fv portions of an anti-mouse FR beta monoclonal antibody and Pseudomonas exotoxin A. Injection of the immunotoxin into C6 glioma xenografts in nude mice significantly depleted TAMs and reduced tumor growth. The immunotoxin targeting FR beta-expressing macrophages will provide a therapeutic tool for human glioblastomas.

This study examined the relationship between external environmental factors and Epstein-Barr virus (EBV) infection in nasal natural killer (NK)/T-cell lymphomagenesis. Archival paraffin sections from 134 cases of nasopharyngeal lymphomas in the northeast of China were investigated by in situ hybridization of EBV-encoded small RNA-1 (EBER-1) and by immunohistochemistry of the status of programmed cell death (PCD). The cases examined included 74 (55.2%) cases of NK/T-cell lymphomas (NKTCL) in T-cell and NK-cell neoplasms as well as 32 (23.9%) cases of B-cell neoplasms (B-MLs) and 9 (6.7%) cases of carcinomas. These cases indicated a significant dominant occurrence of NKTCL in the nasal cavity and of B-MLs in the pharynx. Many EBV-associated NKTCLs were seen in the nasopharynx, all three cases of EBV-associated B-MLs were in the nasal cavity and all three cases of EBV-associated carcinomas were only seen in the pharynx. The low number of NKTCL cases showing little or no EBV association, together with the existence of EBER-1-free lymphoma cells in EBV-associated NKTCLs, suggested EBV-related lymphoma cell expansion during lymphomagenesis. Peculiar necrosis, frequently observed in NKTCLs, was due to accelerated PCD. This PCD was autophagic cell death as judged by labeling of Beclin-1 and LC3, which possibly occurred due to EBV infection, when apoptosis was suppressed by survivin. Very minute squamous carcinomas, observed in 10 of 23 cases of NKTCLs with residual epithelia that were survivin-positive but not EBV-associated suggested that carcinogenesis occurred before lymphomagenesis. These data suggest that external environmental oncogenic factors initiate nasopharyngeal carcinomas and lymphomas whereas EBV infection promotes them.

Recently we reported the different frequencies of p53 and c-kit gene mutations among sinonasal NK/T cell lymphoma (NKTCL) in Korea, north China (Beijing), and Japan, suggesting some racial, environmental, or life-style differences as a possible cause of nasal tumorigenesis. In this study, gene mutations in p53, c-kit, Kras, and β β β β-catenin gene were analyzed by polymerase chain reaction (

This study investigated autophagy in 37 cases of nasopharyngeal lymphomas including 23 nasal natural killer (NK)/T-cell lymphomas (NKTCL), 3 cytotoxic T-cell lymphomas (cytotoxic-TML) and 9 B-cell lymphomas (BML) by means of antigen-retrieval immunohistochemistry of beclin-1, LC3, mitochondria (AE-1) and cathepsin D. Peculiar necrosis was noted in EBV+ lymphomas comprising 21 NKTCL, 2 cytotoxic-TML and 1 BML. Lymphomas without peculiar necrosis showed high expression of beclin-1, macrogranular cytoplasmal stain of LC3 with sporadic nuclear stain, a hallmark of autophagic cell death (ACD), some aggregated mitochondria and high expression of cathepsin D, suggesting a state of growth with enhanced autophagy with sporadic ACD. EBV+ NKTCL with the peculiar necrosis, showed significantly low level of macrogranular staining of LC3, aggregated mitochondria and low expression of cathepsin D in the cellular areas when degenerative lymphoma cells showed decreased beclin-1, significantly advanced LC3-labeled autophagy, residual aggregated mitochondria and significantly reduced expression of cathepsin D, suggesting advanced autophagy with regional ACD. Consequently it was suggested that enhanced autophagy and reduced expression of lysosomal enzymes induced regional ACD under EBV infection in NKTCL.