Author
Brian Gliniak
Bio: Brian Gliniak is an academic researcher. The author has contributed to research in topics: In vivo & Peptide sequence. The author has an hindex of 4, co-authored 4 publications receiving 3896 citations.
Papers
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TL;DR: Recurrent treatments with LZ–huTRAIL actively suppressed growth of the TRAIL–sensitive human mammary adenocarcinoma cell line MDA–231 in CB.17 (SCID) mice, and histologic examination of tumors from SCID mice treated with Lz–hu TRAIL demonstrated clear areas of apoptotic necrosis within 9–12 hours of injection.
Abstract: To evaluate the utility of tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) as a cancer therapeutic, we created leucine zipper (LZ) forms of human (hu) and murine (mu) TRAIL to promote and stabilize the formation of trimers. Both were biologically active, inducing apoptosis of both human and murine target cells in vitro with similar specific activities. In contrast to the fulminant hepatotoxicity of LZ-huCD95L in vivo, administration of either LZ-huTRAIL or LZ-muTRAIL did not seem toxic to normal tissues of mice. Finally, repeated treatments with LZ-huTRAIL actively suppressed growth of the TRAIL-sensitive human mammary adenocarcinoma cell line MDA-231 in CB.17 (SCID) mice, and histologic examination of tumors from SCID mice treated with LZ-huTRAIL demonstrated clear areas of apoptotic necrosis within 9-12 hours of injection.
2,512 citations
TL;DR: These findings not only provide a novel insight into the pathogenesis of the transplant-related atherosclerosis, but also point to a new therapeutic strategy that involves targeting of homing, differentiation and proliferation of putative smooth-muscle progenitor cells derived from the recipient.
Abstract: Our findings not only provide a novel insight into the pathogenesis of the transplant-related atherosclerosis, but also point to a new therapeutic strategy that involves targeting of homing, differentiation and proliferation of putative smooth-muscle progenitor cells derived from the recipient. This is the first report demonstrating that circulating progenitor cells contribute to the development of proliferative diseases. AKIO SAIURA, MASATAKA SATA, YASUNOBU HIRATA, RYOZO NAGAI MASATOSHI MAKUUCHI Department of Surgery, University of Tokyo, Graduate School of Medicine, Tokyo, Japan, Department of Cardiovascular Medicine University of Tokyo, Graduate School of Medicine, Tokyo, Japan A.S. and M.S. supervised this study equally as senior authors Email: sata-2im@h.u-tokyo.ac.jp 1. McKay, R. Stem cells-hype and hope. Nature 406, 361–364 (2000). 2. Asahara, T. et al. Isolation of putative progenitor endothelial cells for angiogenesis. Science 275, 964–967 (1997). 3. Yamashita, J. et al. Flk1-positive cells derived from embryonic stem cells serve as vascular progenitors. Nature 408, 92–96 (2000). 4. Carmeliet, P. One cell, two fates. Nature 408, 43–45 (2000). 5. Clarke, D.L. et al. Generalized potential of adult neural stem cells. Science 288, 1660–1663 (2000).
724 citations
TL;DR: The recombinant human ligand enhances the proliferation of CD3-activated T cells yet induces differential responses, including cell death, in several CD30+ lymphoma-derived clones.
569 citations
TL;DR: TRAIL/Apo2L is important in controlling tumors in vivo, but is not an essential regulator of osteoprotegerin‐mediated biology, under normal physiological conditions.
Abstract: To define the normal physiological role for the TRAIL/Apo2L in vivo, we generated TRAIL/Apo2L gene-targeted mice. These mice develop normally and show no defects in lymphoid or myeloid cell homeostasis or function. Although TRAIL/Apo2L kills transformed cells in vitro, TRAIL/Apo2L–/– mice do not spontaneously develop overt tumors at an early age. However, in the A20 B cell lymphoma-transferred tumor model, TRAIL/Apo2L–/– mice are clearly more susceptible to death from overwhelming tumor burden, due to increased lymphoma load in the liver. A20 tumors are susceptible to TRAIL/Apo2L killing in vitro, indicating that TRAIL/Apo2L may act directly to control A20 cells in vivo. Despite the fact that TRAIL binds osteoprotegerin and osteoprotegerin-transgenic mice are osteopetrotic, TRAIL/Apo2L–/– mice show no evidence of altered gross bone density, and no alterations in frequency or in vitro differentiationof bone marrow precursor osteoclasts. Moreover, leucine zipper TRAIL has no toxicity when repeatedly administered to osteoprotegerin–/– mice. Thus, TRAIL/Apo2L is important in controlling tumors in vivo, but is not an essential regulator of osteoprotegerin-mediated biology, under normal physiological conditions.
186 citations
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TL;DR: The authors regret the inability to cite all of the primary literature contributing to this review due to length considerations, but wish to thank F. Chan, T. Migone, and J. Wang for insightful comments on the manuscript.
3,756 citations
TL;DR: Deregulated cell proliferation provides a minimal 'platform' necessary to support further neoplastic progression and should be targeted withroit targeting to have potent and specific therapeutic consequences.
Abstract: Beneath the complexity and idiopathy of every cancer lies a limited number of 'mission critical' events that have propelled the tumour cell and its progeny into uncontrolled expansion and invasion One of these is deregulated cell proliferation, which, together with the obligate compensatory suppression of apoptosis needed to support it, provides a minimal 'platform' necessary to support further neoplastic progression Adroit targeting of these critical events should have potent and specific therapeutic consequences
3,151 citations
TL;DR: A novel tumor necrosis factor (TNF) family member has been cloned and characterized, and the TRAIL gene is located on chromosome 3 at position 3q26, which is not close to any other known TNF ligand family members.
2,996 citations
TL;DR: Northern hybridization revealed that Fas ligand is expressed in activated splenocytes and thymocytes, consistent with its involvement in T cell-mediated cytotoxicity and in several nonlymphoid tissues, such as testis.
2,600 citations
TL;DR: In the predicted hybrid protein, the amino terminus of nucleophosmin (NPM) is linked to the catalytic domain of anaplastic lymphoma kinase (ALK), and unscheduled expression of the truncated ALK may contribute to malignant transformation in these lymphomas.
Abstract: The 2;5 chromosomal translocation occurs in most anaplastic large-cell non-Hodgkin's lymphomas arising from activated T lymphocytes. This rearrangement was shown to fuse the NPM nucleolar phosphoprotein gene on chromosome 5q35 to a previously unidentified protein tyrosine kinase gene, ALK, on chromosome 2p23. In the predicted hybrid protein, the amino terminus of nucleophosmin (NPM) is linked to the catalytic domain of anaplastic lymphoma kinase (ALK). Expressed in the small intestine, testis, and brain but not in normal lymphoid cells, ALK shows greatest sequence similarity to the insulin receptor subfamily of kinases. Unscheduled expression of the truncated ALK may contribute to malignant transformation in these lymphomas.
2,260 citations