PMID- 11704827
OWN - NLM
STAT- MEDLINE
DCOM- 20011207
LR  - 20131121
IS  - 0950-9232 (Print)
IS  - 0950-9232 (Linking)
VI  - 20
IP  - 48
DP  - 2001 Oct 25
TI  - Induction of a TRAIL-mediated suicide program by interferon alpha in primary 
      effusion lymphoma.
PG  - 7029-40
AB  - Gammaherpes viruses are often detected in lymphomas arising in immunocompromised 
      patients. We have found that Azidothymidine (AZT) alone induces apoptosis in 
      Epstein Barr Virus (EBV) positive Burkitt's lymphoma (BL) cells but requires 
      interferon alpha (IFN-alpha) to induce apoptosis in Human Herpes Virus Type 8 
      (HHV-8) positive Primary Effusion Lymphomas (PEL). Our analysis of a series of 
      AIDS lymphomas revealed that IFN-alpha selectively induced very high levels of 
      the Death Receptor (DR) tumor necrosis factor-related apoptosis-inducing ligand 
      (TRAIL) in HHV-8 positive PEL lines and primary tumor cells whereas little or no 
      induction was observed in primary EBV+ AIDS lymphomas and EBV-Burkitt's lines. 
      AZT and IFN-alpha mediated apoptosis in PEL was blocked by stable overexpression 
      of dominant negative Fas Associated Death Domain (FADD), decoy receptor 2 (DcR2), 
      soluble TRAIL receptor fusion proteins (DR-4 and DR-5) and thymidine. Trimeric 
      TRAIL (in place of IFN-alpha) similarly synergized with AZT to induce apoptosis 
      in HHV-8 positive PEL cells. This is the first demonstration that IFN-alpha 
      induces functional TRAIL in a malignancy that can be exploited to effect a 
      suicide program. This novel antiviral approach to Primary Effusion lymphomas is 
      targeted and may represent a highly effective and relatively non-toxic therapy.
FAU - Toomey, N L
AU  - Toomey NL
AD  - Department of Medicine, University of Miami School of Medicine, Miami, Florida, 
      FL 33136, USA.
FAU - Deyev, V V
AU  - Deyev VV
FAU - Wood, C
AU  - Wood C
FAU - Boise, L H
AU  - Boise LH
FAU - Scott, D
AU  - Scott D
FAU - Liu, L H
AU  - Liu LH
FAU - Cabral, L
AU  - Cabral L
FAU - Podack, E R
AU  - Podack ER
FAU - Barber, G N
AU  - Barber GN
FAU - Harrington, W J Jr
AU  - Harrington WJ Jr
LA  - eng
GR  - CA39201/CA/NCI NIH HHS/United States
GR  - CA77837/CA/NCI NIH HHS/United States
GR  - CA80228/CA/NCI NIH HHS/United States
GR  - CA82274/CA/NCI NIH HHS/United States
PT  - Comparative Study
PT  - Journal Article
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - England
TA  - Oncogene
JT  - Oncogene
JID - 8711562
RN  - 0 (Antimetabolites, Antineoplastic)
RN  - 0 (Antiviral Agents)
RN  - 0 (Apoptosis Regulatory Proteins)
RN  - 0 (Arabidopsis Proteins)
RN  - 0 (BCL2L1 protein, human)
RN  - 0 (Biopolymers)
RN  - 0 (Immunologic Factors)
RN  - 0 (Interferon-alpha)
RN  - 0 (Membrane Glycoproteins)
RN  - 0 (Neoplasm Proteins)
RN  - 0 (Proto-Oncogene Proteins c-bcl-2)
RN  - 0 (Receptors, TNF-Related Apoptosis-Inducing Ligand)
RN  - 0 (Receptors, Tumor Necrosis Factor)
RN  - 0 (TNF-Related Apoptosis-Inducing Ligand)
RN  - 0 (TNFRSF10A protein, human)
RN  - 0 (TNFRSF10B protein, human)
RN  - 0 (TNFSF10 protein, human)
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - 0 (bcl-X Protein)
RN  - 4B9XT59T7S (Zidovudine)
RN  - 6PLQ3CP4P3 (Etoposide)
RN  - EC 1.14.19.- (Fatty Acid Desaturases)
RN  - EC 1.14.99.- (Fad7 protein, Arabidopsis)
RN  - EC 3.4.22.- (Cysteine Endopeptidases)
RN  - VC2W18DGKR (Thymidine)
SB  - IM
MH  - Antimetabolites, Antineoplastic/pharmacology/therapeutic use
MH  - Antiviral Agents/*pharmacology/therapeutic use
MH  - Apoptosis/*drug effects
MH  - Apoptosis Regulatory Proteins
MH  - *Arabidopsis Proteins
MH  - Biopolymers
MH  - Cysteine Endopeptidases/metabolism
MH  - Drug Synergism
MH  - Enzyme Activation/drug effects
MH  - Epstein-Barr Virus Infections/complications
MH  - Etoposide/pharmacology
MH  - Fatty Acid Desaturases/biosynthesis/genetics/physiology
MH  - Gene Expression Regulation, Neoplastic/drug effects
MH  - Genes, bcl-2
MH  - HIV Infections/complications
MH  - Herpesviridae Infections/complications
MH  - Herpesvirus 4, Human/isolation & purification
MH  - Herpesvirus 8, Human/isolation & purification
MH  - Humans
MH  - Immunocompromised Host
MH  - Immunologic Factors/*pharmacology/therapeutic use
MH  - Interferon-alpha/*pharmacology/therapeutic use
MH  - Lymphoma, AIDS-Related/etiology/immunology/pathology/*therapy
MH  - Lymphoma, B-Cell/etiology/immunology/pathology/*therapy
MH  - Membrane Glycoproteins/biosynthesis/chemistry/genetics/pharmacology/*physiology
MH  - Neoplasm Proteins/biosynthesis/genetics/physiology
MH  - Proto-Oncogene Proteins c-bcl-2/biosynthesis/genetics
MH  - Receptors, TNF-Related Apoptosis-Inducing Ligand
MH  - Receptors, Tumor Necrosis Factor/biosynthesis/genetics/physiology
MH  - TNF-Related Apoptosis-Inducing Ligand
MH  - Thymidine/pharmacology
MH  - Tumor Cells, Cultured/drug effects/metabolism
MH  - Tumor Necrosis 
      Factor-alpha/biosynthesis/chemistry/genetics/pharmacology/*physiology
MH  - Tumor Virus Infections/complications
MH  - Zidovudine/pharmacology/therapeutic use
MH  - bcl-X Protein
EDAT- 2001/11/13 10:00
MHDA- 2002/01/05 10:01
CRDT- 2001/11/13 10:00
PHST- 2001/05/14 00:00 [received]
PHST- 2001/07/17 00:00 [revised]
PHST- 2001/08/02 00:00 [accepted]
PHST- 2001/11/13 10:00 [pubmed]
PHST- 2002/01/05 10:01 [medline]
PHST- 2001/11/13 10:00 [entrez]
AID - 10.1038/sj.onc.1204895 [doi]
PST - ppublish
SO  - Oncogene. 2001 Oct 25;20(48):7029-40. doi: 10.1038/sj.onc.1204895.