PMID- 18240144
OWN - NLM
STAT- MEDLINE
DCOM- 20080508
LR  - 20221207
IS  - 1097-0215 (Electronic)
IS  - 0020-7136 (Linking)
VI  - 122
IP  - 11
DP  - 2008 Jun 1
TI  - The DNA demethylating agent 5-aza-2'-deoxycytidine activates NY-ESO-1 
      antigenicity in orthotopic human glioma.
PG  - 2542-53
LID - 10.1002/ijc.23407 [doi]
AB  - Cancer/testis antigens (CTAs) are considered to be suitable targets for the 
      immunotherapy of human malignancies. It has been demonstrated that in a variety 
      of tumors, the expression of certain CTAs is activated via the demethylation of 
      their promoter CpG islands. In our study, we have shown that while the composite 
      expression of 13 CTAs in 30 human glioma specimens and newly established cell 
      lines from the Japanese population was nearly imperceptible, the 
      DNA-demethylating agent 5-aza-2'-deoxycytidine (5-aza-CdR) markedly reactivated 
      CTA expression in glioma cells but not in normal human cells. We quantified the 
      diminished methylation status of NY-ESO-1-one of the most immunogenic 
      CTAs-following 5-aza-CdR treatment by using a novel Pyrosequencing technology and 
      methylation-specific PCR. Microarray analysis revealed that 5-aza-CdR is capable 
      of signaling the immune system, particularly, human leukocyte antigen (HLA) class 
      I upregulation. (51)Cr-release cytotoxicity assays and cold target inhibition 
      assays using NY-ESO-1-specific cytotoxic T lymphocyte (CTL) lines demonstrated 
      the presentation of de novo NY-ESO-1 antigenic peptides on the cell surfaces. In 
      an orthotopic xenograft model, the systemic administration of 5-aza-CdR resulted 
      in a significant volume reduction of the transplanted tumors and prolonged the 
      survival of the animals after the adoptive transfer of NY-ESO-1-specific CTLs. 
      These results suggested that 5-aza-CdR induces the expression of epigenetically 
      silenced CTAs in poorly immunogenic gliomas and thereby presents a new strategy 
      for tumor immunotherapy targeting 5-aza-CdR-induced CTAs.
CI  - (c) 2008 Wiley-Liss, Inc.
FAU - Natsume, Atsushi
AU  - Natsume A
AD  - Department of Neurosurgery, Nagoya University School of Medicine, Nagoya, Japan. 
      anatsume@med.nagoya-u.ac.jp
FAU - Wakabayashi, Toshihiko
AU  - Wakabayashi T
FAU - Tsujimura, Kunio
AU  - Tsujimura K
FAU - Shimato, Shinji
AU  - Shimato S
FAU - Ito, Motokazu
AU  - Ito M
FAU - Kuzushima, Kiyotaka
AU  - Kuzushima K
FAU - Kondo, Yutaka
AU  - Kondo Y
FAU - Sekido, Yoshitaka
AU  - Sekido Y
FAU - Kawatsura, Hitomi
AU  - Kawatsura H
FAU - Narita, Yuji
AU  - Narita Y
FAU - Yoshida, Jun
AU  - Yoshida J
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Int J Cancer
JT  - International journal of cancer
JID - 0042124
RN  - 0 (Antigens, Neoplasm)
RN  - 0 (Antimetabolites, Antineoplastic)
RN  - 0 (CTAG1B protein, human)
RN  - 0 (Histocompatibility Antigens Class I)
RN  - 0 (Membrane Proteins)
RN  - 776B62CQ27 (Decitabine)
RN  - M801H13NRU (Azacitidine)
SB  - IM
MH  - Adoptive Transfer
MH  - Analysis of Variance
MH  - Animals
MH  - Antigens, Neoplasm/*immunology
MH  - Antimetabolites, Antineoplastic/immunology/*pharmacology
MH  - Asian People
MH  - Azacitidine/*analogs & derivatives/immunology/pharmacology
MH  - Blotting, Western
MH  - Brain Neoplasms/drug therapy/immunology
MH  - Chromosome Mapping
MH  - CpG Islands
MH  - DNA Methylation/*drug effects
MH  - Decitabine
MH  - Flow Cytometry
MH  - Gene Expression Regulation, Neoplastic
MH  - Glioma/*drug therapy/*immunology/mortality
MH  - Histocompatibility Antigens Class I/metabolism
MH  - Humans
MH  - Kaplan-Meier Estimate
MH  - Male
MH  - Membrane Proteins/*immunology
MH  - Mice
MH  - Mice, Inbred NOD
MH  - Mice, SCID
MH  - Microarray Analysis
MH  - Promoter Regions, Genetic
MH  - Reverse Transcriptase Polymerase Chain Reaction
MH  - T-Lymphocytes, Cytotoxic
MH  - Testis
MH  - Transplantation, Heterologous
MH  - Up-Regulation
EDAT- 2008/02/02 09:00
MHDA- 2008/05/09 09:00
CRDT- 2008/02/02 09:00
PHST- 2008/02/02 09:00 [pubmed]
PHST- 2008/05/09 09:00 [medline]
PHST- 2008/02/02 09:00 [entrez]
AID - 10.1002/ijc.23407 [doi]
PST - ppublish
SO  - Int J Cancer. 2008 Jun 1;122(11):2542-53. doi: 10.1002/ijc.23407.