PMID- 10644974
OWN - NLM
STAT- MEDLINE
DCOM- 20000207
LR  - 20231120
IS  - 0950-9232 (Print)
IS  - 0950-9232 (Linking)
VI  - 19
IP  - 1
DP  - 2000 Jan 6
TI  - A mutant oncolytic adenovirus targeting the Rb pathway produces anti-glioma 
      effect in vivo.
PG  - 2-12
AB  - Effective anti cancer strategies necessitate the use of agents that target tumor 
      cells rather than normal tissues. In this study, we constructed a tumor-selective 
      adenovirus, Delta24, that carries a 24-bp deletion in the E1A region responsible 
      for binding Rb protein. Immunoprecipitation analyses verified that this deletion 
      rendered Delta24 unable to bind the Rb protein. However, titration experiments in 
      293 cells demonstrated that the Delta24 adenovirus could replicate in and lyse 
      cancer cells with great efficiency. Lysis of most human glioma cells was observed 
      within 10 - 14 days after infection with Delta24 at 10 PFU/cell. In vivo, a 
      single dose of the Delta24 virus induced a 66.3% inhibition (P<0.005) and 
      multiple injections, an 83.8% inhibition (P<0.01) of tumor growth in nude mice. 
      However, normal fibroblasts or cancer cells with restored Rb activity were 
      resistant to the Delta24 adenovirus. These results suggest that the E1A-mutant 
      Delta24 adenovirus may be clinically and therapeutically useful against gliomas 
      and possibly other cancers with disrupted Rb pathway.
FAU - Fueyo, J
AU  - Fueyo J
AD  - Department of Neuro-Oncology, The University of Texas M.D. Anderson Cancer 
      Center, 1515 Holcombe Blvd., Houston, Texas, TX 77030, USA.
FAU - Gomez-Manzano, C
AU  - Gomez-Manzano C
FAU - Alemany, R
AU  - Alemany R
FAU - Lee, P S
AU  - Lee PS
FAU - McDonnell, T J
AU  - McDonnell TJ
FAU - Mitlianga, P
AU  - Mitlianga P
FAU - Shi, Y X
AU  - Shi YX
FAU - Levin, V A
AU  - Levin VA
FAU - Yung, W K
AU  - Yung WK
FAU - Kyritsis, A P
AU  - Kyritsis AP
LA  - eng
PT  - Journal Article
PL  - England
TA  - Oncogene
JT  - Oncogene
JID - 8711562
RN  - 0 (Retinoblastoma Protein)
SB  - IM
EIN - Oncogene 2000 Oct 12;19(43):5038
MH  - Adenoviridae/*genetics
MH  - Animals
MH  - *Genetic Therapy
MH  - Glioma/*therapy
MH  - Humans
MH  - Mice
MH  - Mice, Inbred BALB C
MH  - Mice, Nude
MH  - Mutation
MH  - Retinoblastoma Protein/*physiology
MH  - S Phase
MH  - Tumor Cells, Cultured
MH  - Virus Replication
EDAT- 2000/01/25 00:00
MHDA- 2000/01/25 00:01
CRDT- 2000/01/25 00:00
PHST- 2000/01/25 00:00 [pubmed]
PHST- 2000/01/25 00:01 [medline]
PHST- 2000/01/25 00:00 [entrez]
AID - 10.1038/sj.onc.1203251 [doi]
PST - ppublish
SO  - Oncogene. 2000 Jan 6;19(1):2-12. doi: 10.1038/sj.onc.1203251.