PMID- 21567204
OWN - NLM
STAT- MEDLINE
DCOM- 20120321
LR  - 20211020
IS  - 1573-4978 (Electronic)
IS  - 0301-4851 (Print)
IS  - 0301-4851 (Linking)
VI  - 39
IP  - 1
DP  - 2012 Jan
TI  - A self-contained enzyme activating prodrug cytotherapy for preclinical melanoma.
PG  - 157-65
LID - 10.1007/s11033-011-0720-7 [doi]
AB  - Gene-directed enzyme prodrug therapy (GDEPT) has been investigated as a means of 
      cancer treatment without affecting normal tissues. This system is based on the 
      delivery of a suicide gene, a gene encoding an enzyme which is able to convert 
      its substrate from non-toxic prodrug to cytotoxin. In this experiment, we have 
      developed a targeted suicide gene therapeutic system that is completely contained 
      within tumor-tropic cells and have tested this system for melanoma therapy in a 
      preclinical model. First, we established double stable RAW264.7 
      monocyte/macrophage-like cells (Mo/Ma) containing a Tet-On(R) Advanced system for 
      intracellular carboxylesterase (InCE) expression. Second, we loaded a prodrug 
      into the delivery cells, double stable Mo/Ma. Third, we activated the enzyme 
      system to convert the prodrug, irinotecan, to the cytotoxin, SN-38. Our double 
      stable Mo/Ma homed to the lung melanomas after 1 day and successfully delivered 
      the prodrug-activating enzyme/prodrug package to the tumors. We observed that our 
      system significantly reduced tumor weights and numbers as targeted tumor therapy 
      after activation of the InCE. Therefore, we propose that this system may be a 
      useful targeted melanoma therapy system for pulmonary metastatic tumors with 
      minimal side effects, particularly if it is combined with other treatments.
FAU - Seo, Gwi-Moon
AU  - Seo GM
AD  - Department of Anatomy and Physiology, College of Veterinary Medicine, Kansas 
      State University, 1800 Denison Avenue, Manhattan, KS, 66506, USA.
FAU - Rachakatla, Raja Shekar
AU  - Rachakatla RS
FAU - Balivada, Sivasai
AU  - Balivada S
FAU - Pyle, Marla
AU  - Pyle M
FAU - Shrestha, Tej B
AU  - Shrestha TB
FAU - Basel, Matthew T
AU  - Basel MT
FAU - Myers, Carl
AU  - Myers C
FAU - Wang, Hongwang
AU  - Wang H
FAU - Tamura, Masaaki
AU  - Tamura M
FAU - Bossmann, Stefan H
AU  - Bossmann SH
FAU - Troyer, Deryl L
AU  - Troyer DL
LA  - eng
GR  - R21 CA135599/CA/NCI NIH HHS/United States
GR  - R21 CA135599-01/CA/NCI NIH HHS/United States
GR  - R21 CA135599-02/CA/NCI NIH HHS/United States
GR  - 1R21CA135599/CA/NCI NIH HHS/United States
PT  - Evaluation Study
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20110513
PL  - Netherlands
TA  - Mol Biol Rep
JT  - Molecular biology reports
JID - 0403234
RN  - 0 (Antineoplastic Agents, Phytogenic)
RN  - 0 (DNA Primers)
RN  - 0 (Drug Carriers)
RN  - 0 (Prodrugs)
RN  - 7673326042 (Irinotecan)
RN  - EC 3.1.1.1 (Carboxylesterase)
RN  - XT3Z54Z28A (Camptothecin)
SB  - IM
MH  - Animals
MH  - Antineoplastic Agents, Phytogenic/administration & dosage/metabolism/*therapeutic 
      use
MH  - Camptothecin/analogs & derivatives/metabolism
MH  - Carboxylesterase/metabolism
MH  - Cell Transplantation/*methods
MH  - DNA Primers/genetics
MH  - Drug Carriers/*metabolism
MH  - Drug Evaluation, Preclinical
MH  - Female
MH  - Genes, Transgenic, Suicide/*genetics
MH  - Irinotecan
MH  - Lung Neoplasms/*drug therapy/pathology
MH  - Magnetics
MH  - Melanoma/*drug therapy/pathology
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Monocyte-Macrophage Precursor Cells/*metabolism
MH  - Nanoparticles
MH  - Prodrugs/administration & dosage/metabolism/*therapeutic use
PMC - PMC3222711
MID - NIHMS304695
EDAT- 2011/05/14 06:00
MHDA- 2012/03/22 06:00
PMCR- 2013/01/01
CRDT- 2011/05/14 06:00
PHST- 2010/12/08 00:00 [received]
PHST- 2011/04/23 00:00 [accepted]
PHST- 2011/05/14 06:00 [entrez]
PHST- 2011/05/14 06:00 [pubmed]
PHST- 2012/03/22 06:00 [medline]
PHST- 2013/01/01 00:00 [pmc-release]
AID - 10.1007/s11033-011-0720-7 [doi]
PST - ppublish
SO  - Mol Biol Rep. 2012 Jan;39(1):157-65. doi: 10.1007/s11033-011-0720-7. Epub 2011 
      May 13.