PMID- 22238072
OWN - NLM
STAT- MEDLINE
DCOM- 20120705
LR  - 20231106
IS  - 1613-6829 (Electronic)
IS  - 1613-6810 (Print)
IS  - 1613-6810 (Linking)
VI  - 8
IP  - 6
DP  - 2012 Mar 26
TI  - A cell-delivered and cell-activated SN38-dextran prodrug increases survival in a 
      murine disseminated pancreatic cancer model.
PG  - 913-20
LID - 10.1002/smll.201101879 [doi]
AB  - Enzyme-activated prodrugs have been investigated and sought after as highly 
      specific, low-side-effect treatments, especially for cancer therapy. 
      Unfortunately, excellent targets for enzyme-activated therapy are rare. Here a 
      system based on cell delivery that can carry both a prodrug and an activating 
      enzyme to the cancer site is demonstrated. Raw264.7 cells (mouse 
      monocyte/macrophage-like cells, Mo/Ma) are engineered to express intracellular 
      rabbit carboxylesterase (InCE), which is a potent activator of the prodrug 
      irinotecan to SN38. InCE expression is regulated by the TetOn(R) system, which 
      silences the gene unless a tetracycline, such as doxycycline, is present. 
      Concurrently, an irinotecan-like prodrug, which is conjugated to dextran and can 
      be loaded into the cytoplasm of Mo/Ma, is synthesized. To test the system, a 
      murine pancreatic cancer model is generated by intraperitoneal (i.p.) injection 
      of Pan02 cells. Engineered Mo/Ma are loaded with the prodrug and are injected 
      i.p. Two days later, doxycycline was given i.p. to activate InCE, which activated 
      the prodrug. A survival study demonstrates that this system significantly 
      increased survival in a murine pancreatic cancer model. Thus, for the first time, 
      a prodrug/activating enzyme system, which is self-contained within tumor-homing 
      cells and can prolong the life of i.p. pancreatic tumor bearing mice, is 
      demonstrated.
CI  - Copyright (c) 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.
FAU - Basel, Matthew T
AU  - Basel MT
AD  - Department of Anatomy and Physiology, Kansas State University, 1600 Denison Ave., 
      Coles Hall 228, Manhattan, KS 66506, USA. mbasel@vet.ksu.edu
FAU - Balivada, Sivasai
AU  - Balivada S
FAU - Shrestha, Tej B
AU  - Shrestha TB
FAU - Seo, Gwi-Moon
AU  - Seo GM
FAU - Pyle, Marla M
AU  - Pyle MM
FAU - Tamura, Masaaki
AU  - Tamura M
FAU - Bossmann, Stefan H
AU  - Bossmann SH
FAU - Troyer, Deryl L
AU  - Troyer DL
LA  - eng
GR  - P20 RR016475/RR/NCRR NIH HHS/United States
GR  - R21 CA135599/CA/NCI NIH HHS/United States
GR  - 1R21CA135599/CA/NCI NIH HHS/United States
GR  - P20 RR0117686/RR/NCRR NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
DEP - 20120111
PL  - Germany
TA  - Small
JT  - Small (Weinheim an der Bergstrasse, Germany)
JID - 101235338
RN  - 0 (Dextrans)
RN  - 0 (Prodrugs)
RN  - 7673326042 (Irinotecan)
RN  - XT3Z54Z28A (Camptothecin)
SB  - IM
MH  - Animals
MH  - Camptothecin/administration & dosage/*analogs & derivatives
MH  - Dextrans/*administration & dosage
MH  - Disease Models, Animal
MH  - Irinotecan
MH  - Mice
MH  - Pancreatic Neoplasms/*pathology
MH  - Prodrugs/*administration & dosage
MH  - Rabbits
PMC - PMC3583224
MID - NIHMS414142
EDAT- 2012/01/13 06:00
MHDA- 2012/07/06 06:00
PMCR- 2013/03/26
CRDT- 2012/01/13 06:00
PHST- 2011/09/08 00:00 [received]
PHST- 2012/01/13 06:00 [entrez]
PHST- 2012/01/13 06:00 [pubmed]
PHST- 2012/07/06 06:00 [medline]
PHST- 2013/03/26 00:00 [pmc-release]
AID - 10.1002/smll.201101879 [doi]
PST - ppublish
SO  - Small. 2012 Mar 26;8(6):913-20. doi: 10.1002/smll.201101879. Epub 2012 Jan 11.