PMID- 17307870
OWN - NLM
STAT- MEDLINE
DCOM- 20070613
LR  - 20220729
IS  - 0027-8424 (Print)
IS  - 1091-6490 (Electronic)
IS  - 0027-8424 (Linking)
VI  - 104
IP  - 9
DP  - 2007 Feb 27
TI  - Improvement of cancer-targeting therapy, using nanocarriers for intractable solid 
      tumors by inhibition of TGF-beta signaling.
PG  - 3460-5
AB  - Transforming growth factor (TGF)-beta plays a pivotal role in regulation of 
      progression of cancer through effects on tumor microenvironment as well as on 
      cancer cells. TGF-beta inhibitors have recently been shown to prevent the growth 
      and metastasis of certain cancers. However, there may be adverse effects caused 
      by TGF-beta signaling inhibition, including the induction of cancers by the 
      repression of TGF-beta-mediated growth inhibition. Here, we present an 
      application of a short-acting, small-molecule TGF-beta type I receptor (TbetaR-I) 
      inhibitor at a low dose in treating several experimental intractable solid 
      tumors, including pancreatic adenocarcinoma and diffuse-type gastric cancer, 
      characterized by hypovascularity and thick fibrosis in tumor microenvironments. 
      Low-dose TbetaR-I inhibitor altered neither TGF-beta signaling in cancer cells 
      nor the amount of fibrotic components. However, it decreased pericyte coverage of 
      the endothelium without reducing endothelial area specifically in tumor 
      neovasculature and promoted accumulation of macromolecules, including anticancer 
      nanocarriers, in the tumors. Compared with the absence of TbetaR-I inhibitor, 
      anticancer nanocarriers exhibited potent growth-inhibitory effects on these 
      cancers in the presence of TbetaR-I inhibitor. The use of TbetaR-I inhibitor 
      combined with nanocarriers may thus be of significant clinical and practical 
      importance in treating intractable solid cancers.
FAU - Kano, Mitsunobu R
AU  - Kano MR
AD  - Department of Molecular Pathology, Graduate School of Medicine, University of 
      Tokyo, Tokyo 113-0033 Japan.
FAU - Bae, Younsoo
AU  - Bae Y
FAU - Iwata, Caname
AU  - Iwata C
FAU - Morishita, Yasuyuki
AU  - Morishita Y
FAU - Yashiro, Masakazu
AU  - Yashiro M
FAU - Oka, Masako
AU  - Oka M
FAU - Fujii, Tomoko
AU  - Fujii T
FAU - Komuro, Akiyoshi
AU  - Komuro A
FAU - Kiyono, Kunihiko
AU  - Kiyono K
FAU - Kaminishi, Michio
AU  - Kaminishi M
FAU - Hirakawa, Kosei
AU  - Hirakawa K
FAU - Ouchi, Yasuyoshi
AU  - Ouchi Y
FAU - Nishiyama, Nobuhiro
AU  - Nishiyama N
FAU - Kataoka, Kazunori
AU  - Kataoka K
FAU - Miyazono, Kohei
AU  - Miyazono K
LA  - eng
PT  - Comparative Study
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20070216
PL  - United States
TA  - Proc Natl Acad Sci U S A
JT  - Proceedings of the National Academy of Sciences of the United States of America
JID - 7505876
RN  - 0 (HTS 466284)
RN  - 0 (Pyrazoles)
RN  - 0 (Pyrroles)
RN  - 0 (Receptors, Transforming Growth Factor beta)
RN  - 0 (Transforming Growth Factor beta)
RN  - EC 2.7.11.1 (Protein Serine-Threonine Kinases)
RN  - EC 2.7.11.30 (Receptor, Transforming Growth Factor-beta Type I)
SB  - IM
MH  - Animals
MH  - Cell Line, Tumor
MH  - Drug Delivery Systems/*methods
MH  - Endothelium, Vascular/drug effects
MH  - Humans
MH  - Immunohistochemistry
MH  - Mice
MH  - Mice, Inbred BALB C
MH  - Nanoparticles/*therapeutic use
MH  - Neoplasms/*drug therapy
MH  - Protein Serine-Threonine Kinases/*antagonists & inhibitors
MH  - Pyrazoles/*pharmacology
MH  - Pyrroles/*pharmacology
MH  - Receptor, Transforming Growth Factor-beta Type I
MH  - Receptors, Transforming Growth Factor beta
MH  - Signal Transduction/*drug effects
MH  - Transforming Growth Factor beta/metabolism
PMC - PMC1800736
COIS- The authors declare no conflict of interest.
EDAT- 2007/02/20 09:00
MHDA- 2007/06/15 09:00
PMCR- 2007/02/27
CRDT- 2007/02/20 09:00
PHST- 2007/02/20 09:00 [pubmed]
PHST- 2007/06/15 09:00 [medline]
PHST- 2007/02/20 09:00 [entrez]
PHST- 2007/02/27 00:00 [pmc-release]
AID - 0611660104 [pii]
AID - 5262 [pii]
AID - 10.1073/pnas.0611660104 [doi]
PST - ppublish
SO  - Proc Natl Acad Sci U S A. 2007 Feb 27;104(9):3460-5. doi: 
      10.1073/pnas.0611660104. Epub 2007 Feb 16.