PMID- 20673348
OWN - NLM
STAT- MEDLINE
DCOM- 20110203
LR  - 20211020
IS  - 1471-2407 (Electronic)
IS  - 1471-2407 (Linking)
VI  - 10
DP  - 2010 Jul 30
TI  - GU81, a VEGFR2 antagonist peptoid, enhances the anti-tumor activity of 
      doxorubicin in the murine MMTV-PyMT transgenic model of breast cancer.
PG  - 397
LID - 10.1186/1471-2407-10-397 [doi]
AB  - BACKGROUND: Vascular endothelial growth factor (VEGF) is a primary stimulant of 
      angiogenesis under physiological and pathological conditions. Anti-VEGF therapy 
      is a clinically proven strategy for the treatment of a variety of cancers 
      including colon, breast, lung, and renal cell carcinoma. Since VEGFR2 is the 
      dominant angiogenic signaling receptor, it has become an important target in the 
      development of novel anti-angiogenic therapies. We have reported previously the 
      development of an antagonistic VEGFR2 peptoid (GU40C4) that has promising 
      anti-angiogenic activity in vitro and in vivo. METHODS: In the current study, we 
      utilize a derivative of GU40C4, termed GU81 in therapy studies. GU81 was tested 
      alone or in combination with doxorubicin for in vivo efficacy in the MMTV-PyMT 
      transgenic model of breast cancer. RESULTS: The derivative GU81 has increased in 
      vitro efficacy compared to GU40C4. Single agent therapy (doxorubicin or GU81 
      alone) had no effect on tumor weight, histology, tumor fat content, or tumor 
      growth index. However, GU81 is able to significantly to reduce total vascular 
      area as a single agent. GU81 used in combination with doxorubicin significantly 
      reduced tumor weight and growth index compared to all other treatment groups. 
      Furthermore, treatment with combination therapy significantly arrested tumor 
      progression at the premalignant stage, resulting in increased tumor fat content. 
      Interestingly, treatment with GU81 alone increased tumor-VEGF levels and 
      macrophage infiltration, an effect that was abrogated when used in combination 
      with doxorubicin. CONCLUSION: This study demonstrates the VEGFR2 antagonist 
      peptoid, GU81, enhances the anti-tumor activity of doxorubicin in spontaneous 
      murine MMTV-PyMT breast tumors.
FAU - Lynn, Kristi D
AU  - Lynn KD
AD  - Division of Surgical Oncology, Department of Surgery, UT Southwestern Medical 
      Center, 5323 Harry Hines Blvd., Dallas, TX 76259, USA.
FAU - Udugamasooriya, D Gomika
AU  - Udugamasooriya DG
FAU - Roland, Christina L
AU  - Roland CL
FAU - Castrillon, Diego H
AU  - Castrillon DH
FAU - Kodadek, Thomas J
AU  - Kodadek TJ
FAU - Brekken, Rolf A
AU  - Brekken RA
LA  - eng
GR  - K26RR024196/RR/NCRR NIH HHS/United States
GR  - N01-HV-28185/HV/NHLBI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, Non-P.H.S.
DEP - 20100730
PL  - England
TA  - BMC Cancer
JT  - BMC cancer
JID - 100967800
RN  - 0 (Antineoplastic Agents)
RN  - 0 (GU 81 compound)
RN  - 0 (Peptides)
RN  - 0 (Peptoids)
RN  - 0 (Vascular Endothelial Growth Factor A)
RN  - 80168379AG (Doxorubicin)
RN  - EC 2.7.10.1 (Vascular Endothelial Growth Factor Receptor-2)
SB  - IM
MH  - Animals
MH  - Antineoplastic Agents/*pharmacology
MH  - Doxorubicin/*pharmacology
MH  - Drug Synergism
MH  - Drug Therapy, Combination
MH  - Enzyme-Linked Immunosorbent Assay
MH  - Female
MH  - Humans
MH  - Immunoenzyme Techniques
MH  - Macrophages/metabolism/pathology
MH  - Mammary Neoplasms, Experimental/*drug therapy/metabolism/pathology
MH  - Mammary Tumor Virus, Mouse/genetics
MH  - Mice
MH  - Mice, Transgenic
MH  - Peptides/*pharmacology
MH  - Peptoids/*pharmacology
MH  - Tumor Cells, Cultured
MH  - Vascular Endothelial Growth Factor A/pharmacology
MH  - Vascular Endothelial Growth Factor Receptor-2/*antagonists & 
      inhibitors/metabolism
MH  - Xenograft Model Antitumor Assays
PMC - PMC2920882
EDAT- 2010/08/03 06:00
MHDA- 2011/02/04 06:00
PMCR- 2010/07/30
CRDT- 2010/08/03 06:00
PHST- 2010/03/25 00:00 [received]
PHST- 2010/07/30 00:00 [accepted]
PHST- 2010/08/03 06:00 [entrez]
PHST- 2010/08/03 06:00 [pubmed]
PHST- 2011/02/04 06:00 [medline]
PHST- 2010/07/30 00:00 [pmc-release]
AID - 1471-2407-10-397 [pii]
AID - 10.1186/1471-2407-10-397 [doi]
PST - epublish
SO  - BMC Cancer. 2010 Jul 30;10:397. doi: 10.1186/1471-2407-10-397.