PMID- 11929816
OWN - NLM
STAT- MEDLINE
DCOM- 20020507
LR  - 20221207
IS  - 0008-5472 (Print)
IS  - 0008-5472 (Linking)
VI  - 62
IP  - 7
DP  - 2002 Apr 1
TI  - Blockade of vascular endothelial growth factor receptor and epidermal growth 
      factor receptor signaling for therapy of metastatic human pancreatic cancer.
PG  - 1996-2003
AB  - We determined whether concurrent blockage of vascular endothelial growth factor 
      (VEGF) receptor and epidermal growth factor (EGF) receptor signaling by two novel 
      tyrosine kinase inhibitors, PTK 787 and PKI 166, respectively, can inhibit 
      angiogenesis and, hence, the growth and metastasis of human pancreatic carcinoma 
      in nude mice. Highly metastatic human pancreatic carcinoma L3.6pl cells were 
      injected into the pancreas of nude mice. Seven days later, groups of mice began 
      receiving oral doses of PTK 787 and PKI 166 three times weekly. Some groups of 
      mice also received i.p. injections of gemcitabine twice a week. The mice were 
      necropsied when the control mice became moribund. Treatment with PTK 787 and PKI 
      166, with gemcitabine alone, or with the combination of PTK 787, PKI 166, and 
      gemcitabine produced 69, 50, and 97% reduction in the volume of pancreatic 
      tumors, respectively. Administration of protein tyrosine kinase inhibitors and 
      gemcitabine also significantly decreased the incidence of lymph node and liver 
      metastasis. The therapeutic efficacy directly correlated with a decrease in 
      circulating proangiogenic molecules (VEGF, interleukin-8), a decrease in 
      microvessel density, a decrease in proliferating cell nuclear antigen staining, 
      and an increase in apoptosis of tumor cells and endothelial cells. Therapies 
      produced by combining gemcitabine with either PKI 166 or PTK 787 were similar to 
      those produced by combining gemcitabine with both PKI 166 and PTK 787. These 
      results suggest that blockade of either epidermal growth factor receptor or VEGF 
      receptor signaling combined with chemotherapy provides an effective approach to 
      the therapy of pancreatic cancer.
FAU - Baker, Cheryl H
AU  - Baker CH
AD  - Department of Cancer Biology, The University of Texas M. D. Anderson Cancer 
      Center, Houston, Texas 77030, USA.
FAU - Solorzano, Carmen C
AU  - Solorzano CC
FAU - Fidler, Isaiah J
AU  - Fidler IJ
LA  - eng
GR  - CA 16672/CA/NCI NIH HHS/United States
GR  - CA90270/CA/NCI NIH HHS/United States
GR  - CA93639/CA/NCI NIH HHS/United States
GR  - R35-CA42107/CA/NCI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - Cancer Res
JT  - Cancer research
JID - 2984705R
RN  - 0 (Angiogenesis Inhibitors)
RN  - 0 (Phthalazines)
RN  - 0 (Pyridines)
RN  - 0 (Pyrimidines)
RN  - 0 (Pyrroles)
RN  - 0 (Receptors, Growth Factor)
RN  - 0W860991D6 (Deoxycytidine)
RN  - 5DX9U76296 (vatalanib)
RN  - 9RIE5HW38P (PKI 166)
RN  - EC 2.7.10.1 (ErbB Receptors)
RN  - EC 2.7.10.1 (Receptor Protein-Tyrosine Kinases)
RN  - EC 2.7.10.1 (Receptors, Vascular Endothelial Growth Factor)
RN  - 0 (Gemcitabine)
SB  - IM
MH  - Angiogenesis Inhibitors/administration & dosage/pharmacology
MH  - Animals
MH  - Antineoplastic Combined Chemotherapy Protocols/*pharmacology
MH  - Apoptosis/drug effects
MH  - Cell Division/drug effects
MH  - Deoxycytidine/administration & dosage/*analogs & derivatives/pharmacology
MH  - Endothelium, Vascular/drug effects/pathology
MH  - ErbB Receptors/*antagonists & inhibitors
MH  - Humans
MH  - Immunohistochemistry
MH  - Male
MH  - Mice
MH  - Mice, Nude
MH  - Neoplasm Metastasis
MH  - Neovascularization, Pathologic/drug therapy/pathology
MH  - Pancreatic Neoplasms/blood supply/*drug therapy/pathology
MH  - Phthalazines/administration & dosage/pharmacology
MH  - *Pyridines
MH  - Pyrimidines/administration & dosage/pharmacology
MH  - Pyrroles/administration & dosage/pharmacology
MH  - Receptor Protein-Tyrosine Kinases/*antagonists & inhibitors/physiology
MH  - Receptors, Growth Factor/*antagonists & inhibitors/physiology
MH  - Receptors, Vascular Endothelial Growth Factor
MH  - Signal Transduction/*drug effects/physiology
MH  - Xenograft Model Antitumor Assays
MH  - Gemcitabine
EDAT- 2002/04/04 10:00
MHDA- 2002/05/08 10:01
CRDT- 2002/04/04 10:00
PHST- 2002/04/04 10:00 [pubmed]
PHST- 2002/05/08 10:01 [medline]
PHST- 2002/04/04 10:00 [entrez]
PST - ppublish
SO  - Cancer Res. 2002 Apr 1;62(7):1996-2003.