PMID- 16699793
OWN - NLM
STAT- MEDLINE
DCOM- 20070112
LR  - 20171116
IS  - 0344-5704 (Print)
IS  - 0344-5704 (Linking)
VI  - 59
IP  - 1
DP  - 2007 Jan
TI  - Combination therapy of human pancreatic cancer implanted in nude mice by oral 
      fluoropyrimidine anticancer agent (S-1) with interferon-alpha.
PG  - 113-26
AB  - PURPOSE: We evaluated the antitumor and antiangiogenic activities of human 
      natural interferon-alpha (IFN-alpha) alone or in combination with S-1 against 
      human pancreatic cancer cells. METHODS: Three days after the subcutaneous (s.c.) 
      implantation of tumor cells, mice (n = 12) were received s.c. injection with 
      IFN-alpha alone (10,000 U six times a week), oral administration with S-1 alone 
      (8 mg/kg six times a week), or both with IFN-alpha and S-1 (8, 10, 12 mg/kg six 
      times a week). RESULTS: Administration of IFN-alpha in combination with S-1 
      significantly decreased progressive growth and angiogenesis of human pancreatic 
      cancer cells. The combination therapy produced more significant inhibition in 
      expression of the representative proangiogenic molecules, vascular endothelial 
      growth factor and basic fibroblast growth factor than individual treatment either 
      IFN-alpha or S-1 alone did. These treatments also decreased the staining of 
      proliferating cell nuclear antigen, induced apoptosis and decreased microvessel 
      density. In order to better understand the precise molecular mechanisms by which 
      IFN-alpha and S-1 exert its effects, we have utilized cDNA microarray including 
      124 known genes to determine the gene expression profile altered by IFN-alpha and 
      S-1 treatment. We found a total of seven genes which showed a twofold change 
      after IFN-alpha and S-1 treatment in addition to VEGF, bFGF, CD31, MMP-2, MMP-7 
      and MMP-9. Among these genes, we found down-regulation of six genes and 
      up-regulation of one gene, which are related to angiogenesis, tumor cell invasion 
      and metastasis. CONCLUSIONS: These data suggest that administration of IFN-alpha 
      in combination with S-1 may provide a novel and effective approach to the 
      treatment of human pancreatic cancer.
FAU - Miyake, Kotaro
AU  - Miyake K
AD  - Department of Digestive and Pediatric Surgery, Institute of Health Biosciences, 
      The University of Tokushima Graduate School, 3-18-15 Kuramoto, Tokushima, 
      770-8503, Japan.
FAU - Tsuchida, Kunihiro
AU  - Tsuchida K
FAU - Sugino, Hiromu
AU  - Sugino H
FAU - Imura, Satoru
AU  - Imura S
FAU - Morine, Yuji
AU  - Morine Y
FAU - Fujii, Masahiko
AU  - Fujii M
FAU - Shimada, Mitsuo
AU  - Shimada M
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20060513
PL  - Germany
TA  - Cancer Chemother Pharmacol
JT  - Cancer chemotherapy and pharmacology
JID - 7806519
RN  - 0 (Angiogenesis Inhibitors)
RN  - 0 (Antibiotics, Antineoplastic)
RN  - 0 (DNA, Complementary)
RN  - 0 (Interferon-alpha)
RN  - 0 (Platelet Endothelial Cell Adhesion Molecule-1)
RN  - 0 (Proliferating Cell Nuclear Antigen)
RN  - 0 (Vascular Endothelial Growth Factor A)
RN  - 103107-01-3 (Fibroblast Growth Factor 2)
RN  - 1548R74NSZ (Tegafur)
RN  - EC 1.3.1.2 (Dihydrouracil Dehydrogenase (NADP))
RN  - EC 3.4.24.- (Matrix Metalloproteinases)
SB  - IM
MH  - Angiogenesis Inhibitors/administration & dosage
MH  - Animals
MH  - Antibiotics, Antineoplastic/administration & dosage
MH  - Antineoplastic Combined Chemotherapy Protocols/*therapeutic use
MH  - DNA, Complementary/biosynthesis/genetics
MH  - Dihydrouracil Dehydrogenase (NADP)/metabolism
MH  - Fibroblast Growth Factor 2/biosynthesis
MH  - Humans
MH  - Immunohistochemistry
MH  - In Situ Nick-End Labeling
MH  - Interferon-alpha/administration & dosage
MH  - Matrix Metalloproteinases/biosynthesis
MH  - Mice
MH  - Mice, Nude
MH  - Neoplasm Transplantation
MH  - Oligonucleotide Array Sequence Analysis
MH  - Pancreatic Neoplasms/*drug therapy/pathology
MH  - Platelet Endothelial Cell Adhesion Molecule-1/biosynthesis
MH  - Proliferating Cell Nuclear Antigen/biosynthesis
MH  - Survival Analysis
MH  - Tegafur/administration & dosage
MH  - Vascular Endothelial Growth Factor A/biosynthesis
EDAT- 2006/05/16 09:00
MHDA- 2007/01/16 09:00
CRDT- 2006/05/16 09:00
PHST- 2006/02/02 00:00 [received]
PHST- 2006/03/27 00:00 [accepted]
PHST- 2006/05/16 09:00 [pubmed]
PHST- 2007/01/16 09:00 [medline]
PHST- 2006/05/16 09:00 [entrez]
AID - 10.1007/s00280-006-0250-5 [doi]
PST - ppublish
SO  - Cancer Chemother Pharmacol. 2007 Jan;59(1):113-26. doi: 
      10.1007/s00280-006-0250-5. Epub 2006 May 13.