PMID- 17972943
OWN - NLM
STAT- MEDLINE
DCOM- 20080326
LR  - 20171116
IS  - 1476-5551 (Electronic)
IS  - 0887-6924 (Linking)
VI  - 22
IP  - 2
DP  - 2008 Feb
TI  - Combination therapy of an anticancer drug with the FNIII14 peptide of fibronectin 
      effectively overcomes cell adhesion-mediated drug resistance of acute myelogenous 
      leukemia.
PG  - 353-60
AB  - We investigated whether FNIII14, a 22-mer peptide derived from fibronectin (FN) 
      that potently impairs interaction of FN with beta1-integrin, could overcome cell 
      adhesion-mediated drug resistance (CAM-DR) induced by very late antigen 
      (VLA)-4-to-FN interaction in acute myelogenous leukemia (AML). Two AML cell 
      lines, U937 cells and HL-60 cells, and fresh leukemic cells from six AML patients 
      with high alpha4-integrin expression exhibited CAM-DR to cytosine arabinoside 
      (Ara C) through VLA-4-to-FN interaction, while fresh leukemic cells from two AML 
      patients with low alpha4-integrin expression did not display CAM-DR to Ara C. 
      FNIII14 impaired VLA-4-to-FN interaction and restored sensitivity to Ara C in the 
      CAM-DR leukemic cells. In these CAM-DR leukemic cells, upregulation of Bcl-2, 
      which was induced through the focal adhesion kinase/Akt signal pathway upon 
      VLA-4-to-FN interaction, was inhibited by FNIII14 treatment. In a mouse model of 
      minimal residual disease (MRD) in bone marrow, 100% survival was achieved by 
      combining FNIII14 with Ara C, whereas Ara C alone prolonged survival only 
      slightly. The myelosuppression induced by Ara C was not augmented by the 
      combination of FNIII14 in mouse experiments. Thus, the combination of anticancer 
      drugs and FNIII14 holds promise to eradicate MRD in bone marrow after 
      chemotherapy.
FAU - Matsunaga, T
AU  - Matsunaga T
AD  - Fourth Department of Internal Medicine, Sapporo Medical University, School of 
      Medicine, Sapporo, Japan.
FAU - Fukai, F
AU  - Fukai F
FAU - Miura, S
AU  - Miura S
FAU - Nakane, Y
AU  - Nakane Y
FAU - Owaki, T
AU  - Owaki T
FAU - Kodama, H
AU  - Kodama H
FAU - Tanaka, M
AU  - Tanaka M
FAU - Nagaya, T
AU  - Nagaya T
FAU - Takimoto, R
AU  - Takimoto R
FAU - Takayama, T
AU  - Takayama T
FAU - Niitsu, Y
AU  - Niitsu Y
LA  - eng
PT  - Journal Article
DEP - 20071101
PL  - England
TA  - Leukemia
JT  - Leukemia
JID - 8704895
RN  - 0 (Antineoplastic Agents)
RN  - 0 (Fibronectins)
RN  - 0 (Integrin beta1)
RN  - 0 (Peptide Fragments)
RN  - 0 (Proto-Oncogene Proteins c-bcl-2)
RN  - 04079A1RDZ (Cytarabine)
SB  - IM
MH  - Animals
MH  - Antineoplastic Agents/*pharmacology/therapeutic use
MH  - Bone Marrow/pathology
MH  - Cell Adhesion/drug effects
MH  - Cell Line, Tumor
MH  - Cytarabine/pharmacology/therapeutic use
MH  - Drug Resistance/*drug effects
MH  - Drug Therapy, Combination
MH  - Fibronectins/*pharmacology/therapeutic use
MH  - Humans
MH  - Integrin beta1
MH  - Leukemia, Myeloid, Acute/*drug therapy/pathology
MH  - Mice
MH  - Neoplasm, Residual/*drug therapy
MH  - Peptide Fragments/*pharmacology/therapeutic use
MH  - Proto-Oncogene Proteins c-bcl-2/antagonists & inhibitors
MH  - Tumor Cells, Cultured
EDAT- 2007/11/02 09:00
MHDA- 2008/03/28 09:00
CRDT- 2007/11/02 09:00
PHST- 2007/11/02 09:00 [pubmed]
PHST- 2008/03/28 09:00 [medline]
PHST- 2007/11/02 09:00 [entrez]
AID - 2405017 [pii]
AID - 10.1038/sj.leu.2405017 [doi]
PST - ppublish
SO  - Leukemia. 2008 Feb;22(2):353-60. doi: 10.1038/sj.leu.2405017. Epub 2007 Nov 1.