PMID- 18386001
OWN - NLM
STAT- MEDLINE
DCOM- 20080820
LR  - 20240426
IS  - 0340-7004 (Print)
IS  - 1432-0851 (Electronic)
IS  - 0340-7004 (Linking)
VI  - 57
IP  - 9
DP  - 2008 Sep
TI  - Impact of IFNalpha2b upon pSTAT3 and the MEK/ERK MAPK pathway in melanoma.
PG  - 1315-21
LID - 10.1007/s00262-008-0466-9 [doi]
AB  - PURPOSE: High-dose IFNalpha2b (HDI) was established as the first effective 
      adjuvant therapy for patients with high-risk resected melanoma more than a decade 
      ago, but its fundamental molecular mechanism of action remains unclear. STAT3 and 
      the mitogen activated protein kinases (MAPKs), especially ERK (extracellular 
      signal-regulating kinase) and MEK (MAPK/ERK kinase), play roles in melanoma 
      progression and host immunity. We have therefore evaluated STAT3 and MEK/ERK MAP 
      kinases in patients with regional lymph node metastasis (stage IIIB) of melanoma 
      in the context of a prospective neoadjuvant trial of HDI (UPCI 00-008). PATIENTS 
      AND METHODS: In the context of this trial, HDI was administered daily for 20 
      doses following diagnostic biopsy, and prior to definitive surgery. 
      Immunohistochemistry for pSTAT3, phospho-MEK1/2, phospho-ERK1/2, and EGFR was 
      performed on paired fixed (nine patients) biopsies. RESULTS: HDI was found to 
      down-regulate pSTAT3 (P = 0.008) and phospho-MEK1/2 (P = 0.008) levels 
      significantly in tumor cells. Phospho-ERK1/2 was down-regulated by HDI in tumor 
      cells (P = 0.015), but not in lymphoid cells. HDI down-regulated EGFR (P = 
      0.013), but pSTAT3 activation appeared not to be associated with EGFR expression 
      and the MEK/ERK MAPK pathway. CONCLUSION: We conclude that HDI regulates MAPK 
      signaling differentially in melanoma tumor cells and host lymphoid cells in vivo. 
      STAT3 activation is independent of the EGFR/MEK/ERK signaling pathway.
FAU - Wang, Wenjun
AU  - Wang W
AD  - Department of Medicine, Division of Hematology/Oncology, University of 
      Pittsburgh, Hillman Cancer Center, Research Pavilion, Suite 1.32, 5117 Centre 
      Avenue, Pittsburgh, PA 15213-2584, USA.
FAU - Edington, Howard D
AU  - Edington HD
FAU - Jukic, Drazen M
AU  - Jukic DM
FAU - Rao, Uma N M
AU  - Rao UN
FAU - Land, Stephanie R
AU  - Land SR
FAU - Kirkwood, John M
AU  - Kirkwood JM
LA  - eng
PT  - Clinical Trial
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20080403
PL  - Germany
TA  - Cancer Immunol Immunother
JT  - Cancer immunology, immunotherapy : CII
JID - 8605732
RN  - 0 (Interferon alpha-2)
RN  - 0 (Interferon-alpha)
RN  - 0 (Recombinant Proteins)
RN  - 0 (STAT3 Transcription Factor)
RN  - 0 (STAT3 protein, human)
RN  - EC 2.7.11.24 (Extracellular Signal-Regulated MAP Kinases)
SB  - IM
MH  - Cell Line, Tumor
MH  - Extracellular Signal-Regulated MAP Kinases/metabolism
MH  - *Gene Expression Regulation, Enzymologic
MH  - *Gene Expression Regulation, Neoplastic
MH  - Humans
MH  - Immunohistochemistry/methods
MH  - Interferon alpha-2
MH  - Interferon-alpha/*metabolism/*therapeutic use
MH  - Lymph Nodes/pathology
MH  - Lymphatic Metastasis
MH  - *MAP Kinase Signaling System
MH  - Melanoma/*metabolism
MH  - Models, Statistical
MH  - Recombinant Proteins
MH  - STAT3 Transcription Factor/*metabolism
MH  - Signal Transduction
PMC - PMC11030104
EDAT- 2008/04/04 09:00
MHDA- 2008/08/21 09:00
PMCR- 2008/04/03
CRDT- 2008/04/04 09:00
PHST- 2007/09/13 00:00 [received]
PHST- 2008/01/28 00:00 [accepted]
PHST- 2008/04/04 09:00 [pubmed]
PHST- 2008/08/21 09:00 [medline]
PHST- 2008/04/04 09:00 [entrez]
PHST- 2008/04/03 00:00 [pmc-release]
AID - 466 [pii]
AID - 10.1007/s00262-008-0466-9 [doi]
PST - ppublish
SO  - Cancer Immunol Immunother. 2008 Sep;57(9):1315-21. doi: 
      10.1007/s00262-008-0466-9. Epub 2008 Apr 3.