PMID- 20664817
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20240502
IS  - 1424-8247 (Print)
IS  - 1424-8247 (Electronic)
IS  - 1424-8247 (Linking)
VI  - 3
IP  - 4
DP  - 2010 Mar 30
TI  - Antiproliferative Properties of Type I and Type II Interferon.
PG  - 994-1015
AB  - The clinical possibilities of interferon (IFN) became apparent with early studies 
      demonstrating that it was capable of inhibiting tumor cells in culture and in 
      vivo using animal models. IFN gained the distinction of being the first 
      recombinant cytokine to be licensed in the USA for the treatment of a malignancy 
      in 1986, with the approval of IFN-alpha2a (Hoffman-La Roche) and IFN-alpha2b 
      (Schering-Plough) for the treatment of Hairy Cell Leukemia. In addition to this 
      application, other approved antitumor applications for IFN-alpha2a are AIDS-related 
      Kaposi's Sarcoma and Chronic Myelogenous Leukemia (CML) and other approved 
      antitumor applications for IFN-alpha2b are Malignant Melanoma, Follicular Lymphoma, 
      and AIDS-related Kapoisi's Sarcoma. In the ensuing years, a considerable number 
      of studies have been conducted to establish the mechanisms of the induction and 
      action of IFN's anti-tumor activity. These include identifying the role of 
      Interferon Regulatory Factor 9 (IRF9) as a key factor in eliciting the 
      antiproliferative effects of IFN-alpha as well as identifying genes induced by IFN 
      that are involved in recognition of tumor cells. Recent studies also show that 
      IFN-activated human monocytes can be used to achieve >95% eradication of select 
      tumor cells. The signaling pathways by which IFN induces apoptosis can vary. IFN 
      treatment induces the tumor suppressor gene p53, which plays a role in apoptosis 
      for some tumors, but it is not essential for the apoptotic response. IFN-alpha also 
      activates phosphatidylinositol 3-kinase (PI3K), which is associated with cell 
      survival. Downstream of PI3K is the mammalian target of rapamycin (mTOR) which, 
      in conjunction with PI3K, may act in signaling induced by growth factors after 
      IFN treatment. This paper will explore the mechanisms by which IFN acts to elicit 
      its antiproliferative effects and more closely examine the clinical applications 
      for the anti-tumor potential of IFN.
FAU - Bekisz, Joseph
AU  - Bekisz J
AD  - National Institute of Allergy and Infectious Diseases, National Institutes of 
      Health, Bethesda, MD 20892, USA.
FAU - Baron, Samuel
AU  - Baron S
FAU - Balinsky, Corey
AU  - Balinsky C
FAU - Morrow, Angel
AU  - Morrow A
FAU - Zoon, Kathryn C
AU  - Zoon KC
LA  - eng
GR  - Z99 AI999999/ImNIH/Intramural NIH HHS/United States
PT  - Journal Article
PL  - Switzerland
TA  - Pharmaceuticals (Basel)
JT  - Pharmaceuticals (Basel, Switzerland)
JID - 101238453
PMC - PMC2907165
MID - NIHMS199733
EDAT- 2010/07/29 06:00
MHDA- 2010/07/29 06:01
PMCR- 2010/04/01
CRDT- 2010/07/29 06:00
PHST- 2010/07/29 06:00 [entrez]
PHST- 2010/07/29 06:00 [pubmed]
PHST- 2010/07/29 06:01 [medline]
PHST- 2010/04/01 00:00 [pmc-release]
AID - pharmaceuticals-03-00994 [pii]
AID - 10.3390/ph3040994 [doi]
PST - ppublish
SO  - Pharmaceuticals (Basel). 2010 Mar 30;3(4):994-1015. doi: 10.3390/ph3040994.