The current STATe of biomarkers to predict the response to anti-angiogenic therapies

Department of Radiation Oncology, Stanford University School of Medicine, Stanford, California 94305-5151, USA.
Cancer biology & therapy (Impact Factor: 3.07). 01/2009; 7(12):2004-6. DOI: 10.4161/cbt.7.12.7191
Source: PubMed
Download full-text


Available from: Phuoc T Tran
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: The cyclic adenosine monophosphate-inducible basic helix-loop-helix (bHLH) domain containing class-B2 transcriptional factor BHLHB2 is differentially expressed in a number of human malignancies. In the present study, the expression, regulation, functions and prognostic impact of BHLHB2 in pancreatic cancer were investigated. Expression analyses were carried out in tissues of the normal pancreas (n=10) and pancreatic ductal adenocarcinoma (n=77) as well as in eight pancreatic cancer cell lines using quantitative RT-PCR, semiquantitative immunohistochemistry, and immunoblot analyses. In vitro functional experiments were conducted using siRNA transfection, hypoxia, serum starvation, apoptosis induction with gemcitabine and actinomycin-D, and invasion assays. Survival analysis was performed using the Kaplan-Meier method. Prognostic factors were determined in a multivariable analysis using a Cox proportional hazards model. BHLHB2 mRNA and protein expressions were strongly induced by hypoxia and by serum starvation in pancreatic cancer cell lines. BHLHB2 silencing with RNAi had no significant effects on growth and invasion but increased apoptosis resistance against gemcitabine by reducing caspace-3 cleavage. In BHLHB2 silenced cells the ED50 of gemcitabine increased from 13.95 ± 1.353 to 38.70 ± 5.262 nM (p<0.05). Ex vivo, the weak/absent nuclear staining in normal pancreatic ducts and acinar cells was replaced by moderate to strong nuclear/cytoplasmic staining in PanIN lesions and pancreatic cancer cells. Patients with weak/absent nuclear BHLHB2 staining had significantly worse median survival compared to those with strong staining (13 months vs. 27 months, p=0.03). In a multivariable analysis, BHLHB2 staining was an independent prognostic factor (Hazard-Ratio=2.348, 95% CI=1.250-4.411, p=0.008). Hypoxia-inducible BHLHB2 expression is a novel independent prognostic marker in pancreatic cancer patients and indicates increased chemosensitivity towards gemcitabine.
    Full-text · Article · Oct 2010 · Biochemical and Biophysical Research Communications
  • [Show abstract] [Hide abstract]
    ABSTRACT: Glioblastoma multiforme (GBM) is the most common and aggressive primary brain tumor. Signal transducers and activators of transcription 3 (STAT3) is a transcription factor that translocates to the nucleus to modulate the expression of a variety of genes associated with cell survival, differentiation, proliferation, angiogenesis, and immune function. Several cancers induce constitutive STAT3 activation. Most studies have reported that STAT3 inhibition has antineoplastic activity; however, emerging evidence suggests that the role of STAT3 activity in GBM may be more nuanced than initially appreciated. The authors review the roles of STAT3 in GBM and discuss potential strategies for targeting STAT3.
    No preview · Article · Jul 2012 · Neurosurgery clinics of North America