20 research outputs found
The Tumor-Immune Microenvironment and Response to Radiation Therapy
Chemotherapy and radiation therapy (RT) are standard therapeutic modalities for patients with cancer, including breast cancer. Historic studies examining tissue and cellular responses to RT have predominantly focused on damage caused to proliferating malignant cells leading to their death. However, there is increasing evidence that RT also leads to significant alterations in the tumor microenvironment, particularly with respect to effects on immune cells infiltrating tumors. This review focuses on tumor-associated immune cell responses following RT and discusses how immune responses may be modified to enhance durability and efficacy of RT
Calcineurin Activates Cytoglobin Transcription in Hypoxic Myocytes*
Cardiac hypertrophy develops in response to a variety of cardiovascular
stresses and results in activation of numerous signaling cascades and
proteins. In the present study, we demonstrate that cytoglobin is a
stress-responsive hemoprotein in the hypoxia-induced hypertrophic myocardium
and it is transcriptionally regulated by calcineurin-dependent transcription
factors. The cytoglobin transcript level is abundantly expressed in the adult
heart and in response to hypoxia cytoglobin expression is markedly
up-regulated within the hypoxia-induced hypertrophic heart. To define the
molecular mechanism resulting in the induction of cytoglobin, we undertook a
transcriptional analysis of the 5β² upstream regulatory region of the
cytoglobin gene. Evolutionarily conserved binding elements for transcription
factors HIF-1, AP-1, and NFAT are located within the upstream region of the
cytoglobin gene. Transcriptional assays demonstrated that calcineurin activity
modulates cytoglobin transcription. Increased calcineurin activity enhances
the ability of NFAT and AP-1 to bind to the putative cytoglobin promoter,
especially under hypoxic conditions. In addition, inhibition of calcineurin,
NFAT, and/or AP-1 activities decreases endogenous cytoglobin transcript and
protein levels. Thus, the regulation of cytoglobin transcription by
calcineurin-dependent transcription factors suggests that cytoglobin may have
a functional role in calcium-dependent events accompanying cardiac
remodeling