<i>In vivo</i>, abemaciclib, when administered in an adjuvant setting for the second week after fractionated IR, further inhibited vasculogenesis and tumor regrowth, with sustained inhibition of RB/E2F activity, mTOR pathway, and HIF-1 expression.
19/30 (63%) of BRCA1 tumors showed perinecrotic (hypoxia induced) and 8/30 (27%) a diffuse HIF-1alpha overexpression pattern, the latter more likely related to genetic alterations in oncogenes and tumor suppressor genes.
Tumors derived from HIF-1alpha-overexpressing cells revealed an increase in apoptosis when compared to control tumors, in spite of a marked increase in vascular density.
Tumor tissues from mice treated with the Pmp53 plasmid showed increased expression of p21 and decreased expression of hypoxia-inducible factor 1α proteins, with an increased apoptotic effect.
Tumor tissue was examined histologically for presence of the KRAS mutations and for expression of hypoxia-inducible factor-1 (HIF-1) and minichromosome maintenance protein 2 (mcm2).
Tumors that hemorrhaged had higher IHC staining for CD34 and CD105. mRNA expression analysis revealed tumor hemorrhage was associated with increased expression of HIF1α and MDK, and decreased expression of F3.
Tumors with intact HIF-1α subjected to HD-SFRT immediately following hypoxia exposure were less responsive to treatment than tumors without functional HIF-1α, and tumors irradiated under air breathing conditions regardless of HIF-1α status.
TumorHIF-1α-positivity correlated to increased breast cancer mortality, and negative prognostic factors including low age at diagnosis and ER-negativity.
HIF-1 controls cellular and systemic responses to oxygen availability and coordinates up-regulation of genes involved in many pathways concerned with tumour growth and metabolism including angiogenesis, glucose and energy metabolism, cellular proliferation, differentiation and viability, apoptosis, pH regulation and matrix metabolism.
HIF-1alpha mRNA expression is differentially upregulated in esophageal squamous cell carcinoma compared to adenocarcinomas, but does not predicttumor regression or prognosis.
HIF-1 plays a central role in malignant progression by inducing the expression of various genes, whose functions are strongly associated with malignant alteration of the entire tumor.
HIF-1alpha action may also modulate mitochondrial function and oxygen consumption by inactivating the pyruvate dehydrogenase complex in some tumor types, or by modulating cytochrome c oxidase subunit 4 expression to increase oxidative phosphorylation in other cancer cell lines.
HIF-1alpha expression correlated with high tumour grade (P=0.009), negative oestrogen receptor (ER) status (P=0.001) and the absence of lymph node metastasis (P=0.028).