HIF-1α is over-expressed in leukemic cells from TP53-disrupted patients and is a promising therapeutic target in chronic lymphocytic leukemia

Abstract

HIF-1a is overexpressed in leukemic cells from TP53-disrupted patients and is a promising therapeutic target in chronic lymphocytic leukemia.

Meloxicam, a Selective COX-2 Inhibitor, Mediates Hypoxia-Inducible Factor- (HIF-) 1α Signaling in Hepatocellular Carcinoma

“…and Expression in a VHL-Dependent Manner. Accumulated evidence has demonstrated that HIF-1α has a dominant role in tumor progression, and HIF-1α-regulation of expression of VEGFA is regarded as the main inducer of angiogenesis [27][28][29]. In the current study, we hypothesized if meloxicam 10 0 10 4 10 3 10 2 10 1 10 0 10 4 10 3 10 2 10 1 10 0 10 4 10 3 10 2 10 1 10 0 10 4 10 3 10 2 10 1 10 0 10 4 10 3 10 2 10 1 10 0 10 4 10 3 10 2 10 1 10 0 10 4 10 3 10 2 10 1 10 0 10 4 10 3 10 2 10 1 10 0 10 4 10 3 10 2 10 1 10 0 Oxidative Medicine and Cellular Longevity could inhibit HIF-1α expression and its target gene VEGFA.…”

Baicalin promotes extracellular matrix synthesis in chondrocytes via the activation of hypoxia‑inducible factor‑1α

“…The HIF-1α pathway generally involves chondrogenesis and cartilage formation of chondrocytes (16). BAY-87-2243 is a potent and selective HIF-1α blocker and inhibitor (26,27), it is suggested that BAY-87-2243 could block of HIF-1α expression mediated IL-17 and CoCl 2 in RAW 264.7 macrophage cells (27). Although it is known that BA has a protective effect on chondrocytes, the effect and mechanism of BA on the HIF-1α pathway in chondrocytes has not yet been elucidated.…”

HIF-1α: a potential treatment target in chronic lymphocytic leukemia

“…In this issue of Haematologica, Griggio et al report that disrupting mutations in the tumor-suppressor gene TP53 are associated with higher HIF-1α levels and activity in patients with chronic lymphocytic leukemia (CLL). 3 They further show that elevated HIF-1α levels are due to an increased transcription as well as a decreased protein degradation of HIF-1α. Evidence for both regulatory mechanisms have already been described in CLL and are summarized in Figure 1.…”

“…In line with this, Griggio et al observed increased expression of HIF-1α in CLL cells upon co-culture with stromal cells to a level that is comparable to hypoxic conditions. 3 They further showed that HIF-1α transcript levels of primary CLL cells positively correlate with CLL cell survival in culture. This is likely related to the observation that HIF-1α critically regulates the interaction of CLL cells with their microenvironment.…”

“…16,17 Pharmacological inhibition of HIF-1α with BAY87-2243 in primary CLL cells induced cell death in vitro, regardless of the TP53 mutational status, with a generally weaker effect under hypoxia or in co-culture with stromal cells. 3 Pre-clinical testing of this drug in the Em-TCL1 adoptive transfer model of CLL resulted in lower numbers of malignant B cells in the BM and among them a higher frequency of apoptotic cells. In all other organs that are affected by CLL, including spleen and blood where the majority of leukemia cells accumulate, HIF-1α inhibition had no effect.…”