HypOxygen's Blog - Latest News from HypOxygen

Automated Hypoxia Workstation for Proton Irradiation Research

Don Whitley Monthly Report
July 2024

Traditional radiation therapy comes at a cost of significant side effects, damaging healthy tissues surrounding the tumour. This collateral damage can lead to debilitating consequences for patients undergoing treatment, especially in young children.
Recognising the limitations of conventional treatments, NHS England funded by the Department of Health completed a £250,000,000 investment into the development of two high-energy proton beam therapy centres. These centres represent a paradigm shift in cancer research and treatment in the UK, offering more precise and targeted treatments for cancer patients whilst reducing damage to surrounding tissues.

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Neph-er forget the importance of kidney research

Date: April 19, 2024
By: DWS microbiologist Kirsty McTear
Click here to view the original article at DSWScientific.com

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Among the causes of CKD, acute kidney injury (AKI), which is characterised by a sudden decline in renal function, is an area of ongoing research for scientists [2]. AKI itself can be caused by renal ischemia-reperfusion (IR) injury, by which the kidneys have been exposed to a period of hypoxia and then reintroduced to normal oxygen levels via blood circulation, which causes aggravation [2].  More specifically, the production of reactive oxygen species (ROS) in the kidney is exacerbated resulting in oxidative stress [2]. Usually, the transcription factor, nuclear factor erythroid factor 2-related factor 2 (Nrf2), binds to kelch-like epichlorohydrin-associated protein 1 (Keap1) in the cytoplasm, where it is then tagged for degradation by ubiquitin, but under oxidative stress this interaction is prevented [2]. Instead, Nrf2 translocates into the nucleus where it initiates activation of antioxidants, making this process an ideal target for therapeutic treatment of kidney damage [2].

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Bespoke Solutions: The Whitley GMP Hypoxystation

HypDNA

Whitley GMP Hypoxystationsare specifically designed to be used as clean-air isolators in processes following Good Manufacturing Practice (GMP). This type of workstation provides Grade A air cleanliness (EU GMP) and combines sterile hypoxic unidirectional airflow, positive operating pressure, and physical isolation to provide highly effective product protection. Due to being a completely closed, re-circulating, isolator system, this workstation can be housed in a Grade D cleanroom during GMP compliant use.

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Travel Grant Awardees

 Serina Cheung BiographyHYPTravelAwardRibbon 01

Serina Cheung is currently a second year MSc student in Dr. Marianne Koritzinsky’s lab. She is investigating the role of p38 mitogen-activation protein kinase in promoting the survival of castration-resistant prostate cancer under hypoxia. She will be presenting this work at the Keystone Symposia Tumor Metabolism conference in Banff, Alberta. 

AbstractIdentifying mechanisms that determine sensitivity to p38 MAPK inhibition in castration-resistant prostate cancer

Androgen receptor (AR) signaling is the major driver of castration-resistant prostate cancer (CRPC). Tumor hypoxia increases AR signaling and is associated with treatment resistance. p38 MAP kinase is involved in AR signaling by activating heat shock protein 27, a chaperone for AR translocation. Additionally, the activation of p38 has been found to be an early response to hypoxia. However, the role of p38 in AR signaling under hypoxia in CRPC has not been explored. In this study, we evaluated the role of p38 on AR signaling under hypoxia in CRPC cells. Our results demonstrate that p38 activation is an early response to hypoxia. Hypoxia increased ligand-dependent AR binding to androgen-responsive element and expression of AR target genes. Pharmacological p38 inhibition decreased the hypoxia-induced increase in AR activity. Additionally, pharmacological inhibition and siRNA knockdown of p38 decreased cell proliferation and survival in prostate cancer cells dependent on AR signaling for survival. These results suggest further investigation of p38 inhibition as a therapeutic strategy to disrupt AR signaling in CPRC.

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Hypoxia and the Hallmarks of Cancer: Metabolic Reprogramming

Hanahan and Weinberg’s seminal papers on the Hallmarks of Cancer describe how cancer cells accommodate the frenzied growth characteristic of tumors. Low oxygen is eminently characteristic of tumors, and in this hypoxic environment, metabolism is reprogrammed to satisfy energetic and synthetic needs of the cells.

Read more: Hypoxia and the Hallmarks of Cancer: Metabolic Reprogramming