Detection and Characterization of Tumor Hypoxia Using pO₂ Histography

Abstract

Data from 125 studies describing the pretreatment oxygenation status as measured in the clinical setting using the computerized Eppendorf pO2 histography system have been compiled in this article. Tumor oxygenation is heterogeneous and severely compromised as compared to normal tissue. Hypoxia results from inadequate perfusion and diffusion within tumors and from a reduced O2 transport capacity in anemic patients. The development of tumor hypoxia is independent of a series of relevant tumor characteristics (e.g., clinical size, stage, histology, and grade) and various patient demographics. Overall median pO2 in cancers of the uterine cervix, head and neck, and breast is 10 mm Hg with the overall hypoxic fraction (pO2 <or= 2.5 mm Hg) being approx. 25%. Metastatic lesions do not substantially deviate from the oxygenation status of (their) primary tumors. Whereas normal tissue oxygenation is independent of the hemoglobin level over the range of 8-15 g/dL, hypoxia is more pronounced in anemic patients and above this range in some cancers. Identification of tumor hypoxia may allow an assessment of a tumor's potential to develop an aggressive phenotype or acquired treatment resistance, both of which lead to poor prognosis. Detection of hypoxia in the clinical setting may therefore be helpful in selecting high-risk patients for individual and/or more intensive treatment schedules.

Cycling hypoxia and free radicals regulate angiogenesis and radiotherapy response

“…In practice, the cathode is embedded into a needle that can be introduced into tissues and the anode is placed on the body surface. This technique has been used extensively in preclinical and clinical studies; the presence of hypoxia is an independent predictive factor for poor prognosis in many different tumour types 154 . Optical probes have also been developed: these are implanted into tissues and contain a fluorochrome that emits fluorescent light with a certain decay rate when illuminated.…”

Variation in dermcidin expression in a range of primary human tumours and in hypoxic/oxidatively stressed human cell lines

“…To simulate the hypoxic conditions within a solid tumour in vivo, cells were incubated for 48 h within a humidified hypoxia incubator at 0.2% oxygen (pO 2 B1.5 mm Hg) using a PROOX 110 oxygen controller (BioSpherix Ltd, NY, USA) (Brown and Wilson, 2004;Vaupel et al, 2007). This level of hypoxia resulted in a mean of 62.7% cell death after 48 h. RNA was then isolated and assessed for DCD expression.…”

“…Prostate cancer represents the first tumour in which DCD/HCAP was described whereas the upper gastrointestinal cancer types are associated significantly with the development of cancer cachexia (DeWys et al, 1980). Finally, to determine if DCD expression is upregulated in response to stressors found in the cancer microenvironment (Brown and Revised 7 May 2008;accepted 12 May 2008;published online 1 July 2008Wilson, 2004Valko et al, 2006;Vaupel et al, 2007), we have analysed changes in the expression of DCD mRNA in prostate and pancreatic cell lines in vitro in response to hypoxia or oxidative stress.…”

Hypoxia-inducible factor-1: Physiological and Pathological Response to Hypoxia of Cell

“…Örne-ğin, VHL hastalıklarında belirtildiği gibi VHL fonksiyon kaybı, temelde HIF-1alfa protein miktarının artışına sebep olur. 75 İn-san kanserlerinin pek çoğunda fonksiyon kaybı tespit edilen p53'ün, HIF-1alfa'nın ve HIF-2alfa'nın hedef gen transkripsiyonlarının artmasına sebep olduğu belirtilmektedir. 76,77 Diğer yandan, Rous sarkom (v-Src) retroviral onkogeninin transformasyon potansiyelinin kısmen HIF-1 indüklemesine bağlı olduğu ve v-Src'nin fonksiyon kazanmasının da HIF-1alfa ekspresyonunu artırdığına dair deliller bulunmaktadır 78 .…”