Measurements of hypoxia using pimonidazole and polarographic oxygen-sensitive electrodes in human cervix carcinomas

Nordsmark, Marianne; Loncaster, Juliette A; Aquino‐Parsons, Christina; Chou, Shu-Chuan; Ladekarl, Morten; Havsteen, Hanne; Lindegaard, J.C.; Davidson, Susan E; Varia, Mahesh A.; West, Catharine M L; Hunter, Robin D; Overgaard, Jens; Raleigh, James A.

doi:10.1016/s0167-8140(03)00010-0

Cited by 140 publications

(93 citation statements)

References 26 publications

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“…Previous in vitro investigations [6,50,51] have focused on the effects of low O 2 typical of diseases in vivo [52][53][54]. However, cells treated under these conditions were often compared to cells cultured under air, incorrectly inferring that this oxygenation was representative of "healthy" tissues, and studies have often used short-term decreases in O 2 concentration [4,5], rather than longer periods associated with disease.…”

Section: Discussionmentioning

confidence: 99%

Altered cellular redox homeostasis and redox responses under standard oxygen cell culture conditions versus physioxia

Ferguson

Smerdon

Harries

et al. 2018

Free Radical Biology and Medicine

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In vivo, mammalian cells reside in an environment of 0.5-10% O 2 (depending on the tissue location within the body), whilst standard in vitro cell culture is carried out under room air. Little is known about the effects of this hyperoxic environment on treatment-induced oxidative stress, relative to a physiological oxygen environment. In the present study we investigated the effects of long-term culture under hyperoxia (air) on photodynamic treatment. Upon photodynamic irradiation, cells which had been cultured long-term under hyperoxia generated higher concentrations of mitochondrial reactive oxygen species, compared with cells in a physioxic (2% O 2 ) environment. However, there was no significant difference in viability between hyperoxic and physioxic cells. The expression of genes encoding key redox homeostasis proteins and the activity of key antioxidant enzymes was significantly higher after the long-term culture of hyperoxic cells compared with physioxic cells. The induction of antioxidant genes and increased antioxidant enzyme activity appear to contribute to the development of a phenotype that is resistant to oxidative stress-induced cellular damage and death when using standard cell culture conditions. The results from experiments using selective inhibitors suggested that the thioredoxin antioxidant system contributes to this phenotype. To avoid artefactual results, in vitro cellular responses should be studied in mammalian cells that have been cultured under physioxia. This investigation provides new insights into the effects of physioxic cell culture on a model of a clinically relevant photodynamic treatment and the associated cellular pathways.

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Section: Discussionmentioning

confidence: 99%

Altered cellular redox homeostasis and redox responses under standard oxygen cell culture conditions versus physioxia

Ferguson

Smerdon

Harries

et al. 2018

Free Radical Biology and Medicine

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“…Oxygen electrodes have proved useful in a number of tumour types (Nordsmark et al, 2003), but have limited use in gastric cancer because of poor accessibility.…”

Section: Discussionmentioning

confidence: 99%

“…Other approaches such as the immunohistochemical expression of hypoxia-specific markers such as pimonidazole (Nordsmark et al, 2003) and noninvasive imaging (Koch and Evans, 2003) are being developed and could be carried out in patients with gastric cancer. Few studies have assessed both HIF-1a and HIF-2a in relation to patient outcome.…”

Section: Discussionmentioning

confidence: 99%

Hypoxia-associated markers in gastric carcinogenesis and HIF-2α in gastric and gastro-oesophageal cancer prognosis

et al. 2008

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The study investigated hypoxia-associated markers (HIF-2a, Epo, Epo-R, Glut-1 and VEGF) along with Ki-67 in a gastric carcinogenesis model, and the prognostic significance of hypoxia-inducible factor (HIF)-2a in surgically treated gastro-oesophageal cancer. Protein expression was examined using immunohistochemistry on formalin-fixed, paraffin-embedded biopsies of normal mucosa (n ¼ 20), Helicobacter pylori-associated gastritis (n ¼ 24), intestinal metaplasia (n ¼ 24), dysplasia (n ¼ 12) and intestinal (n ¼ 19) and diffuse (n ¼ 21) adenocarcinoma. Relationships between HIF-2a expression and prognosis were assessed in resection specimens from 177 patients with gastric and gastro-oesophageal junction adenocarcinoma. Expression of all markers increased with progression along the gastric carcinogenesis sequence (P ¼ 0.0001). Hypoxia-inducible factor-2a was expressed in 63% of 177 resection specimens and at a high level in 44%. The median overall survival in patients with HIF-2a-expressing tumours was 22 (95% CI 18À26) months, whereas those with HIF-2a-negative tumours had a median survival of 37 (95% CI 29À44) months (P ¼ 0.015). Hypoxia-inducible factor-2a had no independent prognostic significance in multivariate analysis. In view of the lack of independent prognostic significance, HIF-2a has no role as a routine prognostic indicator. However, the high expression of HIF-2a suggests that it may be of value as a potential therapeutic target.

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“…Clinical studies have shown a strong correlation between low pretreatment tumour pO 2 and poor tumour control and overall survival in patients with head and neck squamous cell carcinoma (Brizel et al, 1999;Nordsmark et al, 2003).…”

mentioning

confidence: 99%

Expression of carbonic anhydrase 9, a potential intrinsic marker of hypoxia, is associated with poor prognosis in oesophageal squamous cell carcinoma

et al. 2008

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Carbonic anhydrase 9 (CA9) is a protein to be upregulated under exposure to hypoxic conditions. Hypoxic conditions are known to be associated with resistance to chemotherapy and radiotherapy, and with poor cancer prognosis. We examined CA9 expression in surgical specimens from oesophageal squamous cell carcinoma (ESCC) patients (n ¼ 127) using immunohistochemistry and real-time RT -PCR. We also examined CA9 expression and cell proliferation in ESCC cell lines (TE-2, TE-8 and TE-15) and an immortalised human oesophageal cell line (CHEK-1) using real-time RT -PCR, Western blotting, ELISA and MTT assay. Immunohistochemistry, high expression of CA9 was found in 63 of the 127 primary tumour specimens and was correlated with poor outcome (P ¼ 0.0003) and more aggressive/less favourable clinicopathological parameters (tumour size (P ¼ 0.0235), tumour depth (Po0.0001), regional lymph node metastasis (P ¼ 0.0031), distant lymph node metastasis (P ¼ 0.0077), stage (Po0.0001) and blood vessel invasion (P ¼ 0.006)). In vitro, CA9 expression in cultured cells and culture medium was also induced by hypoxia (Po0.01). CA9 is correlated with poor prognosis and malignant phenotype in patients with ESCC, and was upregulated by hypoxia. It is suggested that control of CA9 expression might improve the effectiveness of chemotherapy and radiotherapy in ESCC.

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Measurements of hypoxia using pimonidazole and polarographic oxygen-sensitive electrodes in human cervix carcinomas

Cited by 140 publications

References 26 publications

Altered cellular redox homeostasis and redox responses under standard oxygen cell culture conditions versus physioxia

Altered cellular redox homeostasis and redox responses under standard oxygen cell culture conditions versus physioxia

Hypoxia-associated markers in gastric carcinogenesis and HIF-2α in gastric and gastro-oesophageal cancer prognosis

Expression of carbonic anhydrase 9, a potential intrinsic marker of hypoxia, is associated with poor prognosis in oesophageal squamous cell carcinoma

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