The prognostic value of pimonidazole and tumour pO2 in human cervix carcinomas after radiation therapy: A prospective international multi-center study

Nordsmark, Marianne; Loncaster, Juliette A; Aquino‐Parsons, Christina; Chou, Shu-Chuan; Gebski, Val; West, Catharine M L; Lindegaard, Jacob Christian; Havsteen, Hanne; Davidson, Susan E; Hunter, Robin D; Raleigh, James A.; Overgaard, Jens

doi:10.1016/j.radonc.2006.07.010

Cited by 98 publications

(63 citation statements)

References 41 publications

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“…In a large study of 127 patients with cervix cancer, pimonidazole binding was not predictive of patient outcome 42 . In a HNSCC study by Kaanders, HNSCC patients with larger regions of pimonidazole binding had a better 2-year local control rate after treatment with ARCON (Accelerated Radiation Therapy with Oxygen and Nicotinamide) than patients with hypoxic tumors treated with standard therapy 35 .…”

Section: Discussionmentioning

confidence: 95%

Patterns and Levels of Hypoxia in Head and Neck Squamous Cell Carcinomas and Their Relationship to Patient Outcome

Evans¹,

Du²,

Chalian³

et al. 2007

International Journal of Radiation Oncology*Biology*Physics

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Purpose-EF5, a 2-nitroimidazole hypoxia marker, was used to study the presence, levels and prognostic significance of hypoxia in primary head and neck squamous cell tumors.Methods and Materials-22 patients with newly diagnosed squamous cell carcinoma of the oral cavity, oropharynx or larynx with at least 2 years of clinical follow-up were included in this study. Quantitative analysis of EF5 immunofluorescence was carried out and these data were compared to patient outcome.Results-EF5 immunostaining demonstrated substantial inter-tumoral hypoxic heterogeneity. The majority of cells in all tumors were well oxygenated. Three patterns of EF5 binding in cells were identified using criteria of the cellular region that was stained (peripheral or central) and the relationship of binding to necrosis. We tested the association between EF5 binding levels with eventfree and overall survival, irrespective of the pattern of cellular binding or treatment regime. Patients with tumors containing EF5 binding regions corresponding to severe hypoxia (≤0.1% oxygen) had a shorter event-free survival time than patients with pO 2 values >0.1% (p=0.032). Nodal status was also predictive for outcome.Conclusions-These data illustrate the potential utility of EF5 binding based on quantitative immunohistochemistry of tissue pO 2 and provide support for development of noninvasive hypoxia PET studies with 18 F-EF5.

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Section: Discussionmentioning

confidence: 95%

Patterns and Levels of Hypoxia in Head and Neck Squamous Cell Carcinomas and Their Relationship to Patient Outcome

Evans¹,

Du²,

Chalian³

et al. 2007

International Journal of Radiation Oncology*Biology*Physics

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“…[41][42][43][44][45][46][47][48] Early reports suggested that semiquantitative scoring of CAIX labeling was correlated with direct pO 2 measurements in solid tumors, but this has not been confirmed by other groups. [32][33][34][35][36][49][50][51][52][53] When we examined a series of single punch biopsies obtained from Figure 5 The 95% CI of the averaged per patient % carbonic anhydrase IX (CAIX) value, in full sections (a) and in tissue microarray (TMA) simulations (b and c). Solid black circles indicate averaged % CAIX staining of full sections, crosses-simulated microarray cores, dashed line-95% confidence limits, horizontal reference lines are drawn through 5 and 10% CAIX values.…”

Section: Discussionmentioning

confidence: 99%

Effect of distributional heterogeneity on the analysis of tumor hypoxia based on carbonic anhydrase IX

Iakovlev

Pintilie

Morrison

et al. 2007

Laboratory Investigation

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“…[32][33][34][35][36] The resulting hypoxic complexes are immunologically recognized by the Hypoxyprobe-1-mAB1 monoclonal antibody. White adipose tissue derived from lean male C57BL/6J mice was essentially devoid of Hypoxyprobe immunoreactivity (Figure 5a).…”

Section: White Adipose Tissue Hypoxia and Inflammationmentioning

confidence: 99%

Obesity in C57BL/6J mice is characterized by adipose tissue hypoxia and cytotoxic T-cell infiltration

et al. 2007

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Background: Obesity is currently viewed as a state of chronic low-grade inflammation in which there is a pro-inflammatory alteration in the serum adipocytokine profile as well as an infiltration of white adipose tissue by activated macrophages. The etiology of this inflammation, however, is poorly understood. Methods: Hypothesizing that local hypoxia within expanding white adipose tissue depots may contribute to obesity-related inflammation, we compared body composition, serum inflammatory marker concentrations and the expression of several hypoxia-regulated genes in white adipose tissue derived from lean, dietary-induced obese (DIO) and ob/ob male C57BL/6J mice. We also examined white adipose tissue for the presence of hypoxia using both a pimonidazole-based antibody system and a fiberoptic sensor for real-time pO 2 quantification in vivo. Finally, using cell-specific leukocyte antibodies, we performed immunohistochemistry and flow cytometric analyses to further characterize the cellular nature of adipose inflammation. Results: We determined that obesity in male C57BL/6J mice is associated with increased expression of HIF (hypoxia-inducible factor) isoforms and GLUT-1, and that white adipose tissue hypoxia was present in the obese mice. Immunohistochemistry revealed hypoxic areas to colocalize predominantly with F4/80 þ macrophages. Interestingly, CD3 þ T cells were present in large numbers within the adipose of both DIO and ob/ob obese mice, and flow cytometry revealed their adipose to possess significantly more CD8 þ T cells than their lean cohort. Conclusions: White adipose hypoxia and cytotoxic T-cell invasion are features of obesity in C57BL/6J mice and are potential contributors to their local and generalized inflammatory state.

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The prognostic value of pimonidazole and tumour pO2 in human cervix carcinomas after radiation therapy: A prospective international multi-center study

Cited by 98 publications

References 41 publications

Patterns and Levels of Hypoxia in Head and Neck Squamous Cell Carcinomas and Their Relationship to Patient Outcome

Patterns and Levels of Hypoxia in Head and Neck Squamous Cell Carcinomas and Their Relationship to Patient Outcome

Effect of distributional heterogeneity on the analysis of tumor hypoxia based on carbonic anhydrase IX

Obesity in C57BL/6J mice is characterized by adipose tissue hypoxia and cytotoxic T-cell infiltration

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