Expression and Prognostic Significance of a Panel of Tissue Hypoxia Markers in Head-and-Neck Squamous Cell Carcinomas

Le, Quynh Thu; Kong, Christina S.; Lavori, Phillip W.; O’Byrne, Kenneth J.; Erler, Janine T.; Huang, Xin; Chen, Yujin; Cao, Hongbin; Tibshirani, Robert; Denko, Nick; Giaccia, Amato J.; Koong, Albert C.

doi:10.1016/j.ijrobp.2007.01.071

Cited by 109 publications

(93 citation statements)

References 39 publications

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“…Some of the more promising endogenous markers include carbonic anhydrase IX (CA9), plasminogen activator inhibitor 1 (PAI1, also known as SERPINE), osteopontin and lysyl oxidase. Combinations of markers might prove to be better predictors of clinical outcome than any single marker 153 .…”

Section: Hypoxia Marker Proteinsmentioning

confidence: 99%

Cycling hypoxia and free radicals regulate angiogenesis and radiotherapy response

2008

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Hypoxia and free radicals, such as reactive oxygen and nitrogen species, can alter the function and/or activity of the transcription factor hypoxia-inducible factor 1 (HIF1). Interplay between free radicals, hypoxia and HIF1 activity is complex and can influence the earliest stages of tumour development. The hypoxic environment of tumours is heterogeneous, both spatially and temporally, and can change in response to cytotoxic therapy. Free radicals created by hypoxia, hypoxia-reoxygenation cycling and immune cell infiltration after cytotoxic therapy strongly influence HIF1 activity. HIF1 can then promote endothelial and tumour cell survival. As discussed here, a constant theme emerges: inhibition of HIF1 activity will have therapeutic benefit.Virchow first described the abnormal structure of tumour vessels using contrast agents in human tumours as early as the mid 1800s 1 . A few decades later, Goldman was among the first to suggest that angiogenesis was associated with tumour growth 2 . A number of other investigators in the nineteenth and early twentieth centuries evaluated tumour angiogenesis, using techniques such as microangiography, vascular casting and window chamber models. Warren has reviewed this early work in great detail 3 . Folkman illuminated the crucial role of tumour angiogenesis by hypothesizing that tumour growth was dependent upon angiogenesis and that, if angiogenesis could be inhibited, it could maintain tumour deposits in a quiescent state 4 . These early works set the stage for the concept that tumours require angiogenesis to provide a nutrient supply. Although it is well-established that angiogenesis occurs in nearly all human solid tumours, it does not occur in an efficient manner, leading to spatial and temporal inadequacies in delivery of oxygen and other nutrients. These inefficiencies in nutrient delivery lead to a brutal cycle of unsatisfied demand by the tumour, which drives continued aberrant angiogenesis.The transcription factor hypoxia-inducible factor 1 (HIF1) plays an important part in tumour progression by upregulating genes that control angiogenesis, meta-stasis and resistance to oxidative stress. It also controls the switch to anaerobic metabolism, which can maintain cell NIH-PA Author ManuscriptNIH-PA Author Manuscript NIH-PA Author Manuscript viability under hypoxic conditions. Further, HIF1 activity can promote treatment resistance by promoting endothelial and tumour cell survival after cytotoxic therapy. The mechanisms that control HIF1 activity are complex and are influenced by microenvironmental factors involving hypoxia, oxidative and nitrosative stress.In this Review we will discuss four important and interrelated aspects of tumour hypoxia. First, we will define the hypoxic response, discussing its relevance in influencing tumour cell survival, behaviour and angiogenesis. We will examine the physiological factors that contribute to hypoxia, emphasizing a perspective based on spatial and temporal dysfunction of tumour microcirculation. The question of whethe...

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Section: Hypoxia Marker Proteinsmentioning

confidence: 99%

Cycling hypoxia and free radicals regulate angiogenesis and radiotherapy response

2008

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“…Endogenous hypoxia markers have the potential to indicate therapeutically relevant levels of hypoxia within tumors and predict a benefit from specific hypoxia-directed treatment (Vordermark and Brown, 2003). Assessing hypoxia using endogenous molecular markers would be a cost effective approach that could be used by oncologists worldwide (Le et al, 2007). Endogenous molecular markers need not additional invasive procedure beyond that of a tumor biopsy at diagnosis (Davda and Bezabeh, 2006).…”

Section: Discussionmentioning

confidence: 99%

Expression of Endogenous Hypoxia Markers in Vulvar Squamous Cell Carcinoma

Li²,

Li³

et al. 2012

Asian Pacific Journal of Cancer Prevention

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Objective: To investigate the expression of endogenous hypoxia-related markers identified as being involved in vulvar squamous cell carcinoma (VSCC). Methods: We performed immunohistochemical staining of hypoxia-inducible factor-1α (HIF-1α), glucose transporter-1 (GLUT-1), carbonic anhydrase 9 (CA-9) and vascular endothelial growth factor (VEGF), on tissue sections of 25 VSCC patients, 10 vulvar intraepithelial neoplasia (VIN) patients and 12 healthy controls. Results: HIF-1α expression was found in all sections, with no significant difference between controls, VIN and VSCC sections (all P<0.05). Glut-1 expression was found in 25% of control, 90% of VIN and 100% of VSCC sections. A significant difference between control and VIN or VSCC was observed (all P<0.05), while no difference was found between VIN and VSCC sections (P>0.05). CA-9 expression was negative in control sections, but it was found in 30% of VIN sections and 52% of VSCC sections with strong staining. Similarly, CA-9 expression also showed obvious differences between controls and VIN or VSCC sections (all P<0.05). However, there was no significant difference between VIN and VSCC (P>0.05). There were only 25% of control sections with weak VEGF expression, while strong staining was found in about 60% of VIN sections and 25% of VSCC sections (all P<0.05). In addition, a difference was also found between VIN and VSCC sections (P<0.05). Conclusion: Expression of endogenous hypoxia markers (HIF-1α, GLUT-1, CA-9 and VEGF) might be involved in the malignant progression of VSCC.

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“…Recently, lysyl oxidase (LOX) has been identified as an important regulator of hypoxia induced tumor progression via an HIF-1α-dependent mechanism in a range of cancers, such as head and neck carcinomas (Le et al, 2007), colon (Tammali et al, 2011), breast (Wong et al, 2012) and prostate (Stewart et al, 2009). The primary function of LOX is the covalent cross-linking of collagens or elastin in extracellular matrix (ECM).…”

Section: Introductionmentioning

confidence: 99%

Expression and Significance of Hypoxia Inducible Factor-1α and Lysyl Oxidase in Non-small Cell Lung Cancer

Wei

Jiang²,

Chen³

et al. 2013

Asian Pacific Journal of Cancer Prevention

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Expression and Prognostic Significance of a Panel of Tissue Hypoxia Markers in Head-and-Neck Squamous Cell Carcinomas

Cited by 109 publications

References 39 publications

Cycling hypoxia and free radicals regulate angiogenesis and radiotherapy response

Cycling hypoxia and free radicals regulate angiogenesis and radiotherapy response

Expression of Endogenous Hypoxia Markers in Vulvar Squamous Cell Carcinoma

Expression and Significance of Hypoxia Inducible Factor-1α and Lysyl Oxidase in Non-small Cell Lung Cancer

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