Evaluation of Hypoxia Inducible Factor-1α and Glucose Transporter-1 Expression in Non Melanoma Skin Cancer: An Immunohistochemical Study

Seleit, Iman; Bakry, Ola Ahmed; Al-Sharaky, Dalia Rifaat; Ragab, Rania Abdel Aziz; Al-Shiemy, Shimaa Ahmed

doi:10.7860/jcdr/2017/25077.10022

Cited by 22 publications

(32 citation statements)

References 48 publications

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“…Little attention has been given to the role of HIF-1a in cutaneous SCC. The evaluation of HIF-1a expression at different stages of SCC genesis in human skin biopsy samples indicated the continuous up-regulation of HIF-1a (Figure 5eeg), which is consistent with previous reports of the overexpression of HIF-1a in cutaneous SCC (An et al, 2014;Elson et al, 2000;Seleit et al, 2017). Scortegagna et al (2009) showed that HIF-1a acted as a tumor suppressor in a transgenic mouse model, expressing a stabilized form in keratinocytes.…”

Section: Discussionsupporting

confidence: 89%

Loss of Epidermal HIF-1α Blocks UVB-Induced Tumorigenesis by Affecting DNA Repair Capacity and Oxidative Stress

Mahfouf

Hosseini

Muzotte

et al. 2019

Journal of Investigative Dermatology

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HIF-1a is constitutively expressed in mouse and human epidermis. It plays a crucial role in skin physiology, including the response of keratinocytes to UVR. However, little information is available about its role in photocarcinogenesis. Using a multistage model of UVB radiation-induced skin cancer, we show that the knockout of Hif-1a in the epidermis prevents tumorigenesis but at the same time triggers the formation of hyperkeratotic plaques. Our results indicate that the absence of oncogenic transformation in Hif-1aeablated mice is related to increased DNA repair in keratinocytes, whereas the formation of hyperkeratotic plaques is caused by an increase in the levels of reactive oxygen species. Indeed, impairing the DNA repair machinery by ablating xeroderma pigmentosum C restored the UVB-induced neoplastic transformation of Hif-1aeablated keratinocytes, whereas the development of hyperkeratotic plaques was blocked by chronic antioxidant treatment. We conclude that HIF-1a plays a procarcinogenic role in UVB-induced tumorigenesis.

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Section: Discussionsupporting

confidence: 89%

Loss of Epidermal HIF-1α Blocks UVB-Induced Tumorigenesis by Affecting DNA Repair Capacity and Oxidative Stress

Mahfouf

Hosseini

Muzotte

et al. 2019

Journal of Investigative Dermatology

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“…As reported by Seleit et al . 30 , in normal conditions HIF-1α is expressed in the basal and suprabasal layers in 90% of normal skin biopsies. During low or mild oxygen, nuclear translocation of HIF-α occurs, leading to transcriptional activation of HIF target genes 31 .…”

Section: Introductionmentioning

confidence: 99%

Human skin equivalents cultured under hypoxia display enhanced epidermal morphogenesis and lipid barrier formation

Mieremet

García

Boiten

et al. 2019

Sci Rep

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Human skin equivalents (HSEs) are three-dimensional cell models mimicking characteristics of native human skin (NHS) in many aspects. However, a limitation of HSEs is the altered in vitro morphogenesis and barrier formation. Differences between in vitro and in vivo skin could have been induced by suboptimal cell culture conditions, of which the level of oxygen in vitro (20%) is much higher than in vivo (0.5–8%). Our aim is to study how external oxygen levels affect epidermal morphogenesis and barrier formation in HSEs. In the present study, fibroblast and keratinocyte monocultures, and HSEs were generated under 20% (normoxia) and 3% (hypoxia) oxygen level. In all cultures under hypoxia, expression of hypoxia-inducible factor target genes was increased. Characterization of HSEs generated under hypoxia using immunohistochemical analyses of morphogenesis biomarkers revealed a reduction in epidermal thickness, reduced proliferation, similar early differentiation, and an attenuated terminal differentiation program compared to normoxia, better mimicking NHS. The stratum corneum ceramide composition was studied with liquid chromatography coupled to mass spectrometry. Under hypoxia, HSEs exhibited a ceramide composition that more closely resembles that of NHS. Consequently, the lipid organization was improved. In conclusion, epidermal morphogenesis and barrier formation in HSEs reconstructed under hypoxia better mimics that of NHS.

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“…We next investigated the impact of SBP (32 mg/kg)/Gem (35 mg/kg) treatment on the TME. While hypoxic microenvironment is a typical characteristic of solid tumors, which is strongly correlated with cancer progression and chemoresistance (Martin et al, 2016; Gupta et al, 2017; Seleit, 2017). Angiogenesis has been reported to help in reducing tumor hypoxia (Wong et al, 2015).…”

Section: Resultsmentioning

confidence: 99%

“…Our data demonstrated that by increasing tumor vascular density, blood perfusion, vascular permeability and tumor vessel dilation, co-used SBP could achieve better drug delivery efficiency. Furthermore, recent studies have shed light upon the critical role of tumor microenvironment for cancer progression, which is strongly correlated with cancer progression and chemoresistance (Martin et al, 2016; Gupta et al, 2017; Seleit, 2017). Angiogenesis has been reported to help in reducing tumor hypoxia (Wong et al, 2015).…”

Section: Discussionmentioning

confidence: 99%

Co-administration of Shexiang Baoxin Pill and Chemotherapy Drugs Potentiated Cancer Therapy by Vascular-Promoting Strategy

Yang

et al. 2019

Front. Pharmacol.

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Effective delivery of chemotherapeutic agents to tumors is a critical objective of improved cancer therapy. Traditional antiangiogenic therapy aims at eradicating tumor blood vessels, but the subsequently reduced blood perfusion may limit the drug amount delivered into the tumor and potentially lead to tumor hypoxia, which has been proved to be unable to meet the therapeutic expectations. “Shexiang Baoxin Pill” (SBP) is a well-known traditional Chinese medicine (TCM) used in clinical treatment of cardiovascular diseases, which has the pharmacological effect of pro-angiogenesis demonstrated recently. In this study, we disclosed our finding that SBP could enhance the effective treatment performance of gemcitabine (GEM) while minimizing the toxic side effects caused by GEM. Mechanistically, SBP increased tumor angiogenesis, blood perfusion, vascular permeability, and vessel dilation, which subsequently favored the delivery of GEM to the tumor lesion. Moreover, combined treatment with SBP and GEM could modify tumor microenvironment and consequently overcome multidrug resistance, and this combination therapy is also suitable for combination of SBP with some other chemotherapeutic drugs as well. These results suggest that combining SBP with chemotherapeutic agents achieves better treatment efficiency, which can open an avenue for expanding the combined treatment of anti-cancer chemotherapeutic drugs with TCM.

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Evaluation of Hypoxia Inducible Factor-1α and Glucose Transporter-1 Expression in Non Melanoma Skin Cancer: An Immunohistochemical Study

Cited by 22 publications

References 48 publications

Loss of Epidermal HIF-1α Blocks UVB-Induced Tumorigenesis by Affecting DNA Repair Capacity and Oxidative Stress

Loss of Epidermal HIF-1α Blocks UVB-Induced Tumorigenesis by Affecting DNA Repair Capacity and Oxidative Stress

Human skin equivalents cultured under hypoxia display enhanced epidermal morphogenesis and lipid barrier formation

Co-administration of Shexiang Baoxin Pill and Chemotherapy Drugs Potentiated Cancer Therapy by Vascular-Promoting Strategy

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