Hypoxia in Head and Neck Squamous Cell Carcinoma

Li, John Zeng Hong; Gao, Wei; Chan, Jimmy Yu‐Wai; Ho, Wai Yin; Wong, Thomas K. F.

doi:10.5402/2012/708974

Cited by 35 publications

(25 citation statements)

References 75 publications

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“…We have confirmed here that PKM2 and hnRNPA1 both are over-expressed after TLR3 stimulation in a process dependent on Myc, MEK, and HIF in normoxia. We also verified that similar expression patterns occur in hypoxia which is a natural environment for pharyngeal cancer cells in vivo [24]. However, interestingly we have determined 3 that poly(I:C) stimulation decreased, whereas poly (A:U) stimulation increased PKM2 mRNA level.…”

Section: Discussionsupporting

confidence: 79%

Toll‐like receptor 3 stimulation triggers metabolic reprogramming in pharyngeal cancer cell line through Myc, MAPK, and HIF

Glavan

Gašparović

Vérillaud

et al. 2016

Molecular Carcinogenesis

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Toll-like receptor 3 (TLR3) has a dual role in cancer; its activation can trigger apoptosis as well as stimulate cancer cell survival, proliferation, and progression. We have shown here that TLR3 activation can induce metabolic reprogramming in a pharyngeal cancer cell line, leading to increased aerobic glycolysis, cell migration, elevated levels of reactive oxidative species (ROS), and decreased anti-oxidative response. Key proteins in these signaling pathways are heterogeneous nuclear ribonucleoprotein A1 (hnRNPA1), pyruvate kinase M2 (PKM2), and CD44 variants, which were over-expressed after TLR3 stimulation. TLR3 activation also induced upregulation of different genes involved in cancer progression (VEGF, MMP9, uPAR) and enzymes involved in glycolytic pathway. Most of the observed effects were Myc-dependent; however, some of them were also connected with MAPK and HIF signaling pathways. Since TLR3 agonists are being investigated as potential novel cancer therapy adjuvants and apoptosis inducers, alone or in combination with other therapeutic options, data presented here suggest extreme caution before their introduction into clinical practice. The fact that TLR3 ligands [poly(I:C) and poly(A:U)] can also aid cancer survival and progression, through induction of metabolic reprogramming, emphasizes the need to investigate this particular topic. Our data suggest that the combination of TLR3 ligands with Myc or MAPK inhibitors may be a way to neutralize their undesirable effects while enhancing their anti-tumor effect. © 2016 Wiley Periodicals, Inc.

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Section: Discussionsupporting

confidence: 79%

Toll‐like receptor 3 stimulation triggers metabolic reprogramming in pharyngeal cancer cell line through Myc, MAPK, and HIF

Glavan

Gašparović

Vérillaud

et al. 2016

Molecular Carcinogenesis

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“…The surgery outcome was always related to the degree of neurological deficit, while the determinants of the prognosis of radiotherapy were residual tumor and tumor metastasis. Hypoxia is a common feature of tumors, and contributes to the development of tumorous aggression and metastasis, and reportedly plays a key role in radioresistance, chemoresistance, and poor prognosis (Li et al, 2012).…”

Section: Discussionmentioning

confidence: 99%

Management of clinically negative nodes (N0) in supraglottic laryngeal carcinoma: A systematic review

Liu

2016

Genet. Mol. Res.

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ABSTRACT. The purpose of this study was to evaluate the treatment of clinically negative cervical lymph nodes in supraglottic carcinoma by a meta-analysis. The search words were "supraglottic carcinoma", "cervical lymph nodes negative/cN0", "radical neck dissection", and "radiotherapy". The databases included the Chinese biomedical literature database, Medline, Cochrane library, EMBASE database, journals, and theses, etc. from 1989 onwards. Using the 5-year overall survival, disease-free survival, and disease-specific survival rates, and the recurrence and distant metastasis rates as observation indexes, the proper model and method were selected after a heterogeneity test to allow combined statistic tests, sensitivity analysis, and publication bias analysis to be conducted. Four studies (807 cases) were included in the analysis. Comparisons of the 5-year overall survival, diseasefree survival, and disease-specific survival rates as well as lymph node metastasis and the recurrence rate for radical neck dissection and radiotherapy showed no significant differences. There was no advantage of radical neck dissection in supraglottic carcinoma with clinically negative cervical lymph nodes compared to radiotherapy. However, owing to the lack of a prospective study and large number of cases, selection bias and measurement bias may still exist.

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“…Radiosensitizing agents such as ARCON (Accelerated Radiotherapy with Carbogen and Nicotinamide) [20,24] which alleviates acute hypoxia by reducing the intermittent closure of blood vessels, have also been investigated for their ability to improve the results of radiotherapy in patients with advanced HNSCC. [2,10] The identification of patients who might benefit from the radiosensitizers is a difficult task, as the hypoxic fraction inside tumors needs to be assessed. T 2 -weighted MR techniques show promise in being able to identify such regions within tumors non-invasively.…”

Section: Bold Contrast Principlementioning

confidence: 99%

“…It indicates an imbalance between the increased oxygen demand of the rapidly proliferating cancer cells and the decreased oxygen delivery due to poor vascularization and blood supply. [2] The resultant compensatory mechanisms utilized by tumors in response to hypoxia has an unfavorable impact on the therapeutic response, irrespective of the treatment modality employed. [1] Hence, tumor hypoxia has become a central issue in cancer treatment.…”

Section: Introductionmentioning

confidence: 99%

A BOLD appraisal of cancer

Asha¹,

Ghorai²,

Rajarathnam³

et al. 2015

JMRPS

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Tissue hypoxia is a biological condition characterized by oxygen deficiency at the tissue level. Hypoxia has been seen to play a crucial role in tumor recurrence in head and neck cancer patients. The detection and assessment of tumor hypoxia plays a critical role in both validation and development of hypoxia modification therapies. Hypoxic cancers being more resistant to radiotherapy and chemotherapy, attempts have been made to improve the response of hypoxic cancers to radiotherapy through the use of radiosensitizers such as carbogen and others. Several techniques to assess the status of tumor oxygenation have been developed in the past, among which functional imaging techniques remain the most validated. Blood-oxygen-leveldependent magnetic resonance imaging (BOLD MRI) is a non-invasive functional imaging technique that can recognize hypoxic cancers which will respond to accelerated radiotherapeutic treatment with radiosensitizers. BOLD MRI employs a T-sensitive sequence which can detect a transient rise in signal during oxygen inhalation. This increase in signal intensity is caused by the reduced paramagnetic effect due to a decrease in the blood deoxyhaemoglobin level within cancer. Hence, BOLD MRI can detect reduced hypoxia in the malignant solid tumors and may pave the path for more conservative treatment approach for hypoxic head and neck cancers in future.

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Hypoxia in Head and Neck Squamous Cell Carcinoma

Cited by 35 publications

References 75 publications

Toll‐like receptor 3 stimulation triggers metabolic reprogramming in pharyngeal cancer cell line through Myc, MAPK, and HIF

Toll‐like receptor 3 stimulation triggers metabolic reprogramming in pharyngeal cancer cell line through Myc, MAPK, and HIF

Management of clinically negative nodes (N0) in supraglottic laryngeal carcinoma: A systematic review

A BOLD appraisal of cancer

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