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Hypoxia and HNSCC

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https://www.readbyqxmd.com/read/28901527/hypoxia-promotes-migration-invasion-and-glycolysis-in-head-and-neck-squamous-cell-carcinoma-via-an-hif-1%C3%AE-mtdh-loop
#1
Gangcai Zhu, Fusen Peng, Wei Gong, Li She, Ming Wei, Haolei Tan, Changhan Chen, Diekuo Zhang, Guo Li, Donghai Huang, Xin Zhang, Yong Liu
Hypoxia is a hallmark of progressive cancer. Hypoxic cancer cells trigger glycolysis in response to a decreased O2 supply to meet metabolic and bioenergetic demands. Meanwhile, these responses to hypoxia and alterations of the microenvironment promote cancer cell metastasis by increasing transcription of hypoxia-inducible factor (HIF)-regulated genes. However, the detailed mechanism by which hypoxia regulates cancer cell metastasis and glycolysis remains to be investigated. In the present study, we identified that metadherin (MTDH), a multifaceted oncogene, is involved in the regulation of head and neck squamous cell carcinoma (HNSCC) metastasis and invasion under hypoxic conditions...
September 7, 2017: Oncology Reports
https://www.readbyqxmd.com/read/28891398/geometric-analysis-of-loco-regional-recurrences-in-relation-to-pre-treatment-hypoxia-in-patients-with-head-and-neck-cancer
#2
Simon Boeke, Daniela Thorwarth, David Mönnich, Christina Pfannenberg, Gerald Reischl, Christian La Fougère, Konstantin Nikolaou, Paul-Stefan Mauz, Frank Paulsen, Daniel Zips, Stefan Welz
INTRODUCTION: A previous pattern-of-failure study has suggested that up to 50% of the loco-regional failures (LRF) in head and neck squamous cell carcinoma (HNSCC) occur outside the initial hypoxic volume determined by [(18)F]-fluoromisonidazole-PET ([(18)F]-FMISO-PET). The aim of the present analysis was to correlate spatial patterns of failure with respect to the pretherapeutic dynamic [(18)F]-FMISO-PET/CT in HNSCC after radiochemotherapy (RCT). MATERIAL AND METHODS: Within a running phase 2 trial using [(18)F]-FMISO-PET imaging prior to RCT in HNSCC patients (n = 54), we have observed so far 11 LRF with a minimum follow-up of 12 months...
September 11, 2017: Acta Oncologica
https://www.readbyqxmd.com/read/28843726/residual-tumour-hypoxia-in-head-and-neck-cancer-patients-undergoing-primary-radiochemotherapy-final-results-of-a-prospective-trial-on-repeat-fmiso-pet-imaging
#3
Steffen Löck, Rosalind Perrin, Annekatrin Seidlitz, Anna Bandurska-Luque, Sebastian Zschaeck, Klaus Zöphel, Mechthild Krause, Jörg Steinbach, Jörg Kotzerke, Daniel Zips, Esther G C Troost, Michael Baumann
BACKGROUND: Hypoxia is a well recognised parameter of tumour resistance to radiotherapy, a number of anticancer drugs and potentially immunotherapy. In a previously published exploration cohort of 25 head and neck squamous cell carcinoma (HNSCC) patients on [(18)F]fluoromisonidazole positron emission tomography (FMISO-PET) we identified residual tumour hypoxia during radiochemotherapy, not before start of treatment, as the driving mechanism of hypoxia-mediated therapy resistance. Several quantitative FMISO-PET parameters were identified as potential prognostic biomarkers...
September 2017: Radiotherapy and Oncology: Journal of the European Society for Therapeutic Radiology and Oncology
https://www.readbyqxmd.com/read/28756482/epr-oximetry-of-cetuximab-treated-head-and-neck-tumours-in-a-mouse-model
#4
H Gustafsson, A Kale, A Dasu, A Lund, P-H Edqvist, K Roberg
Head and neck squamous cell carcinoma (HNSCC) tumours are associated with high mortality despite advances in therapy. The monoclonal antibody cetuximab (Erbitux(®)) has been approved for the treatment of advanced HNSCC. However, only a subset of HNSC patients receiving cetuximab actually responds to treatment, underlining the need for a means to tailor treatments of individual patients. The aim of the present study was to investigate the effect of cetuximab treatment on tumour growth, on tumour partial oxygen pressure as measured by LiPc electron paramagnetic resonance oximetry and on the expression of proteins involved in tumour growth, metabolism and hypoxia...
July 29, 2017: Cell Biochemistry and Biophysics
https://www.readbyqxmd.com/read/28485160/mir-34a-suppresses-hnscc-growth-through-modulating-cell-cycle-arrest-and-senescence
#5
Y Wang, J Chen, X Chen, F Jiang, Y Sun, Y Pan, W Zhang, J Zhang
MiR-34a acts as a tumor suppressor in various malignancies. In HNSCC, the role of miR-34a in proliferation has not been fully elaborated and the target genes are still bind. Here, we addressed that forced miR-34a expression induced cell cycle arrest and senescence. Hypoxia/HIF1α was found to negatively correlate to the expression of miR-34a in HNSCC tissues and partially reverse miR-34a-imposed cell senescence through suppressing miR-34a expression. In order to screen the possible target genes of miR-34a in HNSCC, the differential genes mediated by miR-34a were screened by mRNA microarray...
May 9, 2017: Neoplasma
https://www.readbyqxmd.com/read/28468237/hypoxia-mediates-differential-response-to-anti-egfr-therapy-in-hnscc-cells
#6
Emilia Wiechec, Katharina Tiefenböck Hansson, Lisa Alexandersson, Jan-Ingvar Jönsson, Karin Roberg
Despite advances in the head and neck squamous cell carcinoma (HNSCC) treatment modalities, drug resistance and cancer recurrence are often reported. Hypoxia signaling through hypoxia-inducible factor 1 (HIF-1) promotes angiogenesis and metastasis by inducing epithelial-mesenchymal-transition (EMT). The aim of this study was to evaluate the impact of hypoxia on response to therapy as well as EMT and expression of stem cell markers in HNSCC cells. Five HNSCC cell lines (UT-SCC-2, UT-SCC-14, LK0412, LK0827, and LK0923) were selected for this study...
April 29, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28407653/differential-pattern-of-hif-1%C3%AE-expression-in-hnscc-cancer-stem-cells-after-carbon-ion-or-photon-irradiation-one-molecular-explanation-of-the-oxygen-effect
#7
Anne-Sophie Wozny, Alexandra Lauret, Priscillia Battiston-Montagne, Jean-Baptiste Guy, Michael Beuve, Micaela Cunha, Yannick Saintigny, Emilie Blond, Nicolas Magne, Philippe Lalle, Dominique Ardail, Gersende Alphonse, Claire Rodriguez-Lafrasse
BACKGROUND: Head and neck squamous cell carcinoma (HNSCC) are resistant to standard treatments, partly due to cancer stem cells (CSCs) localised in hypoxic niches. Compared to X-rays, carbon ion irradiation relies on better ballistic properties, higher relative biological effectiveness and the absence of oxygen effect. Hypoxia-inducible factor-1α (HIF-1α) is involved in the resistance to photons, whereas its role in response to carbon ions remains unclear. METHODS: Two HNSCC cell lines and their CSC sub-population were studied in response to photons or carbon ion irradiation, in normoxia or hypoxia, after inhibition or not of HIF-1α...
May 9, 2017: British Journal of Cancer
https://www.readbyqxmd.com/read/28314789/noninvasive-imaging-of-cycling-hypoxia-in-head-and-neck-cancer-using-intrinsic-susceptibility-mri
#8
Rafal Panek, Liam Welsh, Lauren C J Baker, Maria A Schmidt, Kee H Wong, Angela M Riddell, Dow-Mu Koh, Alex Dunlop, Dualta Mcquaid, James A d'Arcy, Shreerang A Bhide, Kevin J Harrington, Christopher M Nutting, Georgina Hopkinson, Cheryl Richardson, Carol Box, Suzanne A Eccles, Martin O Leach, Simon P Robinson, Kate L Newbold
Purpose: To evaluate intrinsic susceptibility (IS) MRI for the identification of cycling hypoxia, and the assessment of its extent and spatial distribution, in head and neck squamous cell carcinoma (HNSCC) xenografts and patients.Experimental Design: Quantitation of the transverse relaxation rate, R2*, which is sensitive to paramagnetic deoxyhemoglobin, using serial IS-MRI acquisitions, was used to monitor temporal oscillations in levels of paramagnetic deoxyhemoglobin in human CAL(R) xenografts and patients with HNSCC at 3T...
August 1, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28263977/gata3-interacts-with-and-stabilizes-hif-1%C3%AE-to-enhance-cancer-cell-invasiveness
#9
M-C Lin, J-J Lin, C-L Hsu, H-F Juan, P-J Lou, M-C Huang
GATA binding protein 3 (GATA3) is indispensable in development of human organs. However, the role of GATA3 in cancers remains elusive. Hypoxia inducible factor (HIF)-1 plays an important role in pathogenesis of human cancers. Regulation of HIF-1α degradation is orchestrated through collaboration of its interacting proteins. In this study, we discover that GATA3 is upregulated in head and neck squamous cell carcinoma (HNSCC) and is an independent predictor for poor disease-free survival. GATA3 promotes invasive behaviours of HNSCC and melanoma cells in vitro and in immunodeficient mice...
July 27, 2017: Oncogene
https://www.readbyqxmd.com/read/28114271/phenotypic-heterogeneity-of-disseminated-tumour-cells-is-preset-by-primary-tumour-hypoxic-microenvironments
#10
Georg Fluegen, Alvaro Avivar-Valderas, Yarong Wang, Michael R Padgen, James K Williams, Ana Rita Nobre, Veronica Calvo, Julie F Cheung, Jose Javier Bravo-Cordero, David Entenberg, James Castracane, Vladislav Verkhusha, Patricia J Keely, John Condeelis, Julio A Aguirre-Ghiso
Hypoxia is a poor-prognosis microenvironmental hallmark of solid tumours, but it is unclear how it influences the fate of disseminated tumour cells (DTCs) in target organs. Here we report that hypoxic HNSCC and breast primary tumour microenvironments displayed upregulation of key dormancy (NR2F1, DEC2, p27) and hypoxia (GLUT1, HIF1α) genes. Analysis of solitary DTCs in PDX and transgenic mice revealed that post-hypoxic DTCs were frequently NR2F1(hi)/DEC2(hi)/p27(hi)/TGFβ2(hi) and dormant. NR2F1 and HIF1α were required for p27 induction in post-hypoxic dormant DTCs, but these DTCs did not display GLUT1(hi) expression...
February 2017: Nature Cell Biology
https://www.readbyqxmd.com/read/28031935/interaction-between-hypoxia-akt-and-hif-1-signaling-in-hnscc-and-nsclc-implications-for-future-treatment-strategies
#11
Hanneke Stegeman, Paul N Span, Wenny Jm Peeters, Marieke Mg Verheijen, Reidar Grénman, Tineke Wh Meijer, Johannes Ham Kaanders, Johan Bussink
BACKGROUND: Hypoxia is a negative prognostic factor and this study investigated the relationship between hypoxia, hypoxia inducible factor 1 (HIF-1) and AKT signaling in head and neck squamous cell carcinoma (HNSCC) and non-small-cell lung cancer (NSCLC). RESULTS/METHODOLOGY: pAKT was induced by hypoxia (0.5% O2) in a part of HNSCC (3/4) and squamous (2/3) and adenocarcinoma (1/3) NSCLS lines. AKT-inhibitor MK-2206 reduced hypoxic HIF-1 signaling in most HNSCC cell lines...
March 2016: Future Science OA
https://www.readbyqxmd.com/read/27919941/ectopic-myoglobin-expression-is-associated-with-a-favourable-outcome-in-head-and-neck-squamous-cell-carcinoma-patients
#12
Sebastian Meller, Anne VAN Ellen, Heidrun Gevensleben, Anne Bicker, Thomas Hankeln, Thomas A Gorr, Verena Sailer, Freya Dröge, Friederike Schröck, Friedrich Bootz, Andreas Schröck, Sven Perner, Dimo Dietrich, Glen Kristiansen
BACKGROUND/AIM: Ectopic myoglobin (MB) expression, mediated by alternative and hypoxia-inducible transcription, has recently been demonstrated in several epithelial tumours. This study aimed to examine the expression of MB in hormone-independent head and neck squamous cell carcinomas (HNSCCs). PATIENTS AND METHODS: Using imunohistochemistry, ectopic MB expression was analyzed on tissue microarrays (TMAs) of 524 patients with localized and locally advanced primary and recurrent HNSCC who had undergone surgical treatment with curative intent...
2016: Anticancer Research
https://www.readbyqxmd.com/read/27913065/hpv-status-cancer-stem-cell-marker-expression-hypoxia-gene-signatures-and-tumour-volume-identify-good-prognosis-subgroups-in-patients-with-hnscc-after-primary-radiochemotherapy-a-multicentre-retrospective-study-of-the-german-cancer-consortium-radiation-oncology
#13
MULTICENTER STUDY
Annett Linge, Fabian Lohaus, Steffen Löck, Alexander Nowak, Volker Gudziol, Chiara Valentini, Cläre von Neubeck, Martin Jütz, Inge Tinhofer, Volker Budach, Ali Sak, Martin Stuschke, Panagiotis Balermpas, Claus Rödel, Anca-Ligia Grosu, Amir Abdollahi, Jürgen Debus, Ute Ganswindt, Claus Belka, Steffi Pigorsch, Stephanie E Combs, David Mönnich, Daniel Zips, Frank Buchholz, Daniela E Aust, Gustavo B Baretton, Howard D Thames, Anna Dubrovska, Jan Alsner, Jens Overgaard, Mechthild Krause, Michael Baumann
OBJECTIVE: To investigate the impact of the tumour volume, HPV status, cancer stem cell (CSC) marker expression and hypoxia gene signatures, as potential markers of radiobiological mechanisms of radioresistance, in a contemporary cohort of patients with locally advanced head and neck squamous cell carcinoma (HNSCC), who received primary radiochemotherapy (RCTx). MATERIALS AND METHODS: For 158 patients with locally advanced HNSCC of the oral cavity, oropharynx or hypopharynx who were treated at six DKTK partner sites, the impact of tumour volume, HPV DNA, p16 overexpression, p53 expression, CSC marker expression and hypoxia-associated gene signatures on outcome of primary RCTx was retrospectively analyzed...
December 2016: Radiotherapy and Oncology: Journal of the European Society for Therapeutic Radiology and Oncology
https://www.readbyqxmd.com/read/27884018/blood-transfusion-during-radical-chemo-radiotherapy-does-not-reduce-tumour-hypoxia-in-squamous-cell-cancer-of-the-head-and-neck
#14
Liam Welsh, Rafal Panek, Angela Riddell, Kee Wong, Martin O Leach, Mahvash Tavassoli, Durdana Rahman, Maria Schmidt, Tara Hurley, Lorna Grove, Thomas Richards, Dow-Mu Koh, Christopher Nutting, Kevin Harrington, Kate Newbold, Shreerang Bhide
BACKGROUND: Patients with head and neck squamous cell carcinoma (HNSCC) undergoing radical chemo-radiation (CRT) frequently receive transfusion with packed red cells (PRCT) during radiotherapy on the basis that PRCT increases tumour oxygenation and overcomes hypoxia-induced radio-resistance. This is likely to be a significant oversimplification given the fact that tumour hypoxia is the result of several intrinsic and extrinsic factors, including many that are not directly related to serum haemoglobin (Hb)...
January 3, 2017: British Journal of Cancer
https://www.readbyqxmd.com/read/27802455/downregulation-of-egfr-in-hypoxic-diffusion-limited-areas-of-squamous-cell-carcinomas-of-the-head-and-neck
#15
Arnulf Mayer, Sebastian Zahnreich, Jürgen Brieger, Peter Vaupel, Heinz Schmidberger
BACKGROUND: The receptor for the epidermal growth factor (EGFR) is widely considered to be one of the central drivers of oncogenesis in squamous cell carcinomas of the head and neck region (HNSCC). Inhibition of EGFR using monoclonal antibodies is established both in the curative and the palliative setting in this disease. HNSCCs are known to contain abundant hypoxic tissue areas and hypoxia has been shown to be involved in the (down)regulation of EGFR membrane expression. METHODS: A novel method for multiplex immunofluorescence and single-cell segmentation (via DAPI-stained nuclei) was established, to study the expression of EGFR, the endogenous hypoxia marker CA IX, and intratumoural diffusion distances from microvessels (using CD34 staining) in 58 human HNSCCs and 9 normal/cancer adjacent tissues...
November 22, 2016: British Journal of Cancer
https://www.readbyqxmd.com/read/27791989/stimulation-of-the-toll-like-receptor-3-promotes-metabolic-reprogramming-in-head-and-neck-carcinoma-cells
#16
Mathieu Veyrat, Sylvère Durand, Marion Classe, Tanja Matijevic Glavan, Natalie Oker, Nikiforos-Ioannis Kapetanakis, Xiaojun Jiang, Aurore Gelin, Philippe Herman, Odile Casiraghi, David Zagzag, David Enot, Pierre Busson, Benjamin Vérillaud
In this study, a possible link between the innate immune recognition receptor TLR3 and metabolic reprogramming in Head and Neck carcinoma (HNC) cells was investigated. The effects of TLR3 stimulation/knock-down were assessed under several culture conditions in 4 HNC cell-lines by cell growth assays, targeted metabolomics, and glycolysis assays based on time-resolved analysis of proton release (Seahorse analyzer). The stimulation of TLR3 by its synthetic agonist Poly(A:U) resulted in a faster growth of HNC cells under low foetal calf serum conditions...
December 13, 2016: Oncotarget
https://www.readbyqxmd.com/read/27788497/macrophage-migration-inhibitory-factor-a-potential-driver-and-biomarker-for-head-and-neck-squamous-cell-carcinoma
#17
REVIEW
Sha-Sha Wang, Xiao Cen, Xin-Hua Liang, Ya-Ling Tang
Macrophage migration inhibitory factor (MIF), a pleiotropic proinflammatory cytokine, has been showed to be associated with the immunopathogenesis of many diseases. Recent study demonstrated that MIF promoted tumorigenesis and tumor progression and played a critical role in various kinds of human cancer including head and neck squamous cell carcinoma(HNSCC). Hence, in this paper we retrospected the relationship between MIF and angiogenesis, epithelial-mesenchymal transition (EMT), inflammation, immune response, hypoxia microenvironment, and discussed whether it is a promising biomarker for diagnosis and supervisor of HNSCC...
February 7, 2017: Oncotarget
https://www.readbyqxmd.com/read/27370131/correlation-of-fmiso-simulations-with-pimonidazole-stained-tumor-xenografts-a-question-of-o2-consumption
#18
L J Wack, D Mönnich, A Yaromina, D Zips, M Baumann, D Thorwarth
PURPOSE: To compare a dedicated simulation model for hypoxia PET against tumor microsections stained for different parameters of the tumor microenvironment. The model can readily be adapted to a variety of conditions, such as different human head and neck squamous cell carcinoma (HNSCC) xenograft tumors. METHODS: Nine different HNSCC tumor models were transplanted subcutaneously into nude mice. Tumors were excised and immunoflourescently labeled with pimonidazole, Hoechst 33342, and CD31, providing information on hypoxia, perfusion, and vessel distribution, respectively...
July 2016: Medical Physics
https://www.readbyqxmd.com/read/27251643/evaluation-of-tumour-hypoxia-during-radiotherapy-using-18-f-hx4-pet-imaging-and-blood-biomarkers-in-patients-with-head-and-neck-cancer
#19
Catharina M L Zegers, Frank J P Hoebers, Wouter van Elmpt, Judith A Bons, Michel C Öllers, Esther G C Troost, Daniëlle Eekers, Leo Balmaekers, Marlies Arts-Pechtold, Felix M Mottaghy, Philippe Lambin
BACKGROUND AND PURPOSE: Increased tumour hypoxia is associated with a worse overall survival in patients with head and neck squamous cell carcinoma (HNSCC). The aims of this study were to evaluate treatment-associated changes in [(18)F]HX4-PET, hypoxia-related blood biomarkers, and their interdependence. MATERIAL AND METHODS: [(18)F]HX4-PET/CT scans of 20 patients with HNSCC were acquired at baseline and after ±20Gy of radiotherapy. Within the gross-tumour-volumes (GTV; primary and lymph nodes), mean and maximum standardized uptake values, the hypoxic fraction (HF) and volume (HV) were calculated...
November 2016: European Journal of Nuclear Medicine and Molecular Imaging
https://www.readbyqxmd.com/read/27161763/validation-of-a-15-gene-hypoxia-classifier-in-head-and-neck-cancer-for-prospective-use-in-clinical-trials
#20
Kasper Toustrup, Brita Singers Sørensen, Mohamed A Hassan Metwally, Trine Tramm, Lise Saksø Mortensen, Jens Overgaard, Jan Alsner
BACKGROUND: In head and neck squamous cell carcinomas (HNSCC) hypoxic radioresistance can be reduced by use of the hypoxic modifier nimorazole, as shown in the DAHANCA 5 trial. Recently, a 15-gene hypoxia classifier has shown predictive impact for the effect of nimorazole by identifying 'more' and 'less' hypoxic tumors in the DAHANCA 5 cohort. A prospective multicentre EORTC-1219 study is initiated, where nimorazole and prospective use of the classifier as a predictor is tested in relation to the most recent accelerated chemoradiotherapy treatment...
May 10, 2016: Acta Oncologica
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