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Hypoxia and HNSCC

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
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...
June 1, 2016: European Journal of Nuclear Medicine and Molecular Imaging
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
C Cleary, J E Leeman, D S Higginson, N Katabi, E Sherman, L Morris, S McBride, N Lee, N Riaz
Head and neck squamous cell carcinomas (HNSCC) are the sixth most common malignancy globally, and an increasing proportion of oropharyngeal HNSCCs are associated with the human papillomavirus (HPV). Patients with HPV-associated tumours have markedly improved overall and disease-specific survival compared with their HPV-negative counterparts when treated with chemoradiation. Although the difference in outcomes between these two groups is clearly established, the mechanism underlying these differences remains an area of investigation...
July 2016: Clinical Oncology: a Journal of the Royal College of Radiologists
Takuya Kakuki, Makoto Kurose, Ken-Ichi Takano, Atsushi Kondoh, Kazufumi Obata, Kazuaki Nomura, Ryo Miyata, Yakuto Kaneko, Takumi Konno, Syunta Takahashi, Tsubasa Hatakeyama, Takayuki Kohno, Tetsuo Himi, Takashi Kojima
Junctional adhesion molecule-A (JAM-A), which belongs to the IgG superfamily, is a tight junction molecule associated with epithelial and endothelial barrier function. Overexpression of JAM-A is also closely associated with invasion and metastasis of cancers such as breast cancer, lung cancer and pancreatic cancer. However, little is known about the mechanism in overexpression of JAM-A in head and neck squamous cell carcinoma (HNSCC). In the present study, we found high expression of JAM-A at the protein and mRNA levels in HNSCC tissues, including those of the oropharynx, larynx, and hypopharynx, together with high protein expression of β-catenin, p63, ΔNp63 and GATA-3...
June 7, 2016: Oncotarget
Paolo Bossi, Cristiana Bergamini, Marco Siano, Maria Cossu Rocca, Andrea P Sponghini, Federica Favales, Marco Giannoccaro, Edoardo Marchesi, Barbara Cortelazzi, Federica Perrone, Silvana Pilotti, Laura D Locati, Lisa Licitra, Silvana Canevari, Loris De Cecco
PURPOSE: To identify the tumor portrait of the minority of head and neck squamous cell carcinoma (HNSCC) patients with recurrent-metastatic (RM) disease who upon treatment with platinum-based chemotherapy plus cetuximab present a long-lasting response. EXPERIMENTAL DESIGN: The gene expression of pretreatment samples from 40 HNSCC-RM patients, divided in two groups [14 long-progression-free survival (PFS) and 26 short-PFS (median = 19 and 3 months, respectively)], was associated with PFS and was challenged against a dataset from metastatic colon cancer patients treated with cetuximab...
August 1, 2016: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
Zhi-Jun Sun, Guang-Tao Yu, Cong-Fa Huang, Lin-Lin Bu, Jian-Feng Liu, Si-Rui Ma, Wen-Feng Zhang, Bing Liu, Lu Zhang
To assess the role of transcription factor μE3 (TFE3) in the tumorigenesis of head and neck squamous cell carcinoma (HNSCC), human HNSCC tissue arrays were investigated for TFE3 expression. Human HNSCC tissues with neoadjuvant inductive chemotherapey (docetaxel, cisplatin and fluorouracil, TPF) and mice HNSCC tissues from transgenic mice model were evaluated for TFE3 expression and the hypoxia pathway. The roles of EGF/EGFR mediated hypoxia in TFE3 nuclear expression were analyzed in vitro and in vivo. TFE3 expression was higher in human HNSCC tissues compared with that in normal oral mucosa...
March 8, 2016: Oncotarget
Bouchra Tawk, Christian Schwager, Oliver Deffaa, Gerhard Dyckhoff, Rolf Warta, Annett Linge, Mechthild Krause, Wilko Weichert, Michael Baumann, Christel Herold-Mende, Jürgen Debus, Amir Abdollahi
BACKGROUND AND PURPOSE: Hypoxia renders tumors resistant to radiotherapy. However, the paucity of sensitive and reliable methods for detection of tumor hypoxia limits the translation of novel therapy strategies targeting this well-known resistance factor. We sought to investigate the ability of three previously discovered transcriptomics based hypoxia signatures to identify hypoxic tumors and consequently discriminate between patients with poor- vs. good prognosis. MATERIAL AND METHODS: Three different hypoxia gene signatures developed by Toustrup et al...
February 2016: Radiotherapy and Oncology: Journal of the European Society for Therapeutic Radiology and Oncology
Martina Becker-Schiebe, Matthias Sperling, Uwe Pinkert, Wolfgang Hoffmann
BACKGROUND: Human papilloma virus (HPV) infection, p16 expression and hypoxia may play important roles in the carcinogenesis, treatment response and toxicities of head and neck squamous cell carcinoma (HNSCC). The aim of this analysis was to assess whether there is any correlation between pre-radiotherapy (RT) anemia, p16 expression and toxicities and local control for patients undergoing definitive therapy. METHODS: 79 HNSCC patients who had undergone radiochemotherapy (RCT) or RT-antibody therapy were retrospectively analyzed...
2015: Oncology Research and Treatment
David Mönnich, Stefan Welz, Daniela Thorwarth, Christina Pfannenberg, Gerald Reischl, Paul-Stefan Mauz, Konstantin Nikolaou, Christian la Fougère, Daniel Zips
BACKGROUND: Previous studies suggested the maximum tumor to background ratio (TBRmax) in FMISO PET images as a potentially predictive parameter for local control after radio-chemotherapy (CRT) in head and neck squamous cell carcinomas (HNSCC). However, different TBRmax thresholds for stratification were reported, implying that a common threshold cannot readily be used among different institutions without the risk of reducing prediction accuracy. Therefore, this study investigated the robustness of using a common pre-defined TBRmax, simulating a multicenter clinical trial...
2015: Acta Oncologica
Jay K Ferrell, Davide Cattano, Robert E Brown, Chirag B Patel, Ron J Karni
The prognosis and disease-free survival rates for head and neck squamous cell carcinoma (HNSCC) have remained relatively stagnant for the last several decades. Moreover, as is the case with other malignancies, locoregional recurrence and distant metastasis are all too common even after seemingly successful oncologic surgery and adjuvant therapy. Recently, increased focus has been placed on understanding the influence of perioperative factors on tumor cell behavior and surgical outcomes. More specifically, emerging research suggests that anesthetic agents may play a role in cancer recurrence by interacting with prosurvival protein signaling pathways which harden tumor cells against oncologic treatments...
December 2015: Translational Research: the Journal of Laboratory and Clinical Medicine
Vlad C Sandulache, Yunyun Chen, Heath D Skinner, Tongtong Lu, Lei Feng, Laurence E Court, Jeffrey N Myers, Raymond E Meyn, Clifton D Fuller, James A Bankson, Stephen Y Lai
Ionizing radiation is the primary nonsurgical treatment modality for solid tumors. Its effectiveness is impacted by temporal constraints such as fractionation, hypoxia, and development of radioresistant clones. Biomarkers of acute radiation response are essential to developing more effective clinical algorithms. We hypothesized that acute perturbations in tumor lactate levels act as a surrogate marker of radiation response. In vitro experiments were carried out using validated human-derived cell lines from three histologies: anaplastic thyroid carcinoma (ATC), head and neck squamous cell carcinoma (HNSCC), and papillary thyroid carcinoma (PTC)...
December 2015: Molecular Cancer Therapeutics
Magnus T Dillon, Kevin J Harrington
Human papillomavirus-negative head and neck squamous cell carcinoma (HNSCC) carries a poor prognosis, and despite optimal treatment with chemoradiotherapy to the limit of tolerance, many patients will relapse. A number of methods for intensifying treatment of HNSCC have been investigated, leading to the current standards of care. Novel agents targeting tumor cell and stromal signaling, DNA damage response, and immune system are now reaching clinical trials in combination with chemoradiotherapy. In this review, we discuss the evidence for the current treatment of locally advanced human papillomavirus-negative HNSCC, as well as investigational therapies, such as hypoxia modification, molecular targeting of epidermal growth factor receptor family, vascular endothelial growth factor receptor or DNA damage response proteins in combination with radiation therapy...
October 10, 2015: Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology
Rajesh Kar Narayanaswamy, Mahadev Potharaju, A N Vaidhyswaran, Karthikeyan Perumal
INTRODUCTION: Radiation plays a major role in treatment of locoregional control of Head and Neck Squamous cell carcinoma (HNSCC). Anaemia is considered a contributor to intra-tumour hypoxia and tumour resistance to ionizing radiation and most evidences are from developed world, we prospectively investigated the exact role of anaemia in treatment outcome of Stage III/IVA HNSCC in our patient population. AIM OF THE STUDY: Primary end point: To analyse the Pre-Radiotherapy haemoglobin level and early response of treatment in stage III/IVA HNSCC and to determine the relationship of Pre-Radiotherapy haemoglobin level with other prognostic factors...
June 2015: Journal of Clinical and Diagnostic Research: JCDR
Monique C de Jong, Jelle J Ten Hoeve, Reidar Grénman, Lodewyk F Wessels, Ron Kerkhoven, Hein Te Riele, Michiel W M van den Brekel, Marcel Verheij, Adrian C Begg
PURPOSE: Predominant causes of head and neck cancer recurrence after radiotherapy are rapid repopulation, hypoxia, fraction of cancer stem cells, and intrinsic radioresistance. Currently, intrinsic radioresistance can only be assessed by ex vivo colony assays. Besides being time-consuming, colony assays do not identify causes of intrinsic resistance. We aimed to identify a biomarker for intrinsic radioresistance to be used before start of treatment and to reveal biologic processes that could be targeted to overcome intrinsic resistance...
December 15, 2015: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
Laura K van Dijk, Otto C Boerman, Johannes H A M Kaanders, Johan Bussink
Molecular imaging of specific biomarkers can have prognostic, predictive or monitoring value in head and neck squamous cell carcinoma (HNSCC). The epidermal growth factor receptor (EGFR) is involved in various radiation resistance mechanisms as it steers the pathways related to DNA damage repair, proliferation, hypoxia and apoptosis. Radiolabeled labeled F(ab')2 fragments of the EGFR antibody cetuximab can be applied for non-invasive imaging of this receptor. Preclinical studies have shown that radioresistant tumors had a higher tracer uptake after irradiation, probably due to upregulation of membranous EGFR, thereby increasing target availability possibly as a compensation mechanism...
2015: Acta Oncologica
Carmen Muñoz, Miguel Caballero, Sofia Hakim, Eugenia Verger, Juan Jose Grau
Although cetuximab plus radiotherapy is a standard treatment for patients with inoperable head and neck squamous cell carcinoma (HNSCC), its efficacy varies greatly among individuals. To identify predictive markers of efficacy, we examined the effects of single nucleotide polymorphisms (SNPs) in hypoxia-related and DNA repair genes on the clinical outcome and occurrence of skin toxicity. We analyzed 61 consecutive patients with HNSCC for the presence of specific SNPs (HIF-1α, HIF-2α, HIF-1β, VHL, FIH-1, XRCC1, and XRCC5)...
August 2016: European Archives of Oto-rhino-laryngology
Catharina M L Zegers, Wouter van Elmpt, Frank J P Hoebers, Esther G C Troost, Michel C Öllers, Felix M Mottaghy, Philippe Lambin
BACKGROUND: Tumour hypoxia and a high tumour metabolism increase radioresistance in patients with head and neck squamous cell carcinoma (HNSCC). The aim of this study was to evaluate the correlation between hypoxia ([(18)F]HX4 PET) and glucose metabolism ([(18)F]FDG PET) molecular imaging. MATERIAL AND METHODS: [(18)F]HX4 and [(18)F]FDG PET/CT images of 20 HNSCC patients were acquired prior to (chemo)radiotherapy, in an immobilisation mask, with a median time interval of seven days (NCT01347281)...
2015: Acta Oncologica
Brita Singers Sørensen, Anders Knudsen, Catja Foged Wittrup, Steffen Nielsen, Ninna Aggerholm-Pedersen, Morten Busk, Michael Horsman, Morten Høyer, Pierre Nourdine Bouchelouche, Jens Overgaard, Jan Alsner
BACKGROUND AND PURPOSE: A 15-gene hypoxia profile has previously demonstrated to have both prognostic and predictive impact for hypoxic modification in squamous cell carcinoma of the head and neck. This gene expression profile may also have a prognostic value in other histological cancer types, and could potentially have a function as a universal hypoxia profile. The hypoxia induced upregulation of the included genes, and the validity of the previously used reference genes was established in this study, in a range of different cell lines representing carcinomas of the prostate, colon, and esophagus...
September 2015: Radiotherapy and Oncology: Journal of the European Society for Therapeutic Radiology and Oncology
Tom G Keulers, Marco B E Schaaf, Hanneke J M Peeters, Kim G M Savelkouls, Marc A Vooijs, Johan Bussink, Barry Jutten, Kasper M A Rouschop
BACKGROUND AND PURPOSE: The epidermal growth factor receptor (EGFR) is overexpressed, amplified or mutated in various human epithelial tumors and hypoxia is a common feature of solid tumors. Both EGFR and hypoxia are associated with therapy resistance and poor treatment outcome. To survive hypoxia, cells adapt by activation of hypoxia responsive pathways and expression of hypoxia-induced plasma membrane proteins. We observed that GABAA receptor associated protein like1 (GABARAPL1) and plasma membrane expression of EGFR were increased during hypoxia...
September 2015: Radiotherapy and Oncology: Journal of the European Society for Therapeutic Radiology and Oncology
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