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GLUT-1 and head and neck cancers

Nadine Fabienne Voelxen, Sebastian Blatt, Pascal Knopf, Maurice Henkel, Christina Appelhans, Leonardo A R Righesso, Andreas Pabst, Jutta Goldschmitt, Stefan Walenta, Andreas Neff, Wolfgang Mueller-Klieser, Thomas Ziebart
OBJECTIVES: Chronic accumulation of lactate in malignant tumor tissue is associated with increased malignancy and radioresistance. For this study, biopsies of primary head and neck squamous cell carcinoma (HNSCC) and of the normal gingiva of the same patient were compared via metabolic profiling to the healthy gingiva from cancer-free patients. MATERIALS AND METHODS: Cryobiopsies of 140 HNSCC patients were used to determine ATP, lactate, and glucose concentrations of the tumor and normal gingiva via induced metabolic bioluminescence imaging (imBI)...
March 2018: Clinical Oral Investigations
Gesche Frohwitter, Horst Buerger, Eberhard Korsching, Paul J van Diest, Johannes Kleinheinz, Thomas Fillies
BACKGROUND: Squamous cell carcinomas (SCCs) are the most prevalent malignant tumours within the head and neck. Evidence exists that distinct genes are differentially regulated in SCCs of the oral cavity compared to other head and neck regions. Given this background, the aim of this study was to investigate whether such tumour site-specific gene expression can also be observed in different localizations within the oral cavity. METHODS: Using tissue microarrays (TMAs), we investigated 76 SCCs of the floor of the mouth, 49 SCCs of the tongue and 68 SCCs of other anatomic regions within the oral cavity...
May 10, 2017: Head & Face Medicine
Marius G Bredell, Jutta Ernst, Ilhem El-Kochairi, Yuliya Dahlem, Kristian Ikenberg, Desiree M Schumann
Head and Neck cancer (HNC) is a complex mix of cancers and one of the more common cancers with a relatively poor prognosis. One of the factors that may assist us in predicting survival and allow us to adjust our treatment strategies is the presence of tumor hypoxia. In this overview we aim to evaluate the current evidence and potential clinical relevance of tumor hypoxia in head and neck cancer according to an extensive search of current literature.An abundance of evidence and often contradictory evidence is found in the literature...
August 2, 2016: Oncotarget
Elodie Hanns, Sylvie Job, Pierre Coliat, Christine Wasylyk, Ludivine Ramolu, Erwan Pencreach, Meggy Suarez-Carmona, Michael Herfs, Sonia Ledrappier, Christine Macabre, Joseph Abecassis, Bohdan Wasylyk, Alain C Jung
OBJECTIVES: Human Papillomavirus (HPV)-related oropharyngeal squamous cell carcinoma (OSCC) patients have improved prognosis compared to other head and neck (HNSCC) cancers. Since poor prognosis is associated with tumour hypoxia, we studied whether the hypoxic response is different in HPV-related cells and tumours. MATERIAL AND METHODS: HPV-positive and -negative cells were incubated in hypoxia and analyzed by qRTPCR, western blotting and cell proliferation assays...
September 2015: Oral Oncology
Justin E Swartz, Ajit J Pothen, Inge Stegeman, Stefan M Willems, Wilko Grolman
Awareness increases that the tumor biology influences treatment outcome and prognosis in cancer. Tumor hypoxia is thought to decrease sensitivity to radiotherapy and some forms of chemotherapy. Presence of hypoxia may be assessed by investigating expression of endogenous markers of hypoxia (EMH) using immunohistochemistry (IHC). In this systematic review we investigated the effect of EMH expression on local control and survival according to treatment modality in head and neck cancer (head and neck squamous cell carcinoma [HNSCC])...
July 2015: Cancer Medicine
M Beloueche-Babari, C Box, V Arunan, H G Parkes, M Valenti, A De Haven Brandon, L E Jackson, S A Eccles, M O Leach
BACKGROUND: Acquired resistance to molecularly targeted therapeutics is a key challenge in personalised cancer medicine, highlighting the need for identifying the underlying mechanisms and early biomarkers of relapse, in order to guide subsequent patient management. METHODS: Here we use human head and neck squamous cell carcinoma (HNSCC) models and nuclear magnetic resonance (NMR) spectroscopy to assess the metabolic changes that follow acquired resistance to EGFR tyrosine kinase inhibitors (TKIs), and which could serve as potential metabolic biomarkers of drug resistance...
March 31, 2015: British Journal of Cancer
Katarzyna Starska, Ewa Forma, Paweł Jóźwiak, Magdalena Bryś, Iwona Lewy-Trenda, Ewa Brzezińska-Błaszczyk, Anna Krześlak
Increased glucose uptake mediated by glucose transporters and reliance on glycolysis are common features of malignant cells. Hypoxia-inducible factor-1α supports the adaptation of hypoxic cells by inducing genes related to glucose metabolism. The contribution of glucose transporter (GLUT) and hypoxia-inducible factor-1α (HIF-1α) activity to tumor behavior and their prognostic value in head and neck cancers remains unclear. The aim of this study was to examine the predictive value of GLUT1, GLUT3, and HIF-1α messenger RNA (mRNA)/protein expression as markers of tumor aggressiveness and prognosis in laryngeal cancer...
April 2015: Tumour Biology: the Journal of the International Society for Oncodevelopmental Biology and Medicine
Kui Zhao, Shu-Ye Yang, Shui-Hong Zhou, Meng Jie Dong, Yang-Yang Bao, Hong-Tian Yao
High fluorodeoxyglucose (FDG) uptake by human carcinomas, including head and neck cancers, is associated with a poor prognosis. Glucose transporter-1 (Glut-1) is believed to be an intrinsic marker of hypoxia in malignant tumors. The expression of hypoxia-inducible factor-1α (HIF-1α) and correlated target genes, including Glut-1, is regulated by the phosphoinositide 3-kinase/protein kinase B (PI3K/Akt) pathway. However, it remains unclear whether the PI3K/Akt signaling pathway is involved in regulating FDG uptake directly...
April 2014: Oncology Letters
Yang-Yang Bao, Shui-Hong Zhou, Jun Fan, Qin-Ying Wang
Apigenin, a natural phytoestrogen flavonoid, has potential biological effects, including antioxidative, anti-inflammatory and anticancer activities. The mechanisms of anticancer activities of apigenin are unknown. Some studies have found that apigenin inhibits GLUT-1 mRNA and protein expression in cancer cells. Thus, we hypothesized that apigenin exerts similar effects on head and neck cancers through its inhibition of GLUT-1 expression. In this article, we review the anticancer mechanism of apigenin and the implications of GLUT-1 expression in head and neck cancers...
September 2013: Future Oncology
X-M Luo, S-H Zhou, J Fan
Treatment options for laryngeal carcinoma, one of the most common head and neck malignancies, consist of radiotherapy, surgery, chemotherapy or a combination thereof. The functional treatment of laryngeal carcinoma poses a considerable challenge because of its resistance to chemotherapy and radiotherapy, and its tendency for local recurrence. Finding ways to inhibit the energy supply of malignant tumours is becoming an increasingly attractive proposition. Glucose transporter-1 (Glut-1; encoded by the SLC2A1 gene in humans) is the main transporter of glucose in solid carcinomas and has become a focus of cancer research...
2010: Journal of International Medical Research
Sébastien Vergez, Jean-Pierre Delord, Fabienne Thomas, Philippe Rochaix, Olivier Caselles, Thomas Filleron, Séverine Brillouet, Pierre Canal, Frédéric Courbon, Ben C Allal
PURPOSE: There is a clinical need to identify predictive markers of the responses to epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKI). Deoxy-2-[(18)F]fluoro-d-glucose positron emission tomography with computed tomography ((18)FDG-PET/CT) could be a tool of choice for monitoring the early effects of this class of agent on tumor activity. EXPERIMENTAL DESIGN: Using models of human head and neck carcinoma (CAL33 and CAL166 cell lines), we first tested in vitro and in vivo whether the in vivo changes in (18)FDG-PET/CT uptake were associated with the molecular and cellular effects of the EGFR-TKI erlotinib...
September 1, 2010: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
Ling-Fa Li, Shui-Hong Zhou, Kui Zhao, Shen-Qing Wang, Qiu-Liang Wu, Jun Fan, Ke-Jia Cheng, Ling Ling
BACKGROUND: The metabolic changes of malignant cells are earlier than these of morphology. (18)F-fluorodeoxyglucose (FDG) single-photon emission computed tomography (SPECT)-computed tomography (CT) systems provide functional and anatomic images that could significantly improve its diagnostic capability. The molecular mechanisms of increased FDG uptake are still not fully understood. The correlation between FDG uptake and the expression of Glut in various tumor cells is still under debate...
December 2008: Cancer Biotherapy & Radiopharmaceuticals
Jong-Lyel Roh, Kyung-Ja Cho, Gui Young Kwon, Chang Hwan Ryu, Hyo Won Chang, Seung-Ho Choi, Soon Yuhl Nam, Sang Yoon Kim
Tumor hypoxia is associated with poorer outcome in patients with head and neck carcinomas, but little is known about hypoxia biomarkers in oral tongue cancer. We evaluated whether hypoxia biomarkers and clinicopathologic variables were prognostic predictors in patients with T2-staged squamous cell carcinoma (SCC) of the oral tongue. Tissue microarrays were constructed from formalin-fixed tumor blocks of 43 patients with T2-staged tongue SCCs treated by surgical resection and neck dissection. Tissue samples were stained with monoclonal antibodies to hypoxia-inducible factor (HIF)-1alpha, HIF-2alpha, carbonic anhydrase (CA)-9, glucose transporter (GLUT)-1, and erythropoietin receptor (EPOR)...
January 2009: Oral Oncology
Shuihong Zhou, Shenqing Wang, Qiuliang Wu, Jun Fan, Qinying Wang
OBJECTIVE: The aim of this study was to determine the biological significance of glucose transporter (Glut)-1 and Glut-3 expression in head and neck carcinoma (HNC). METHODS: We detected expression of Glut-1 and -3 in 38 HNCs and analyzed the relationship between increased expression and the biological behavior of HNCs. RESULTS: The gene expression levels of Glut-1 and -3 in HNCs were significantly higher than those in adjacent cancer tissues or in normal tissues...
2008: ORL; Journal for Oto-rhino-laryngology and its related Specialties
Mark R Albertella, Paul M Loadman, Philip H Jones, Roger M Phillips, Roy Rampling, Neil Burnet, Chris Alcock, Alan Anthoney, Egils Vjaters, Chris R Dunk, Peter A Harris, Alvin Wong, Alshad S Lalani, Chris J Twelves
PURPOSE: AQ4N is a novel bioreductive prodrug under clinical investigation. Preclinical evidence shows that AQ4N penetrates deeply within tumors and undergoes selective activation to form AQ4, a potent topoisomerase II inhibitor, in hypoxic regions of solid tumors. This proof-of-principle, phase I study evaluated the activation, hypoxic selectivity, and safety of AQ4N in patients with advanced solid tumors. EXPERIMENTAL DESIGN: Thirty-two patients with cancer (8 glioblastoma, 9 bladder, 8 head and neck, 6 breast, and 1 cervix) received a single 200 mg/m(2) dose of AQ4N before elective surgery...
February 15, 2008: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
Panomwat Amornphimoltham, Vyomesh Patel, Kantima Leelahavanichkul, Robert T Abraham, J Silvio Gutkind
Emerging evidence supporting the activation of the Akt-mammalian target of rapamycin (mTOR) signaling network in head and neck squamous cell carcinoma (HNSCC) progression has provided the rationale for exploring the therapeutic potential of inhibiting this pathway for HNSCC treatment. Indeed, rapamycin, a clinically relevant mTOR inhibitor, promotes the rapid regression of HNSCC-tumor xenografts in mice. However, rapamycin does not affect the growth of HNSCC cells in vitro, thus raising the possibility that, as for other cancer types, rapamycin may not target cancer cells directly but may instead act on a component of the tumor microenvironment, such as tumor-associated vasculature...
February 15, 2008: Cancer Research
Peter Vaupel, Arnulf Mayer
Hypoxia, a characteristic feature of locally advanced solid tumors, has emerged as a pivotal factor of the tumor (patho-)physiome since it can promote tumor progression and resistance to therapy. Hypoxia represents a "Janus face" in tumor biology because (a) it is associated with restrained proliferation, differentiation, necrosis or apoptosis, and (b) it can also lead to the development of an aggressive phenotype. Independent of standard prognostic factors, such as tumor stage and nodal status, hypoxia has been suggested as an adverse prognostic factor for patient outcome...
June 2007: Cancer Metastasis Reviews
Shui-Hong Zhou, Qiu-Liang Wu, Shen-Qing Wang, Jun Fan, Ling-Fa Li
OBJECTIVE: To study the value of (18)F-FDG dual-head tomography with coincidence (DHTC) and single photon emission computerized tomography (SPECT) coincidence imaging in diagnosis and treatment of head and neck tumors and mechanism thereof and analyze the value of glucose transporter proteins in the mechanism of increased uptake glucose of head and neck malignant tumor. METHODS: Twenty-five patients with head and neck tumors were examined by CT or MRI and underwent (18)F-FDG DHTC and coincidence imaging...
January 9, 2007: Zhonghua Yi Xue za Zhi [Chinese medical journal]
Ruth A Jonathan, Karien I E M Wijffels, Wenny Peeters, Peter C M de Wilde, Henri A M Marres, Matthias A W Merkx, Egbert Oosterwijk, Albert J van der Kogel, Johannes H A M Kaanders
BACKGROUND AND PURPOSE: Hypoxic radioresistance is an important cause for treatment failure in a number of tumor types including head and neck cancers. Recent studies suggest that outcome can be improved by oxygenation modifying treatments such as ARCON. A robust endogenous marker of hypoxia might be a valuable aid to select patients for such treatments. The aim of this investigation was to study associations between the putative endogenous hypoxia markers CA-IX, Glut-1 and Glut-3 and clinical tumor and patient characteristics and to evaluate the prognostic value of these markers...
June 2006: Radiotherapy and Oncology: Journal of the European Society for Therapeutic Radiology and Oncology
Michael F Weiner, Roberto N Miranda, Ricardo H Bardales, Perkins Mukunyadzi, Sandra J Baker, Soheila Korourian, Luis E De Las Casas
The distinction of cystic squamous-cell carcinoma (SCC) from benign cystic squamous lesions (BCSLs) of the head and neck can be problematic on fine-needle aspiration biopsy (FNAB) material, particularly when BCSLs display epithelial reactive atypia or when SCC is well differentiated. Glucose transporter 1 (GLUT-1), a facilitative cell surface glucose transport protein, is aberrantly expressed in many cancers including oral and hypopharyngeal SCC. We evaluated the expression of GLUT-1 by immunochemistry on FNAB material to determine its value in distinguishing cystic SCC from BCSL of the head and neck...
November 2004: Diagnostic Cytopathology
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