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S Bentz, A Cee, E Endlicher, K A Wojtal, A Naami, T Pesch, S Lang, P Schubert, M Fried, A Weber, J F Coy, S Goelder, R Knüchel, M Hausmann, G Rogler
BACKGROUND AND AIMS: Transketolase-like (TKTL) 1 is one of the key enzymes for anaerobic sugar degradation even in the presence of oxygen (aerobic glycolysis). Transketolase-dependent reactions supply malignant tumors with ribose and NADPH. Therefore, TKTL1 activity could be crucial for tumor proliferation and survival. The aim of the study was to evaluate the expression of TKTL1 in colorectal cancer (CRC) and its regulation under hypoxic conditions. METHODS: We studied TKTL1 mRNA and protein expression in CRC cell lines and human CRC biopsies by quantitative real-time PCR, Western blotting and immunohistochemistry...
2013: Digestion
Clemens A Lange, Jan Tisch-Rottensteiner, Daniel Böhringer, Gottfried Martin, Johannes Schwartzkopff, Claudia Auw-Haedrich
PURPOSE: Malignant tumors metabolize glucose to lactate even in the presence of oxygen via the pentose-phosphate pathway. The metabolic switch from oxidative glycolysis to nonoxidative fermentation in tumors has been associated with overexpression of the transketolase-like-1-gene (TKTL1), which encodes an essential and rate-limiting enzyme in the nonoxidative part of the pentose-phosphate pathway. This study investigates the role of TKTL1 in ocular adnexal tumors and analyzes how its expression correlates with the clinical outcomes against the background of tumor thickness and mitotic rate...
September 2012: Ophthalmology
Peter Fritz, Johannes F Coy, Thomas E Mürdter, German Ott, Mark Dominik Alscher, Godehard Friedel
Study of the physiological changes associated with the development of malignancy demonstrates a metabolic signature for the different stages of tumorigenesis. Increased glucose uptake and lactate production have been detected during malignant transformation. Based on energy production, malignancies can be divided into two subclasses: (a) tumor cells which use the mitochondrial machinery for ATP synthesis, and (b) tumor cells which generate ATP by glucose fermentation and lactate production even in the presence of oxygen (aerobic glycolysis)...
April 15, 2012: Pathology, Research and Practice
Juliana Schwaab, Karoline Horisberger, Philipp Ströbel, Beatrice Bohn, Deniz Gencer, Georg Kähler, Peter Kienle, Stefan Post, Frederik Wenz, Wolf-Karsten Hofmann, Ralf-Dieter Hofheinz, Philipp Erben
BACKGROUND: For patients with locally advanced rectal cancer (LARC) neoadjuvant chemoradiotherapy is recommended as standard therapy. So far, no predictive or prognostic molecular factors for patients undergoing multimodal treatment are established. Increased angiogenesis and altered tumour metabolism as adaption to hypoxic conditions in cancers play an important role in tumour progression and metastasis. Enhanced expression of Vascular-endothelial-growth-factor-receptor (VEGF-R) and Transketolase-like-1 (TKTL1) are related to hypoxic conditions in tumours...
2011: BMC Cancer
Arnulf Mayer, Angelika von Wallbrunn, Peter Vaupel
Based on studies performed with a selected mouse monoclonal anti-transketolase- like (TKTL)-1 antibody (clone JFC12T10), overexpression of TKTL-1 has been shown to be correlated with poor survival and increased metastatic spread in several human tumor entities. Since the clinical aggressiveness mediated by TKTL-1 has been partially related to resistance to hypoxia,we originally aimed to explore the influence of hypoxia on the expression of TKTL-1. Unexpectedly, results of our experiments indicated that the antibody clone JFC12T10 lacks target specificity...
2011: Advances in Experimental Medicine and Biology
Susanne Bentz, Theresa Pesch, Lutz Wolfram, Cheryl de Vallière, Katharina Leucht, Michael Fried, Johannes F Coy, Martin Hausmann, Gerhard Rogler
Transketolase-like (TKTL) 1 indirectly replenishes NADPH preventing damage induced by reactive oxygen species (ROS) formed upon intestinal inflammation. We investigated the function of TKTL1 during murine colitis and ROS detoxification for prevention of tissue damage. Mucosal damage in TKTL1(-/-) and wild-type (WT) mice was assessed by miniendoscopy and histology during dextran sodium sulfate (DSS) colitis. mRNA levels of interferon (IFN)-γ, inducible nitric oxide synthase (iNOS), interleukin (IL)-6, tumor necrosis factor (TNF), transketolase (TKT), and TKTL2 were determined by PCR and/or Western blotting...
April 2011: American Journal of Physiology. Gastrointestinal and Liver Physiology
Arnulf Mayer, Angelika Von Wallbrunn, Peter Vaupel
An isoenzyme of transketolase, transketolase-like (TKTL)-1, has been hypothesized to play a pivotal role in the pathophysiology of malignant tumors. Available data are based on the detection of the putative TKTL-1 protein with one particular mouse monoclonal anti-TKTL-1 antibody, clone JFC12T10. In this study it was demonstrated that a) JFC12T10 detects multiple unspecific bands in Western blots, b) a 75-kDa band hitherto referred to as TKTL-1 corresponds to a nuclear protein and c) immunohistochemical detection of TKTL-1 in benign leiomyomas yields an expression pattern identical to that found in a variety of malignant tumors...
August 2010: International Journal of Oncology
Hans-Ullrich Völker, Matthias Scheich, Annette Berndt, Imme Haubitz, Alexandra Metzger, Hans-Konrad Müller-Hermelink, Ulrike Kämmerer, Melanie Schmidt
BACKGROUND: Adenoid cystic carcinomas are rare tumors with an indolent clinical course, but frequent local relapses. The identification of tumors with a higher relapse risk seems to be interesting. Hence we investigated parameters of glucose metabolism, which were found associated with poor prognosis in other malignancies. METHODS: Specimen of 29 patients were investigated immunohistochemically with antibodies against p-AKT, TKTL-1 (transketolase-like 1), M2PK (M2 pyruvate kinase), and GLUT-1...
2009: Diagnostic Pathology
Eleonore Fröhlich, Inge Fink, Richard Wahl
Radioactive iodine-refractory [(18)F] fluorodeoxy-glucose-positron emission tomography-positive thyroid carcinomas represent especially aggressive tumors. Targeting glucose metabolism by the transketolase isoenzyme transketolase like 1 (TKTL-1) which is over-expressed in various neoplasms, may be effective. The correlation of TKTL-1 expression and the response to oxythiamine as the currently best-characterized inhibitor of transketolases was studied in differentiated thyroid cancer cell lines. We determined TKTL-1 expression, proliferation, glucose uptake and GLUT-1 expression in non-treated thyroid cells and recorded the effect of oxythiamine on iodide uptake and on thymidine uptake...
August 2009: Investigational New Drugs
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