{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T04:46:38Z","timestamp":1787028398136,"version":"build-2736575974"},"reference-count":49,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2017,4,20]],"date-time":"2017-04-20T00:00:00Z","timestamp":1492646400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Epitope detection in monocytes (EDIM) represents a liquid biopsy exploiting the innate immune system. Activated monocytes (macrophages) phagocytose unwanted cells\/cell fragments from the whole body including solid tissues. As they return to the blood, macrophages can be used for a non-invasive detection of biomarkers, thereby providing high sensitivity and specificity, because the intracellular presence of biomarkers is due to an innate immune response. Flow cytometry analysis of blood enables the detection of macrophages and phagocytosed intracellular biomarkers. In order to establish a pan-cancer test, biomarkers for two fundamental biophysical mechanisms have been exploited. The DNaseX\/Apo10 protein epitope is a characteristic of tumor cells with abnormal apoptosis and proliferation. Transketolase-like 1 (TKTL1) is a marker for an anaerobic glucose metabolism (Warburg effect), which is concomitant with invasive growth\/metastasis and resistant to radical and apoptosis inducing therapies. The detection of Apo10 and TKTL1 in blood macrophages allowed a sensitive (95.8%) and specific (97.3%) detection of prostate, breast and oral squamous cell carcinomas. Since TKTL1 represents a drugable target, the EDIM based detection of TKTL1 enables a targeted cancer therapy using the vitamin derivatives oxythiamine or benfo-oxythiamine.<\/jats:p>","DOI":"10.3390\/ijms18040878","type":"journal-article","created":{"date-parts":[[2017,4,21]],"date-time":"2017-04-21T04:51:46Z","timestamp":1492750306000},"page":"878","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":25,"title":["EDIM-TKTL1\/Apo10 Blood Test: An Innate Immune System Based Liquid Biopsy for the Early Detection, Characterization and Targeted Treatment of Cancer"],"prefix":"10.3390","volume":"18","author":[{"given":"Johannes","family":"Coy","sequence":"first","affiliation":[{"name":"Zyagnum AG, Lyoner Stra\u00dfe 20, D-60528 Frankfurt am Main, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2017,4,20]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1349","DOI":"10.2217\/fon.12.98","article-title":"EDIM-TKTL1 blood test: A noninvasive method to detect upregulated glucose metabolism in patients with malignancies","volume":"8","author":"Feyen","year":"2012","journal-title":"Future Oncol."},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Grimm, M., Schmitt, S., Teriete, P., Biegner, T., Stenzl, A., Hennenlotter, J., Muhs, H.J., Munz, A., Nadtotschi, T., and K\u00f6nig, K. (2013). A biomarker based detection and characterization of carcinomas exploiting two fundamental biophysical mechanisms in mammalian cells. BMC Cancer, 13.","DOI":"10.1186\/1471-2407-13-569"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"329","DOI":"10.1007\/s00784-015-1518-0","article-title":"Evaluation of a biomarker based blood test for monitoring surgical resection of oral squamous cell carcinomas","volume":"20","author":"Grimm","year":"2016","journal-title":"Clin. Oral Investig."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"605","DOI":"10.2217\/fon.13.8","article-title":"Diagnostic use of epitope detection in monocytes blood test for early detection of colon cancer metastasis","volume":"9","author":"Jansen","year":"2013","journal-title":"Future Oncol."},{"key":"ref_5","first-page":"166","article-title":"Ki67 assessment in breast cancer: An update","volume":"49","year":"2017","journal-title":"Pathology"},{"key":"ref_6","first-page":"1","article-title":"Current therapeutic strategies of anti-HER2 treatment in advanced breast cancer patients","volume":"20","author":"Huszno","year":"2016","journal-title":"Contemp. Oncol."},{"key":"ref_7","doi-asserted-by":"crossref","unstructured":"Ueland, F.R. (2017). A Perspective on Ovarian Cancer Biomarkers: Past, Present and Yet-To-Come. Diagnostics, 7.","DOI":"10.3390\/diagnostics7010014"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"875","DOI":"10.1007\/s00120-013-3193-6","article-title":"PSA screening 2013: Background and perspectives","volume":"53","author":"Recker","year":"2014","journal-title":"Urol. A"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"184","DOI":"10.3816\/CGC.2004.n.029","article-title":"Measurement of intracellular versus extracellular prostate-specific antigen levels in peripheral macrophages: A new approach to noninvasive diagnosis of prostate cancer","volume":"3","author":"Herwig","year":"2004","journal-title":"Clin. Prostate Cancer"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"301","DOI":"10.1016\/j.oooo.2015.10.024","article-title":"Analysis of circulating CD14+\/CD16+ monocyte-derived macrophages (MDMs) in the peripheral blood of patients with oral squamous cell carcinoma","volume":"121","author":"Grimm","year":"2016","journal-title":"Oral Surg. Oral Med. Oral Pathol. Oral Radiol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"649","DOI":"10.1309\/THWWRU8L42U5H9PB","article-title":"Circulating PSA-containing macrophages as a possible target for the detection of prostate cancer: A three-color\/five-parameter flow cytometric study on peripheral blood samples","volume":"129","author":"Leers","year":"2008","journal-title":"Am. J. Clin. Pathol."},{"key":"ref_12","first-page":"3245","article-title":"CEA in activated macrophages. New diagnostic possibilities for tumor markers in early colorectal cancer","volume":"29","author":"Japink","year":"2009","journal-title":"Anticancer Res."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"435","DOI":"10.1007\/s13277-011-0269-z","article-title":"Activated macrophages containing tumor marker in colon carcinoma: Immunohistochemical proof of a concept","volume":"33","author":"Faber","year":"2012","journal-title":"Tumor Biol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"295","DOI":"10.1007\/s10006-016-0549-2","article-title":"Monitoring carcinogenesis in a case of oral squamous cell carcinoma using a panel of new metabolic blood biomarkers as liquid biopsies","volume":"20","author":"Grimm","year":"2016","journal-title":"Oral Maxillofac. Surg."},{"key":"ref_15","first-page":"199","article-title":"Isolation, differential splicing and protein expression of a DNase on the human X chromosome","volume":"3","author":"Coy","year":"1996","journal-title":"Cell Death Differ."},{"key":"ref_16","first-page":"2727","article-title":"Altered deoxyribonuclease activity in cancer cells and its role in non-toxic adjuvant cancer therapy with mixed vitamins C and K3","volume":"28","author":"Taper","year":"2008","journal-title":"Anticancer Res."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"376","DOI":"10.1016\/S0090-8258(03)00061-1","article-title":"Changes in the topological expression of markers of differentiation and apoptosis in defined stages of human cervical dysplasia and carcinoma","volume":"89","author":"Zanotti","year":"2003","journal-title":"Gynecol. Oncol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"309","DOI":"10.1006\/geno.1996.0124","article-title":"Molecular cloning of tissue-specific transcripts of a transketolase-related gene: Implications for the evolution of new vertebrate genes","volume":"32","author":"Coy","year":"1996","journal-title":"Genomics"},{"key":"ref_19","first-page":"257","article-title":"Mutations in the transketolase-like gene TKTL1: Clinical implications for neurodegenerative diseases, diabetes and cancer","volume":"51","author":"Coy","year":"2005","journal-title":"Clin. Lab."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"578","DOI":"10.1038\/sj.bjc.6602962","article-title":"Expression of transketolase TKTL1 predicts colon and urothelial cancer patient survival: Warburg effect reinterpreted","volume":"94","author":"Langbein","year":"2006","journal-title":"Br. J. Cancer"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"1330","DOI":"10.1002\/ijc.24078","article-title":"Transketolase-like protein 1 (TKTL1) is required for rapid cell growth and full viability of human tumor cells","volume":"124","author":"Xu","year":"2009","journal-title":"Int. J. Cancer"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"857","DOI":"10.1158\/1078-0432.CCR-09-2604","article-title":"TKTL1 is activated by promoter hypomethylation and contributes to head and neck squamous cell carcinoma carcinogenesis through increased aerobic glycolysis and HIF1\u03b1 stabilization","volume":"16","author":"Sun","year":"2010","journal-title":"Clin. Cancer Res."},{"key":"ref_23","doi-asserted-by":"crossref","unstructured":"Jayachandran, A., Lo, P.H., Chueh, A.C., Prithviraj, P., Molania, R., Davalos-Salas, M., Anaka, M., Walkiewicz, M., Cebon, J., and Behren, A. (2016). Transketolase-like 1 ectopic expression is associated with DNA hypomethylation and induces the Warburg effect in melanoma cells. BMC Cancer, 16.","DOI":"10.1186\/s12885-016-2185-5"},{"key":"ref_24","first-page":"309","article-title":"\u00dcber den Stoffwechsel der Carcinomzelle","volume":"152","author":"Warburg","year":"1924","journal-title":"Biochem. Z."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"51875","DOI":"10.18632\/oncotarget.10429","article-title":"A key role for Transketolase-like 1 in tumor metabolic reprogramming","volume":"7","author":"Aguilar","year":"2016","journal-title":"Oncotarget"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"20","DOI":"10.1016\/j.canlet.2010.08.017","article-title":"Transketolase-like protein 1 confers resistance to serum withdrawal in vitro","volume":"300","author":"Hartmannsberger","year":"2011","journal-title":"Cancer Lett."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"199","DOI":"10.1093\/humrep\/des360","article-title":"Identification of genital tract markers in the human seminal plasma using an integrative genomics approach","volume":"28","author":"Rolland","year":"2013","journal-title":"Hum. Reprod."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"367","DOI":"10.1111\/acel.12181","article-title":"Downregulation of the Werner syndrome protein induces a metabolic shift that compromises redox homeostasis and limits proliferation of cancer cells","volume":"13","author":"Li","year":"2014","journal-title":"Aging Cell"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"2","DOI":"10.1186\/1742-4682-7-2","article-title":"Cancer proliferation and therapy: The Warburg effect and quantum metabolism","volume":"7","author":"Demetrius","year":"2010","journal-title":"Theor. Biol. Med. Model."},{"key":"ref_30","first-page":"99","article-title":"The living state and cancer","volume":"12","year":"1980","journal-title":"Physiol. Chem. Phys."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"393","DOI":"10.1016\/S0021-9258(18)71280-5","article-title":"The mechanism of pentose phosphate conversion to hexose monophosphate. I. With a liver enzyme preparation","volume":"207","author":"Horecker","year":"1954","journal-title":"J. Biol. Chem."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"1477","DOI":"10.1038\/ncb1807","article-title":"Glucose metabolism inhibits apoptosis in neurons and cancer cells by redox inactivation of cytochrome c","volume":"10","author":"Vaughn","year":"2008","journal-title":"Nat. Cell Biol."},{"key":"ref_33","doi-asserted-by":"crossref","unstructured":"Newington, J.T., Pitts, A., Chien, A., Arseneault, R., Schubert, D., and Cumming, R.C. (2011). Amyloid beta resistance in nerve cell lines is mediated by the Warburg effect. PLoS ONE, 6.","DOI":"10.1371\/journal.pone.0019191"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"43","DOI":"10.1038\/nature12886","article-title":"The complete genome sequence of a Neanderthal from the Altai Mountains","volume":"505","author":"Racimo","year":"2014","journal-title":"Nature"},{"key":"ref_35","doi-asserted-by":"crossref","unstructured":"Schwaab, J., Horisberger, K., Str\u00f6bel, P., Bohn, B., Gencer, D., K\u00e4hler, G., Kienle, P., Post, S., Wenz, F., and Hofmann, W.K. (2011). Expression of Transketolase like gene 1 (TKTL1) predicts disease-free survival in patients with locally advanced rectal cancer receiving neoadjuvant chemoradiotherapy. BMC Cancer, 11.","DOI":"10.1186\/1471-2407-11-363"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"293","DOI":"10.1111\/j.1447-0756.2008.00749.x","article-title":"Expression of transketolase-like 1 (TKTL1) and p-Akt correlates with the progression of cervical neoplasia","volume":"34","author":"Kohrenhagen","year":"2008","journal-title":"J. Obstet. Gynaecol. Res."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"43","DOI":"10.1186\/1756-9966-28-43","article-title":"Overexpression of transketolase-like gene 1 is associated with cell proliferation in uterine cervix cancer","volume":"28","author":"Chen","year":"2009","journal-title":"J. Exp. Clin. Cancer Res."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"936","DOI":"10.1002\/cncr.23683","article-title":"Increased expression of transketolase-like-1 in papillary thyroid carcinomas smaller than 1.5 cm in diameter is associated with lymph-node metastases","volume":"113","author":"Zerilli","year":"2008","journal-title":"Cancer"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"719","DOI":"10.1097\/PAT.0b013e32834c352b","article-title":"Poor outcome in primary non-small cell lung cancers is predicted by transketolase TKTL1 expression","volume":"43","author":"Kayser","year":"2011","journal-title":"Pathology"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"591","DOI":"10.3233\/CBM-150499","article-title":"TKTL1 and p63 are biomarkers for the poor prognosis of gastric cancer patients","volume":"15","author":"Song","year":"2015","journal-title":"Cancer Biomark."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"71","DOI":"10.1016\/j.biopha.2015.07.004","article-title":"TKTL1 promotes cell proliferation and metastasis in esophageal squamous cell carcinoma","volume":"74","author":"Li","year":"2015","journal-title":"Biomed. Pharmacother."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"163","DOI":"10.1080\/15384047.2015.1121347","article-title":"Transketolase-like protein 1 expression predicts poor prognosis in colorectal cancer","volume":"17","author":"Ahopelto","year":"2016","journal-title":"Cancer Biol. Ther."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"3812","DOI":"10.1182\/blood-2006-07-035972","article-title":"Inhibitory effect of tumor cell-derived lactic acid on human T cells","volume":"109","author":"Fischer","year":"2007","journal-title":"Blood"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"657","DOI":"10.1016\/j.cmet.2016.08.011","article-title":"LDHA-Associated Lactic Acid Production Blunts Tumor Immunosurveillance by T and NK Cells","volume":"24","author":"Brand","year":"2016","journal-title":"Cell Metab."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"E725","DOI":"10.1073\/pnas.1508779113","article-title":"Transketolase counteracts oxidative stress to drive cancer development","volume":"113","author":"Xu","year":"2016","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"2962","DOI":"10.1038\/onc.2010.67","article-title":"Imatinib resistance associated with BCR-ABL upregulation is dependent on HIF-1alpha-induced metabolic reprograming","volume":"29","author":"Zhao","year":"2010","journal-title":"Oncogene"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"866","DOI":"10.1002\/pmic.201200303","article-title":"Increased anaerobic metabolism is a distinctive signature in a colorectal cancer cellular model of resistance to antiepidermal growth factor receptor antibody","volume":"13","author":"Monteleone","year":"2013","journal-title":"Proteomics"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"441","DOI":"10.1007\/s10585-015-9718-1","article-title":"Transketolase is upregulated in metastatic peritoneal implants and promotes ovarian cancer cell proliferation","volume":"32","author":"Ricciardelli","year":"2015","journal-title":"Clin. Exp. Metastasis"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"672","DOI":"10.1016\/j.biopha.2016.11.078","article-title":"Knockdown of TKTL1 additively complements cisplatin-induced cytotoxicity in nasopharyngeal carcinoma cells by regulating the levels of NADPH and ribose-5-phosphate","volume":"85","author":"Dong","year":"2017","journal-title":"Biomed. Pharmacother."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/18\/4\/878\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T18:33:06Z","timestamp":1760207586000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/18\/4\/878"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2017,4,20]]},"references-count":49,"journal-issue":{"issue":"4","published-online":{"date-parts":[[2017,4]]}},"alternative-id":["ijms18040878"],"URL":"https:\/\/doi.org\/10.3390\/ijms18040878","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2017,4,20]]}}}