Gene Symbol: HB-EGF
Description: heparin binding EGF like growth factor
Alias: DTR, DTS, DTSF, HEGFL, proheparin-binding EGF-like growth factor, diphtheria toxin receptor (heparin-binding EGF-like growth factor), diphtheria toxin receptor (heparin-binding epidermal growth factor-like growth factor), heparin-binding epidermal growth factor
Species: human
Products:     HB-EGF

Top Publications

  1. Koshikawa N, Mizushima H, Minegishi T, Eguchi F, Yotsumoto F, Nabeshima K, et al. Proteolytic activation of heparin-binding EGF-like growth factor by membrane-type matrix metalloproteinase-1 in ovarian carcinoma cells. Cancer Sci. 2011;102:111-6 pubmed publisher
    ..b>HB EGF-like growth factor has been reported to promote the malignant progression of ovarian carcinoma...
  2. Rittie L, Kansra S, Stoll S, Li Y, Gudjonsson J, Shao Y, et al. Differential ErbB1 signaling in squamous cell versus basal cell carcinoma of the skin. Am J Pathol. 2007;170:2089-99 pubmed
    ..Our results suggest that targeting ErbB1 signaling might be of benefit in the treatment of SCC. ..
  3. Kinugasa Y, Hieda M, Hori M, Higashiyama S. The carboxyl-terminal fragment of pro-HB-EGF reverses Bcl6-mediated gene repression. J Biol Chem. 2007;282:14797-806 pubmed
    ..These findings suggest that HB-EGF-CTF is a potent regulator of gene expression via its interaction with the transcriptional repressor Bcl6. ..
  4. Kodama T, Ikeda E, Okada A, Ohtsuka T, Shimoda M, Shiomi T, et al. ADAM12 is selectively overexpressed in human glioblastomas and is associated with glioblastoma cell proliferation and shedding of heparin-binding epidermal growth factor. Am J Pathol. 2004;165:1743-53 pubmed
  5. Hirata Y, Ogasawara N, Sasaki M, Mizushima T, Shimura T, Mizoshita T, et al. BCL6 degradation caused by the interaction with the C-terminus of pro-HB-EGF induces cyclin D2 expression in gastric cancers. Br J Cancer. 2009;100:1320-9 pubmed publisher
    ..Inhibition of HB-EGF-CTF nuclear translocation and maintenance of BCL6 function are important for the regulation of gastric cancer progression. ..
  6. Revillion F, Lhotellier V, Hornez L, Bonneterre J, Peyrat J. ErbB/HER ligands in human breast cancer, and relationships with their receptors, the bio-pathological features and prognosis. Ann Oncol. 2008;19:73-80 pubmed
    ..Our study demonstrates that (i) ErbB/HER ligands, including BTC and EREG, are expressed in most breast cancers; and (ii) TGFalpha, HB-EGF and NRG2 high expressions are related to the biological aggressiveness of the tumours. ..
  7. Thompson S, Higashiyama S, Wood K, Pollitt N, Damm D, McEnroe G, et al. Characterization of sequences within heparin-binding EGF-like growth factor that mediate interaction with heparin. J Biol Chem. 1994;269:2541-9 pubmed
  8. Higashiyama S, Abraham J, Miller J, Fiddes J, Klagsbrun M. A heparin-binding growth factor secreted by macrophage-like cells that is related to EGF. Science. 1991;251:936-9 pubmed
    ..HB-EGF is also expressed in cultured human macrophages and may be involved in macrophage-mediated cellular proliferation. ..
  9. Rittie L, Varani J, Kang S, Voorhees J, Fisher G. Retinoid-induced epidermal hyperplasia is mediated by epidermal growth factor receptor activation via specific induction of its ligands heparin-binding EGF and amphiregulin in human skin in vivo. J Invest Dermatol. 2006;126:732-9 pubmed
    ..These data demonstrate the central role of EGFR activation in retinoid-induced epidermal hyperplasia, and suggest that EGFR inhibitors can mitigate retinoid-induced scaling. ..

More Information


  1. Stoll S, Johnson J, Bhasin A, Johnston A, Gudjonsson J, Rittie L, et al. Metalloproteinase-mediated, context-dependent function of amphiregulin and HB-EGF in human keratinocytes and skin. J Invest Dermatol. 2010;130:295-304 pubmed publisher
    ..These data show that distinct EGFR ligands stimulate KC behavior in different cellular contexts, and in an MP-dependent fashion. ..
  2. Yagi H, Yotsumoto F, Miyamoto S. Heparin-binding epidermal growth factor-like growth factor promotes transcoelomic metastasis in ovarian cancer through epithelial-mesenchymal transition. Mol Cancer Ther. 2008;7:3441-51 pubmed publisher
    ..Thus, HB-EGF is a mutual validating target in the peritoneal dissemination of ovarian cancer, and CRM197 may be useful as a anticancer agent for advanced ovarian cancer. ..
  3. Kobrin M, Funatomi H, Friess H, Buchler M, Stathis P, Korc M. Induction and expression of heparin-binding EGF-like growth factor in human pancreatic cancer. Biochem Biophys Res Commun. 1994;202:1705-9 pubmed
    ..These findings suggest that HB-EGF may participate in aberrant autocrine and paracrine activation of the EGF receptor, thereby contributing to pancreatic cancer cell growth. ..
  4. Nanba D, Mammoto A, Hashimoto K, Higashiyama S. Proteolytic release of the carboxy-terminal fragment of proHB-EGF causes nuclear export of PLZF. J Cell Biol. 2003;163:489-502 pubmed
    ..These results indicate that released HB-EGF-C functions as an intracellular signal and coordinates cell cycle progression with HB-EGF. ..
  5. Ohnishi Y, Inoue H, Furukawa M, Kakudo K, Nozaki M. Heparin-binding epidermal growth factor-like growth factor is a potent regulator of invasion activity in oral squamous cell carcinoma. Oncol Rep. 2012;27:954-8 pubmed publisher
    ..These data indicate that HB-EGF released from HSC3 cells by TACE stimulates EGFR in an autocrine manner, which in turn activates invasion activity via MMP-9 upregulation. ..
  6. Yagi H, Miyamoto S, Tanaka Y, Sonoda K, Kobayashi H, Kishikawa T, et al. Clinical significance of heparin-binding epidermal growth factor-like growth factor in peritoneal fluid of ovarian cancer. Br J Cancer. 2005;92:1737-45 pubmed
    ..These results suggested that HB-EGF in peritoneal fluid might play a key role in cell survival and in the proliferation of OVCA. ..
  7. Hashimoto K, Higashiyama S, Asada H, Hashimura E, Kobayashi T, Sudo K, et al. Heparin-binding epidermal growth factor-like growth factor is an autocrine growth factor for human keratinocytes. J Biol Chem. 1994;269:20060-6 pubmed
    ..9-fold at 1 h. These results suggest that HB-EGF is an autocrine growth factor for human keratinocytes, and HB-EGF and TGF-alpha act not only by an autoinductive mechanism but also by mutual amplification. ..
  8. Shimura T, Yoshida M, Fukuda S, Ebi M, Hirata Y, Mizoshita T, et al. Nuclear translocation of the cytoplasmic domain of HB-EGF induces gastric cancer invasion. BMC Cancer. 2012;12:205 pubmed publisher
    ..The present study demonstrated that HB-EGF-C nuclear translocation might be crucial in gastric cancer invasion. HB-EGF-C nuclear translocation may offer a prognostic marker and a new molecular target for gastric cancer therapy. ..
  9. Chen J, Capdevila J, Harris R. Heparin-binding EGF-like growth factor mediates the biological effects of P450 arachidonate epoxygenase metabolites in epithelial cells. Proc Natl Acad Sci U S A. 2002;99:6029-34 pubmed
    ..This mechanism involves EET-dependent activation of metalloproteinases and release of the potent mitogenic EGFR ligand, HB-EGF. ..
  10. Hamaoka M, Chinen I, Murata T, Takashima S, Iwamoto R, Mekada E. Anti-human HB-EGF monoclonal antibodies inhibiting ectodomain shedding of HB-EGF and diphtheria toxin binding. J Biochem. 2010;148:55-69 pubmed publisher
    ..Hence, these new anti-HB-EGF mAbs may advance clinical as well as basic research on HB-EGF. ..
  11. Lue H, Yang X, Wang R, Qian W, Xu R, LYLES R, et al. LIV-1 promotes prostate cancer epithelial-to-mesenchymal transition and metastasis through HB-EGF shedding and EGFR-mediated ERK signaling. PLoS ONE. 2011;6:e27720 pubmed publisher
    ..LIV-1 could be an attractive therapeutic target for the eradication of pre-existing human prostate cancer and bone and soft tissue metastases. ..
  12. Tolino M, Block E, Klarlund J. Brief treatment with heparin-binding EGF-like growth factor, but not with EGF, is sufficient to accelerate epithelial wound healing. Biochim Biophys Acta. 2011;1810:875-8 pubmed publisher
    ..EGF has been used experimentally to treat poorly healing wounds, but the frequent applications that are necessary have hampered its use clinically. The findings imply that HB-EGF may be a useful long-acting alternative to EGF. ..
  13. Higashiyama S, Lau K, Besner G, Abraham J, Klagsbrun M. Structure of heparin-binding EGF-like growth factor. Multiple forms, primary structure, and glycosylation of the mature protein. J Biol Chem. 1992;267:6205-12 pubmed
    ..Further analysis of the most predominant form of HB-EGF found in U-937 cell conditioned medium indicated that it has a pI of 7.2-7.8 and is O-glycosylated. ..
  14. Mitamura T, Higashiyama S, Taniguchi N, Klagsbrun M, Mekada E. Diphtheria toxin binds to the epidermal growth factor (EGF)-like domain of human heparin-binding EGF-like growth factor/diphtheria toxin receptor and inhibits specifically its mitogenic activity. J Biol Chem. 1995;270:1015-9 pubmed
    ..These results confirmed further that DT interacts with the EGF-like domain of HB-EGF and that this interaction is specific for human HB-EGF. ..
  15. Dateoka S, Ohnishi Y, Kakudo K. Effects of CRM197, a specific inhibitor of HB-EGF, in oral cancer. Med Mol Morphol. 2012;45:91-7 pubmed publisher
    ..Also, the coadministration of CDDP and CRM197 at 1 mg/kg/day completely inhibited tumor formation. These results suggest that HB-EGF is a target for oral cancer and that CRM197 is effective in oral cancer therapy. ..
  16. Wang F, Liu R, Lee S, Sloss C, Couget J, Cusack J. Heparin-binding EGF-like growth factor is an early response gene to chemotherapy and contributes to chemotherapy resistance. Oncogene. 2007;26:2006-16 pubmed
    ..Therefore, therapeutic intervention aimed at inhibiting HB-EGF activity may be useful in cancer prevention and treatments. ..
  17. Giltaire S, Lambert S, Poumay Y. HB-EGF synthesis and release induced by cholesterol depletion of human epidermal keratinocytes is controlled by extracellular ATP and involves both p38 and ERK1/2 signaling pathways. J Cell Physiol. 2011;226:1651-9 pubmed publisher
    ..ATP induces HB-EGF synthesis and release by interacting with the P2 purinergic receptor and through p38 and ERK1/2 signaling in response to a challenging environment. A release of ATP acts as an early stress response in keratinocytes. ..
  18. Murayama Y, Miyagawa J, Shinomura Y, Kanayama S, Isozaki K, Yamamori K, et al. Significance of the association between heparin-binding epidermal growth factor-like growth factor and CD9 in human gastric cancer. Int J Cancer. 2002;98:505-13 pubmed
    ..These results indicate that the coexpression of proHB-EGF and CD9 may be involved in the tumorigenesis and/or proliferation of gastric cancers in a juxtacrine manner. ..
  19. Iwamoto R, Higashiyama S, Mitamura T, Taniguchi N, Klagsbrun M, Mekada E. Heparin-binding EGF-like growth factor, which acts as the diphtheria toxin receptor, forms a complex with membrane protein DRAP27/CD9, which up-regulates functional receptors and diphtheria toxin sensitivity. EMBO J. 1994;13:2322-30 pubmed
    DRAP27, the monkey homolog of human CD9 antigen (DRAP27/CD9) and diphtheria toxin receptor (DTR) were expressed in mouse L cells...
  20. Gschwind A, Hart S, Fischer O, Ullrich A. TACE cleavage of proamphiregulin regulates GPCR-induced proliferation and motility of cancer cells. EMBO J. 2003;22:2411-21 pubmed
    ..Thus, TACE can function as an effector of GPCR-mediated signalling and represents a key element of the cellular receptor cross-talk network. ..
  21. Zhao Y, He D, Saatian B, Watkins T, Spannhake E, Pyne N, et al. Regulation of lysophosphatidic acid-induced epidermal growth factor receptor transactivation and interleukin-8 secretion in human bronchial epithelial cells by protein kinase Cdelta, Lyn kinase, and matrix metalloproteinases. J Biol Chem. 2006;281:19501-11 pubmed
  22. Mathay C, Giltaire S, Minner F, Bera E, Herin M, Poumay Y. Heparin-binding EGF-like growth factor is induced by disruption of lipid rafts and oxidative stress in keratinocytes and participates in the epidermal response to cutaneous wounds. J Invest Dermatol. 2008;128:717-27 pubmed
  23. Ongusaha P, Kwak J, Zwible A, Macip S, Higashiyama S, Taniguchi N, et al. HB-EGF is a potent inducer of tumor growth and angiogenesis. Cancer Res. 2004;64:5283-90 pubmed
    ..These findings establish s-HB-EGF as a potent inducer of tumor growth and angiogenesis and suggest that therapeutic intervention aimed at the inhibition of s-HB-EGF functions may be useful in cancer treatment. ..
  24. Lin J, Hutchinson L, Gaston S, Raab G, Freeman M. BAG-1 is a novel cytoplasmic binding partner of the membrane form of heparin-binding EGF-like growth factor: a unique role for proHB-EGF in cell survival regulation. J Biol Chem. 2001;276:30127-32 pubmed
  25. Elenius K, Paul S, Allison G, Sun J, Klagsbrun M. Activation of HER4 by heparin-binding EGF-like growth factor stimulates chemotaxis but not proliferation. EMBO J. 1997;16:1268-78 pubmed
    ..It was concluded that HER4 is a newly described receptor for HB-EGF and that HB-EGF can activate two EGF receptor subtypes, HER1 and HER4, but with different biological responses. ..
  26. Gao J, Ulekleiv C, Halstensen T. Epidermal growth factor (EGF) receptor-ligand based molecular staging predicts prognosis in head and neck squamous cell carcinoma partly due to deregulated EGF- induced amphiregulin expression. J Exp Clin Cancer Res. 2016;35:151 pubmed
    ..Not applicable as the clinical data of the 498 HNSCC patients and their mRNA expression profiles were collected from the open TCGA database: http://cancergenome.nih.gov/cancersselected/headandneck . ..
  27. Svensson K, Kucharzewska P, Christianson H, Sköld S, Löfstedt T, Johansson M, et al. Hypoxia triggers a proangiogenic pathway involving cancer cell microvesicles and PAR-2-mediated heparin-binding EGF signaling in endothelial cells. Proc Natl Acad Sci U S A. 2011;108:13147-52 pubmed publisher
    ..The identified pathway may constitute an interesting target for the development of additional strategies to treat aggressive brain tumors. ..
  28. Bijelic Donova J, Garoushi S, Vallittu P, Lassila L. Mechanical properties, fracture resistance, and fatigue limits of short fiber reinforced dental composite resin. J Prosthet Dent. 2016;115:95-102 pubmed publisher
    ..The properties investigated were flexural strength (FS), compression strength (CS), diametral-tensile strength (DTS), and single-edge-notched-bend fracture toughness (FT) following ISO standards...
  29. Finger Stadler A, Patel M, Pacholczyk R, Cutler C, Arce R. Long-term sustainable dendritic cell-specific depletion murine model for periodontitis research. J Immunol Methods. 2017;449:7-14 pubmed publisher
    ..Hence, the objectives of this study were to validate the zDC-DTR knockin mouse model of conventional DCs (cDCs) depletion, as well as to investigate whether this depletion could be ..
  30. Tokarek T, Szpor J, Pankowski J, Okoń K. Desmoid tumor of lung with pleural involvement - the case of unique location of aggressive fibromatosis. Folia Med Cracov. 2015;55:53-9 pubmed
    Desmoid tumors (DTs) are rare mesenchymal neoplasms with unpredictable natural history. There is a high risk of recurrence despite adequate surgical resection, however DTs do not have the capacity to metastasize...
  31. Tang J, Xiao C, Li Y, Zhang J, Zhai H, Geng X, et al. Effects of diurnal temperature range on mortality in Hefei city, China. Int J Biometeorol. 2018;62:851-860 pubmed publisher
    Although several studies indicated an association between diurnal temperature range (DTR) and mortality, the results about modifiers are inconsistent, and few studies were conducted in developing inland country...
  32. . Anti-Human HB-EGF Monoclonal Antibody. Monoclon Antib Immunodiagn Immunother. 2016;35:123 pubmed publisher
  33. Hatch A, Sibley A, Starr M, Brady J, Jiang C, Jia J, et al. Blood-based markers of efficacy and resistance to cetuximab treatment in metastatic colorectal cancer: results from CALGB 80203 (Alliance). Cancer Med. 2016;5:2249-60 pubmed publisher
    ..049). Although these results are preliminary, and confirmatory studies are necessary before clinical application, the data suggest that HER3 and CD73 may play important roles in the biological response to cetuximab. ..
  34. Toki F, Nanba D, Matsuura N, Higashiyama S. Ectodomain shedding of membrane-anchored heparin-binding EGF like growth factor and subcellular localization of the C-terminal fragment in the cell cycle. J Cell Physiol. 2005;202:839-48 pubmed
  35. Shishido Y, Tanaka T, Piao Y, Araki K, Takei N, Higashiyama S, et al. Activity-dependent shedding of heparin-binding EGF-like growth factor in brain neurons. Biochem Biophys Res Commun. 2006;348:963-70 pubmed
    ..Therefore, we propose that glutamatergic neurotransmission in the central nervous system plays a crucial role in regulating ectodomain shedding of pro-HB-EGF. ..
  36. Armant D, Kilburn B, Petkova A, Edwin S, Duniec Dmuchowski Z, Edwards H, et al. Human trophoblast survival at low oxygen concentrations requires metalloproteinase-mediated shedding of heparin-binding EGF-like growth factor. Development. 2006;133:751-9 pubmed
    ..These findings have a high clinical significance, as the downregulation of HBEGF in pre-eclampsia is likely to be a contributing factor leading to the demise of trophoblasts. ..
  37. Diaz B, Yuen A, Iizuka S, Higashiyama S, Courtneidge S. Notch increases the shedding of HB-EGF by ADAM12 to potentiate invadopodia formation in hypoxia. J Cell Biol. 2013;201:279-92 pubmed publisher
    ..This signaling pathway might regulate the coordinated acquisition of invasiveness by neighboring cells and mediate the communication between normoxic and hypoxic areas of tumors to facilitate cancer cell invasion. ..
  38. Liu S, Guo J, Hu X, Zhang H, Shang Q, Xu W, et al. [Comparative study of X-ray digital DTS imaging and kidney ureter bladder radiography in urinary calculi]. Zhonghua Yi Xue Za Zhi. 2015;95:2010-3 pubmed
    To investigate the value of X-ray digital tomosynthesis (DTS) in the diagnosis of urinary stones compared with kidney ureter bladder radiography...
  39. Schiefenhövel F, Immig K, Prodinger C, Bechmann I. Indications for cellular migration from the central nervous system to its draining lymph nodes in CD11c-GFP+ bone-marrow chimeras following EAE. Exp Brain Res. 2017;235:2151-2166 pubmed publisher
    ..Using CD11c-diphtheria toxin receptor (DTR)-green fluorescent protein (GFP) transgenic (tg) mice, we have shown the existence of CD11c+ cells, a ..
  40. Long D, Ulici V, Chubinskaya S, Loeser R. Heparin-binding epidermal growth factor-like growth factor (HB-EGF) is increased in osteoarthritis and regulates chondrocyte catabolic and anabolic activities. Osteoarthritis Cartilage. 2015;23:1523-31 pubmed publisher
    ..HB-EGF is a new factor identified in OA cartilage that promotes chondrocyte catabolic activity while inhibiting anabolic activity suggesting it could contribute to the catabolic-anabolic imbalance seen in OA cartilage. ..
  41. Yamamoto T, Akisue T, Marui T, Nakatani T, Kawamoto T, Hitora T, et al. Expression of betacellulin, heparin-binding epidermal growth factor and epiregulin in human malignant fibrous histiocytoma. Anticancer Res. 2004;24:2007-10 pubmed
    ..It is suggested that HB-EGF and EPR might be more important tumor growth regulators of MFH through autocrine or paracrine pathways, when compared with BTC. ..
  42. Thornton K, Kamanga Sollo E, White M, Dayton W. Active G protein-coupled receptors (GPCR), matrix metalloproteinases 2/9 (MMP2/9), heparin-binding epidermal growth factor (hbEGF), epidermal growth factor receptor (EGFR), erbB2, and insulin-like growth factor 1 receptor (IGF-1R) are necessary for t. J Anim Sci. 2016;94:2332-43 pubmed publisher
    ..Furthermore, it appears the protein kinase B pathway is involved in TBA's effects on fused BSC cultures. ..
  43. Zhao D, Zhang X, Xie M, Cheng J, Zhang H, Wang S, et al. Is greater temperature change within a day associated with increased emergency admissions for schizophrenia?. Sci Total Environ. 2016;566-567:1545-1551 pubmed publisher
    Diurnal temperature range (DTR), as an important index of climate change, has been increasingly used to evaluate the impacts of temperature variability on human health. However, little is known about the effects of DTR on schizophrenia...
  44. Shirako T, Churei H, Wada T, Uo M, Ueno T. Establishment of experimental models to evaluate the effectiveness of dental trauma splints. Dent Mater J. 2017;36:731-739 pubmed publisher
    The purpose was to describe a novel simple experimental model of injured teeth for developing dental trauma splints (DTS), and to test various splints by combining use of this model and the Periotest® device...
  45. Harendra G, Jayasekara R, Dissanayake V. Haplotypes of heparin-binding epidermal-growth-factor-like growth factor gene are associated with pre-eclampsia. J Obstet Gynaecol Res. 2012;38:239-46 pubmed publisher
    ..The haplotypes are likely to exert their effects through the numerous transcription regulation factors binding to the polymorphic sites, namely GATA-1, GATA-3, MZF-1 and AML-1a. ..
  46. Zhu W, Qiu J, Ma L, Lei H, Cai Z, Zhao H, et al. A new scoring system for evaluating coronary artery disease by using blood pressure variability. Australas Phys Eng Sci Med. 2017;40:751-758 pubmed publisher
    ..Pearson's tests were first performed to identify the parameters that correlated with Duke Treadmill Score (DTS)...
  47. Tan M, Cao X, Li P, Zhai Y, Zhou Y, Liu Y, et al. Effectively enhancing cytotoxic and apoptotic effects of alpha-momorcharin by integrating a heparin-binding peptide. Biotechnol Appl Biochem. 2017;64:918-926 pubmed publisher
    ..Our study provided a new practical way to greatly improve the antitumor activity of ?-MMC, which could significantly expand the pharmaceutical applications of ?-MMC. ..
  48. Zhang Y, Velez Delgado A, Mathew E, Li D, Mendez F, Flannagan K, et al. Myeloid cells are required for PD-1/PD-L1 checkpoint activation and the establishment of an immunosuppressive environment in pancreatic cancer. Gut. 2017;66:124-136 pubmed publisher
    ..Primary mouse pancreatic cancer cells were transplanted into CD11b-diphtheria toxin receptor (DTR) mice. Alternatively, the iKras* mouse model of pancreatic cancer was crossed into CD11b-DTR mice...
  49. Oshiro T, Sato Y, Nabekura T, Kitahara T, Sato A, Kadoya K, et al. Proximal Gastrectomy with Double Tract Reconstruction Is an Alternative Revision Surgery for Intractable Complications After Sleeve Gastrectomy. Obes Surg. 2017;27:3333-3336 pubmed publisher
    ..We describe two cases in which proximal gastrectomy with double tract reconstruction (PG with DTR) was performed in patients with chronic gastric fistula and twisted gastric tube after SG...
  50. Tschumperlin D, Shively J, Swartz M, Silverman E, Haley K, Raab G, et al. Bronchial epithelial compression regulates MAP kinase signaling and HB-EGF-like growth factor expression. Am J Physiol Lung Cell Mol Physiol. 2002;282:L904-11 pubmed
    ..These results demonstrate that compressive stress is a selective and potent activator of signal transduction and gene expression in bronchial epithelial cells. ..
  51. Inoue H, Sakaue T, Ozawa T, Higashiyama S. Spatiotemporal visualization of proHB-EGF ectodomain shedding in living cells. J Biochem. 2013;154:67-76 pubmed publisher
    ..Fluhemb might be very useful for detecting the activity of proHB-EGF shedding in various types of cells under different conditions in vitro and in vivo. ..
  52. McGovern T, Risse P, Tsuchiya K, Hassan M, Frigola G, Martin J. LTD? induces HB-EGF-dependent CXCL8 release through EGFR activation in human bronchial epithelial cells. Am J Physiol Lung Cell Mol Physiol. 2010;299:L808-15 pubmed publisher
    ..These effects may contribute to epithelial-mediated airway remodeling in asthma and other conditions associated with cysteinyl leukotriene release. ..
  53. Kasai N, Yoshikawa Y, Enokizono J. Effect of antigen-dependent clearance on pharmacokinetics of anti-heparin-binding EGF-like growth factor (HB-EGF) monoclonal antibody. MAbs. 2014;6:1220-8 pubmed publisher
    ..Given that its antigen is expressed in a wide range of normal tissue, it is estimated that the rapid elimination of KHK2866 from cynomolgus monkey serum is caused by antigen-dependent clearance. ..
  54. Bou Nasser Eddine F, Forlani G, Lombardo L, Tedeschi A, Tosi G, Accolla R. CIITA-driven MHC class II expressing tumor cells can efficiently prime naive CD4+ TH cells in vivo and vaccinate the host against parental MHC-II-negative tumor cells. Oncoimmunology. 2017;6:e1261777 pubmed publisher
    ..By using a transgenic H-2b mouse model, the CD11c.DTR C57BL/6 mice, in which DC can be functionally deleted by administration of diphteria toxin, we show that CIITA-..
  55. Garner L, Van Kirk N, Tifft E, Krompinger J, Mathes B, Fraire M, et al. Validation of the distress tolerance scale-short form in obsessive compulsive disorder. J Clin Psychol. 2017;: pubmed publisher
    This study aimed to develop and validate the Distress Tolerance Scale-Short Form (DTS-SF), a modification of the original Distress Tolerance Scale, in a severe/complex sample of individuals with obsessive compulsive disorder (OCD)...
  56. Sharafkhani R, Khanjani N, Bakhtiari B, Jahani Y, Entezar Mahdi R. Diurnal temperature range and mortality in Urmia, the Northwest of Iran. J Therm Biol. 2017;69:281-287 pubmed publisher
    Diurnal Temperature Range (DTR) is a meteorological index which represents temperature variation within a day. This study assesses the impact of high and low values of DTR on mortality...
  57. Davis Fleische K, Brigstock D, Besner G. Site-directed mutagenesis of heparin-binding EGF-like growth factor (HB-EGF): analysis of O-glycosylation sites and properties. Growth Factors. 2001;19:127-43 pubmed
    ..Comparisons between glycosylation mutants and wild-type HB-EGF revealed no significant apparent differences in receptor binding activity. ..
  58. Radulescu A, Zorko N, Yu X, Besner G. Preclinical neonatal rat studies of heparin-binding EGF-like growth factor in protection of the intestines from necrotizing enterocolitis. Pediatr Res. 2009;65:437-42 pubmed publisher
    ..Thus, large-scale production of GMP-grade HB-EGF in Pichia pastoris yeast produces a biologically active molecule suitable for human clinical trials. ..
  59. Lee W, Lim Y, Dang T, Seposo X, Honda Y, Guo Y, et al. An Investigation on Attributes of Ambient Temperature and Diurnal Temperature Range on Mortality in Five East-Asian Countries. Sci Rep. 2017;7:10207 pubmed publisher
    Interest in the health effects of extremely low/high ambient temperature and the diurnal temperature range (DTR) on mortality as representative indices of temperature variability is growing...
  60. Fukaya T, Takagi H, Uto T, Arimura K, Sato K. Analysis of DC Functions Using CD205-DTR Knock-In Mice. Methods Mol Biol. 2016;1423:291-308 pubmed publisher
    ..of CD205(+) cDCs to the immune system, we engineered knock-in (KI) mice that express the diphtheria toxin receptor (DTR) under the control of the Cd205 gene, which allows the selective conditional ablation of CD205(+) cDCs in vivo...
  61. Engmann S, Ro H, Herzing A, DeLongchamp D, Snyder C, Richter L, et al. Reduced Bimolecular Recombination in Blade-Coated, High-Efficiency, Small-Molecule Solar Cells. J Mater Chem A Mater Energy Sustain. 2017;5:6893-6904 pubmed publisher
    ..the performance and morphology of blade-coated bulk heterojunction devices based on the small molecule donor p-DTS(FBTTh2)2 when treated with a post-deposition solvent vapor annealing (SVA) process...
  62. Miyata K, Yotsumoto F, Fukagawa S, Kiyoshima C, Ouk N, Urushiyama D, et al. Serum Heparin-binding Epidermal Growth Factor-like Growth Factor (HB-EGF) as a Biomarker for Primary Ovarian Cancer. Anticancer Res. 2017;37:3955-3960 pubmed
    ..In addition, serum HB-EGF levels increased as the cancer advanced. These data suggest that serum HB-EGF may be a target for the design of novel therapies for ovarian cancer. ..
  63. Liu Q, Lin B, Guo Z, Ding Z, Lian K, Lin D. Shapes of distal tibiofibular syndesmosis are associated with risk of recurrent lateral ankle sprains. Sci Rep. 2017;7:6244 pubmed publisher
    Distal tibiofibular syndesmosis (DTS) has wide anatomic variability in depth of incisura fibularis and shape of tibial tubercles...
  64. Iwamoto R, Senoh H, Okada Y, Uchida T, Mekada E. An antibody that inhibits the binding of diphtheria toxin to cells revealed the association of a 27-kDa membrane protein with the diphtheria toxin receptor. J Biol Chem. 1991;266:20463-9 pubmed
    ..However, there is a correlation between the sensitivity of a cell line to diphtheria toxin and the number of DRAP27 molecules on the cell surface, suggesting that DRAP27 is involved in the entry of diphtheria toxin into the target cell. ..
  65. Carroll M, Kapur A, Felder M, Patankar M, Kreeger P. M2 macrophages induce ovarian cancer cell proliferation via a heparin binding epidermal growth factor/matrix metalloproteinase 9 intercellular feedback loop. Oncotarget. 2016;7:86608-86620 pubmed publisher
    ..Identification of multi-cellular interactions such as this may provide insight into how to most effectively control ovarian cancer progression. ..
  66. Garneau J, Depardieu F, Fortier L, Bikard D, Monot M. PhageTerm: a tool for fast and accurate determination of phage termini and packaging mechanism using next-generation sequencing data. Sci Rep. 2017;7:8292 pubmed publisher
    ..e. 5'cos (Lambda), 3'cos (HK97), pac (P1), headful without a pac site (T4), DTR (T7) and host fragment (Mu)...
  67. Mohan J, Kohler R, Hill J, Weissleder R, Mathis D, Benoist C. Imaging the emergence and natural progression of spontaneous autoimmune diabetes. Proc Natl Acad Sci U S A. 2017;114:E7776-E7785 pubmed publisher
    ..Using advanced intravital imaging approaches and newly created reporter mice (Flt3-BFP2, Mertk-GFP-DTR, Cd4-tdTomato, Cd8a-tdTomato), we show that the autoimmune process initiates first with a T cell ..
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    ..Inhibition of NF-kappaB may represent one of the mechanisms by which HB-EGF exerts its potent anti-inflammatory and cytoprotective effects. ..
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    ..Moreover, we found that exogenously added uPA stimulates autocrine production of HB-EGF, and that blocking HB-EGF activity curbed DU-145 cell invasive potential. ..
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    b>DTS-201 is a doxorubicin (Dox) prodrug that shows encouraging data in experimental models in terms of both efficacy and safety compared with conventional Dox...
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    ..To investigate the role of inflammatory Ly6ChiCCR2+ monocytes in alphavirus pathogenesis, we used CCR2-DTR transgenic mice, enabling depletion of these cells by administration of diptheria toxin (DT)...
  72. Rattik S, Wigren M, Björkbacka H, Fredrikson G, Hedblad B, Siegbahn A, et al. High plasma levels of heparin-binding epidermal growth factor are associated with a more stable plaque phenotype and reduced incidence of coronary events. Arterioscler Thromb Vasc Biol. 2015;35:222-8 pubmed publisher
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    To examine the association between diabetes therapy-related quality of life (DTR-QOL) and physical activity levels, and identify factors associated with high diabetes therapy-related quality of life...
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    We aimed to investigate the impact of taking dedicated time for research (DTR) during training and/or getting a PhD on subsequent career achievements of US academic cardiothoracic surgeons...
  75. Smirnova I, Gonchar I, Shatrova A, Nikol skiĭ N, Burova E. [Metalloprotease-mediated HB-EGF release regulates EGF receptor transactivation in A431 cells under oxidative stress]. Tsitologiia. 2010;52:357-63 pubmed
    ..Taken together, our data suggest that, in human epidermoid carcinoma A431 cells, H2O2 stimulates EGF receptor transactivation via metalloprotease-dependent HB-EGF release and autophosphorylation. ..
  76. Cho K, Kim J, Yoon S, Ryu K, Jang S, Lim B, et al. Reducing Trap-Assisted Recombination in Small Organic Molecule-Based Photovoltaics by the Addition of a Conjugated Block Copolymer. Macromol Rapid Commun. 2017;: pubmed publisher
    The performance of organic photovoltaics (OPVs) based on the small-molecule organic semiconductor p-DTS(FBTTh2 )2 is greatly improved by the addition of a conjugated block copolymer composed of difluoroquinoxaline ..
  77. David M, Sahay D, Mege F, Descotes F, Leblanc R, Ribeiro J, et al. Identification of heparin-binding EGF-like growth factor (HB-EGF) as a biomarker for lysophosphatidic acid receptor type 1 (LPA1) activation in human breast and prostate cancers. PLoS ONE. 2014;9:e97771 pubmed publisher
    ..All together our results demonstrate that HB-EGF is a new and relevant biomarker with potentially high value in quantifying LPA? activation state in patients receiving anti-LPA? therapies. ..
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    ..The spatial and temporal pattern of HB-EGF expression suggest that HB-EGF may an important local regulator of ovarian function and structure. ..
  79. Furtos G, Naghiu M, Declercq H, Gorea M, Prejmerean C, Pana O, et al. Nano forsterite biocomposites for medical applications: Mechanical properties and bioactivity. J Biomed Mater Res B Appl Biomater. 2016;104:1290-301 pubmed publisher
    ..12 MPa), compressive modulus (CM) (1.67-2.75 GPa), diametral tensile strength (DTS) (27.33-31.55 MPa), flexural strength (FS) (59.47-83.20 MPa) and flexural modulus (FM) (2.05-8.60 GPa)...
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    ..Each HB-EGF disulfide analogue lacked the ability to stimulate tyrosine phosphorylation of the 170 kDa EGFR. These results suggest that HB-EGF-Cys/Ser(134/143) antagonizes EGFRs. ..