Dang NH

References (18)

Title : CD26\/Dipeptidyl Peptidase IV and Its Multiple Biological Functions - Pan_2021_Cureus_13_e13495
Author(s) : Pan K , Ohnuma K , Morimoto C , Dang NH
Ref : Cureus , 13 :e13495 , 2021
Abstract : CD26/Dipeptidyl peptidase IV (DPPIV) is a cell surface glycoprotein with numerous roles including glucose metabolism, immunomodulation, and tumorigenesis. CD26/DPPIV is well recognized in diabetes, with DPPIV inhibitors being a class of oral hypoglycemic drugs called gliptins that are commonly used to treat type two diabetes mellitus. Recent work also indicated a potential role for CD26 in infectious diseases, including COVID-19, and immune-mediated disorders such as rheumatoid arthritis, inflammatory bowel disease, and graft-versus-host disease. In cancer, CD26/DPPIV expression has been characterized in numerous tumors such as hematologic malignancies, malignant pleural mesothelioma (MPM), renal cell carcinoma (RCC), hepatocellular carcinoma (HCC), gastrointestinal stromal tumor (GIST), and prostate, lung, colorectal, and ovarian (PLCO) cancer. Hence, CD26 has been frequently studied as a tumor biomarker and therapeutic target. CD26/DPPIV-targeted therapies have been evaluated in various cancers, including the use of anti-CD26 monoclonal antibodies as anticancer treatment in selected neoplasms. This review highlights our current understanding of the role of CD26 in cancer, diabetes, immune-mediated diseases, and infectious diseases. Enhanced understanding of CD26 biology and function may lead to novel therapeutic approaches in multiple human diseases.
ESTHER : Pan_2021_Cureus_13_e13495
PubMedSearch : Pan_2021_Cureus_13_e13495
PubMedID: 33777580

Title : Serum soluble CD26\/DPP4 titer variation is a potential prognostic biomarker in cancer therapy with a humanized anti-CD26 antibody - Kaneko_2021_Biomark.Res_9_21
Author(s) : Kaneko Y , Hatano R , Hirota N , Isambert N , Trillet-Lenoir V , You B , Alexandre J , Zalcman G , Valleix F , Podoll T , Umezawa Y , Takao S , Iwata S , Hosono O , Taguchi T , Yamada T , Dang NH , Ohnuma K , Angevin E , Morimoto C
Ref : Biomark Res , 9 :21 , 2021
Abstract : BACKGROUND: The phase I trial of the humanized anti-CD26 monoclonal antibody YS110 for CD26-expressing tumors was conducted recently. The present study identifies a potential prognostic biomarker for CD26-targeted therapy based on the phase I data. METHODS: Box and Whisker plot analysis, Scatter plot analysis, Peason product moment correlation/Spearman's rank-difference correlation, Bar graph analysis, and Receiver Operating Characteristics (ROC) were used to examine the correlation between sCD26 titer variation with YS110 administration and tumor volume change, RECIST criteria evaluation and progression free survival (PFS). Mechanism for serum sCD26 titer variation was confirmed by in vitro experimentation. RESULTS: Serum sCD26/DPP4 titer was reduced following YS110 administration and gradually recovered until the next infusion. Serum sCD26/DPP4 titer before the next infusion was sustained at lower levels in Stable Disease (SD) cases compared to Progressive Disease cases. ROC analysis defined the cut-off level of serum sCD26/DPP4 titer variation at day 29 pre/post for the clinical outcome of SD as tumor response or PFS. In vitro experimentation confirmed that YS110 addition reduced sCD26 production from CD26-expressing tumor and non-tumor cells. CONCLUSIONS: Our study indicates that serum sCD26/DPP4 titer variation in the early phase of YS110 treatment is a predictive biomarker for evaluating therapeutic efficacy.
ESTHER : Kaneko_2021_Biomark.Res_9_21
PubMedSearch : Kaneko_2021_Biomark.Res_9_21
PubMedID: 33757558

Title : A multi-center retrospective analysis of the effect of DPP4 inhibitors on progression-free survival in advanced airway and colorectal cancers - Ali_2019_Mol.Clin.Oncol_10_118
Author(s) : Ali A , Fuentes A , Skelton Iv WP , Wang Y , McGorray S , Shah C , Bishnoi R , Dang LH , Dang NH
Ref : Mol Clin Oncol , 10 :118 , 2019
Abstract : Cluster of differentiation 26 (CD26), also known as dipeptidyl peptidase IV (DPP4), is a cell surface protein with exopeptidase activity and is expressed by most cell types. CD26/DPP4 is a multifunctional molecule with diverse biological effects, including regulatory effects on tumor growth, invasion and metastasis, and is a potential novel therapeutic target for selected cancers. In this study, we retrospectively analyzed diabetic patients with concurrent advanced airway or colorectal cancer to examine the effect of DPP4-inhibitors on progression-free survival (PFS). We performed a multi-center retrospective review of patients with advanced colorectal or airway (lung, head and neck) cancer and a concurrent diagnosis of diabetes. The control group included patients on metformin and a sulfonylurea, and the study group included patients on metformin and a DPP4 inhibitor. Ninety-six patients were eligible for the study. The cancers progressed in 23.7% of patients treated with DPP4 inhibitors compared to 50.9% of patients in the control group with an odds ratio of 0.303 [95% confidence interval (CI): 0.106-0.809] and P=0.010. There was a statistically significant improvement in PFS in the study group as compared to the control group, hazard ratio=0.42 (95% CI: 0.21-0.84) and P=0.014. There was a trend toward improvement in overall survival, although this effect was not statistically significant (P=0.11). Exposure to DPP4 inhibitors in the study group led to higher PFS in patients with advanced colorectal and airway cancers. Additional investigations with larger patient cohorts are needed to validate the relationship between DPP4 inhibition and the clinical outcome of selected malignancies.
ESTHER : Ali_2019_Mol.Clin.Oncol_10_118
PubMedSearch : Ali_2019_Mol.Clin.Oncol_10_118
PubMedID: 30655986

Title : DPP8 is a novel therapeutic target for multiple myeloma - Sato_2019_Sci.Rep_9_18094
Author(s) : Sato T , Tatekoshi A , Takada K , Iyama S , Kamihara Y , Jawaid P , Rehman MU , Noguchi K , Kondo T , Kajikawa S , Arita K , Wada A , Murakami J , Arai M , Yasuda I , Dang NH , Hatano R , Iwao N , Ohnuma K , Morimoto C
Ref : Sci Rep , 9 :18094 , 2019
Abstract : Dipeptidyl peptidases (DPPs) are proteolytic enzymes that are ideal therapeutic targets in human diseases. Indeed, DPP4 inhibitors are widely used in clinical practice as anti-diabetic agents. In this paper, we show that DPP4 inhibitors also induced cell death in multiple human myeloma cells. Among five DPP4 inhibitors, only two of them, vildagliptin and saxagliptin, exhibited apparent cytotoxic effects on myeloma cell lines, without any difference in suppression of DPP4 activity. As these two DPP4 inhibitors are known to have off-target effects against DPP8/9, we employed the specific DPP8/9 inhibitor 1G244. 1G244 demonstrated anti-myeloma effects on several cell lines and CD138+ cells from patients as well as in murine xenograft model. Through siRNA silencing approach, we further confirmed that DPP8 but not DPP9 is a key molecule in inducing cell death induced by DPP8/9 inhibition. In fact, the expression of DPP8 in CD38+ cells from myeloma patients was higher than that of healthy volunteers. DPP8/9 inhibition induced apoptosis, as evidenced by activated form of PARP, caspases-3 and was suppressed by the pan-caspase inhibitor Z-VAD-FMK. Taken together, these results indicate that DPP8 is a novel therapeutic target for myeloma treatment.
ESTHER : Sato_2019_Sci.Rep_9_18094
PubMedSearch : Sato_2019_Sci.Rep_9_18094
PubMedID: 31792328
Gene_locus related to this paper: human-DPP8

Title : A novel role for CD26\/dipeptidyl peptidase IV as a therapeutic target - Ohnuma_2018_Front.Biosci.(Landmark.Ed)_23_1754
Author(s) : Ohnuma K , Hatano R , Komiya E , Otsuka H , Itoh T , Iwao N , Kaneko Y , Yamada T , Dang NH , Morimoto C
Ref : Front Biosci (Landmark Ed) , 23 :1754 , 2018
Abstract : CD26 is a 110 kDa surface glycoprotein with intrinsic dipeptidyl peptidase IV activity that is expressed on numerous cell types and has a multitude of biological functions. The role of CD26 in immune regulation has been extensively characterized, with recent findings elucidating its linkage with signaling pathways and structures involved in T-lymphocyte activation as well as antigen presenting cell-T-cell interaction. In this paper, we will review emerging data on CD26-mediated immune regulation suggesting that CD26 may be an appropriate therapeutic target for the treatment of selected immune disorders as well as Middle East respiratory syndrome coronavirus. Moreover, we have had a long-standing interest in the role of CD26 in cancer biology and its suitability as a novel therapeutic target in selected neoplasms. We reported robust in vivo data on the anti-tumor activity of anti-CD26 monoclonal antibody in mouse xenograft models. We herein review significant novel findings and the early clinical development of a CD26-targeted therapy in selected immune disorders and cancers, advances that can lead to a more hopeful future for patients with these intractable diseases.
ESTHER : Ohnuma_2018_Front.Biosci.(Landmark.Ed)_23_1754
PubMedSearch : Ohnuma_2018_Front.Biosci.(Landmark.Ed)_23_1754
PubMedID: 29772527

Title : Anti-amnesic effect of alkaloid fraction from Lycopodiella cernua (L.) Pic. Serm. on scopolamine-induced memory impairment in mice - Chuong_2014_Neurosci.Lett_575_42
Author(s) : Chuong NN , Trung BH , Luan TC , Hung TM , Dang NH , Dat NT
Ref : Neuroscience Letters , 575 :42 , 2014
Abstract : Lycopodiella cernua (L.) Pic. Serm. (Licopodiaceae) has been used in Vietnamese folk medicine for treating central nervous system conditions. In this study, the alkaloid fraction from the methanol extract of this plant (VLC) was evaluated for in vitro acetylcholinesterase (AChE) inhibitory activity in cognition-relevant brain areas of mice. In in vivo study, the cognitive-enhancing effect of VLC on amnesic mice induced by scopolamine was investigated by assessing a passive avoidance and a Morris water maze test. VLC inhibited AChE activity in mouse frontal cortex, hippocampus and striatum with IC50 values of 26.7, 32.2 and 25.7mug/mL, respectively. Administration of VLC (10, 20, 50 and 100mg/kg, p.o.) significantly reversed cognitive impairments in mice by passive avoidance test. Treating with VLC (50mg/kg) reduced escape latencies in training trials and prolonged swimming times in the target quadrant during the probe trial in the water maze task (P<0.05). These results indicated that L. cernua originated from Vietnam has anti-cholinesterase activity and might be useful for the treatment of cognitive impairment.
ESTHER : Chuong_2014_Neurosci.Lett_575_42
PubMedSearch : Chuong_2014_Neurosci.Lett_575_42
PubMedID: 24861508

Title : Inhibition of Middle East respiratory syndrome coronavirus infection by anti-CD26 monoclonal antibody - Ohnuma_2013_J.Virol_87_13892
Author(s) : Ohnuma K , Haagmans BL , Hatano R , Raj VS , Mou H , Iwata S , Dang NH , Bosch BJ , Morimoto C
Ref : J Virol , 87 :13892 , 2013
Abstract : We identified the domains of CD26 involved in the binding of Middle East respiratory syndrome coronavirus (MERS-CoV) using distinct clones of anti-CD26 monoclonal antibodies (MAbs). One clone, named 2F9, almost completely inhibited viral entry. The humanized anti-CD26 MAb YS110 also significantly inhibited infection. These findings indicate that both 2F9 and YS110 are potential therapeutic agents for MERS-CoV infection. YS110, in particular, is a good candidate for immediate testing as a therapeutic modality for MERS.
ESTHER : Ohnuma_2013_J.Virol_87_13892
PubMedSearch : Ohnuma_2013_J.Virol_87_13892
PubMedID: 24067970

Title : Inhibition of dipeptidyl peptidase 4 regulates microvascular endothelial growth induced by inflammatory cytokines - Takasawa_2010_Biochem.Biophys.Res.Commun_401_7
Author(s) : Takasawa W , Ohnuma K , Hatano R , Endo Y , Dang NH , Morimoto C
Ref : Biochemical & Biophysical Research Communications , 401 :7 , 2010
Abstract : CD26/DPP-4 is abundantly expressed on capillary of inflamed lesion as well as effector T cells. Recently, CD26/dipeptidyl peptidase 4 (DPP-4) inhibition has been used as a novel oral therapeutic approach for patients with type 2 diabetes. While accumulating data indicate that vascular inflammation is a key feature of both micro- and macro-vascular complications in diabetes, the direct role of CD26/DPP-4 in endothelial biology is to be elucidated. We herein showed that proinflammatory cytokines such as tumor necrosis factor or interleukin-1 reduce expression of CD26 on microvascular endothelial cells, and that genetical or pharmacological inhibition of CD26/DPP-4 enhances endothelial growth both in vitro and in vivo. With DPP-4 inhibitors being used widely in the treatment of type 2 diabetes, our data strongly suggest that DPP-4 inhibition plays a pivotal role in endothelial growth and may have a potential role in the recovery of local circulation following diabetic vascular complications.
ESTHER : Takasawa_2010_Biochem.Biophys.Res.Commun_401_7
PubMedSearch : Takasawa_2010_Biochem.Biophys.Res.Commun_401_7
PubMedID: 20828536

Title : Alkaloids from roots of Stephania rotunda and their cholinesterase inhibitory activity - Hung_2010_Planta.Med_76_1762
Author(s) : Hung TM , Dang NH , Kim JC , Jang HS , Ryoo SW , Lee JH , Choi JS , Bae K , Min BS
Ref : Planta Med , 76 :1762 , 2010
Abstract : In the course of screening plants used in folk medicine as memory enhancers, a 70% ethanolic extract of Stephania rotunda roots showed significant AChE inhibitory activity. Repeated column chromatography led to the isolation of a new protoberberine alkaloid, which we named stepharotudine (1), and seven known compounds (2-8). The chemical structures of the isolated compounds were elucidated based on extensive 1D and 2D NMR spectroscopic data. Compounds 1-8 were investigated in vitro for their anticholinesterase activity using a rat cortex AChE enzyme.
ESTHER : Hung_2010_Planta.Med_76_1762
PubMedSearch : Hung_2010_Planta.Med_76_1762
PubMedID: 20391319

Title : The role of CD26\/dipeptidyl peptidase IV in cancer - Havre_2008_Front.Biosci_13_1634
Author(s) : Havre PA , Abe M , Urasaki Y , Ohnuma K , Morimoto C , Dang NH
Ref : Front Biosci , 13 :1634 , 2008
Abstract : CD26/DPPIV is a multifunctional cell surface protein that is widely expressed in most cell types including T lymphocytes, on which it is a marker of activation. It is also present in serum and other body fluids in a truncated form (sCD26/DPPIV). It preferentially cleaves N-terminal dipeptides from polypeptides with proline or alanine in the penultimate position, and in doing so, regulates the activities of a number of cytokines and chemokines. Due in part to this ability to regulate the activity of biopeptides, it can act as a tumor suppressor or activator. It can associate with several proteins, among them fibroblast activating protein-alpha (FAP-alpha), plasminogen, adenosine deaminase (ADA), the tyrosine phosphatase CD45, and the chemokine receptor CXCR4. It can also bind to the extracellular matrix (ECM) and depending on the presence of other ligands, this process can either lead to increased or decreased invasive activity of the cells on which it is expressed. As a result of these characteristics, CD26/DPPIV plays an important role in tumor biology, and is useful as a marker for various cancers, with its levels either on the cell surface or in the serum being increased in some neoplasms and decreased in others. Our group has shown that CD26/DPPIV can be manipulated by such agents as CD26 cDNA-carrying plasmids, siRNA and monoclonal antibodies, resulting in both in vitro and in vivo inhibition of cell growth, enhanced sensitivity to selected chemotherapeutic agents, and enhanced survival of mouse xenograft models. These studies have demonstrated the utility of these tools as potential targeted therapies for specific cancers expressing CD26/DPPIV.
ESTHER : Havre_2008_Front.Biosci_13_1634
PubMedSearch : Havre_2008_Front.Biosci_13_1634
PubMedID: 17981655

Title : Role of CD26\/dipeptidyl peptidase IV in human T cell activation and function - Ohnuma_2008_Front.Biosci_13_2299
Author(s) : Ohnuma K , Takahashi N , Yamochi T , Hosono O , Dang NH , Morimoto C
Ref : Front Biosci , 13 :2299 , 2008
Abstract : CD26 is a 110 kDa surface glycoprotein with intrinsic dipeptidyl peptidase IV (DPPIV, EC activity that is expressed on numerous cell types and has a multitude of biological functions. CD26 role in immune regulation has been extensively characterized, with recent findings elucidating its linkage with signaling pathways and structures involved in T-lymphocyte activation as well as antigen presenting cell (APC)-T-cell interaction. In this paper, we will review emerging data on CD26-mediated T-cell costimulation, suggesting that CD26 may be an appropriate therapeutic target for the treatment of immune disorders. However, the identity of its putative natural ligand had not yet been clearly elucidated. Recently, using protein engineering and proteomic approach, we have recently characterized the putative costimulatory ligand for CD26 in T-cells and the proximal signaling events directly associated with the cytoplasmic region of CD26 in CD26-associated T-cell costimulation, processes that are independent of the CD28 costimulatory pathway. Our work therefore presents novel findings that contribute to the area of T-cell costimulation and signal transduction.
ESTHER : Ohnuma_2008_Front.Biosci_13_2299
PubMedSearch : Ohnuma_2008_Front.Biosci_13_2299
PubMedID: 17981712

Title : CD26\/dipeptidyl peptidase IV as a novel therapeutic target for cancer and immune disorders - Thompson_2007_Mini.Rev.Med.Chem_7_253
Author(s) : Thompson MA , Ohnuma K , Abe M , Morimoto C , Dang NH
Ref : Mini Rev Med Chem , 7 :253 , 2007
Abstract : CD26 is a 110 kDa surface glycoprotein with intrinsic dipeptidyl peptidase IV (DPPIV) activity that is expressed on numerous cell types and has a multitude of biological functions. An important aspect of CD26 biology is its peptidase activity and its functional and physical association with molecules with key roles in various cellular pathways and biological programs. CD26 role in immune regulation has been extensively characterized, with recent findings elucidating its linkage with signaling pathways and structures involved in T-lymphocyte activation as well as antigen presenting cell-T-cell interaction. Recent work also suggests that CD26 has a significant role in tumor biology, being both a marker of disease behavior clinically as well as playing an important role in tumor pathogenesis and development. In this paper, we will review emerging data that suggest CD26 may be an appropriate therapeutic target for the treatment of selected neoplasms and immune disorders. Through the use of various experimental approaches and agents to influence CD26/DPPIV expression and activity, such as anti-CD26 antibodies, CD26/DPPIV chemical inhibitors, siRNAs to inhibit CD26 expression, overexpressing CD26 transfectants and soluble CD26 molecules, our group has shown that CD26 interacts with structures with essential cellular functions. Its association with such key molecules as topoisomerase IIalpha, p38 MAPK, and integrin beta1, has important clinical implications, including its potential ability to regulate tumor sensitivity to selected chemotherapies and to influence tumor migration/metastases and tumorigenesis. Importantly, our recent in vitro and in vivo data support the hypothesis that CD26 may indeed be an appropriate target for therapy for selected cancers and immune disorders.
ESTHER : Thompson_2007_Mini.Rev.Med.Chem_7_253
PubMedSearch : Thompson_2007_Mini.Rev.Med.Chem_7_253
PubMedID: 17346218

Title : T-cell activation via CD26 and caveolin-1 in rheumatoid synovium - Ohnuma_2006_Mod.Rheumatol_16_3
Author(s) : Ohnuma K , Inoue H , Uchiyama M , Yamochi T , Hosono O , Dang NH , Morimoto C
Ref : Mod Rheumatol , 16 :3 , 2006
Abstract : CD26 is a T-cell costimulatory molecule with dipeptidyl peptidase IV (DPPIV) activity in its extracellular region. We previously reported that recombinant soluble CD26 enhances peripheral blood T-cell proliferation induced by the recall antigen tetanus toxoid (TT). Recently, we demonstrated that CD26 binds caveolin-1 on antigen-presenting cell (APC), and that residues 201-211 of CD26 along with the serine catalytic site at residue 630, which constitute a pocket structure of CD26/DPPIV, contribute to binding to caveolin-1 scaffolding domain. In addition, following CD26-caveolin-1 interaction on TT-loaded monocytes, caveolin-1 is phosphorylated, with linkage to NF-kappaB activation, followed by upregulation of CD86. Finally, reduced caveolin-1 expression on APC inhibits CD26-mediated CD86 upregulation and abrogates CD26 effect on TT-induced T-cell proliferation, and immunohistochemical studies revealed an infiltration of CD26+ T cells in the sub-lining region of rheumatoid synovium and high expression of caveolin-1 in the increased vasculature and synoviocytes of the rheumatoid synovium. Taken together, these results strongly suggest that CD26-cavolin-1 interaction plays a role in the upregulation of CD86 on TT-loaded APC and subsequent engagement with CD28 on T cells, leading to antigen-specific T-cell activation such as the T-cell-mediated antigen-specific response in rheumatoid arthritis.
ESTHER : Ohnuma_2006_Mod.Rheumatol_16_3
PubMedSearch : Ohnuma_2006_Mod.Rheumatol_16_3
PubMedID: 16622717

Title : CD26 mediates dissociation of Tollip and IRAK-1 from caveolin-1 and induces upregulation of CD86 on antigen-presenting cells - Ohnuma_2005_Mol.Cell.Biol_25_7743
Author(s) : Ohnuma K , Yamochi T , Uchiyama M , Nishibashi K , Iwata S , Hosono O , Kawasaki H , Tanaka H , Dang NH , Morimoto C
Ref : Molecular & Cellular Biology , 25 :7743 , 2005
Abstract : CD26 is a T-cell costimulatory molecule with dipeptidyl peptidase IV enzyme activity in its extracellular region. We have previously reported that the addition of recombinant soluble CD26 resulted in enhanced proliferation of human T lymphocytes induced by the recall antigen tetanus toxoid (TT) via upregulation of CD86 on monocytes and that caveolin-1 was a binding protein of CD26, and the CD26-caveolin-1 interaction resulted in caveolin-1 phosphorylation (p-cav-1) as well as TT-mediated T-cell proliferation. However, the mechanism involved in this immune enhancement has not yet been elucidated. In the present work, we perform experiments to identify the molecular mechanisms by which p-cav-1 leads directly to the upregulation of CD86. Through proteomic analysis, we identify Tollip (Toll-interacting protein) and IRAK-1 (interleukin-1 receptor-associated serine/threonine kinase 1) as caveolin-1-interacting proteins in monocytes. We also demonstrate that following stimulation by exogenous CD26, Tollip and IRAK-1 dissociate from caveolin-1, and IRAK-1 is then phosphorylated in the cytosol, leading to the upregulation of CD86 via activation of NF-kappaB. Binding of CD26 to caveolin-1 therefore regulates signaling pathways in antigen-presenting cells to induce antigen-specific T-cell proliferation.
ESTHER : Ohnuma_2005_Mol.Cell.Biol_25_7743
PubMedSearch : Ohnuma_2005_Mol.Cell.Biol_25_7743
PubMedID: 16107720

Title : Regulation of p38 phosphorylation and topoisomerase IIalpha expression in the B-cell lymphoma line Jiyoye by CD26\/dipeptidyl peptidase IV is associated with enhanced in vitro and in vivo sensitivity to doxorubicin - Yamochi_2005_Cancer.Res_65_1973
Author(s) : Yamochi T , Aytac U , Sato T , Sato K , Ohnuma K , McKee KS , Morimoto C , Dang NH
Ref : Cancer Research , 65 :1973 , 2005
Abstract : CD26 is a Mr 110,000 surface-bound glycoprotein with diverse functional properties, including having a key role in normal T-cell physiology and the development of certain cancers. In this article, we show that surface expression of CD26, especially its intrinsic dipeptidyl peptidase IV (DPPIV) enzyme activity, results in enhanced topoisomerase IIalpha level in the B-cell line Jiyoye and subsequent in vitro sensitivity to doxorubicin-induced apoptosis. In addition, we show that expression of CD26/DPPIV is associated with increased phosphorylation of p38 and its upstream regulators mitogen-activated protein kinase kinase 3/6 and apoptosis signal-regulating kinase 1 and that p38 signaling pathway plays a role in the regulation of topoisomerase IIalpha expression. Besides demonstrating that CD26 effect on topoisomerase IIalpha and doxorubicin sensitivity is applicable to cell lines of both B-cell and T-cell lineages, the potential clinical implication of our work lies with the fact that we now show for the first time that our in vitro results can be extended to a severe combined immunodeficient mouse model. Our findings that CD26 expression can be an in vivo marker of tumor sensitivity to doxorubicin treatment may lead to future treatment strategies targeting CD26/DPPIV for selected human cancers in the clinical setting. Our article thus characterizes the biochemical linkage among CD26, p38, and topoisomerase IIalpha while providing evidence that CD26-associated topoisomerase IIalpha expression results in greater in vitro and in vivo tumor sensitivity to the antineoplastic agent doxorubicin.
ESTHER : Yamochi_2005_Cancer.Res_65_1973
PubMedSearch : Yamochi_2005_Cancer.Res_65_1973
PubMedID: 15753397

Title : CD26\/dipeptidyl peptidase IV and its role in cancer - Pro_2004_Histol.Histopathol_19_1345
Author(s) : Pro B , Dang NH
Ref : Histol Histopathol , 19 :1345 , 2004
Abstract : CD26/Dipeptidyl Peptidase IV (DPPIV) is a 110-kDa glycoprotein that is expressed on numerous cell types and has multiple biological functions. A key facet of CD26/DPPIV biology is its enzymatic activity and its physical and functional interaction with other molecules. The substrates of CD26/DPPIV are proline-containing peptides and include growth factors, chemokines, neuropeptides, and vasoactive peptides. DPPIV plays an important role in immune regulation, signal transduction, and apoptosis. Furthermore, CD26 appears to play an important role in tumor progression. In the present review, we summarize key aspects of CD26/DPPIV involvement in tumor biology and its potential role in cancer development and behavior.
ESTHER : Pro_2004_Histol.Histopathol_19_1345
PubMedSearch : Pro_2004_Histol.Histopathol_19_1345
PubMedID: 15375776

Title : CD26\/dipeptidyl peptidase IV: a regulator of immune function and a potential molecular target for therapy - Aytac_2004_Curr.Drug.Targets.Immune.Endocr.Metabol.Disord_4_11
Author(s) : Aytac U , Dang NH
Ref : Curr Drug Targets Immune Endocr Metabol Disord , 4 :11 , 2004
Abstract : CD26 is a 110 kDa surface-bound ectopeptidase with intrinsic dipeptidyl peptidase IV (DPP IV) activity, which has multiple biological functions. In this review, we will focus specifically on work demonstrating that CD26 has a key role in immune function as a T cell activation molecule and a regulator of the functional effect of selected biological factors through its DPP IV enzyme activity. As further evidence of the important role played by this multifaceted molecule in immune regulation, we will also discuss experimental attempts from our laboratory and others to influence immune-mediated conditions through CD26 monoclonal antibodies and DPP IV activity with various agents, including anti-CD26 monoclonal antibodies and DPP IV chemical inhibitors. Of special significance from a clinical perspective is also CD26 effect on glucose metabolism through its DPP IV activity and its potential role as a therapeutic target in diabetes. In addition, we will review recent studies that describe the physical and functional interaction of CD26 with other essential cellular structures and the biological consequences of their association. In particular, we will present recent data from our laboratory that demonstrates the correlation between CD26, especially its DPP IV activity, and the key nuclear protein topoisomerase II alpha, an interaction that has important clinical implications. In summary, we will examine the biology of the multifaceted CD26/DPP IV molecule, focusing particularly on its function in immune regulation and its potential role as a molecular target for novel treatment modalities for a number of disease states, ranging from autoimmune diseases, diabetes to malignancies.
ESTHER : Aytac_2004_Curr.Drug.Targets.Immune.Endocr.Metabol.Disord_4_11
PubMedSearch : Aytac_2004_Curr.Drug.Targets.Immune.Endocr.Metabol.Disord_4_11
PubMedID: 15032621

Title : Cloning and functional expression of the T cell activation antigen CD26 - Tanaka_1992_J.Immunol_149_481
Author(s) : Tanaka T , Camerini D , Seed B , Torimoto Y , Dang NH , Kameoka J , Dahlberg HN , Schlossman SF , Morimoto C
Ref : J Immunol , 149 :481 , 1992
Abstract : A cDNA encoding the T cell activation Ag CD26 was isolated from human PHA-activated T cells by using an expression cloning method. The nucleotide sequence obtained predicts a protein of 766 amino acids of type II membrane topology, with six amino acids in the cytoplasmic region. The predicted amino acid sequence of the Ag was 85% homologous to that of the dipeptidyl peptidase IV enzyme isolated from rat liver. Derivatives of the human leukemic T cell line Jurkat transfected with a CD26 expression plasmid were established. Characterization of the CD26 Ag expressed by the transfected Jurkat cells revealed that the Ag could be immunoprecipitated as a 110-kDa molecule similar to that found on peripheral blood T cells and that the Ag had dipeptidyl peptidase IV activity. Functional analysis of these Jurkat transfectants showed that cross-linking of the CD26 and CD3 Ag with their respective antibodies resulted in enhanced intracellular calcium mobilization and IL-2 production. These results provide direct evidence that the CD26 Ag plays a role in T cell activation.
ESTHER : Tanaka_1992_J.Immunol_149_481
PubMedSearch : Tanaka_1992_J.Immunol_149_481
PubMedID: 1352530
Gene_locus related to this paper: human-DPP4