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| 1 | Therapeutic ACPA inhibits NET formation: a potential therapy for neutrophil-mediated inflammatory diseases显示文摘Excessive release of neutrophil extracellular traps(NETs)is associated with disease severity and contributes to tissue injury,followed by severe organ damage.Pharmacological or genetic inhibition of NET release reduces pathology in multiple inflammatory disease models,indicating that NETs are potential therapeutic targets.Here,we demonstrate using a preclinical basket approach that our therapeutic anti-citrullinated protein antibody(tACPA)has broad therapeutic potential.Treatment with tACPA prevents disease symptoms in various mouse models with plausible NET-mediated pathology,including inflammatory arthritis(IA),pulmonary fibrosis,inflammatory bowel disease and sepsis.We show that citrulline residues in the N-termini of histones 2A and 4 are specific targets for therapeutic intervention,whereas antibodies against other N-terminal post-translational histone modifications have no therapeutic effects.Because citrullinated histones are generated during NET release,we investigated the ability of tACPA to inhibit NET formation.tACPA suppressed NET release from human neutrophils triggered with physiologically relevant human disease-related stimuli.Moreover,tACPA diminished NET release and potentially initiated NET uptake by macrophages in vivo,which was associated with reduced tissue damage in the joints of a chronic arthritis mouse model of IA.To our knowledge,we are the first to describe an antibody with NET-inhibiting properties and thereby propose tACPA as a drug candidate for NET-mediated inflammatory diseases,as it eliminates the noxious triggers that lead to continued inflammation and tissue damage in a multidimensional manner. | Renato G.S.Chirivi Jos W.Gvan Rosmalen Maarten van der Linden Maximilien Euler Gonny Schmets Galina Bogatkevich Konstantinos Kambas Jonas Hahn Quinte Braster Oliver Soehnlein Markus H.Hoffmann Helmuth H.Gvan Es Jos M.H.Raats | 2021 | Cellular & Molecular Immunology2021，18，6： | 5 |
| 2 | Novel methylxanthine derivative-mediated anti-inflammatory effects in inflammatory bowel disease显示文摘Family 18 chitinases have a binding capacity with chitin, a polymer of N-acetylglucosamine. Recent studies strongly suggested that chitinase 3-like 1(CHI3L1, also known as YKL-40) and acidic mammalian chitinase, the two major members of family 18 chitinases, play a pivotal role in the pathogenesis of inflammatory bowel disease(IBD), bronchial asthma and several other inflammatory disorders. Based on the data from highthroughput screening, it has been found that three methylxanthine derivatives, caffeine, theophylline, and pentoxifylline, have competitive inhibitory effects against a fungal family 18 chitinase by specifically interacting with conserved tryptophans in the active site of this protein. Methylxanthine derivatives are also known as adenosine receptor antagonists, phosphodiesterase inhibitors and histone deacetylase inducers. Anti-in-flammatory effects of methylxanthine derivatives have been well-documented in the literature. For example, a beneficial link between coffee or caffeine consumption and type 2 diabetes as well as liver cirrhosis has been reported. Furthermore, theophylline has a long history of being used as a bronchodilator in asthma therapy, and pentoxifylline has an immuno-modulating effect for peripheral vascular disease. However, it is still largely unknown whether these methylxanthine derivativemediated anti-inflammatory effects are associated with the inhibition of CHI3L1-induced cytoplasmic signaling cascades in epithelial cells. In this review article we will examine the above possibility and summarize the biological significance of methylxanthine derivatives in intestinal epithelial cells. We hope that this study will provide a rationale for the development of methylxanthine derivatives, in particular caffeine,-based antiinflammatory therapeutics in the field of IBD and IBDassociated carcinogenesis. | In-Ah Lee Alan Kamba Daren Low Emiko Mizoguchi | 2014 | World Journal of Gastroenterology2014，20，5： | 3 |
| 3 | Overexpression of ETS-1 is associated with malignan' biological features of prostate cancer显示文摘E26 transformation-specific-1 ( ETS-1 ),一个 et 家庭抄写因素,被报导了在前列腺癌症( PCa )在 ETS-1 表示的许多生理、病理学的过程,而是临床的含意起一个重要作用,特别地高风险的案例,包括对雄激素剥夺的反应,治疗( ADT )还得被阐明。我们用针活体检视从 69 个主要先进的 PCa 病人获得的嵌入石蜡的前列腺癌织物染色的 immunohistochemical 检验了 ETS-1 的表示。ETS-1 表示与 69 个病人的 clinicopathological 特征相比,包括 25 作为主要治疗经历了 ADT。作为结果,有 ETS-1 的更高的表示的 PCa 病人是显著地,可能舞台高的更多得分(P< 0.05 ) 。在 ETS-1 表示和起始的前列腺特定的抗原(PSA ) 水平之间没有重要协会。在 ADT 对待的 25 个病人,为 ETS-1 的染色的分数显著地在 24 个月以内与阉割抵抗的疾病的快速的开发被联系(P< 0.05 ) ,而格利森分数和 PSA 水平不是。在结论,增加了 ETS-1 表示与到阉割抵抗的前进的一个更高的阶段,更高级的格利森分数和更短的时间被联系。这些数据建议为 ETS-1 的 immunostaining 能是为为 PCa 病人预言差的临床的结果的一个分子的标记,特别地那些与高风险的疾病。 | Bo Li Yosuke Shimizu Takashi Kobayashi Naoki Terada Koji Yoshimura Tomomi Kamba Yoshiki Mikami Takahiro Inoue Hiroyuki Nishiyama Osamu Ogawa | 2012 | Asian Journal of Andrology2012，14，6： | 2 |
| 4 | Mechanisms of adverse effects of anti-VEGF therapy for cancer 显示文摘 | Kamba T Mc Donald D M | 2007 | Br J Cancer2007，96，12： | 1 |
| 5 | VEGF-dependent plasticity of fenestrated capillaries in the normal adult microvasculature显示文摘 | Kamba T | 2006 | Am J Physiol Heart Circ Physiol2006，290，2： | 1 |
| 6 | Learning personal preferences on online newspaper articles from user behaviors 显示文摘 | Sakagami H Kamba T | 1997 | Computer Networks1997，29，813： | 1 |
| 7 | JunB promotes cell invasion and angiogenesis in VHL-defective renal cell carcinoma显示文摘 | Kanno T Kamba T Yamasaki T | 2011 | Oncogene2011，31，25： | 1 |
| 8 | A unique dosage form to evaluate the mechanical destructive forces in the gastrointestinal tract 显示文摘 | Kamba M Seta Y Kusai A | 2000 | Int J Pharm2000，208，： | 1 |
| 9 | Acell-cycleregulatorpotentiallyinvolvedingenesisofmanytumortypes显示文摘 | KambA CruisMA Weaver-FeldousJ etal | 1994 | Science1994，264，5157： | 1 |
| 10 | Evaluation of the mechanical destructive force in the stomach of dog 显示文摘 | Kamba M Seta Y Kusai A | 2001 | Int J Pharm2001，228，： | 1 |
| 11 | Endothelin-1 signaling promotes fibrosis in vitro in a bronchopulmonary dys- plasia model by activating the extrinsic coagulation cascade显示文摘 | Kambas K Chrysanthopoulou A Kourtzelis I | 2011 | J Immunol2011，186，11： | 1 |
| 12 | Regulation of the autophagic machinery in human neutrophils 显示文摘 | Mitroulis I Kourtzelis I Kambas K | 2010 | Eur J Immunol2010，40，5： | 1 |
| 13 | C5a and TNF -α up - regulate the expression of tissue factor in intra - alveolar neutrophils of patients with the acute respiratory distress syndrome显示文摘 | Kambas K Markiewski MM Pneumatikos IA | 2008 | J Immunol2008，180，11： | 1 |
| 14 | Effective personalization of push-type systems:visualizing information freshness显示文摘 | SAKAGAMI H KAMBA T SUGIURA A | 1998 | Computer Networks and ISDN Systems1998，30，17： | 1 |
| 15 | Use of three-dimensional segmented flash sequence with Magnetization transfer contrast to improve Gd-DTPA-enhanced intrahepatic MR portography显示文摘 | Suto Y Kimura T Kamba M | 1997 | J Magn Reson Imaging1997，7，2： | 1 |
| 16 | VEGF-dependent plasticity of fenestrated capillaries in the normal adult micro- vasculature 显示文摘 | Kamba T Tam BY Hashizume H | 2006 | Am J Physiol Heart Circ Physiol2006，290，： | 1 |
| 17 | Physical activity is associated with bone geometry of premenarcheal girls in a dose-dependent manner 显示文摘 | Maria Michalopoulou Antonis Kambas Diamanda Leontsi- ni | 2013 | Metabolism2013，62，12： | 1 |
| 18 | The multivalent activity ofthe tissue factor -thrombin pathway in thrombotic and non -thrombotic disorders as a target for therapeutic intervention 显示文摘 | Mitroulis I Kambas K Anyfanti P | 2011 | Expert Opin Ther Target2011，15，1： | 1 |
| 19 | A case of small cell carcinoma of the ureter显示文摘 | Masui K Kamba T Watanabe J | 2008 | Hinyokika Kiyo2008，54，6： | 1 |
| 20 | Cerebral metabolic impairment in patients with obstructive sleep apnoea: an independent association of obstructive sleep apnoea with white matter change 显示文摘 | Kamba M Inoue Y Higami S | 2001 | J Neurol Neurosurg Psychiatry2001，71，： | 1 |
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