Read by QxMD icon Read


Zhe Fan, Yan Wang, Xingxin Xu, Yonggui Wu
Accumulating evidence has shown that macrophages play a vital role in development and pathogenesis of diabetic nephropathy (DN) by secreting inflammatory cytokines. Although Bruton's tyrosine kinases (Btk) is a biologically important molecule implicated in immune regulation, the role of Btk in high glucose (HG)-stimulated inflammatory response in macrophages and the mechanism involved need further investigation. In our study, we used bone marrow-derived macrophages (BMMs) to investigate the involvement of Btk on HG-induced inflammatory cytokines expression and to explore the underlying mechanisms...
May 2018: International Immunopharmacology
Jon M Florence, Agnieszka Krupa, Laela M Booshehri, Sandra A Davis, Michael A Matthay, Anna K Kurdowska
Infection with seasonal influenza A virus (IAV) leads to lung inflammation and respiratory failure, a main cause of death in influenza infected patients. Previous experiments in our laboratory indicated that Bruton's tyrosine kinase (Btk) plays a substantial role in regulating inflammation in the respiratory region during acute lung injury (ALI) in mice, therefore we sought to determine if blocking Btk activity had a protective effect in the lung during influenza induced inflammation. A Btk inhibitor (Btk Inh...
March 8, 2018: American Journal of Physiology. Lung Cellular and Molecular Physiology
Jing Ma, Wei Gong, Su Liu, Qian Li, Mengzheng Guo, Jinhan Wang, Suying Wang, Naiyao Chen, Yafei Wang, Qiang Liu, Hui Zhao
The oncogenic microRNA-21 contributes to the pathogenesis of multiple myeloma. Ibrutinib (also referred to as PCI-32765), an inhibitor of Bruton's tyrosine kinase, while its effects on multiple myeloma have not been well described. Here, we show that microRNA-21 is an oncogenic marker closely linked with progression of multiple myeloma. Moreover, ibrutinib attenuates microRNA-21 expression in multiple myeloma cells by inhibiting nuclear factor-κB and signal transducer and activator of transcription 3 signaling pathways...
January 2018: Tumour Biology: the Journal of the International Society for Oncodevelopmental Biology and Medicine
J Molina-Cerrillo, T Alonso-Gordoa, P Gajate, E Grande
Bruton's tyrosine kinase (BTK) is a non-receptor intracellular kinase that belongs to the TEC-family tyrosine kinases together with bone marrow-expressed kinase (BMX), redundant-resting lymphocyte kinase (RLK), and IL-2 inducible T-Cell kinase (ITK). All these proteins play a key role in the intracellular signaling of both B and T lymphocytes. Recently, some preclinical data have demonstrated that BTK is present in certain tumor subtypes and in other relevant cells that are contributing to the tumor microenvironment such as dendritic cells, macrophages, myeloid derived suppressor cells and endothelial cells...
July 2017: Cancer Treatment Reviews
Kangwei Wang, Xin Nie, Zhuona Rong, Tingting Fan, Juan Li, Xinxin Wang, Huiling Li, Jianyi Dong, Jun Chen, Fujin Wang, Jingyu Wang, Aiguo Wang
Increasing reports show noninflammation underlying HCC, challenging our understanding of the roles of the immune system in hepatocarcinogenesis. By exploring a mouse model of hepatic tumor induced by hepatocyte-specific expression of the Hras12V oncogene without obvious inflammation, we found that the proportion of B cells, but not T cells, progressively and significantly decreased in 3, 5-month-old transgenic mice (Tg) compared with non-transgenic mice. Notably, the proportions of total and activated B and T cells all significantly decreased in 9-month-old Tg with multiple massive hepatic tumors...
September 15, 2017: International Journal of Cancer. Journal International du Cancer
Pan Zhao, Yafang Chen, Zhijie Yue, Ying Yuan, Xiaofang Wang
Bone marrow mesenchymal stem cells (BM-MSCs) are key components of bone marrow microenvironment. Although the importances of BM-MSCs activation in myeloma cells growth, development, progression, angiogenesis are well known, their role in the regulation of myeloma stemness is unclear. In this study, myeloma cell lines (LP-1, U266) were co-cultured with BM-MSCs, we found that BM-MSCs could up-regulate the expression of key stemness genes and proteins (OCT4, SOX2, NANOG) and increase clonogenicity. Similarly, the mechanisms underlying the BM-MSC activation of myeloma stemness remain unclear...
June 2017: Leukemia Research
Hui Zhang, Atish Patel, Yi-Jun Wang, Yun-Kai Zhang, Rishil J Kathawala, Long-Hui Qiu, Bhargav A Patel, Li-Hua Huang, Suneet Shukla, Dong-Hua Yang, Suresh V Ambudkar, Li-Wu Fu, Zhe-Sheng Chen
Paclitaxel is one of the most widely used antineoplastic drugs in the clinic. Unfortunately, the occurrence of cellular resistance has limited its efficacy and application. The ATP-binding cassette subfamily B member 1 (ABCB1/P-glycoprotein) and subfamily C member 10 (ABCC10/MRP7) are the major membrane protein transporters responsible for the efflux of paclitaxel, constituting one of the most important mechanisms of paclitaxel resistance. Here, we demonstrated that the Bruton tyrosine kinase inhibitor, ibrutinib, significantly enhanced the antitumor activity of paclitaxel by antagonizing the efflux function of ABCB1 and ABCC10 in cells overexpressing these transporters...
June 2017: Molecular Cancer Therapeutics
Yuan Deng, Shan-Dong Tao, Xin Zhang, Jing-Jing Ma, Zheng-Mei He, Yue Chen, Zhi-Kui Deng, Liang Yu
OBJECTIVE: To investigate the effects of Btk inhibitor (PCI-32765) and BCR-ABL tyrosine kinase inhibitor (Dasatinib) on proliferation and apoptosis of acute lymphoblastic leukemia (ALL) cell lines (Sup-B15, RS4;11) and the possible mechanism. METHODS: RS4;11 and Sup-B15 cells were treated with PCI-32765 and Dasatinib, the cell proliferation and apoptosis were detected by CCK-8, the Btk and other apoptotic proteins were detected by Western blot. RESULTS: PCI-32765 could inhibit the proliferation of RS4;11 and Sup-B15 cells in a dose-dependent manner, Sup-B15 cells were more sensitive to PCI-32765 than RS4;11 cells, their IC50 were 3 µmol/L and 8 µmol/L respectively, the difference between them was statistically significant (P<0...
February 2017: Zhongguo Shi Yan Xue Ye Xue za Zhi
Tomoko Yasuhiro, Wako Sawada, Christian Klein, Ryohei Kozaki, Shingo Hotta, Toshio Yoshizawa
The activated B-cell diffuse large B-cell-like lymphoma (ABC-DLBCL) correlates with poor prognosis. The B-cell receptor signaling pathway is known to be dysregulated in NHL/CLL and given BTK is a downstream mediator of BCR signaling, BTK constitutes an interesting and obvious therapeutic target. Given the high potency and selectivity of the BTK inhibitor, ONO/GS-4059, it was hypothesized that, the anti-tumor activity of ONO/GS-4059 could be further enhanced by combining it with the anti-CD20 Abs, rituximab (RTX) or obinutuzumab (GA101)...
March 2017: Leukemia & Lymphoma
Xianhui Wang, Jason Wong, Christopher J Sevinsky, Leila Kokabee, Faiza Khan, Yan Sun, Douglas S Conklin
We have reported that a novel isoform of BTK (BTK-C) expressed in breast cancer protects these cells from apoptosis. In this study, we show that recently developed inhibitors of BTK, such as ibrutinib (PCI-32765), AVL-292, and CGI-1746, reduce breast cancer cell survival and prevent drug-resistant clones from arising. Ibrutinib treatment impacts HER2(+) breast cancer cell viability at lower concentrations than the established breast cancer therapeutic lapatinib. In addition to inhibiting BTK, ibrutinib, but not AVL-292 and CGI-1746, efficiently blocks the activation of EGFR, HER2, ErbB3, and ErbB4...
September 2016: Molecular Cancer Therapeutics
Gayathri Natarajan, Cesar Terrazas, Steve Oghumu, Sanjay Varikuti, Jason A Dubovsky, John C Byrd, Abhay R Satoskar
Ibrutinib (PCI-32765) is an irreversible dual Btk/Itk inhibitor shown to be effective in treating several B cell malignancies. However, limited studies have been conducted to study the effect of this drug on myeloid cell function. Hence, we studied the effect of ibrutinib treatment on TLR-4 mediated activation of bone marrow derived dendritic cell culture (DCs). Upon ibrutinib treatment, LPS-treated DCs displayed lower synthesis of TNF-α and nitric oxide (NO) and higher induction of IL-6, TGF-β, IL-10 and IL-18...
2016: Oncoimmunology
Kazumi Hagiwara, Takashi Tokunaga, Hiroatsu Iida, Hirokazu Nagai
BACKGROUND: Bendamustine is effective in B-cell malignancies, including mantle cell lymphoma (MCL), alone and in combination with other agents. This study investigated the combination effect of bendamustine and the Bruton tyrosine kinase (BTK) inhibitor PCI-32765 on MCL cell death and the underlying mechanisms. MATERIALS AND METHODS: Cytotoxicity was examined by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MIT) assay. Apoptosis was assessed by annexin V/propidium iodide staining and protein expression was analyzed by western blotting...
December 2015: Anticancer Research
Xixiang Li, Aoli Wang, Kailin Yu, Ziping Qi, Cheng Chen, Wenchao Wang, Chen Hu, Hong Wu, Jiaxin Wu, Zheng Zhao, Juan Liu, Fengming Zou, Li Wang, Beilei Wang, Wei Wang, Shanchun Zhang, Jing Liu, Qingsong Liu
FLT3-ITD mutant has been observed in about 30% of AML patients and extensively studied as a drug discovery target. On the basis of the structure of PCI-32765 (ibrutinib), a BTK kinase inhibitor that was recently reported to bear FLT3 kinase activity through a structure-guided drug design approach, we have discovered compound 18 (CHMFL-FLT3-122), which displayed an IC50 of 40 nM against FLT3 kinase and achieved selectivity over BTK kinase (over 10-fold). It significantly inhibited the proliferation of FLT3-ITD positive AML cancer cell lines MV4-11 (GI50 = 22 nM), MOLM13/14 (GI50 = 21 nM/42 nM)...
December 24, 2015: Journal of Medicinal Chemistry
Parviz Kokhaei, Farhad Jadidi-Niaragh, Abdolreza Sotoodeh Jahromi, Anders Osterborg, Håkan Mellstedt, Mohammad Hojjat-Farsangi
Targeted therapies have appeared as new treatment options for several disease types, including cancer and autoimmune disorders. Of several targets, tyrosine kinases (TKs) are among the most promising. Overexpression of TKs provides a target for novel therapeutic agents, including small molecule inhibitors of tyrosine kinases (TKI). Ibrutinib (PCI-32765) is a TKI of Bruton's tyrosine kinase (Btk), a key kinase of the B-cell receptor signaling pathway that plays a significant role in the proliferation, differentiation and survival of B cells...
2016: Journal of Drug Targeting
Davide Grisafi, Alessandra Maestro, Camilla Grumi, Ludovica Piazzoni, Giampaolo Tirone, Walter Fiore, Roberto Tessari, Valeria Gianardi, Milo Gatti, Francesca Tasca, Daniele Generali, Andrea Ravelli, Francesco Lanza, Francesco Scaglione
The activation of the B cell receptor (BCR) is nowadays known to play a primary role in the etiopathogenesis of a multitude of B cell malignancies, being one of the main factors responsible for the enhanced proliferation and survival of transformed cells. Thanks to the characterization and continuous discovery of the pathways driving B cell proliferation in consequence to BCR activation, it has been possible to develop a small molecule inhibitor specifically antagonizing the Bruton's tyrosine kinase (BTK), an enzyme located in an early strategic position within the whole pathway...
September 2015: Medical Oncology
Jan de Jong, Donna Skee, Joe Murphy, Juthamas Sukbuntherng, Peter Hellemans, Johan Smit, Ronald de Vries, Juhui James Jiao, Jan Snoeys, Erik Mannaert
Ibrutinib (PCI-32765), a potent covalent inhibitor of Bruton's tyrosine kinase, has shown efficacy against a variety of B-cell malignancies. Given the prominent role of CYP3A in ibrutinib metabolism, effect of coadministration of CYP3A perpetrators with ibrutinib was evaluated in healthy adults. Ibrutinib (120 mg [Study 1, fasted], 560 mg [studies 2 (fasted), and 3 (nonfasted)]) was given alone and with ketoconazole [Study 1; 400 mg q.d.], rifampin [Study 2; 600 mg q.d.], and grapefruit juice [GFJ, Study 3]...
August 2015: Pharmacology Research & Perspectives
H Wu, C Hu, A Wang, E L Weisberg, Y Chen, C-H Yun, W Wang, Y Liu, X Liu, B Tian, J Wang, Z Zhao, Y Liang, B Li, L Wang, B Wang, C Chen, S J Buhrlage, Z Qi, F Zou, A Nonami, Y Li, S M Fernandes, S Adamia, R M Stone, I A Galinsky, X Wang, G Yang, J D Griffin, J R Brown, M J Eck, J Liu, N S Gray, Q Liu
Bruton's tyrosine kinase (BTK) kinase is a member of the TEC kinase family and is a key regulator of the B-cell receptor (BCR)-mediated signaling pathway. It is important for B-cell maturation, proliferation, survival and metastasis. Pharmacological inhibition of BTK is clinically effective against a variety of B-cell malignances, such as mantle cell lymphoma, chronic lymphocytic leukemia (CLL), acute myeloid leukemia (AML) and activated B-cell-diffuse large B-cell lymphoma. MNK kinase is one of the key downstream regulators in the RAF-MEK-ERK signaling pathway and controls protein synthesis via regulating the activity of eIF4E...
January 2016: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
Minako Ito, Takashi Shichita, Masahiro Okada, Ritsuko Komine, Yoshiko Noguchi, Akihiko Yoshimura, Rimpei Morita
Inflammasome activation has been implicated in various inflammatory diseases including post-ischaemic inflammation after stroke. Inflammasomes mediate activation of caspase-1, which subsequently induces secretion of pro-inflammatory cytokines such as IL-1β and IL-18, as well as a form of cell death called pyroptosis. In this study, we report that Bruton's tyrosine kinase (BTK) is an essential component of the NLRP3 inflammasome, in which BTK physically interacts with ASC and NLRP3. Inhibition of BTK by pharmacological or genetic means severely impairs activation of the NLRP3 inflammasome...
June 10, 2015: Nature Communications
Rossana Maffei, Stefania Fiorcari, Silvia Martinelli, Leonardo Potenza, Mario Luppi, Roberto Marasca
Tyrosine kinase inhibitors (TKIs) targeting signaling molecules downstream B cell receptor (BCR) are powerfully spreading in the therapeutic landscape of B cell lymphoproliferative disease, due to a manageable toxicity profile and encouraging clinical effectiveness. In particular, ibrutinib, previously called PCI-32765, is a potent inhibitor of Bruton tyrosine kinase (Btk), recently approved for the treatment of relapsed mantle cell lymphoma (MCL) and chronic lymphocytic leukemia (CLL). Moreover, idelalisib (formerly GS-1101 and CAL-101) is a selective reversible inhibitor of the p110δ isoform of phosphoinositol 3 kinase (PI3K) approved for the treatment of patients with relapsed follicular lymphoma (FL) and CLL...
May 29, 2015: Journal of Hematology & Oncology
Kazumi Hagiwara, Shinji Kunishima, Hiroatsu Iida, Yasuhiko Miyata, Tomoki Naoe, Hirokazu Nagai
Mantle cell lymphoma (MCL) is a B cell malignancy characterized by aberrant expression of cyclin D1 due to a t(11;14) translocation. MCL is refractory to conventional chemotherapy, and treatment remains challenging. We investigated the efficacy of the histone deacetylase (HDAC) inhibitor vorinostat combined with one of several B-cell receptor (BCR) signaling inhibitors on MCL cell death and the underlying mechanisms, using MCL cell lines. The Bruton's tyrosine kinase inhibitor PCI-32765 and the spleen tyrosine kinase inhibitor R406 showed synergistic effects with vorinostat on growth inhibition...
July 2015: Apoptosis: An International Journal on Programmed Cell Death
Fetch more papers »
Fetching more papers... Fetching...
Read by QxMD. Sign in or create an account to discover new knowledge that matter to you.
Remove bar
Read by QxMD icon Read

Search Tips

Use Boolean operators: AND/OR

diabetic AND foot
diabetes OR diabetic

Exclude a word using the 'minus' sign

Virchow -triad

Use Parentheses

water AND (cup OR glass)

Add an asterisk (*) at end of a word to include word stems

Neuro* will search for Neurology, Neuroscientist, Neurological, and so on

Use quotes to search for an exact phrase

"primary prevention of cancer"
(heart or cardiac or cardio*) AND arrest -"American Heart Association"