keyword
MENU ▼
Read by QxMD icon Read
search

BKM120

keyword
https://www.readbyqxmd.com/read/29621784/exosomes-derived-from-dendritic-cells-attenuate-liver-injury-by-modulating-the-balance-of-treg-and-th17-cells-after-ischemia-reperfusion
#1
Lei Zheng, Zhi Li, Wei Ling, Deming Zhu, Zhiwen Feng, Lianbao Kong
BACKGROUND/AIMS: The present study aimed to evaluate the effects as well as the underlying mechanisms of bone marrow-derived dendritic cells (BMDCs) and exosomes produced by BMDCs (DEXs) on hepatic ischemia-reperfusion (I/R) injury (IRI). METHODS: Primary hepatocytes were isolated and used to mimic the liver IR microenvironment. BMDCs were induced and characterized both biochemically with a flow cytometer (FCM) and biophysically with a microscope. Then, we exposed BMDCs to the supernatants from primary hepatocytes and evaluated the maturation of BMDCs by FCM...
March 29, 2018: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/29563327/inhibition-of-the-%C3%AE-subunit-of-phosphoinositide-3-kinase-pi3k-in-heart-increases-late-sodium-current-and-is-arrhythmogenic
#2
Tao Yang, David F Meoli, Javid Moslehi, Dan M Roden
While inhibition of phosphoinositide 3-kinase (PI3K) is an emerging strategy in cancer therapy, we and others have reported that this action can also contribute to drug-induced Q-T prolongation and arrhythmias by increasing cardiac late sodium current (INaL). Previous studies in mice implicate the PI3K-α isoform as the major effector of the INaL action. Here, we have determined the effects of new anticancer drugs targeting specific PI3K isoforms on INaL and action potentials (APs) in mouse cardiomyocytes and CHO cells...
March 21, 2018: Journal of Pharmacology and Experimental Therapeutics
https://www.readbyqxmd.com/read/29552172/effects-of-nvp-bez235-a-dual-phosphatidylinositol-3-kinase-mammalian-target-of-rapamycin-inhibitor-on-htlv-1-infected-t-cell-lines
#3
Chie Ishikawa, Masachika Senba, Naoki Mori
Adult T-cell leukemia (ATL) is an aggressive type of malignancy caused by human T-cell leukemia virus type 1 (HTLV-1). In ATL, the phosphatidylinositol 3-kinase (PI3K)/Akt/mammalian target of rapamycin (mTOR) signaling pathway is constitutively active, promoting cell proliferation, survival and chemoresistance. Thus, the PI3K signaling pathway is an attractive therapeutic target for ATL. In the present study, the effects of RAD001 (an mTOR inhibitor), NVP-BKM120 (a pan-PI3K inhibitor) and NVP-BEZ235 (a novel dual PI3K/mTOR inhibitor) on cultured HTLV-1-infected T-cell lines were compared...
April 2018: Oncology Letters
https://www.readbyqxmd.com/read/29515122/pan-class-i-pi3-kinase-inhibitor-bkm120-induces-mek1-2-dependent-mitotic-catastrophe-in-non-hodgkin-lymphoma-leading-to-apoptosis-or-polyploidy-determined-by-bax-bak-and-p53
#4
Anja Müller, Bernd Gillissen, Antje Richter, Anja Richter, Cindrilla Chumduri, Peter T Daniel, Christian W Scholz
Constitutive signaling of PI3K/Akt/mTOR plays a prominent role in malignant transformation and progression of B-cell non-Hodgkin lymphomas (B-NHL) underscoring the need for PI3K targeted therapies. The pan-class I PI3-kinase inhibitor BKM120 has shown preclinical activity in distinct malignancies and is currently tested in clinical trials. Intratumor heterogeneity is an intrinsic property of cancers that contributes to drug resistance and tumor recurrence. Here, we demonstrate that inhibition of PI3-kinases by BKM120 attenuates growth and survival of B-NHL cell lines by inducing mitotic arrest with subsequent induction of intrinsic apoptosis...
March 7, 2018: Cell Death & Disease
https://www.readbyqxmd.com/read/29495002/synergistic-antitumor-effect-of-bkm120-with-prima-1met-via-inhibiting-pi3k-akt-mtor-and-cpsf4-htert-signaling-and-reactivating-mutant-p53
#5
Zongjuan Li, Xiangdong Xu, Yizhuo Li, Kun Zou, Zhuo Zhang, Xiaoying Xu, Yina Liao, Xinrui Zhao, Wei Jiang, Wendan Yu, Wei Guo, Yiming Chen, Yixin Li, Miao Chen, Wu-Guo Deng, Liren Li, Lijuan Zou
BACKGROUND/AIMS: PI3KCA and mutant p53 are associated with tumorigenesis and the development of cancers. NVP-BKM120, a selective pan-PI3K inhibitor, exerts the antitumor activity by suppressing the PI3K signaling pathway. Prima-1Met, a low molecular weight compound, can rescue the gain-of-function of mutant p53 by restoring its transcriptional function. In this study, we investigated whether PI3K inhibition combined with mutant p53 reactivation could enhance the antitumor effect in thyroid cancer cells...
February 23, 2018: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/29435074/over-activated-pd-1-pd-l1-axis-facilitates-the-chemoresistance-of-diffuse-large-b-cell-lymphoma-cells-to-the-chop-regimen
#6
Juan Liu, Lina Quan, Chunhui Zhang, Aichun Liu, Dongxia Tong, Jinghua Wang
Interaction between the programmed cell death ligand 1 (PD-L1) and programmed cell death 1 (PD-1) contributes to tumor cell resistance to chemotherapeutic agents. PD-L1 is expressed in the cells of diffuse large B-cell lymphoma (DLBCL), one common type of malignant non-Hodgkin lymphomas. However, little is known about how the PD-1/PD-L1 pathway functions in the pathogenesis of DLBCL. Therefore, the present study investigated whether and how the PD-1/PD-L1 axis is involved in regulating the sensitivity of CRL2631, a DLBCL cell line, to the CHOP (Cyclophosphamide, Hydroxydaunorubicin/adriamycin, Oncovin/vincristine and Prednisone) chemotherapeutic regimen...
March 2018: Oncology Letters
https://www.readbyqxmd.com/read/29228564/inhibitors-of-the-pi3k-mtor-pathway-prevent-stat5-phosphorylation-in-jak2v617f-mutated-cells-through-pp2a-cip2a-axis
#7
Niccolò Bartalucci, Laura Calabresi, Manjola Balliu, Serena Martinelli, Maria Caterina Rossi, Jean Luc Villeval, Francesco Annunziato, Paola Guglielmelli, Alessandro M Vannucchi
Inhibition of the constitutively activated JAK/STAT pathway in JAK2V617F mutated cells by the JAK1/JAK2 inhibitor ruxolitinib resulted in clinical benefits in patients with myeloproliferative neoplasms. However, evidence of disease-modifying effects remains scanty; furthermore, some patients do not respond adequately to ruxolitinib, or have transient responses, thus novel treatment strategies are needed. Here we demonstrate that ruxolitinib causes incomplete inhibition of STAT5 in JAK2V617F mutated cells due to persistence of phosphorylated serine residues of STAT5b, that conversely are targeted by PI3K and mTORC1 inhibitors...
November 14, 2017: Oncotarget
https://www.readbyqxmd.com/read/29222171/tankyrase-inhibition-enhances-the-antiproliferative-effect-of-pi3k-and-egfr-inhibition-mutually-affecting-%C3%AE-catenin-and-akt-signaling-in-colorectal-cancer
#8
Nina T Solberg, Jo Waaler, Kaja Lund, Line Mygland, Petter A Olsen, Stefan Krauss
Overactivation of the WNT/β-CATENIN signaling axis is a common denominator in colorectal cancer. Currently, there is no available WNT inhibitor in clinical practice. Although TANKYRASE (TNKS) inhibitors have been proposed as promising candidates, there are many colorectal cancer models that do not respond positively to TNKS inhibition in vitro and in vivo Therefore, a combinatorial therapeutic approach combining a TNKS inhibitor (G007-LK) with PI3K (BKM120) and EGFR (erlotinib) inhibitors in colorectal cancer was investigated...
March 2018: Molecular Cancer Research: MCR
https://www.readbyqxmd.com/read/29198055/phase-ii-study-of-buparlisib-bkm120-and-trastuzumab-in-patients-with-her2-locally-advanced-or-metastatic-breast-cancer-resistant-to-trastuzumab-based-therapy
#9
B Pistilli, T Pluard, A Urruticoechea, D Farci, A Kong, T Bachelot, S Chan, H S Han, G Jerusalem, P Urban, D Robinson, S L Mouhaër, E D Tomaso, C Massacesi, C Saura
PURPOSE: A Phase Ib study in patients with trastuzumab-resistant, human epidermal growth factor receptor-2- (HER2)-positive advanced breast cancer defined the recommended Phase II dose of buparlisib as 100 mg/day in combination with 2 mg/kg weekly trastuzumab, and reported preliminary signs of clinical activity. Here we present results from the Phase II portion. METHODS: Patients with trastuzumab-resistant, HER2-positive advanced breast cancer received buparlisib plus trastuzumab...
April 2018: Breast Cancer Research and Treatment
https://www.readbyqxmd.com/read/29181846/golm1-promotes-prostate-cancer-progression-through-activating-pi3k-akt-mtor-signaling
#10
Guang Yan, Yi Ru, Kerong Wu, Fengqi Yan, Qinhao Wang, Jingxiang Wang, Tao Pan, Mei Zhang, Hua Han, Xia Li, Lian Zou
BACKGROUND: Prostate cancer (PCa) is the most commonly diagnosed cancer in men. Various molecular mechanisms account for PCa progression and elucidation of these mechanisms is key for selection of optimal therapies and improvement of patient outcome. Golgi membrane protein 1 (GOLM1) has been identified as a novel biomarker for PCa, but its biological functions and molecular mechanisms remain poorly understood. METHOD: GOLM1 expression was determined in PCa by tissue microarrays (TMAs) and real-time RT-PCR, Western blot, and immunohistochemistry (IHC) analyses...
February 2018: Prostate
https://www.readbyqxmd.com/read/29151909/bkm120-sensitizes-c6-glioma-cells-to-temozolomide-via-suppression-of-the-pi3k-akt-nf-%C3%AE%C2%BAb-mgmt-signaling-pathway
#11
Mao Li, Ruo Fei Liang, Xiang Wang, Qing Mao, Yan Hui Liu
Glioblastoma is the most common type of malignant intracranial tumor in adults. Temozolomide (TMZ), as the first-line chemotherapy agent used in patients with glioblastoma, has demonstrated different effects in patients due to the expression of O6-methylguanine-DNA methyltransferase (MGMT) which is able to repair the DNA lesions induced by TMZ. The phosphatidylinositol 3-kinase (PI3K)/Akt signaling pathway is over-activated in glioblastoma and has been revealed to be potentially implicated in resistance to TMZ...
December 2017: Oncology Letters
https://www.readbyqxmd.com/read/29137323/nvp-bkm120-inhibits-colon-cancer-growth-via-foxo3a-dependent-puma-induction
#12
Shida Yang, Xin Li, Wenchang Guan, Mingqin Qian, Zhicheng Yao, Xiaoxue Yin, Hongmei Zhao
NVP-BKM120, a potent and highly selective PI3K inhibitor, is currently being investigated in phase I/II clinical trials. The mechanisms of action of NVP-BKM120 in colon cancer cells are unclear. In the present study, we investigated how NVP-BKM120 suppresses colon cancer cells growth and potentiates effects of other chemotherapeutic drugs. We found that NVP-BKM120 treatment enhance PUMA induction irrespective of p53 status through the FoxO3a pathway following AKT inhibition. Furthermore, PUMA is required for NVP-BKM120-induced apoptosis in colon cancer cells...
October 10, 2017: Oncotarget
https://www.readbyqxmd.com/read/29051320/combinatorial-treatment-with-mtor-inhibitors-and-streptozotocin-leads-to-synergistic-in-vitro-and-in-vivo-antitumor-effects-in-insulinoma-cells
#13
Julien Bollard, Céline Patte, Patrick Massoma, Isabelle Goddard, Nicolas Gadot, Noura Benslama, Valérie Hervieu, Carole Ferraro-Peyret, Martine Cordier-Bussat, Jean-Yves Scoazec, Colette Roche, Thomas Walter, Cécile Vercherat
Streptozotocin-based chemotherapy is the first-line chemotherapy recommended for advanced pancreatic neuroendocrine tumors (pNETs), whereas targeted therapies, including mTOR inhibitors, are available in second-line treatment. Unfortunately, objective response rates to both treatments are limited. Because mTOR pathway activation, commonly observed in pNETs, has been reported as one of the major mechanisms accounting for chemoresistance, we investigated the potential benefit of mTOR inhibition combined with streptozotocin treatment in a subset of pNETs, namely insulinomas...
January 2018: Molecular Cancer Therapeutics
https://www.readbyqxmd.com/read/29028222/role-of-rbp2-induced-er-and-igf1r-erbb-signaling-in-tamoxifen-resistance-in-breast-cancer
#14
Hee-Joo Choi, Hyeong-Seok Joo, Hee-Young Won, Kyueng-Whan Min, Hyung-Yong Kim, Taekwon Son, Young-Ha Oh, Jeong-Yeon Lee, Gu Kong
Background: Despite the benefit of endocrine therapy, acquired resistance during or after treatment still remains a major challenge in estrogen receptor (ER)-positive breast cancer. We investigated the potential role of histone demethylase retinoblastoma-binding protein 2 (RBP2) in endocrine therapy resistance of breast cancer. Methods: Survival of breast cancer patients according to RBP2 expression was analyzed in three different breast cancer cohorts including METABRIC (n = 1980) and KM plotter (n = 1764)...
April 1, 2018: Journal of the National Cancer Institute
https://www.readbyqxmd.com/read/29024814/anti-tumor-effects-of-nvp-bkm120-alone-or-in-combination-with-mek162-in-biliary-tract-cancer
#15
Ling Jin, Mei-Hua Jin, Ah-Rong Nam, Ji-Eun Park, Ju-Hee Bang, Do-Youn Oh, Yung-Jue Bang
There are currently no clinically validated therapeutic targets for biliary tract cancer (BTC). Despite promising results in other cancers, compounds targeting the phosphatidylinositol 3-kinase (PI3K)/AKT pathway, alone or in combination with Ras/Raf/MEK pathway inhibitors, have not been evaluated in BTC. Here, we examined the effects of a pan-PI3K inhibitor (BKM120) with or without a MEK inhibitor (MEK162), on eight human BTC cell lines carrying mutations in K-Ras and/or the PI3K catalytic subunit, PI3KCA...
December 28, 2017: Cancer Letters
https://www.readbyqxmd.com/read/28989655/precision-spherical-nucleic-acids-for-delivery-of-anticancer-drugs
#16
Danny Bousmail, Lilian Amrein, Johans J Fakhoury, Hassan H Fakih, John C C Hsu, Lawrence Panasci, Hanadi F Sleiman
We report a spherical nucleic acid (SNA) system for the delivery of BKM120, an anticancer drug for treatment of chronic lymphocytic leukemia (CLL). While promising for cancer treatment, this drug crosses the blood-brain barrier causing significant side-effects in patients. The DNA nanoparticle encapsulates BKM120 in high efficiency, and is unparalleled in its monodispersity, ease of synthesis and stability in different biological media and in serum. These DNA nanostructures demonstrate efficient uptake in human cervical cancer (HeLa) cells, and increased internalization of cargo...
September 1, 2017: Chemical Science
https://www.readbyqxmd.com/read/28971900/pan-phosphatidylinositol-3-kinase-inhibition-with-buparlisib-in-patients-with-relapsed-or-refractory-non-hodgkin-lymphoma
#17
Anas Younes, Gilles Salles, Giovanni Martinelli, Robert Gregory Bociek, Dolores Caballero Barrigon, Eva González Barca, Mehmet Turgut, John Gerecitano, Oliver Kong, Chaitali Babanrao Pisal, Ranjana Tavorath, Won Seog Kim
Activation of the phosphatidylinositol 3-kinase/mechanistic target of rapamycin pathway plays a role in the pathogenesis of non-Hodgkin lymphoma. This multicenter, open-label phase 2 study evaluated buparlisib (BKM120), a pan-class I phosphatidylinositol 3-kinase inhibitor, in patients with relapsed or refractory non-Hodgkin lymphoma. Three separate cohorts of patients (with diffuse large B-cell lymphoma, mantle cell lymphoma, or follicular lymphoma) received buparlisib 100 mg once daily until progression, intolerance, or withdrawal of consent...
December 2017: Haematologica
https://www.readbyqxmd.com/read/28945228/erk-dependent-il-6-autocrine-signaling-mediates-adaptive-resistance-to-pan-pi3k-inhibitor-bkm120-in-head-and-neck-squamous-cell-carcinoma
#18
M R Yun, H M Choi, H N Kang, Yw Lee, H-S Joo, D H Kim, H R Kim, M H Hong, S O Yoon, B C Cho
Hyperactivation of phosphatidylinositol 3-kinase (PI3K) pathway occurs frequently in head and neck squamous cell carcinoma (HNSCC). However, clinical outcomes of targeting the PI3K pathway have been underwhelming. In present study, we investigated the resistant mechanisms and potential combination therapeutic strategy to overcome adaptive resistance to PI3K inhibitor in HNSCC. Treatment of NVP-BKM120, a pan-PI3K inhibitor, led to upregulation of interleukin-6 (IL-6) and subsequent activation of either extracellular signal-regulated kinase (ERK) or signal transducers and activators of transcription 3 (STAT3), causing modest antitumor effects on the growth of HNSCC cells...
January 18, 2018: Oncogene
https://www.readbyqxmd.com/read/28945226/pten-deficiency-sensitizes-endometrioid-endometrial-cancer-to-compound-parp-pi3k-inhibition-but-not-parp-inhibition-as-monotherapy
#19
X Bian, J Gao, F Luo, C Rui, T Zheng, D Wang, Y Wang, T M Roberts, P Liu, J J Zhao, H Cheng
Poly (ADP-ribose) polymerase (PARP) inhibitors have emerged as promising cancer therapeutics especially for tumors with deficient homologous recombination (HR) repair. However, as HR-deficient tumors represent only a small fraction of endometrial cancers, the therapeutic utility of PARP inhibitors is limited in this disease. Somatic loss of phosphatase and tensin homolog (PTEN), a tumor suppressor that counteracts phosphoinositide 3-kinase (PI3K) activity, is one of the most common genetic aberrations in endometrioid endometrial cancer...
January 18, 2018: Oncogene
https://www.readbyqxmd.com/read/28835385/targeting-phosphatidylinositol-3-kinase-signaling-pathway-for-therapeutic-enhancement-of-vascular-targeted-photodynamic-therapy
#20
Daniel Kraus, Pratheeba Palasuberniam, Bin Chen
Vascular-targeted photodynamic therapy (PDT) selectively disrupts vascular function by inducing oxidative damages to the vasculature, particularly endothelial cells. Although effective tumor eradication and excellent safety profile are well demonstrated in both preclinical and clinical studies, incomplete vascular shutdown and angiogenesis are known to cause tumor recurrence after vascular-targeted PDT. We have explored therapeutic enhancement of vascular-targeted PDT with PI3K signaling pathway inhibitors because the activation of PI3K pathway was involved in promoting endothelial cell survival and proliferation after PDT...
November 2017: Molecular Cancer Therapeutics
keyword
keyword
80726
1
2
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"