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https://www.readbyqxmd.com/read/28436683/dexmedetomidine-protects-pc12-cells-from-lidocaine-induced-cytotoxicity-through-downregulation-of-col3a1-mediated-by-mir-let-7b
#1
Qiong Wang, Yingjun She, Xiaobao Bi, Baisong Zhao, Xiangcai Ruan, Yonghong Tan
Safety concerns of some local anesthetics, such as lidocaine, have been raised in recent years due to potential neurological impairment. Dexmedetomidine may protect humans from neurotoxicity, and miR-let-7b is activated by nerve injury; however, the roles of miR-let-7b and its target gene in lidocaine-induced cytotoxicity are not well known. Through bioinformatics and a luciferase reporter assay, COL3A1 was suggested as a direct target gene of miR-let-7b. Here, we confirmed by measuring mRNA and protein levels that miR-let-7b was downregulated and COL3A1 was upregulated in lidocaine-treated cells, an observation that was reversed by dexmedetomidine...
April 24, 2017: DNA and Cell Biology
https://www.readbyqxmd.com/read/28429785/natriuretic-peptide-receptor-guanylyl-cyclase-a-pathway-counteracts-glomerular-injury-evoked-by-aldosterone-through-p38-mitogen-activated-protein-kinase-inhibition
#2
Yukiko Kato, Kiyoshi Mori, Masato Kasahara, Keisuke Osaki, Akira Ishii, Keita P Mori, Naohiro Toda, Shoko Ohno, Takashige Kuwabara, Takeshi Tokudome, Ichiro Kishimoto, Moin A Saleem, Taiji Matsusaka, Kazuwa Nakao, Masashi Mukoyama, Motoko Yanagita, Hideki Yokoi
Guanylyl cyclase-A (GC-A) signaling, a natriuretic peptide receptor, exerts renoprotective effects by stimulating natriuresis and reducing blood pressure. Previously we demonstrated massive albuminuria with hypertension in uninephrectomized, aldosterone-infused, and high salt-fed (ALDO) systemic GC-A KO mice with enhanced phosphorylation of p38 mitogen-activated protein kinase (MAPK) in podocytes. In the present study, we examined the interaction between p38 MAPK and GC-A signaling. The administration of FR167653, p38 MAPK inhibitor, reduced systolic blood pressure (SBP), urinary albumin excretion, segmental sclerosis, podocyte injury, and apoptosis...
April 21, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28428442/combination-of-ibrutinib-and-abt-199-in-diffuse-large-b-cell-lymphoma-and-follicular-lymphoma
#3
Hsu-Ping Kuo, Scott A Ezell, Karl J Schweighofer, Leo Wk Cheung, Sidney Hsieh, Mutiah Apatira, Mint Sirisawad, Karl Eckert, Ssucheng J Hsu, Chun-Te Chen, Darrin M Beaupre, Matthias Versele, Betty Y Chang
Diffuse large B-cell lymphoma (DLBCL) and follicular lymphoma (FL) are the most prevalent B-lymphocyte neoplasms in which abnormal activation of the Bruton's tyrosine kinase (BTK)-mediated B-cell receptor (BCR) signaling pathway contributes to pathogenesis. Ibrutinib is an oral covalent BTK inhibitor that has shown some efficacy in both indications. To improve ibrutinib efficacy through combination therapy, we first investigated differential gene expression in parental and ibrutinib-resistant cell lines to better understand the mechanisms of resistance...
April 20, 2017: Molecular Cancer Therapeutics
https://www.readbyqxmd.com/read/28427017/aromatase-inhibitors-and-apoptotic-inducers-design-synthesis-anticancer-activity-and-molecular-modeling-studies-of-novel-phenothiazine-derivatives-carrying-sulfonamide-moiety-as-hybrid-molecules
#4
Mostafa M Ghorab, Mansour S Alsaid, Nermin Samir, Ghada A Abdel-Latif, Aiten M Soliman, Fatma A Ragab, Dalal A Abou El Ella
Hybrid molecules are used as anticancer agents to improve effectiveness and diminish drug resistance. So, the current study aimed to introduce twenty novel phenothiazine sulfonamide hybrids 5-22, 24 and 25 of promising anticancer activity. Compounds 11 and 13 revealed more potent anticancer properties (IC50 8.1 and 8.8 μM) than that of the reference drug (doxorubicin, IC50 = 9.8 μM) against human breast cancer cell line (T47D). To determine the mechanism of their anticancer activity, compounds 5, 6, 7, 11, 13, 14, 16, 17, 19 and 22 that showed promising activity on T47D, were evaluated for their aromatase inhibitory effect...
April 15, 2017: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28415610/the-tubulin-inhibitor-mg-2477-induces-autophagy-regulated-cell-death-ros-accumulation-and-activation-of-foxo3-in-neuroblastoma
#5
Judith Hagenbuchner, Lorena Lungkofler, Ursula Kiechl-Kohlendorfer, Giampietro Viola, Maria Grazia Ferlin, Michael J Ausserlechner, Petra Obexer
Neuroblastoma is the most frequent extra-cranial solid tumor in children with still high mortality in stage M. Here we studied the tubulin-inhibitor MG-2477 as a possible therapeutic agent for neuroblastoma therapy and uncovered that MG-2477 induces death in neuroblastoma cells independent of PKB-activation status and stage. MG-2477 triggers within 30 minutes extensive autophagosome-formation that finally leads to cell death associated with mitotic catastrophe. Autophagy is critical for MG-2477-induced death and is regulated by the BH3-only protein PMAIP1/NOXA which sequesters the anti-apoptotic BCL2-protein BCLXL and thereby displaces and activates the autophagy-regulator BECN1/beclin1...
March 22, 2017: Oncotarget
https://www.readbyqxmd.com/read/28409693/tpt1-tumor-protein-translationally-controlled-1-negatively-regulates-autophagy-through-the-becn1-interactome-and-an-mtorc1-mediated-pathway
#6
Seong-Yeon Bae, Sanguine Byun, Soo Han Bae, Do Sik Min, Hyun Ae Woo, Kyunglim Lee
TPT1/TCTP (tumor protein, translationally-controlled 1) is highly expressed in tumor cells, known to participate in various cellular activities including protein synthesis, growth and cell survival. In addition, TPT1 was identified as a direct target of the tumor suppressor TP53/p53 although little is known about the mechanism underlying the anti-survival function of TPT1. Here, we describe a role of TPT1 in the regulation of the MTORC1 pathway through modulating the molecular machinery of macroautophagy/autophagy...
February 15, 2017: Autophagy
https://www.readbyqxmd.com/read/28404587/cic-dux4-induces-small-round-cell-sarcomas-distinct-from-ewing-sarcoma
#7
Toyoki Yoshimoto, Miwa Tanaka, Mizuki Homme, Yukari Yamazaki, Yutaka Takazawa, Cristina R Antonescu, Takuro Nakamura
CIC-DUX4 sarcoma (CDS) or CIC-rearranged sarcoma is a  subcategory of small round cell sarcoma resembling the morphological phenotypes of Ewing sarcoma (ES). Hoever, recent clinicopathologic and molecular genetic analyses indicate that CDS is an independent disease entity from ES. Few ancillary markers have been used in the differential diagnosis of CDS, and additional CDS-specific biomarkers are needed for more definitive classification. Here we report the generation of an ex vivo mouse model for CDS by transducing embryonic mesenchymal cells (eMC) with human CIC-DUX4 cDNA...
April 12, 2017: Cancer Research
https://www.readbyqxmd.com/read/28400072/notch-signaling-pathway-promotes-the-development-of-ovine-ovarian-follicular-granulosa-cells
#8
Jiongjie Jing, Xiaolong Jiang, Jianwei Chen, Xiaolei Yao, Miaomiao Zhao, Pengfei Li, Yangyang Pan, Youshe Ren, Wenzhong Liu, Lihua Lyu
The Notch signaling pathway regulates cell proliferation, differentiation and apoptosis involved in development of the organs and tissues such as nervous system, cartilage, lungs, kidneys and prostate as well as the ovarian follicles. This study aimed to investigate the mRNA expression and localization of NOTCH2, as the key factor in Notch signaling pathway. This was determined by PCR, real-time PCR and immunohistochemistry. Additionally, the effects of inhibiting Notch signaling pathway with different concentrations (5μM, 10μM and 20μM) of N-[N-(3, 5-Difuorophenacetyl)-l-alanyl]-S-phenylglycine t-butyl ester (DAPT), an inhibitor of Notch signaling pathway, on ovine granulosa cells was determined in vitro by detecting estradiol production using enzyme linked immunosorbent assay and expressions of the genes related to the cell cycle and apoptosis using real-time polymerase chain reaction (PCR)...
March 28, 2017: Animal Reproduction Science
https://www.readbyqxmd.com/read/28396364/novel-indole-based-tambjamine-analogues-induce-apoptotic-lung-cancer-cell-death-through-p38-mitogen-activated-protein-kinase-activation
#9
Pilar Manuel-Manresa, Luís Korrodi-Gregório, Elsa Hernando, Alberto Villanueva, David Martínez-García, Ananda M Rodilla, Ricard Ramos, Margarida Fardilha, Juan Moya, Roberto Quesada, Vanessa Soto-Cerrato, Ricardo Perez-Tomas
Lung cancer has become the leading killer cancer worldwide, due to late diagnosis and lack of efficient anticancer drugs. We have recently described novel natural-derived tambjamine analogues that are potent anion transporters capable of disrupting cellular ion balance, inducing acidification of the cytosol and hyperpolarization of cellular plasma membranes. Although these tambjamine analogues were able to compromise cell survival, their molecular mechanism of action remains largely unknown. Herein we characterize the molecular cell responses induced by highly active indole-based tambjamine analogues treatment in lung cancer cells...
April 10, 2017: Molecular Cancer Therapeutics
https://www.readbyqxmd.com/read/28391633/comparisons-of-cardioprotective-efficacy-between-fibroblast-growth-factor-21-and-dipeptidyl-peptidase-4-inhibitor-in-pre-diabetic-rats
#10
Pongpan Tanajak, Piangkwan Sa-Nguanmoo, Nattayaporn Apaijai, Xiaojie Wang, Guang Liang, Xiaokun Li, Chao Jiang, Siriporn C Chattipakorn, Nipon Chattipakorn
AIMS: Comparative efficacy between fibroblast growth factor 21 (FGF21) and vildagliptin on metabolic regulation, cardiac mitochondrial function, heart rate variability (HRV) and left ventricular (LV) function is not known. We hypothesized that FGF21 and vildagliptin share a similar efficacy in improving these parameters in high-fat diet (HFD) induced obese-insulin resistant rats. METHODS: Twenty-four male Wistar rats were fed with either a normal diet (ND) or a HFD for 12 weeks...
April 9, 2017: Cardiovascular Therapeutics
https://www.readbyqxmd.com/read/28391274/inhibition-of-brd4-suppresses-cell-proliferation-and-induces-apoptosis-in-renal-cell-carcinoma
#11
Xinchao Wu, Dong Liu, Xuemei Gao, Fei Xie, Dan Tao, Xingyuan Xiao, Liang Wang, Guosong Jiang, Fuqing Zeng
BACKGROUND/AIMS: Renal cell carcinoma (RCC) remains an intractable genitourinary malignancy. Resistance to chemotherapy or targeted therapies in RCC is presumably due to the complicated underlying molecular mechanisms and insufficient understanding. The aim of this research was to assess the expression and role of bromodomain-4 protein (BRD4) in RCC and evaluate the effects of BRD4 inhibitor JQ1 for RCC treatment. METHODS: BRD4 expressionlevels were assessed by qRT-PCR and western blot in RCC tissues and cells...
April 7, 2017: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/28386842/vitamin-k2-inhibits-rat-vascular-smooth-muscle-cell-calcification-by-restoring-the-gas6-axl-akt-anti-apoptotic-pathway
#12
Cuiting Qiu, Haijun Zheng, Huiren Tao, Wenjun Yu, Xiaoyu Jiang, Aiqin Li, Hui Jin, Anlin Lv, Huan Li
Vascular calcification is associated with cardiovascular disease as a complication of hypertension, hyperlipidemia, diabetes mellitus, and chronic kidney disease. Vitamin K2 (VK2) delays vascular calcification by an unclear mechanism. Moreover, apoptosis modulates vascular smooth muscle cell (VSMC) calcification. This paper aimed to study VK2-modified VSMC calcification and survival cell signaling mediated by growth arrest-specific gene 6 (Gas6) and its tyrosine kinase receptor Axl. Primary-cultured VSMCs were dose-dependently treated with VK2 in the presence of calcification medium for 8 days, or pre-treated for 1 h with/without the Axl inhibitor R428 (2 μmol/L) or the caspase inhibitor Z-VAD-fmk (20 μmol/L) followed by treatment with VK2 (10 μmol/L) or rmGas6 (200 nmol/L) in calcification medium for 8 days...
April 6, 2017: Molecular and Cellular Biochemistry
https://www.readbyqxmd.com/read/28381544/modulation-of-bax-and-mtor-for-cancer-therapeutics
#13
Rui Li, Chunyong Ding, Jun Zhang, Maohua Xie, Dongkyoo Park, Ye Ding, Guo Chen, Guojing Zhang, Melissa Gilbert-Ross, Wei Zhou, Adam Marcus, Shi-Yong Sun, Zhuo Georgia Chen, Gabriel L Sica, Suresh S Ramalingam, Andrew Magis, Haian Fu, Fadlo Khuri, Walter J Curran, Taofeek K Owonikoko, Dong M Shin, Jia Zhou, Xingming Deng
A rationale exists for pharmacologic manipulation of the serine (S)184 phosphorylation site of the proapoptotic Bcl2 family member Bax as an anticancer strategy. Here we report the refinement of the Bax agonist SMBA1 to generate CYD-2-11, which has characteristics of a suitable clinical lead compound. CYD-2-11 targeted the structural pocket proximal to S184 in the C-terminal region of Bax, directly activating its proapoptotic activity by inducing a conformational change enabling formation of Bax homooligomers in mitochondrial membranes...
April 5, 2017: Cancer Research
https://www.readbyqxmd.com/read/28379541/resistance-to-apoptosis-and-autophagy-leads-to-enhanced-survival-in-sertoli-cells
#14
Ferial Aslani, Tim Sebastian, Miguel Keidel, Suada Fröhlich, Hans-Peter Elsässer, Hans-Christian Schuppe, Jörg Klug, Poornima Mahavadi, Monika Fijak, Martin Bergmann, Andreas Meinhardt, Sudhanshu Bhushan
STUDY QUESTION: What is the underlying mechanism of Sertoli cell (SC) resistance to cell death? SUMMARY ANSWER: High expression of pro-survival B cell lymphoma-2 (BCL2) proteins and inhibition of apoptosis and autophagy prolongs SC survival upon exposure to stress stimuli. WHAT IS KNOWN ALREADY: In human and in experimental models of orchitis, tolerogenic SC survive stress conditions, while germ cells undergo massive apoptosis. In general, non-dividing highly differentiated cells tend to resist stress conditions for a longer time by favoring activation of pro-survival mechanisms and inhibition of cell death pathways...
April 3, 2017: Molecular Human Reproduction
https://www.readbyqxmd.com/read/28368400/interferon-%C3%AE-is-a-stat1-dependent-direct-inducer-of-bcl6-expression-in-imatinib-treated-chronic-myeloid-leukemia-cells
#15
H S Madapura, N Nagy, D Ujvari, T Kallas, M C L Kröhnke, S Amu, M Björkholm, L Stenke, P K Mandal, J S McMurray, M Keszei, L S Westerberg, H Cheng, F Xue, G Klein, E Klein, D Salamon
B-cell CLL/lymphoma 6 (BCL6) exerts oncogenic effects in several human hematopoietic malignancies including chronic myeloid leukemia (CML), where BCL6 expression was shown to be essential for CML stem cell survival and self-renewal during imatinib mesylate (IM) treatment. As several lines of evidence suggest that interferon γ (IFNγ) production in CML patients might have a central role in the response to tyrosine kinase inhibitor (TKI) therapy, we analyzed if IFNγ modulates BCL6 expression in CML cells. Although separate IFNγ or IM treatment only slightly upregulated BCL6 expression, combined treatment induced remarkable BCL6 upregulation in CML lines and primary human CD34+ CML stem cells...
April 3, 2017: Oncogene
https://www.readbyqxmd.com/read/28367088/regulation-of-dmt1-on-autophagy-and-apoptosis-in-osteoblast
#16
Fei Liu, Wei-Lin Zhang, Hong-Zheng Meng, Zheng-Yu Cai, Mao-Wei Yang
Iron overload has recently been associated with the changes in the bone microstructure that occur in osteoporosis. However, the effect of iron overload on osteoblasts is unclear. The purpose of this study was to explore the function of divalent metal transporter 1 (DMT1) in the pathological processes of osteoporosis. Osteoblast hFOB1.19 cells were cultured in medium supplemented with different concentrations (0, 50, 100, 200, 300, 400, 500 μmol/L) of ferric ammonium citrate (FAC) as a donor of ferric ions...
2017: International Journal of Medical Sciences
https://www.readbyqxmd.com/read/28356992/arctigenin-a-natural-lignan-compound-induces-g0-g1-cell-cycle-arrest-and-apoptosis-in-human-glioma-cells
#17
Aisha Maimaitili, Zunhua Shu, Xiaojiang Cheng, Kadeer Kaheerman, Alifu Sikandeer, Weimin Li
The aim of the current study was to investigate the anticancer potential of arctigenin, a natural lignan compound, in malignant gliomas. The U87MG and T98G human glioma cell lines were treated with various concentrations of arctigenin for 48 h and the effects of arctigenin on the aggressive phenotypes of glioma cells were assessed. The results demonstrated that arctigenin dose-dependently inhibited the growth of U87MG and T98G cells, as determined using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide and bromodeoxyuridine incorporation assays...
February 2017: Oncology Letters
https://www.readbyqxmd.com/read/28340172/repositioning-disulfiram-as-a-radiosensitizer-against-atypical-teratoid-rhabdoid-tumor
#18
Young Eun Lee, Seung Ah Choi, Pil Ae Kwack, Hak Jae Kim, Il Han Kim, Kyu-Chang Wang, Ji Hoon Phi, Ji Yeoun Lee, Sangjoon Chong, Sung-Hye Park, Kyung Duk Park, Do Won Hwang, Kyeung Min Joo, Seung-Ki Kim
Background.: Atypical teratoid/rhabdoid tumor (AT/RT) is one of the most common malignant brain tumors in infants. Although cancer stem cells of AT/RT express aldehyde dehydrogenase (ALDH), effective chemotherapies against AT/RT have not been established. Here, we examined radiosensitizing effects of disulfiram (DSF), an irreversible inhibitor of ALDH against AT/RT for a novel therapeutic method. Methods.: Patient-derived primary cultured AT/RT cells (SNU.AT/RT-5 and SNU...
March 17, 2017: Neuro-oncology
https://www.readbyqxmd.com/read/28334048/hepatoprotective-effect-of-sitagliptin-against-methotrexate-induced-liver-toxicity
#19
Hany M Abo-Haded, Mohamed A Elkablawy, Zeyad Al-Johani, Osama Al-Ahmadi, Dina S El-Agamy
Sitagliptin is selective dipeptidyl peptidase-4 inhibitor (DPP4-I), used clinically as a new oral anti-diabetic agent. This study explored the underlying mechanisms of the hepatoprotective role of sitagliptin pretreatment against methotrexate (MTX) induced hepatotoxicity in mice. Forty mice were divided into four groups (10 mice each); control, MTX, and two sitagliptin groups (pretreated with sitagliptin 10 and 20 mg/kg/day, respectively) for five consecutive days prior to MTX injection. Results showed that MTX induced marked hepatic injury in the form of cloudy swelling, hydropic degeneration, apoptosis and focal necrosis in all hepatic zones...
2017: PloS One
https://www.readbyqxmd.com/read/28301600/the-hdac-inhibitor-sb939-overcomes-resistance-to-bcr-abl-kinase-inhibitors-conferred-by-the-bim-deletion-polymorphism-in-chronic-myeloid-leukemia
#20
Muhammad Rauzan, Charles T H Chuah, Tun Kiat Ko, S Tiong Ong
Chronic myeloid leukemia (CML) treatment has been improved by tyrosine kinase inhibitors (TKIs) such as imatinib mesylate (IM) but various factors can cause TKI resistance in patients with CML. One factor which contributes to TKI resistance is a germline intronic deletion polymorphism in the BCL2-like 11 (BIM) gene which impairs the expression of pro-apoptotic splice isoforms of BIM. SB939 (pracinostat) is a hydroxamic acid based HDAC inhibitor with favorable pharmacokinetic, physicochemical and pharmaceutical properties, and we investigated if this drug could overcome BIM deletion polymorphism-induced TKI resistance...
2017: PloS One
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