Read by QxMD icon Read


Mark Yulis, Miguel Quiros, Roland Hilgarth, Charles A Parkos, Asma Nusrat
Desmosomal cadherins mediate intercellular adhesion and have also been shown to regulate homeostatic signaling in epithelial cells. We have previously reported that select pro-inflammatory cytokines induce Dsg2 ectodomain cleavage and shedding from intestinal epithelial cells (IECs). Dsg2 extracellular cleaved fragments (Dsg2 ECF) function to induce paracrine pro-proliferative signaling in epithelial cells. In this study, we show that exposure of IECs to pro-inflammatory cytokines interferon-gamma (IFN-γ) and tumor necrosis factor-alpha (TNF-α) resulted in Dsg2 intracellular cleavage and generation of a ~55 kDa fragment (Dsg2 ICF)...
March 9, 2018: Cell Death & Disease
Xuecheng Yang, Xin Mao, Xuemei Ding, Fengju Guan, Yuefeng Jia, Lei Luo, Bin Li, Hailin Tan, Caixia Cao
Oxidative stress and miRNAs have been confirmed to play an important role in neurological diseases. The study aimed to explore the underlying effect and mechanisms of miR-146a in H2 O2 -induced injury of PC12 cells. Here, PC12 cells were stimulated with 200 μM of H2 O2 to construct oxidative injury model. Cell injury was evaluated on the basis of the changes in cell viability, migration, invasion, apoptosis, and DNA damage. Results revealed that miR-146a expression was up-regulated in H2 O2 -induced PC12 cells...
February 26, 2018: Cell Biology and Toxicology
Huaqi Wang, Li Wang, Guojun Zhang, Chunya Lu, Heying Chu, Rui Yang, Guoqiang Zhao
In this study, we investigated the mechanism by which lncRNA metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) mediates cisplatin resistance in lung cancer. Lung cancer patients with high MALAT1 levels were associated with cisplatin resistance and low overall survival. Moreover, cisplatin-resistant A549/DDP cells showed higher MALAT1 expression than cisplatin-sensitive lung cancer cells (A549, H460, H1299 and SPC-A1). Dual luciferase reporter and RNA immunoprecipitation assays showed direct binding of miR-101-3p to MALAT1...
January 26, 2018: Oncotarget
Tsung-Hsien Yen, Chia-Ling Hsieh, Tsu-Te Liu, Chih-Sheng Huang, Yen-Chung Chen, Yao-Chen Chuang, Song-Shei Lin, Fei-Ting Hsu
The goal of the present study was to investigate anticancer effect of amentoflavone on glioblastoma cells in vitro. Our results demonstrated that amentoflavone not only significantly reduced cell viability, nuclear factor-ĸappa B (NF-ĸB) activation, and protein expression of cellular Fas-associated protein with death domain-like interleukin 1 beta-converting enzyme inhibitory protein (C-FLIP) and myeloid cell leukemia 1 (MCL1), but significantly triggered cell accumulation at the sub-G1 phase, loss of mitochondrial membrane potential, and expression of active caspase-3 and -8...
March 2018: In Vivo
Nathaniel Robichaud, Brian E Hsu, Roman Istomine, Fernando Alvarez, Julianna Blagih, Eric H Ma, Sebastian V Morales, David L Dai, Glenn Li, Margarita Souleimanova, Qianyu Guo, Sonia V Del Rincon, Wilson H Miller, Santiago Ramón Y Cajal, Morag Park, Russell G Jones, Ciriaco A Piccirillo, Peter M Siegel, Nahum Sonenberg
The translation of mRNAs into proteins serves as a critical regulatory event in gene expression. In the context of cancer, deregulated translation is a hallmark of transformation, promoting the proliferation, survival, and metastatic capabilities of cancer cells. The best-studied factor involved in the translational control of cancer is the eukaryotic translation initiation factor 4E (eIF4E). We and others have shown that eIF4E availability and phosphorylation promote metastasis in mouse models of breast cancer by selectively augmenting the translation of mRNAs involved in invasion and metastasis...
February 20, 2018: Proceedings of the National Academy of Sciences of the United States of America
Randy S Schrecengost, Cecelia L Green, Yan Zhuang, Staci N Keller, Ryan A Smith, Lynn W Maines, Charles D Smith
Glycogen synthase kinase-3s (GSK3α and GSK3β) are constitutively active protein kinases that target over 100 substrates, incorporate into numerous protein complexes, and regulate vital cellular functions such as proliferation, apoptosis and inflammation. Cyclin-dependent kinase 9 (CDK9) regulates RNA production as a component of positive transcription elongation factor b and promotes expression of oncogenic and inflammatory genes. Simultaneous inhibition of these signaling nodes is a promising approach for drug discovery, although previous compounds exhibit limited selectivity and clinical efficacy...
February 6, 2018: Journal of Pharmacology and Experimental Therapeutics
Jing Lin, Aihui Ji, Guanzhong Qiu, Huaizhi Feng, Jian Li, Shuo Li, Yongxiang Zou, Yong Cui, Chaoli Song, Hua He, Yicheng Lu
F-box and WD repeat domain-containing 7(FBW7) is a SCF-type E3 ubiquitin ligase targeting a multitude of oncoproteins for degradation. Acting as one of the most important tumor suppressor it is frequently inactivated in various tumors. In this study we aimed to evaluate the relationship of FBW7 with glioma pathology and prognosis, and examine its effect in glioma malignancies and temozolomide(TMZ)-based therapy. Clinical tissues and TCGA database analysis revealed FBW7 expression was correlated inversely with glioma histology and positively with patient survival time...
February 10, 2018: Cancer Science
Gerard Nuovo, Hue Tran, Andres Gutierrez, Paolo Fadda, Flavia Pichiorri, Enrico Caserta, Craig C Hofmeister, Marta Chesi, P Leif Bergsagel, Don Morris, Qiao Shi, Matt Coffey, Chandini Thirukkumaran
Acute reoviral infection has been extensively studied given the virus's propensity to target malignant cells and activate caspase-3 mediated apoptosis. Reovirus infection of malignant N1E-115 mouse neuroblastoma cells led to significant increased expression of importin-β and exportin-5 mRNAs (qRTPCR) and proteins (immunohistochemistry) which was partially blocked by small interfering LNA oligomers directed against the reoviral genome. Co-expression analysis showed that the N1E-115 cells that contained reoviral capsid protein had accumulated importin-β and exportin-5, as well as activated caspase 3...
February 2018: Annals of Diagnostic Pathology
Ayano Kabashima, Petra Hirsova, Steven F Bronk, Matthew C Hernandez, Mark J Truty, Sumera Rizvi, Scott H Kaufmann, Gregory J Gores
BACKGROUND & AIMS: Myeloid cell leukemia1 (MCL1), a prosurvival member of the BCL2 protein family, plays a pivotal role in human cholangiocarcinoma (CCA) cell survival. We have previously reported that fibroblast growth factor receptor (FGFR) signaling mediates MCL1-dependent survival of CCA cells in vitro and in vivo. However, the mode and mechanisms of cell death in this model were not delineated. METHODS: Human CCA cell lines were treated with the pan-FGFR inhibitor LY2874455 and the mode of cell death examined by several complementary assays...
February 2, 2018: Journal of Hepatology
Jia Cui, William J Placzek
Anti-apoptotic B cell lymphoma 2 (BCL2) family members (BCL2, MCL1, BCLxL, BCLW, and BFL1) are key players in the regulation of intrinsic apoptosis. Dysregulation of these proteins not only impairs normal development, but also contributes to tumor progression and resistance to various anti-cancer therapies. Therefore, cells maintain strict control over the expression of anti-apoptotic BCL2 family members using multiple mechanisms. Over the past two decades, the importance of post-transcriptional regulation of mRNA in controlling gene expression and its impact on normal homeostasis and disease have begun to be appreciated...
January 20, 2018: International Journal of Molecular Sciences
Federico Lucantoni, Andreas U Lindner, Norma O'Donovan, Heiko Düssmann, Jochen H M Prehn
Triple negative breast cancer (TNBC) is an aggressive form of breast cancer which accounts for 15-20% of this disease and is currently treated with genotoxic chemotherapy. The BCL2 (B-cell lymphoma 2) family of proteins controls the process of mitochondrial outer membrane permeabilization (MOMP), which is required for the activation of the mitochondrial apoptosis pathway in response to genotoxic agents. We previously developed a deterministic systems model of BCL2 protein interactions, DR_MOMP that calculates the sensitivity of cells to undergo mitochondrial apoptosis...
January 19, 2018: Cell Death & Disease
Linda S Steelman, Steve L Abrams, Peter Ruvolo, Vivian Ruvolo, Lucio Cocco, Stefano Ratti, Alberto M Martelli, Luca M Neri, Saverio Candido, Massimo Libra, James A McCubrey
Chemotherapeutic drug treatment can result in the emergence of drug-resistant cells. By culturing an interleukin-3 (IL-3)-dependent cell line, FL5.12 cells in the presence of the chemotherapeutic drug doxorubicin, we isolated FL/Doxo cells which are multi-drug resistant. Increased levels of drug efflux were detected in FL/Doxo cells which could be inhibited by the MDR1 inhibitor verapamil but not by the MRP1 inhibitor MK571. The effects of TP53 and MEK1 were examined by infection of FL/Doxo cells with retroviruses encoding either a dominant negative TP-53 gene (FL/Doxo+ TP53 (DN) or a constitutively-activated MEK-1 gene (FL/Doxo + MEK1 (CA)...
December 22, 2017: Oncotarget
Norihiro Ishii, Kenichiro Araki, Takehiko Yokobori, Dorgormaa Gantumur, Takahiro Yamanaka, Bolag Altan, Mariko Tsukagoshi, Takamichi Igarashi, Akira Watanabe, Norio Kubo, Yasuo Hosouchi, Hiroyuki Kuwano, Ken Shirabe
Pancreatic cancer is a highly malignant tumor type with poor outcomes, and elucidation of the mechanisms involved in cancer progression and therapeutic resistance is critical. FBXW7 is a key regulator of tumor malignant potential, and its substrate MCL1 regulates therapeutic resistance in human malignancies. Therefore, determination of the relevance of FBXW7 expression is critical for improving patient outcomes. In this study, we investigated the function and clinical significance of FBXW7 in pancreatic cancer...
December 22, 2017: Oncotarget
Parthiban Marimuthu, Kalaimathy Singaravelu
Myeloid cell leukemia 1 (Mcl1) is an anti-apoptotic protein that plays central role in apoptosis regulation. Also, Mcl1 has the potency to resist apoptotic cues resulting in up-regulation and cancer cell protection. A molecular probe that has the potential to specifically target Mcl1, and thereby provoke its down-regulatory activity is very essential. The aim of the current study is to probe the internal conformational dynamics of protein motions and potential binding mechanism in response to a series of picomolar range Mcl1 inhibitors using explicit-solvent molecular dynamics (MD) simulations...
January 18, 2018: Biochemistry
Yusra A Alyafee, Manal Alaamery, Shahad Bawazeer, Mansour S Almutairi, Badr Alghamdi, Nawaf Alomran, Atia Sheereen, Maha Daghestani, Salam Massadeh
Purpose: Anastrozole (ANS) is an aromatase inhibitor that is widely used as a treatment for breast cancer in postmenopausal women. Despite the wide use of ANS, it is associated with serious side effects due to uncontrolled delivery. In addition, ANS exhibits low solubility and short plasma half-life. Nanotechnology-based drug delivery has the potential to enhance the efficacy of drugs and overcome undesirable side effects. In this study, we aimed to prepare novel ANS-loaded PLA-PEG-PLA nanoparticles (ANS-NPs) and to compare the apoptotic response of MCF-7 cell line to both ANS and ANS-loaded NPs...
2018: International Journal of Nanomedicine
Michelle M Williams, Linus Lee, Thomas Werfel, Meghan M Morrison Joly, Donna J Hicks, Bushra Rahman, David Elion, Courtney McKernan, Violeta Sanchez, Monica V Estrada, Suleiman Massarweh, Richard Elledge, Craig Duvall, Rebecca S Cook
Estrogen receptor-α positive (ERα+) breast cancer accounts for approximately 70-80% of the nearly 25,0000 new cases of breast cancer diagnosed in the US each year. Endocrine-targeted therapies (those that block ERα activity) serve as the first line of treatment in most cases. Despite the proven benefit of endocrine therapies, however, ERα+ breast tumors can develop resistance to endocrine therapy, causing disease progression or relapse, particularly in the metastatic setting. Anti-apoptotic Bcl-2 family proteins enhance breast tumor cell survival, often promoting resistance to targeted therapies, including endocrine therapies...
January 17, 2018: Cell Death & Disease
Kirsteen J Campbell, Sandeep Dhayade, Nicola Ferrari, Andrew H Sims, Emma Johnson, Susan M Mason, Ashley Dickson, Kevin M Ryan, Gabriela Kalna, Joanne Edwards, Stephen G W Tait, Karen Blyth
Analysis of publicly available genomic and gene expression data demonstrates that MCL1 expression is frequently elevated in breast cancer. Distinct from other pro-survival Bcl-2 family members, the short half-life of MCL-1 protein led us to investigate MCL-1 protein expression in a breast cancer tissue microarray and correlate this with clinical data. Here, we report associations between high MCL-1 and poor prognosis in specific subtypes of breast cancer including triple-negative breast cancer, an aggressive form that lacks targeted treatment options...
January 16, 2018: Cell Death & Disease
Yong Huang, Hui Luo, Fang Li, Yun'e Yang, Guangsheng Ou, Xiaolong Ye, Nianchu Li
The present work aimed to probe into the effect of long non-coding RNA (lncRNA) LINC00152 on gastric cancer (GC) cells proliferation by regulating miR-193a-3p and its target gene MCL1 Transfected si-LINC00152 was used to down-regulate LINC00152, and cells proliferation was measured by the CCK-8 assay. Cell apoptosis and cell cycle were analyzed by flow cytometry. Besides, we also detected the potential functional effects of differential expression of LINC00152 in vivo using nude mouse xenograft model. We overexpressed and down-expressed miR-193a-3p to study the in vitro effect of miR-193a-3p on GC cells proliferation and vitality...
January 16, 2018: Bioscience Reports
Shengzhe Zhang, Meiying Zhang, Ying Jing, Xia Yin, Pengfei Ma, Zhenfeng Zhang, Xiaojie Wang, Wen Di, Guanglei Zhuang
MCL1 is a pivot member of the anti-apoptotic BCL-2 family proteins. While a distinctive feature of MCL1 resides in its efficient ubiquitination and destruction, the deubiquitinase USP9X has been implicated in the preservation of MCL1 expression by removing the polyubiquitin chains. Here we perform an unbiased siRNA screen and identify that the second deubiquitinase, USP13, regulates MCL1 stability in lung and ovarian cancer cells. Mechanistically, USP13 interacts with and stabilizes MCL1 via deubiquitination...
January 15, 2018: Nature Communications
Luciano Mazzoccoli, Marcela Cristina Robaina, Alexandre Gustavo Apa, Martin Bonamino, Luciana Wernersbach Pinto, Eduardo Queiroga, Carlos E Bacchi, Claudete Esteves Klumb
PURPOSE: Burkitt lymphoma (BL) is a B-cell lymphoma frequently diagnosed in children. It is characterized by MYC translocations, which lead to the constitutive expression of the MYC oncogene. MYC contributes to miR-29 repression through an E-box MYC binding site on the miR-29b-1/miR-29a promoter region. We evaluated the role of miR-29a/b/c and their predicted targets in BL pathogenesis. METHODS: Mature sequences of miR-29a/b/c were transfected to the BL cell lines BL41 and Raji, and evaluated for DNMT3B, MCL1, BIM, CDK6, AKT and TCL1 protein expression as well as for MCL-1 and CDK6 mRNA expression...
March 2018: Journal of Cancer Research and Clinical Oncology
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"