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Molecular Cancer Research: MCR

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https://www.readbyqxmd.com/read/28314844/abituzumab-targeting-of-alphav-class-integrins-inhibits-prostate-cancer-progression
#1
Yuan Jiang, Jinlu Dai, Zhi Yao, Greg Shelley, Evan T Keller
Integrins that contain an integrin alpha V subunit contribute to multiple functions that promote cancer progression. The goal of this study was to determine if abituzumab (DI17E6, EMD 525797), a humanized monoclonal antibody (mAb) against integrin alpha V impacts, prostate cancer (PCa) progression. To evaluate this, PCa cells were treated with DI17E6 and its effects on proliferation, apoptosis, cell cycle, adhesion, detachment, migration, invasion and phosphorylation of downstream targets, including FAK, Akt and ERK were determined...
March 17, 2017: Molecular Cancer Research: MCR
https://www.readbyqxmd.com/read/28314843/quantitative-proteome-heterogeneity-in-myeloproliferative-neoplasm-subtypes-and-association-with-jak2-mutation-status
#2
Nuria Socoro-Yuste, Cokic Vladan P, Julie Mondet, Isabelle Plo, Pascal Mossuz
Apart from well-known genetic abnormalities, several studies have reported variations in protein expression in Philadelphia negative (Ph-) Myeloproliferative Neoplasm (MPN) patients that could contribute towards their clinical phenotype. In this context, a quantitative mass spectrometry proteomics protocol was used to identify differences in the granulocyte proteome with the goal to characterize the pathogenic role of aberrant protein expression in MPNs. LC MS/MS (LTQ Orbitrap) coupled to iTRAQ labeling showed significant and quantitative differences in protein content among various MPN subtypes [polycythemia vera (PV), essential thrombocythemia (ET) and primary myelofibrosis (PMF)], and according to the genetic status of JAK2 (JAK2V617F presence and JAK2V617F allele burden)...
March 17, 2017: Molecular Cancer Research: MCR
https://www.readbyqxmd.com/read/28289161/distinct-afatinib-resistance-mechanisms-identified-in-lung-adenocarcinoma-harboring-an-egfr-mutation
#3
Toshimitsu Yamaoka, Tohru Ohmori, Motoi Ohba, Satoru Arata, Yasunori Murata, Sojiro Kusumoto, Koichi Ando, Hiroo Ishida, Tsukasa Ohnishi, Yasutsuna Sasaki
Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) are associated with significant responses in non-small cell lung cancer (NSCLC) patients harboring EGFR-activating mutations. However, acquired resistance to reversible EGFR-TKIs remains a major obstacle. In particular, while the second-generation irreversible EGFR-TKI afatinib is currently used for treating NSCLC patients, the mechanisms underlying acquired afatinib resistance remain poorly understood. Here, heterogeneous mechanisms of acquired resistance were identified following long-term exposure to increasing doses of afatinib in EGFR mutant lung adenocarcinoma PC9 cells...
March 13, 2017: Molecular Cancer Research: MCR
https://www.readbyqxmd.com/read/28275089/the-microtubule-network-and-cell-death-are-regulated-by-a-mir-34a-stathmin-1-betaiii-tubulin-axis
#4
Nancy S Vetter, E Anders Kolb, Valerie B Sampson, Christopher Mills
MicroRNA-34a (miR-34a) is a master regulator of signaling networks that maintain normal physiology and disease and is currently in development as a miRNA-based therapy for cancer. Prior studies have reported low miR-34a expression in osteosarcoma (OS); however, the molecular mechanisms underlying miR-34a activity in OS are not well defined. Therefore, this study evaluated the role of miR-34a in regulating signal transduction pathways that influence cell death in OS. Levels of miR-34a were attenuated in human OS cells and xenografts of the Pediatric Preclinical Testing Consortium (PPTC)...
March 8, 2017: Molecular Cancer Research: MCR
https://www.readbyqxmd.com/read/28275088/calcium-sensor-ncs-1-promotes-tumor-aggressiveness-and-predicts-patient-survival
#5
Lauren M Moore, Allison England, Barbara E Ehrlich, David L Rimm
Neuronal Calcium Sensor 1 (NCS1) is a multi-functional Ca2+-binding protein that affects a range of cellular processes beyond those related to neurons. Functional characterization of NCS-1 in neuronal model systems suggests that NCS-1 may influence oncogenic processes. To this end, the biological role of NCS-1 was investigated by altering its endogenous expression in MCF-7 and MB-231 breast cancer (BCa) cells. Overexpression of NCS-1 resulted in a more aggressive tumor phenotype demonstrated by a marked increase in invasion and motility, and a decrease in cell-matrix adhesion to collagen IV...
March 8, 2017: Molecular Cancer Research: MCR
https://www.readbyqxmd.com/read/28258094/nucleome-analysis-reveals-structure-function-relationships-for-colon-cancer
#6
Laura Seaman, Haiming Chen, Markus Brown, Darawalee Wangsa, Geoff Patterson, Jordi Camps, Gilbert S Omenn, Thomas Ried, Indika Rajapakse
Chromosomal translocations and aneuploidy are hallmarks of cancer genomes; however, the impact of these aberrations on the nucleome (i.e., nuclear structure and gene expression) are not yet understood. Here, the nucleome of the colorectal cancer cell line HT-29 was analyzed using chromosome conformation capture (Hi-C) to study genome structure, complemented by RNA sequencing (RNA-seq) to determine consequent changes in genome function. Importantly, translocations and copy number changes were identified at high resolution from Hi-C data and the structure-function relationships present in normal cells were maintained in cancer...
March 3, 2017: Molecular Cancer Research: MCR
https://www.readbyqxmd.com/read/28242813/versican-promotes-tumor-progression-metastasis-and-predicts-poor-prognosis-in-renal-carcinoma
#7
Yozo Mitsui, Hiroaki Shiina, Taku Kato, Shigekatsu Maekawa, Yutaka Hashimoto, Marisa Shiina, Mitsuho Imai-Sumida, Priyanka Kulkarni, Pritha Dasgupta, Ryan Kenji Wong, Miho Hiraki, Naoko Arichi, Shinichiro Fukuhara, Soichiro Yamamura, Shahana Majid, Sharanjot Saini, Guoren Deng, Rajvir Dahiya, Koichi Nakajima, Yuichiro Tanaka
The proteoglycan versican (VCAN) promotes tumor progression and enhances metastasis in several cancers; however, its role in clear cell renal cell carcinoma (ccRCC) remains unknown. Recent evidence suggests that VCAN is an important target of chromosomal 5q gain, one of the most prevalent genetic abnormalities in ccRCC. Thus, we investigated whether VCAN expression is associated with the pathogenesis of ccRCC. VCAN expression was analyzed using three RCC and normal kidney cell lines as well as a clinical cohort of 84 matched ccRCC and normal renal tissues...
February 27, 2017: Molecular Cancer Research: MCR
https://www.readbyqxmd.com/read/28242812/crispr-knockout-of-the-hur-gene-causes-a-xenograft-lethal-phenotype
#8
Shruti Lal, Edwin C Cheung, Mahsa Zarei, Ranjan Preet, Saswati N Chand, Nicole C Mambelli-Lisboa, Carmella Romeo, Matthew C Stout, Eric Londin, Austin Goetz, Cinthya Y Lowder, Avinoam Nevler, Charles J Yeo, Paul M Campbell, Jordan M Winter, Dan A Dixon, Jonathan R Brody
Pancreatic ductal adenocarcinoma (PDA) is the third leading cause of cancer related deaths in the U.S., while colorectal cancer (CRC) is the third most common cancer. The RNA binding protein HuR (ELAVL1), supports a pro-oncogenic network in gastrointestinal (GI) cancer cells through enhanced HuR expression. Using a publically available database, HuR expression levels were determined to be increased in primary PDA and CRC tumor cohorts as compared to normal pancreas and colon tissues, respectively. CRISPR/Cas9 technology was successfully used to delete the HuR gene in both PDA (MIA PaCa-2 and Hs 766T) and CRC (HCT116) cell lines...
February 27, 2017: Molecular Cancer Research: MCR
https://www.readbyqxmd.com/read/28242811/deubiquitinase-usp18-loss-mislocalizes-and-destabilizes-kras-in-lung-cancer
#9
Lisa Maria Mustachio, Yun Lu, Laura J Tafe, Vincent Memoli, Jaime Rodriguez-Canales, Barbara Mino, Pamela Andrea Villalobos, Ignacio Wistuba, Hiroyuki Katayama, Samir M Hanash, Jason Roszik, Masanori Kawakami, Kwang-Jin Cho, John F Hancock, Fadzai Chinyengetere, Shanhu Hu, Xi Liu, Sarah J Freemantle, Ethan Dmitrovsky
KRAS is frequently mutated in lung cancers and is associated with aggressive biology and chemotherapy resistance. Therefore, innovative approaches are needed to treat these lung cancers. Prior work implicated the interferon-stimulated gene 15 (ISG15) deubiquitinase (DUB) USP18 as having anti-neoplastic activity by regulating lung cancer growth and oncoprotein stability. This study demonstrates that USP18 affects the stability of the KRAS oncoprotein. Interestingly, loss of USP18 reduced KRAS expression and engineered gain of USP18 expression increased KRAS protein levels in lung cancer cells...
February 27, 2017: Molecular Cancer Research: MCR
https://www.readbyqxmd.com/read/28235899/dual-targeting-of-mesenchymal-and-amoeboid-motility-hinders-metastatic-behavior
#10
Brandon C Jones, Laura C Kelley, Yuriy V Loskutov, Kristina M Marinak, Varvara K Kozyreva, Matthew B Smolkin, Elena N Pugacheva
Commonly upregulated in human cancers, the scaffolding protein NEDD9/HEF1 is a known regulator of mesenchymal migration and cancer cell plasticity. However, the functional role of NEDD9 as a regulator of different migration/invasion modes in the context of breast cancer metastasis is currently unknown. Here, it is reported that NEDD9 is necessary for both mesenchymal and amoeboid individual cell migration/invasion in triple-negative breast cancer (TNBC). NEDD9 deficiency results in acquisition of the amoeboid morphology, but severely limits all types of cell motility...
February 24, 2017: Molecular Cancer Research: MCR
https://www.readbyqxmd.com/read/28232385/the-cytidine-deaminase-apobec3-family-is-subject-to-transcriptional-regulation-by-p53
#11
Daniel Menendez, Thuy-Ai Nguyen, Joyce Snipe, Michael A Resnick
The APOBEC3 (A3) family of proteins are DNA cytidine deaminases that act as sentinels in the innate immune response against retroviral infections and are responsive to interferon. Recently, a few A3 genes were identified as potent enzymatic sources of mutations in several human cancers. Using human cancer cells and lymphocytes we show that under stress conditions and immune challenges all A3 genes are direct transcriptional targets of the tumor suppressor p53. While the expression of most A3 genes (including A3C and A3H) was stimulated by activation of p53, treatment with the DNA damaging agent doxorubicin or the p53 stabilizer Nutlin, led to repression of the A3B gene...
February 23, 2017: Molecular Cancer Research: MCR
https://www.readbyqxmd.com/read/28232384/the-e3-ligase-chip-mediates-p21-degradation-to-maintain-radioresistance
#12
Kuntal Biswas, Sukumar Sarkar, Kangping Du, David L Brautigan, Tarek Abbas, James M Larner
Lung cancer resists radiation therapy, making it one of the deadliest forms of cancer. Here we show that human lung cancer cell lines can be rendered sensitive to ionizing radiation (IR) by RNAi knockdown of Cterminus of Hsc70-interacting protein (CHIP/STUB1), a U-box-type E3 ubiquitin ligase that targets a number of stress-induced proteins. Mechanistically ubiquitin-dependent degradation of the cyclin-dependent kinase (CDK) inhibitor p21 protein is reduced by CHIP knockdown, leading to enhanced senescence of cells in response to exposure to IR...
February 23, 2017: Molecular Cancer Research: MCR
https://www.readbyqxmd.com/read/28223438/dysregulated-gpcr-signaling-and-therapeutic-options-in-uveal-melanoma
#13
Vivian Chua, Dominic Lapadula, Clinita Randolph, Jeffrey L Benovic, Philip Wedegaertner, Andrew E Aplin
Uveal melanoma (UM) is the most common primary intraocular malignant tumor in adults and arises from the transformation of melanocytes in the uveal tract. Even after treatment of the primary tumor, up to 50% of patients succumb to metastatic disease. The liver is the predominant organ of metastasis. There is an important need to provide effective treatment options for advanced stage UM. In order to provide the preclinical basis for new treatments, it is important to understand the molecular underpinnings of the disease...
February 21, 2017: Molecular Cancer Research: MCR
https://www.readbyqxmd.com/read/28219935/novel-insights-into-gastric-cancer-methylation-of-r-spondins-and-regulation-of-lgr5-by-sp1
#14
Franziska Wilhelm, Eva Simon, Christine Boger, Hans-Michael Behrens, Sandra Kruger, Christoph Rocken
Recently it was shown that leucine-rich repeat-containing receptor 5 (LGR5) expressing stem cells are the cellular origin of intestinal-type gastric cancer. The aim of our study was to uncover regulatory mechanisms of LGR5 expression in gastric mucosa and their implications for cancer development. Reporter assays identified a LGR5 promoter fragment, which is highly relevant for active LGR5 expression. Chromatin immunoprecipitation (ChIP) verified that SP1 is bound within this region and reporter activity increased in SP1 transfected cells...
February 20, 2017: Molecular Cancer Research: MCR
https://www.readbyqxmd.com/read/28213554/hypoxia-selectively-enhances-integrin-receptor-expression-to-promote-metastasis
#15
Julia A Ju, Ines Godet, I Chae Ye, Jungmin Byun, Hasini Jayatilaka, Sun Joo Lee, Lisha Xiang, Debangshu Samanta, Meng Horng Lee, Pei-Hsun Wu, Denis Wirtz, Gregg L Semenza, Daniele M Gilkes
Metastasis is the leading cause of breast cancer (BCa)mortality. Previous studies have implicated hypoxia-induced changes in the composition and stiffness of the extracellular matrix (ECM) in the metastatic process. Therefore, the contribution of potential ECM binding receptors in this process was explored. Using a bioinformatics approach the expression of all integrin receptor subunits, in two independent BCa patient data sets, were analyzed to determine if integrin status correlates with a validated hypoxiainducible gene signature...
February 17, 2017: Molecular Cancer Research: MCR
https://www.readbyqxmd.com/read/28209759/revisiting-seed-and-soil-examining-the-primary-tumor-and-cancer-cell-foraging-in-metastasis
#16
Amber E de Groot, Sounak Roy, Joel S Brown, Kenneth J Pienta, Sarah R Amend
Metastasis is the consequence of a cancer cell that disperses from the primary tumor, travels throughout the body, and invades and colonizes a distant site.  Based on Paget's 1889 hypothesis, the majority of modern metastasis research focuses on the properties of the metastatic "seed and soil," but the implications of the primary tumor "soil" have been largely neglected. The rare lethal metastatic "seed" arises as a result of the selective pressures in the primary tumor. Optimal foraging theory describes how cancer cells adopt a mobile foraging strategy to balance predation risk and resource reward...
February 16, 2017: Molecular Cancer Research: MCR
https://www.readbyqxmd.com/read/28209758/atorvastatin-decreases-hbx-induced-phospho-akt-in-hepatocytes-via-p2x-receptors
#17
Aram Ghalali, Javier Martin-Renedo, Johan Hogberg, Ulla Stenius
Hepatocellular carcinoma (HCC) is rated as the fifth most common malignancy and third in cancer related deaths worldwide. Statins, HMG-CoA reductase inhibitors, are potent cholesterol lowering drugs and recent epidemiological evidence suggests that statins prevent aggressive HCC development. Previous experiments revealed that statins downregulate phosphorylated Akt (pAkt). Here, it is demonstrated that atorvastatin decreases nuclear pAkt levels in pancreatic and lung cancer cell lines within minutes and this rapid effect is mediated by the purinergic P2X receptors...
February 16, 2017: Molecular Cancer Research: MCR
https://www.readbyqxmd.com/read/28209757/cdk4-6-therapeutic-intervention-and-viable-alternative-to-taxanes-in-crpc
#18
James P Stice, Suzanne E Wardell, John D Norris, Alexander P Yllanes, Holly M Alley, Victoria O Haney, Hannah S White, Rachid Safi, Peter S Winter, Kimberly J Cocce, Rigel J Kishton, Scott A Lawrence, Jay C Strum, Donald P McDonnell
Resistance to second generation AR antagonists and CYP17 inhibitors in patients with castrationresistant prostate cancer (CRPC) develops rapidly through reactivation of the androgen signaling axis and has been attributed to androgen receptor (AR) overexpression, production of constitutively active AR splice variants, or the selection for AR mutants with altered ligand binding specificity. It has been established that androgens induce cell cycle progression, in part, through upregulation of cyclin D1 (CCND1) expression and subsequent activation of cyclin-dependent kinases 4 and 6 (CDK4/6)...
February 16, 2017: Molecular Cancer Research: MCR
https://www.readbyqxmd.com/read/28202504/expression-profiling-of-circulating-microvesicles-reveals-intercellular-transmission-of-oncogenic-pathways
#19
Gloria Milani, Tobia Lana, Silvia Bresolin, Sanja Aveic, Anna Pasto, Chiara Frasson, Geertruy Te Kronnie
Circulating microvesicles (MVs) have been described as important players in cell-to-cell communication carrying biological information under normal or pathological condition. MVs released by cancer cells may incorporate diverse biomolecules (e.g. active lipids, proteins and RNA) which can be delivered and internalized by recipient cells, potentially altering gene expression of recipient cells and eventually impacting disease progression. Leukemia in vitro model systems were used to investigate MVs as vehicles of protein-coding messages...
February 15, 2017: Molecular Cancer Research: MCR
https://www.readbyqxmd.com/read/28196852/inpp4b-and-pten-loss-leads-to-pi-3-4-p2-accumulation-and-inhibition-of-pi3k-in-tnbc
#20
Darien E Reed, Kevan M Shokat
Triple-negative breast cancer [TNBC, lacks expression of estrogen receptor (ER), progesterone receptor (PR) and amplification of HER2/Neu] remains one of the most aggressive subtypes, affects the youngest patients and still lacks an effective targeted therapy(1,2). Both phosphatidylinositol-3-kinase (PI3K)-α and -β contribute to oncogenesis of solid tumors, including the development of breast cancer(3). Inositol polyphosphate-4-phosphatase type II (INPP4B) catalyzes the removal of the 4'-phosphate of phosphatidylinositol-(3,4-bisphosphate (PI-3,4-P2) creating phosphatidylinositol-3-phosphate(4)...
February 14, 2017: Molecular Cancer Research: MCR
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