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Molecular Cancer Research: MCR

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https://www.readbyqxmd.com/read/28396463/blind-selex-approach-identifies-rna-aptamer-that-regulate-emt-and-inhibit-metastasis
#1
Sorah Yoon, Brian Armstrong, Nagy Habib, John J Rossi
Identifying targets that are exposed on the plasma membrane of tumor cells, but expressed internally in normal cells, is a fundamental issue for improving the specificity and efficacy of anticancer therpeutics. Using blind cell SELEX (Systemic Evolution of Ligands by EXponetial enrichment) which is untargeted SELEX, we have identified an aptamer, P15, which specifically bound to the human pancreatic adenocarcinoma cells. To identify the aptamer binding plasma membrane protein, liquid chromatography tandem mass spectrometry (LC-MS/MS) was used...
April 10, 2017: Molecular Cancer Research: MCR
https://www.readbyqxmd.com/read/28396462/lncrna-gas5-inhibits-cellular-proliferation-by-targeting-p27kip1
#2
Gang Luo, Dong Liu, Chao Huang, Miao Wang, Xingyuan Xiao, Fuqing Zeng, Liang Wang, Guosong Jiang
Recent studies have demonstrated that long non-coding RNAs (lncRNAs) have important roles in cancer biology, and that the downregulation of lncRNA growth arrest-specific transcript 5 (GAS5) has been reported in a variety of human cancers. However, its role in prostate cancer is largely unknown. This study aims investigated the biological role and underlying mechanism of GAS5 on proliferation in prostate cancer. The results demonstrate that GAS5 expression is significantly decreased in prostate cancer cells compared with prostate epithelial cells...
April 10, 2017: Molecular Cancer Research: MCR
https://www.readbyqxmd.com/read/28389619/differential-expression-of-oatp1b3-mediates-unconjugated-testosterone-influx
#3
Tristan M Sissung, Ariel M Ley, Jonathan D Strope, Edel M McCrea, Shaunna L Beedie, Cody J Peer, Suneet Shukla, Jennifer C van Velkinburgh, Kelie Reece, Sarah Troutman, Tessa Campbell, Elena Fernandez, Phoebe Huang, Jordan Smith, Nilay Thakkar, David Venzon, Steffan Brenner, Wooin Lee, Maria J Merino, Ji Luo, Walter Jager, Cindy H Chau, Douglas K Price, William D Figg
Castration resistant prostate cancer (CRPC) has greater intratumoral testosterone concentrations than similar tumors from eugonadal men; simple diffusion does not account for this observation. The present study was undertaken to ascertain the androgen uptake kinetics, functional, and clinical relevance of de novo expression of the steroid hormone transporter OATP1B3 (SLCO1B3). Experiments testing the cellular uptake of androgens suggest that testosterone is an excellent substrate of OATP1B3 (KM=23.2µM; VMAX=321...
April 7, 2017: Molecular Cancer Research: MCR
https://www.readbyqxmd.com/read/28385910/metformin-reduces-prostate-tumor-growth-in-a-diet-dependent-manner-by-modulating-multiple-signaling-pathways
#4
Andre Sarmento-Cabral, Fernando L-Lopez, Manuel D Gahete, Justo P Castano, Raul M Luque
Prostate-cancer is strongly influenced by obesity, wherein metformin could represent a promising treatment; however, the endocrine-metabolic/cellular/molecular-mechanisms underlying these associations and effects are still unclear. To determine the beneficial anti-tumoral effects of metformin on prostate-cancer progression/aggressiveness and the relative contribution of high-fat diet (HFD; independently of obesity), we used HFD-fed immuno-suppressed mice inoculated with PC3 cells (which exhibited partial resistance to diet-induced obesity) compared with low-fat diet (LFD)-fed control-mice...
April 6, 2017: Molecular Cancer Research: MCR
https://www.readbyqxmd.com/read/28373289/mir-202-diminishes-tgfbeta-receptors-and-attenuates-tgfbeta1-induced-emt-in-pancreatic-cancer
#5
Hardik Mody, Sau Wai Hung, Rakesh Pathak, Jazmine Griffin, Zobeida Cruz-Monserrate, Rajgopal Govindarajan
Previous studies in our laboratory identified that 3-deazaneplanocin A (DZNep), a carbocyclic adenosine analog and histone methyl transferase inhibitor, suppresses TGFβ-induced epithelial-to-mesenchymal (EMT) characteristics. In addition, DZNep epigenetically reprograms miRNAs (miRs) to regulate endogenous TGFbeta1 levels via miR-663/4787 mediated RNA interference (Mol Cancer Res. 2016 Sep 13. pii: molcanres.0083.2016) (1). While DZNep also attenuates exogenous TGFbeta-induced EMT response, the mechanism of this inhibition was unclear...
April 3, 2017: Molecular Cancer Research: MCR
https://www.readbyqxmd.com/read/28360038/insulin-receptor-and-gpcr-crosstalk-stimulates-yap-via-pi3k-and-pkd-in-pancreatic-cancer-cells
#6
Fang Hao, Qinhong Xu, Yinglan Zhao, Jan V Stevens, Steven H Young, James Sinnett-Smith, Enrique Rozengurt
We examined the impact of crosstalk between the insulin receptor (INSR) and G protein-coupled receptor (GPCR) signaling pathways on the regulation of Yes-associated Protein (YAP) localization, phosphorylation and transcriptional activity in the context of human pancreatic ductal adenocarcinoma (PDAC). Stimulation of PANC-1 or MiaPaCa-2 cells with insulin and neurotensin, a potent mitogenic combination of agonists for these cells, promoted striking YAP nuclear localization and decreased YAP phosphorylation at Ser127 and Ser397...
March 30, 2017: Molecular Cancer Research: MCR
https://www.readbyqxmd.com/read/28360037/mitochondrial-dna-integrity-is-maintained-by-ape1-in-carcinogen-induced-colorectal-cancer
#7
Joan Ballista-Hernandez, Magaly Martinez-Ferrer, Roman Velez, Consuelo Climent, Maria M Sanchez-Vazquez, Ceidy Torres, Adlin Rodriguez-Munoz, Sylvette Ayala-Pena, Carlos A Torres-Ramos
Changes in mitochondrial DNA (mtDNA) integrity have been reported in many cancers, however, the contribution of mtDNA integrity to tumorigenesis is not well understood. We used a transgenic mouse model that is haploinsufficient for the apurinic/apyrimidinic endonuclease 1 (Apex1+/-) gene, which encodes the base excision repair (BER) enzyme APE1, to determine its role in protecting mtDNA from the effects of azoxymethane (AOM), a carcinogen used to induce colorectal cancer (CRC). Repair kinetics of AOM-induced mtDNA damage was evaluated using quantitative PCR after a single AOM dose and a significant induction in mtDNA lesions in colonic crypts from both wild type (WT) and Apex1+/-animals were observed...
March 30, 2017: Molecular Cancer Research: MCR
https://www.readbyqxmd.com/read/28356331/dna-damage-induces-a-secretory-program-in-the-quiescent-tme-that-fosters-adverse-cancer-phenotypes
#8
Luis Gomez-Sarosi, Yu Sun, Ilsa Coleman, Daniella Bianchi-Frias, Peter S Nelson
Carcinomas develop in complex environments that include a diverse spectrum of cell types that influence tumor cell behavior. These microenvironments represent dynamic systems that con-tribute to pathological processes. Damage to DNA is a notable inducer of both transient and permanent alterations in cellular phenotypes. Induction of a DNA-damage secretory program is known to promote adverse tumor cell behaviors such as proliferation, invasion, metastasis, and treatment resistance. However, prior studies designed to identify genotoxic stress-induced fac-tors evaluated actively proliferating in vitro cultures of cells such as fibroblasts as experimental models...
March 29, 2017: Molecular Cancer Research: MCR
https://www.readbyqxmd.com/read/28356330/cancer-immunotherapy-whence-and-whither
#9
Peter J Stambrook, John Maher, Farzin Farzaneh
The current concepts and practice of cancer immunotherapy evolved from classical experiments that distinguished "self" from "non-self" and the finding that humoral immunity is complemented by cellular immunity. Elucidation of the biology underlying immune checkpoints and interactions between ligands and ligand receptors that govern the immune system's ability to recognize tumor cells as foreign has led to the emergence of new strategies that mobilize the immune system to reverse this apparent tolerance. Some of these approaches have led to new therapies such as the use of monoclonal antibodies (mAbs) to interfere with the immune checkpoint...
March 29, 2017: Molecular Cancer Research: MCR
https://www.readbyqxmd.com/read/28330997/igfbp3-modulates-lung-tumorigenesis-and-cell-growth-through-igf1-signaling
#10
Yong A Wang, Yunguang Sun, Joshua D Palmer, Charalambos Solomides, Li-Ching Huang, Yu Shyr, Adam P Dicker, Bo Lu
Insulin-like growth factor binding protein 3 (IGFBP3) modulates cell growth through IGF-dependent and -independent mechanisms. Reports suggest that the serum levels of IGFBP3 are associated with various cancers and that IGFBP3 expression is significantly decreased in cisplatin (CDDP)-resistant lung cancer cells. Based on these findings, we investigated whether Igfbp3 deficiency accelerates mouse lung tumorigenesis and if expression of IGFBP3 enhances CDDP response by focusing on the IGF1 signaling cascade. To this end, an Igfbp3-null mouse model was generated in combination with KrasG12D to compare the tumor burden...
March 22, 2017: Molecular Cancer Research: MCR
https://www.readbyqxmd.com/read/28314844/abituzumab-targeting-of-alphav-class-integrins-inhibits-prostate-cancer-progression
#11
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
#12
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
#13
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
#14
Nancy S Vetter, E Anders Kolb, Christopher Mills, Valerie B Sampson
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
#15
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
#16
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
#17
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
#18
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
#19
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
#20
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
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