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https://www.readbyqxmd.com/read/28927142/tumour-growth-suppressive-effect-of-arsenic-trioxide-in-squamous-cell-lung-carcinoma
#1
Leanne Lee Leung, Sze-Kwan Lam, Yuan-Yuan Li, James Chung-Man Ho
Lung squamous cell carcinoma (SCC) is the second most common subtype of non-small cell lung carcinoma. The anticancer effects of arsenic trioxide (ATO) in lung adenocarcinoma and small-cell lung cancer have previously been reported; however its effects in SCC remain unclear. An MTT assay and western blot analysis were performed to determine cell viability and protein expression, respectively, in the SK-MES-1 and SW900 SCC cell lines following treatment with ATO. Phosphatidylserine externalization, mitochondrial membrane depolarization and cell cycle distribution were studied using flow cytometry and the in vivo effects of ATO on tumour growth were investigated with a xenograft model...
September 2017: Oncology Letters
https://www.readbyqxmd.com/read/28925392/atypical-e2fs-inhibit-tumor-angiogenesis
#2
B G M W Weijts, B Westendorp, B T Hien, L M Martínez-López, M Zijp, I Thurlings, R E Thomas, S Schulte-Merker, W J Bakker, A de Bruin
Atypical E2F transcription factors (E2F7 and E2F8) function as key regulators of cell cycle progression and their inactivation leads to spontaneous cancer formation in mice. However, the mechanism of the tumor suppressor functions of E2F7/8 remain obscure. In this study we discovered that atypical E2Fs control tumor angiogenesis, one of the hallmarks of cancer. We genetically inactivated atypical E2Fs in epithelial and mesenchymal neoplasm and analyzed blood vessel formation in three different animal models of cancer...
September 18, 2017: Oncogene
https://www.readbyqxmd.com/read/28920576/the-dream-complex-through-its-subunit-lin37-cooperates-with-rb-to-initiate-quiescence
#3
Christina Fs Mages, Axel Wintsche, Stephan H Bernhart, Gerd A Müller
The retinoblastoma Rb protein is an important factor controlling the cell cycle. Yet, mammalian cells carrying Rb deletions are still able to arrest under growth-limiting conditions. The Rb-related proteins p107 and p130, which are components of the DREAM complex, had been suggested to be responsible for a continued ability to arrest by inhibiting E2f activity and by recruiting chromatin-modifying enzymes. Here, we show that p130 and p107 are not sufficient for DREAM-dependent repression. We identify the MuvB protein Lin37 as an essential factor for DREAM function...
September 18, 2017: ELife
https://www.readbyqxmd.com/read/28919418/the-nampt-e2f2-sirt1-axis-promotes-proliferation-and-inhibits-p53-dependent-apoptosis-in-human-melanoma-cells
#4
Hailong Zhao, Weiwei Tang, Xiaowen Chen, Siyu Wang, Xianyan Wang, Haiyan Xu, Lijuan Li
Melanoma is the most common primary malignant neoplasm in adults, causing more deaths than any other skin cancer, necessitating the development of new target-based approaches. Current evidence suggests SIRT1, the mammalian nicotinamide adenine dinucleotide (NAD(+))-dependent protein deacetylase, and nicotinamide phosphoribosyltransferase (NAMPT), the rate-limiting NAD(+) biosynthetic enzyme, together comprise a novel systemic regulatory network to play a pivotal role in cell proliferation and apoptosis. Nevertheless, how the regulation of this cofactor interfaces with signal transduction network remains poorly understood in melanoma...
September 15, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28903501/sex-differential-responses-of-tumor-promotion-associated-genes-and-dysregulation-of-novel-long-noncoding-rnas-in-constitutive-androstane-receptor-activated-mouse-liver
#5
Nicholas J Lodato, Tisha Melia, Andy Rampersaud, David J Waxman
Xenobiotic agonists of constitutive androstane receptor (CAR) induce many hepatic drug metabolizing enzymes, but following prolonged exposure, promote hepatocellular carcinoma, most notably in male mouse liver. Here, we used nuclear RNA-seq to characterize global changes in the mouse liver transcriptome following exposure to the CAR-specific agonist ligand 1,4-bis-[2-(3,5-dichloropyridyloxy)]benzene (TCPOBOP), including changes in novel long noncoding RNAs that may contribute to xenobiotic-induced pathophysiology...
September 1, 2017: Toxicological Sciences: An Official Journal of the Society of Toxicology
https://www.readbyqxmd.com/read/28903422/cdk4-6-inhibition-is-more-active-against-the-glioblastoma-proneural-subtype
#6
Ming Li, Aizhen Xiao, Desiree Floyd, Inan Olmez, Jeongwu Lee, Jakub Godlewski, Agnieszka Bronisz, Krishna P L Bhat, Erik P Sulman, Ichiro Nakano, Benjamin Purow
Glioblastoma (GBM) is the most common and lethal brain tumor. Gene expression profiling has classified GBM into distinct subtypes, including proneural, mesenchymal, and classical, and identifying therapeutic vulnerabilities of these subtypes is an extremely high priority. We leveraged The Cancer Genome Atlas (TCGA) data, in particular for microRNA expression, to seek druggable core pathways in GBM. The E2F1-regulated miR-17˜92 cluster and its analogs are shown to be highly expressed in proneural GBM and in GSC lines, suggesting the E2F cell cycle pathway might be a key driver in proneural GBM...
August 15, 2017: Oncotarget
https://www.readbyqxmd.com/read/28881801/a-screen-for-inducers-of-bhlh-activity-identifies-pitavastatin-as-a-regulator-of-p21-rb-phosphorylation-and-e2f-target-gene-expression-in-pancreatic-cancer
#7
Nicholas Villarino, Lia Signaevskaia, Jaco van Niekerk, Rachel Medal, Heejung Kim, Reyhaneh Lahmy, Kathleen Scully, Anthony Pinkerton, Sangwun Kim, Andrew Lowy, Pamela Itkin-Ansari
The average survival for patients with Pancreatic Ductal Adenocarcinoma (PDA) is merely 6 months, underscoring the need for new therapeutic approaches. During PDA progression, pancreatic acinar cells lose activity of the ClassI/II bHLH factors that regulate quiescence. We previously found that promoting transcriptional activity of the Class I bHLH factor E47 in highly aggressive PDA cells induced stable growth arrest in vitro and in vivo. To translate these findings for clinical utility, we developed a high throughput screening platform to identify small molecule inducers of Class I/II bHLH activity...
August 8, 2017: Oncotarget
https://www.readbyqxmd.com/read/28881797/upregulation-of-long-noncoding-rna-hoxa-as3-promotes-tumor-progression-and-predicts-poor-prognosis-in-glioma
#8
Fan Wu, Chuanbao Zhang, Jinquan Cai, Fan Yang, Tingyu Liang, Xiaoyan Yan, Haoyuan Wang, Wen Wang, Jing Chen, Tao Jiang
Long noncoding RNAs (lncRNAs) have recently emerged as new potentially promising therapeutic targets in many cancers. However, their prognostic value and biological functions associated with glioma remain to be elucidated. Here, High-throughput RNAseq was performed to detect the expression profiles of lncRNAs in 325 human glioma tissues. It was shown that a novel lncRNA HOXA-AS3 was one of the most significantly upregulated lncRNAs in glioma tissues. Quantitative PCR further verified the increased expression of HOXA-AS3 in patient samples and glioma cell lines...
August 8, 2017: Oncotarget
https://www.readbyqxmd.com/read/28878133/exome-capture-rna-sequencing-of-decade-old-breast-cancers-and-matched-decalcified-bone-metastases
#9
Nolan Priedigkeit, Rebecca J Watters, Peter C Lucas, Ahmed Basudan, Rohit Bhargava, William Horne, Jay K Kolls, Zhou Fang, Margaret Q Rosenzweig, Adam M Brufsky, Kurt R Weiss, Steffi Oesterreich, Adrian V Lee
Bone metastases (BoM) are a significant cause of morbidity in patients with estrogen receptor-positive (ER-positive) breast cancer; yet, characterizations of human specimens are limited. In this study, exome-capture RNA sequencing (ecRNA-seq) on aged (8-12 years), formalin-fixed, paraffin-embedded (FFPE), and decalcified cancer specimens was evaluated. Gene expression values and ecRNA-seq quality metrics from FFPE or decalcified tumor RNA showed minimal differences when compared with matched flash-frozen or nondecalcified tumors...
September 7, 2017: JCI Insight
https://www.readbyqxmd.com/read/28869970/competing-memories-of-mitogen-and-p53-signalling-control-cell-cycle-entry
#10
Hee Won Yang, Mingyu Chung, Takamasa Kudo, Tobias Meyer
Regulation of cell proliferation is necessary for immune responses, tissue repair, and upkeep of organ function to maintain human health. When proliferating cells complete mitosis, a fraction of newly born daughter cells immediately enter the next cell cycle, while the remaining cells in the same population exit to a transient or persistent quiescent state. Whether this choice between two cell-cycle pathways is due to natural variability in mitogen signalling or other underlying causes is unknown. Here we show that human cells make this fundamental cell-cycle entry or exit decision based on competing memories of variable mitogen and stress signals...
September 6, 2017: Nature
https://www.readbyqxmd.com/read/28865712/microrna-31-promotes-adverse-cardiac-remodeling-and-dysfunction-in-ischemic-heart-disease
#11
Eliana C Martinez, Shera Lilyanna, Peipei Wang, Leah A Vardy, Xiaofei Jiang, Arunmozhiarasi Armugam, Kandiah Jeyaseelan, Arthur Mark Richards
RATIONALE: Myocardial infarction (MI) triggers a dynamic microRNA response with the potential of yielding therapeutic targets. OBJECTIVE: We aimed to identify novel aberrantly expressed cardiac microRNAs post-MI with potential roles in adverse remodeling in a rat model, and to provide post-ischemic therapeutic inhibition of a candidate pathological microRNA in vivo. METHODS AND RESULTS: Following microRNA array profiling in rat hearts 2 and 14days post-MI, we identified a time-dependent up-regulation of miR-31 compared to sham-operated rats...
September 1, 2017: Journal of Molecular and Cellular Cardiology
https://www.readbyqxmd.com/read/28865172/intersection-of-retinoblastoma-tumor-suppressor-function-stem-cells-metabolism-and-inflammation
#12
REVIEW
Shunsuke Kitajima, Chiaki Takahashi
The Retinoblastoma (RB) tumor suppressor regulates G1 /S transition during cell cycle progression by modulating the activity of E2F transcription factors. The RB pathway plays a central role in the suppression of most cancers, and RB mutation was initially discovered by virtue of its role in tumor initiation. However, as cancer genome sequencing has evolved to profile more advanced and treatment-resistant cancers, it has become increasingly clear that, in the majority of cancers, somatic RB inactivation occurs during tumor progression...
September 2017: Cancer Science
https://www.readbyqxmd.com/read/28861689/superactive-human-leptin-antagonist-shla-triple-lan1-and-quadruple-lan2-leptin-mutein-as-a-promising-treatment-for-human-folliculoma
#13
E Fiedor, E L Gregoraszczuk
PURPOSE: There are no data showing a direct correlation between obesity and increased blood leptin levels with folliculoma. Moreover, folliculoma is not the best studied among other ovarian cancer types. We investigated whether oestradiol can modulate ObR expression in some oestrogen-responsive tissues and that leptin exerts its activity not only via the leptin receptor but also through cross talk with other signalling systems. We hypothesise that blocking ObR expression could be a novel treatment for gonadal ovarian cancer...
August 31, 2017: Cancer Chemotherapy and Pharmacology
https://www.readbyqxmd.com/read/28861324/microrna-1179-inhibits-glioblastoma-cell-proliferation-and-cell-cycle-progression-via-directly-targeting-e2f-transcription-factor-5
#14
Xiupeng Xu, Ning Cai, Tongle Zhi, Zhongyuan Bao, Dong Wang, Yinlong Liu, Kuan Jiang, Liang Fan, Jing Ji, Ning Liu
Glioblastoma multiforme (GBM) is an extraordinary aggressive disease that requires more effective therapeutic options. In the past few years, many microRNAs (miRNAs) have been demonstrated to have important roles in promoting GBM progression. However, little is known about the role of miR-1179 in GBM. In the present study, we found that miR-1179 was significantly downregulated in glioma tissues and cell lines. Functional experiments showed that introduction of miR-1179 dramatically suppressed GBM cell proliferation and cell cycle progression...
2017: American Journal of Cancer Research
https://www.readbyqxmd.com/read/28855958/proteins-associated-with-the-doubling-time-of-the-nci-60-cancer-cell-lines
#15
Michael Polymenis
The varied nature of human cancers is recapitulated, at least to some extent, in the diverse NCI-60 panel of human cancer cell lines. Here, I used a basic, continuous variable of proliferating cells, their doubling time, to stratify the proteome across the NCI-60 cell lines. Among >7000 proteins quantified in the NCI-60 panel previously, the levels of 84 proteins increase in cells that proliferate slowly. This set overlapped with the hallmark molecular signature "epithelial-mesenchymal transition (EMT)" (p value = 1...
2017: Cell Division
https://www.readbyqxmd.com/read/28843398/effect-of-hpv-e6-e7-sirna-with-chemotherapeutic-agents-on-the-regulation-of-tp53-e2f-dynamic-behavior-for-cell-fate-decisions
#16
Nirmal Rajasekaran, Hun Soon Jung, Soo Hyeon Bae, Chaithanya Chelakkot, Sungyoul Hong, Jong-Sun Choi, Dong-Seok Yim, Yu-Kyoung Oh, Yoon-La Choi, Young Kee Shin
Toxicity and resistance remain major challenges for advanced or recurrent cervical cancer therapies, as treatment requires high doses of chemotherapeutic agents. Restoration of TP53 and hypophosphorylated-retinoblastoma (pRB) proteins by human papillomavirus (HPV) E6/E7 siRNA sensitizes HPV-positive cervical cancer cells toward chemotherapeutic agents. Here, we investigated the therapeutic effects of E6/E7 siRNA on the dynamic behavior of TP53 and RB/E2F signaling networks in deciding the cell fate. The synergistic effect of HPV E6/E7 siRNA pool (SP) with chemotherapeutic agents on TP53 and RB/E2F signaling, proliferation, and apoptosis was analyzed in vitro and in vivo...
August 23, 2017: Neoplasia: An International Journal for Oncology Research
https://www.readbyqxmd.com/read/28841214/tudor-domain-protein-phf20l1-reads-lysine-methylated-retinoblastoma-tumour-suppressor-protein
#17
Simon M Carr, Shonagh Munro, Cari A Sagum, Oleg Fedorov, Mark T Bedford, Nicholas B La Thangue
The retinoblastoma tumour suppressor protein (pRb) classically functions to regulate early cell cycle progression where it acts to enforce a number of checkpoints in response to cellular stress and DNA damage. Methylation at lysine (K) 810, which occurs within a critical CDK phosphorylation site and antagonises a CDK-dependent phosphorylation event at the neighbouring S807 residue, acts to hold pRb in the hypo-phosphorylated growth-suppressing state. This is mediated in part by the recruitment of the reader protein 53BP1 to di-methylated K810, which allows pRb activity to be effectively integrated with the DNA damage response...
August 25, 2017: Cell Death and Differentiation
https://www.readbyqxmd.com/read/28836036/modulation-of-adenylate-cyclase-signaling-in-association-with-mkk3-6-stabilization-under-combination-of-sac-and-berberine-to-reduce-hepg2-cell-survivability
#18
Dipanwita Sengupta, Kaustav Dutta Chowdhury, Sujan Chatterjee, Avik Sarkar, Soumosish Paul, Pradip Kumar Sur, Gobinda Chandra Sadhukhan
Cancer cells often have faulty apoptotic pathways resulting in sustenance of survivability, tumour metastasis and resistance to anticancer drugs. Alternate strategies are sought to improve therapeutic efficacy and therefore HepG2 cells were treated with S-allyl-cysteine (SAC) and berberine (BER) to analyze their mechanistic impact upon necroptosis along with its interacting relationship to apoptosis. In the present study we observed that SAC and BER exposure reduced NFκβ nuclear translocation through adenylate cyclase-cAMP-protein kinaseA axis and eventually evaded c-FLIP inhibition...
August 23, 2017: Apoptosis: An International Journal on Programmed Cell Death
https://www.readbyqxmd.com/read/28831101/growth-differentiation-factor-15-promotes-blood-vessel-growth-by-stimulating-cell-cycle-progression-in-repair-of-critical-sized-calvarial-defect
#19
Shaoyi Wang, Mengyu Li, Wenjie Zhang, Hongfei Hua, Ningtao Wang, Jun Zhao, Jing Ge, Xinquan Jiang, Zhiyuan Zhang, Dongxia Ye, Chi Yang
Repair of large bone defects remains a challenge for surgeons, tissue engineering represents a promising approach. However, the use of this technique is limited by delayed vascularization in central regions of the scaffold. Growth differentiation factor 15(GDF15) has recently been reported to be a potential angiogenic cytokine and has an ability to promote the proliferation of human umbilical vein endothelial cells(HUVECs). Whether it can be applied for promoting vascularized bone regeneration is still unknown...
August 22, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28831039/exit-from-quiescence-displays-a-memory-of-cell-growth-and-division
#20
Xia Wang, Kotaro Fujimaki, Geoffrey C Mitchell, Jungeun Sarah Kwon, Kimiko Della Croce, Chris Langsdorf, Hao Helen Zhang, Guang Yao
Reactivating quiescent cells to proliferate is critical to tissue repair and homoeostasis. Quiescence exit is highly noisy even for genetically identical cells under the same environmental conditions. Deregulation of quiescence exit is associated with many diseases, but cellular mechanisms underlying the noisy process of exiting quiescence are poorly understood. Here we show that the heterogeneity of quiescence exit reflects a memory of preceding cell growth at quiescence induction and immediate division history before quiescence entry, and that such a memory is reflected in cell size at a coarse scale...
August 22, 2017: Nature Communications
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