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https://www.readbyqxmd.com/read/28445988/specific-up-regulation-of-p21-by-a-small-active-rna-sequence-suppresses-human-colorectal-cancer-growth
#1
Lu-Lu Wang, Hui-Hui Guo, Yun Zhan, Chen-Lin Feng, Shuai Huang, Yan-Xing Han, Wen-Sheng Zheng, Jian-Dong Jiang
The double stranded small active RNA (saRNA)- p21-saRNA-322 inhibits tumor growth by stimulating the p21 gene expression. We focused our research of p21-saRNA-322 on colorectal cancer because 1) p21 down-regulation is a signature abnormality of the cancer, and 2) colorectal cancer might be a suitable target for in situ p21-saRNA-322 delivery. The goal of the present study is to learn the activity of p21-saRNA-322 in colorectal cancer. Three human colorectal cancer cell lines, HCT-116, HCT-116 (p53-/-) and HT-29 were transfected with the p21-saRNA-322...
April 11, 2017: Oncotarget
https://www.readbyqxmd.com/read/28445086/long-noncoding-rna-highly-upregulated-in-liver-cancer-activates-p53-p21-pathway-and-promotes-nasopharyngeal-carcinoma-cell-growth
#2
Xue Jiang, Weiwei Liu
Dysfunction of lncRNA has been found in the nasopharyngeal carcinoma (NPC); however, the effect of lncRNA expression on NPC tumorigenesis as well as the molecular mechanism of lncRNA in the pathogenesis of NPC remain largely unknown. In this study, we showed that highly upregulated in liver cancer (HULC), the first identified lncRNA in hepatocellular carcinoma, is highly expressed in NPC patients and correlated with a poor prognosis of cancer patients. Overexpressed HULC promotes NPC cell growth. Downregulation of HULC activated p53 and induced the increased expression of p21, which finally caused cell cycle arrest and cell apoptosis...
April 26, 2017: DNA and Cell Biology
https://www.readbyqxmd.com/read/28444790/aloe-emodin-induces-apoptosis-in-human-liver-hl-7702-cells-through-fas-death-pathway-and-the-mitochondrial-pathway-by-generating-reactive-oxygen-species
#3
Xiaoxv Dong, Jing Fu, Xingbin Yin, Chunjing Yang, Jian Ni
Aloe-emodin (1,8-dihydroxy-3-hydroxymethyl-anthraquinone) is one of the primary active compounds in total rhubarb anthraquinones isolated from some traditional medicinal plants such as Rheum palmatum L. and Cassia occidentalis, which induce hepatotoxicity in rats. Thus, the aim of this study was to determine the potential cytotoxic effects and the underlying mechanism of aloe-emodin on human normal liver HL-7702 cells. The CCK-8 assays demonstrated that aloe-emodin decreased the viability of HL-7702 cells in a dose-dependent and time-dependent manner...
April 26, 2017: Phytotherapy Research: PTR
https://www.readbyqxmd.com/read/28443465/bauerenol-a-triterpenoid-from-indian-suregada-angustifolia-induces-reactive-oxygen-species-mediated-p38mapk-activation-and-apoptosis-in-human-hepatocellular-carcinoma-hepg2-cells
#4
Perumal Sathish Kumar, Madepalli Byrappa Gowdu Viswanathan, Muthappan Venkatesan, Kedike Balakrishna
The triterpenoid, bauerenol, from Suregada angustifolia (Baill. ex Muell.-Arg.) Airy Shaw (Euphorbiaceae) was screened for anti-cancer property using hepatocellular carcinoma cell line, HepG2. Bauerenol exhibited growth inhibitory and apoptosis inducing potential against HepG2 cancer cells. 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide cytotoxic assay revealed that bauerenol treatment significantly reduced the growth of HepG2 cells in a time- and dose-dependent manner with 50% growth inhibitory concentration doses of 45 and 25 µg/mL at 24 and 48 h treatments, respectively...
April 2017: Tumour Biology: the Journal of the International Society for Oncodevelopmental Biology and Medicine
https://www.readbyqxmd.com/read/28443464/increased-haglr-expression-promotes-non-small-cell-lung-cancer-proliferation-and-invasion-via-enhanced-de-novo-lipogenesis
#5
Chunwei Lu, Jun Ma, Dingfang Cai
Lung cancers are broadly classified into small cell lung cancer and non-small cell lung cancer, with non-small cell lung cancer one of the leading causes of cancer-associated deaths worldwide. Presently, the mechanisms underlying lung tumorigenesis remain incompletely understood. Accumulating evidence indicates that abnormal expression of long non-coding RNAs is associated with tumorigenesis in multiple cancers, including lung cancer. HAGLR messenger RNA of non-small cell lung cancer tissues was significantly higher...
April 2017: Tumour Biology: the Journal of the International Society for Oncodevelopmental Biology and Medicine
https://www.readbyqxmd.com/read/28442502/ribonucleotide-reductase-large-subunit-rrm1-as-a-novel-therapeutic-target-in-multiple-myeloma
#6
Morihiko Sagawa, Hiroto Ohguchi, Takeshi Harada, Mehmet K Samur, Yu-Tzu Tai, Nikhil C Munshi, Masahiro Kizaki, Teru Hideshima, Kenneth C Anderson
Purpose: To investigate the biologic and clinical significance of ribonucleotide reductase (RR) in multiple myeloma (MM). <p>Experimental Design: We assessed the impact of RR expression on patient outcome in MM. We then characterized the effect of genetic and pharmacological inhibition of RRM1 on MM growth and survival using siRNA and clofarabine (CLO), respectively, both in vitro and in vivo mouse xenograft model.</p> <p>Results: Newly diagnosed MM patients with higher RRM1 expression have shortened survival...
April 25, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28441948/over-expressed-long-noncoding-rna-hoxa11-as-promotes-cell-cycle-progression-and-metastasis-in-gastric-cancer
#7
Zhili Liu, Zhenyao Chen, Ruihua Fan, Bin Jiang, Xin Chen, Qinnan Chen, Fengqi Nie, Kaihua Lu, Ming Sun
BACKGROUND: Long noncoding RNAs (lncRNAs) have emerged as critical regulators in a variety of human cancers, including gastric cancer (GC). However, the function and mechanisms responsible for these molecules in GC are not fully understood. In our previous study, we found that GC associated lncRNA HOXA11-AS is significantly upregulated in GC tissues. Over-expressed HOXA11-AS promotes GC cells proliferation and invasion through scaffolding the chromatin modification factors PRC2, LSD1 and DNMT1...
April 26, 2017: Molecular Cancer
https://www.readbyqxmd.com/read/28438385/small-molecules-inhibit-stat3-activation-autophagy-and-cancer-cell-anchorage-independent-growth
#8
Donghui Zhou, Maya Z Springer, David Xu, Degang Liu, Andy Hudmon, Kay F Macleod, Samy O Meroueh
Triple-negative breast cancers (TNBCs) lack the signature targets of other breast tumors, such as HER2, estrogen receptor, and progesterone receptor. These aggressive basal-like tumors are driven by a complex array of signaling pathways that are activated by multiple driver mutations. Here we report the discovery of 6 (KIN-281), a small molecule that inhibits multiple kinases including maternal leucine zipper kinase (MELK) and the non-receptor tyrosine kinase bone marrow X-linked (BMX) with single-digit micromolar IC50s...
March 23, 2017: Bioorganic & Medicinal Chemistry
https://www.readbyqxmd.com/read/28436570/bre-enhances-osteoblastic-differentiation-by-promoting-the-mdm2-mediated-degradation-of-p53
#9
Fujun Jin, Yiliang Wang, Xiaojing Wang, Yanting Wu, Xiaoyan Wang, Qiuying Liu, Yexuan Zhu, Enqi Liu, Jianglin Fan, Yifei Wang
Bre is a conserved cellular protein expressed in various tissues. Its major function includes DNA damage repair and anti-apoptosis. Recent studies indicate that Bre is potentially involved in stem cell differentiation although pathophysiological significance along with the molecular mechanisms is still unclear. Here, we report that Bre protein was substantially expressed in the bone tissue and its expression was highly upregulated during the osteogenic differentiation. To test a hypothesis that Bre plays functional roles in the process of osteogenic differentiation, we examined the expression of Bre in an osteoporosis mouse model...
April 24, 2017: Stem Cells
https://www.readbyqxmd.com/read/28436418/oxoaporphine-metal-complexes-co-ii-ni-ii-zn-ii-with-high-antitumor-activity-by-inducing-mitochondria-mediated-apoptosis-and-s-phase-arrest-in-hepg2
#10
Jiao-Lan Qin, Wen-Ying Shen, Zhen-Feng Chen, Li-Fang Zhao, Qi-Pin Qin, Yan-Cheng Yu, Hong Liang
Three new oxoaporphine Co(II), Ni(II) and Zn(II) complexes 1-3 have been synthesized and fully characterized. 1-3 have similar mononuclear structures with the metal and ligand ratio of 1:2. 1-3 exhibited higher cytotoxicity than the OD ligand and cisplatin against HepG2, T-24, BEL-7404, MGC80-3 and SK-OV-3/DDP cells, with IC50 value of 0.23-4.31 μM. Interestingly, 0.5 μM 1-3 significantly caused HepG2 arrest at S-phase, which was associated with the up-regulation of p53, p21, p27, Chk1 and Chk2 proteins, and decrease in cyclin A, CDK2, Cdc25A, PCNA proteins...
April 24, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28436392/the-dna-damage-response-in-neurons-die-by-apoptosis-or-survive-in-a-senescence-like-state
#11
Edward Fielder, Thomas von Zglinicki, Diana Jurk
Neurons are exposed to high levels of DNA damage from both physiological and pathological sources. Neurons are post-mitotic and their loss cannot be easily recovered from; to cope with DNA damage a complex pathway called the DNA damage response (DDR) has evolved. This recognizes the damage, and through kinases such as ataxia-telangiectasia mutated (ATM) recruits and activates downstream factors that mediate either apoptosis or survival. This choice between these opposing outcomes integrates many inputs primarily through a number of key cross-road proteins, including ATM, p53, and p21...
April 18, 2017: Journal of Alzheimer's Disease: JAD
https://www.readbyqxmd.com/read/28435723/formamidinium-iodide-crystal-structure-and-phase-transitions
#12
Andrey A Petrov, Eugene A Goodilin, Alexey B Tarasov, Vladimir A Lazarenko, Pavel V Dorovatovskii, Victor N Khrustalev
At a temperature of 100 K, CH5N2(+)·I(-) (I), crystallizes in the monoclinic space group P21/c. The formamidinium cation adopts a planar symmetrical structure [the r.m.s. deviation is 0.002 Å, and the C-N bond lengths are 1.301 (7) and 1.309 (8) Å]. The iodide anion does not lie within the cation plane, but deviates from it by 0.643 (10) Å. The cation and anion of I form a tight ionic pair by a strong N-H⋯I hydrogen bond. In the crystal of I, the tight ionic pairs form hydrogen-bonded zigzag-like chains propagating toward [20-1] via strong N-H⋯I hydrogen bonds...
April 1, 2017: Acta Crystallographica. Section E, Crystallographic Communications
https://www.readbyqxmd.com/read/28434530/accelerated-cellular-senescence-as-underlying-mechanism-for-functionally-impaired-bone-marrow-derived-progenitor-cells-in-ischemic-heart-disease
#13
Evelien Nollet, Vicky Y Hoymans, Inez R Rodrigus, Dina De Bock, Marc Dom, Viviane O M Van Hoof, Christiaan J Vrints, Emeline M Van Craenenbroeck
BACKGROUND AND AIMS: Bone marrow (BM)-derived progenitor cells are functionally impaired in patients with ischemic heart disease (IHD), thereby hampering the outcome of autologous stem cell therapy. In search for underlying mechanisms for this BM dysfunction, accelerated cellular senescence was explored. METHODS: We analysed telomere length of BM-derived mononuclear cells (MNC) by MMqPCR in patients with coronary artery disease (n = 12), ischemic heart failure (HF; n = 9), non-ischemic HF (n = 7) and controls (n = 10), and related it to their myeloid differentiation capacity...
May 2017: Atherosclerosis
https://www.readbyqxmd.com/read/28434006/unbiased-quantification-of-subplate-neuron-loss-following-neonatal-hypoxia-ischemia-in-a-rat-model
#14
Alexandra Mikhailova, Naveena Sunkara, Patrick S McQuillen
BACKGROUND: Cellular targets of neonatal hypoxia-ischemia (HI) include both oligodendrocyte and neuronal lineages with differences in the patterns of vulnerable cells depending upon the developmental stage at which the injury occurs. Injury to the developing white matter is a characteristic feature of human preterm brain injury. Data are accumulating, however, for neuronal injury in the developing cerebral cortex. In the most widely used rodent model of preterm HI brain injury, conflicting data have been reported regarding the sensitivity of subplate neurons to early neonatal HI, with some reports of selective vulnerability and others that find no increased loss of subplate neurons in comparison with other cortical layers...
April 22, 2017: Developmental Neuroscience
https://www.readbyqxmd.com/read/28432261/ccm2-and-pak4-act-downstream-of-atrial-natriuretic-peptide-signaling-to-promote-cell-spreading
#15
Koichi Miura, Takashi Nojiri, Yoshiharu Akitake, Koji Ando, Shigetomo Fukuhara, Masahiro Zenitani, Toru Kimura, Jun Hino, Mikiya Miyazato, Hiroshi Hosoda, Kenji Kangawa
Atrial natriuretic peptide (ANP) is a cardiac hormone released by the atrium in response to stretching forces. Via its receptor, guanylyl cyclase-A (GC-A), ANP maintains cardiovascular homeostasis by exerting diuretic, natriuretic, and hypotensive effects mediated in part by endothelial cells. Both in vivo and in vitro , ANP enhances endothelial barrier function by reducing RhoA activity and reorganizing the actin cytoskeleton. We established mouse endothelial cells that stably express GC-A, and used them to analyze the molecular mechanisms responsible for actin reorganization...
April 21, 2017: Biochemical Journal
https://www.readbyqxmd.com/read/28431961/ionizing-radiation-induces-long-term-senescence-in-endothelial-cells-through-mitochondrial-respiratory-complex-ii-dysfunction-and-superoxide-generation
#16
Audrey Lafargue, Charlotte Degorre, Isabelle Corre, Marie-Clotilde Alves-Guerra, Marie-Hélène Gaugler, François Vallette, Claire Pecqueur, François Paris
Ionizing radiation causes oxidative stress, leading to acute and late cellular responses. We previously demonstrated that irradiation of non-proliferating endothelial cells, as observed in normal tissues, induces early apoptosis, which can be inhibited by pretreatment with Sphingosine-1-Phosphate. We now propose to better characterize the long-term radiation response of endothelial cells by studying the molecular pathways associated with senescence and its link with acute apoptosis. First, senescence was validated in irradiated quiescent microvascular HMVEC-L in a dose- and time-dependent manner by SA β-galactosidase staining, p16(Ink4a) and p21(Waf1) expression, pro-inflammatory IL-8 secretion and DNA damage response activation...
April 18, 2017: Free Radical Biology & Medicine
https://www.readbyqxmd.com/read/28430840/checkpoint-dependent-phosphorylation-of-med1-trap220-in-response-to-dna-damage
#17
Hyun-Ju Kim, Jeanho Yun
Mediator complex subunit 1 (Med1)/Thyroid hormone receptor-associated protein 220 (TRAP220), an essential component of thyroid hormone receptor-associated proteins (TRAP)/mediator, plays important roles in hormone responses and tumorigenesis. However, the role of Med1 in the DNA damage response has not been studied. In this study, we found that DNA damage, resulted from γ-irradiation, ultraviolet (UV)-irradiation, or hydroxyurea, induced phosphorylation of Med1 in vivo. Phosphorylation of Med1 was abrogated by either caffeine or wortmannin treatment, suggesting that Med1 is phosphorylated through the DNA damage checkpoint pathway...
April 19, 2017: Acta Biochimica et Biophysica Sinica
https://www.readbyqxmd.com/read/28430160/subverting-host-cell-p21-activated-kinase-a-case-of-convergent-evolution-across-pathogens
#18
REVIEW
Simona John Von Freyend, Terry Kwok-Schuelein, Hans Netter, Gholamreza Haqshenas, Jean-Philippe Semblat, Christian Doerig
Intracellular pathogens have evolved a wide range of strategies to not only escape from the immune systems of their hosts, but also to directly exploit a variety of host factors to facilitate the infection process. One such strategy is to subvert host cell signalling pathways to the advantage of the pathogen. Recent research has highlighted that the human serine/threonine kinase PAK, or p21-activated kinase, is a central component of host-pathogen interactions in many infection systems involving viruses, bacteria, and eukaryotic pathogens...
April 21, 2017: Pathogens
https://www.readbyqxmd.com/read/28428754/pu-erh-tea-water-extract-mediates-cell-cycle-arrest-and-apoptosis-in-mda-mb-231-human-breast-cancer-cells
#19
Jing Xie, Haishuang Yu, Shuang Song, Chongye Fang, Xuanjun Wang, Zhongbin Bai, Xiao Ma, Shumei Hao, Hong-Ye Zhao, Jun Sheng
Pu-erh tea is believed to have health benefits, the growth inhibition activity of Pu-erh tea on breast cancer cell has not been investigated. In this study, we examined the activity of Pu-erh tea water extract on apoptosis and cell cycle arrest in the human breast adenocarcinoma cell line MDA-MB-231 and clarified its underlying mechanism of action. We found that Pu-erh tea extract inhibited cell proliferation and induced apoptosis in a dose-dependent manner. We also found that Pu-erh tea extract inhibited tumor cell growth within 24 h via accumulation of cells in S phase...
2017: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/28427193/targeting-high-aurora-kinases-expression-as-an-innovative-therapy-for-hepatocellular-carcinoma
#20
Fuchen Liu, Guangyong Wang, Xiaoqiang Wang, Zhihui Che, Wei Dong, Xinggang Guo, Zhenguang Wang, Ping Chen, Daisen Hou, Qi Zhang, Wenli Zhang, Yida Pan, Dongqin Yang, Hui Liu
The Aurora kinases A and B control tumorigenesis by inhibiting apoptosis and promoting proliferation and metastasis, however, it remains unknown whether Aurora A and B overexpressed concomitantly and its clinical significance in hepatocellular carcinoma (HCC). Here, we obsearved Aurora A and B tended to overexpress parallelly on protein level (r = 0.8679, P < 0.0001) and their co-overexpression (Aurora AHBH), associated with the worst prognosis, was an independent predictor for the survival. Importantly, with the lower IC50 and stronger anti-tumor effect than selective inhibitors, SNS-314, the pan-inhibitor of Aurora kinases, which induced YAP (Yes-associated protein) reduction and resulted in P21 accumulation, significantly promoted the polyploidy (> 4N) formation and apoptosis in HCC...
March 2, 2017: Oncotarget
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