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https://www.readbyqxmd.com/read/28526854/induction-of-senescence-in-primary-glioblastoma-cells-by-serum-and-tgf%C3%AE
#1
Ritesh Kumar, Alexander Gont, Theodore J Perkins, Jennifer E L Hanson, Ian A J Lorimer
Glioblastoma is the most common type of adult brain tumour and has a median survival after diagnosis of a little more than a year. Glioblastomas have a high frequency of mutations in the TERT promoter and CDKN2A locus that are expected to render them resistant to both replicative and oncogene-induced senescence. However, exposure of PriGO8A primary glioblastoma cells to media with 10% serum induced a senescence-like phenotype characterized by increased senescence-associated β galactosidase activity, PML bodies and p21 and morphological changes typical of senescence...
May 19, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28526769/tam-receptor-tyrosine-kinases-in-cancer-drug-resistance
#2
REVIEW
Mikaella Vouri, Sassan Hafizi
Receptor tyrosine kinases (RTK) are major regulators of key biological processes, including cell growth, survival, and differentiation, and were established early on as proto-oncogenes, with aberrant expression linked to tumor progression in many cancers. Therefore, RTKs have emerged as major targets for selective therapy with small-molecule inhibitors. However, despite improvements in survival rates, it is now apparent that the targeting of RTKs with selective inhibitors is only transiently effective, as the majority of patients eventually become resistant to therapy...
May 19, 2017: Cancer Research
https://www.readbyqxmd.com/read/28526132/old-and-novel-functions-of-caspase-2
#3
M A Miles, T Kitevska-Ilioski, C J Hawkins
Although caspase-2 is a highly conserved protease that has received a lot of research attention, consensus about its roles and the molecular mechanisms that underpin them has been elusive. Recent improvements to our understanding of the activities of caspase-2 have been facilitated by the development and refinement of techniques allowing identification of cellular processes instigated by this caspase. Following DNA damage, caspase-2 can be activated in a molecular complex called the "PIDDosome"; however, other stimuli provoke caspase-2-dependent activities that do not appear to involve this complex...
2017: International Review of Cell and Molecular Biology
https://www.readbyqxmd.com/read/28525978/notch-ligand-delta-like-1-as-a-novel-molecular-target-in-childhood-neuroblastoma
#4
P Bettinsoli, G Ferrari-Toninelli, S A Bonini, C Prandelli, M Memo
BACKGROUND: Neuroblastoma is the most common extracranial solid malignancy in childhood, responsible for 15% of all pediatric cancer deaths. It is an heterogeneous disease that does not always respond to classical therapy; so the identification of new and specific molecular targets to improve existing therapy is needed. We have previously demonstrated the involvement of the Notch pathway in the onset and progression of neuroblastoma. In this study we further investigated the role of Notch signaling and identified Delta-like 1 (DLL1) as a novel molecular target in neuroblastoma cells with a high degree of MYCN amplification, which is a major oncogenic driver in neuroblastoma...
May 19, 2017: BMC Cancer
https://www.readbyqxmd.com/read/28525901/direct-inhibition-of-stat-signaling-by-platinum-drugs-contributes-to-their-anti-cancer-activity
#5
Stanleyson V Hato, Carl G Figdor, Susumu Takahashi, Anja E Pen, Altuna Halilovic, Kalijn F Bol, Angela Vasaturo, Yukie Inoue, Nienke de Haas, Dagmar Verweij, Carla M L Van Herpen, Johannes H Kaanders, Johan H J M van Krieken, Hanneke W M Van Laarhoven, Gerrit K J Hooijer, Cornelis J A Punt, Akira Asai, I Jolanda M de Vries, W Joost Lesterhuis
Platinum-based chemotherapeutics are amongst the most powerful anti-cancer drugs. Although their exact mechanism of action is not well understood, it is thought to be mediated through covalent DNA binding. We investigated the effect of platinum-based chemotherapeutics on signaling through signal transducer and activator of transcription (STAT) proteins, which are involved in many oncogenic signaling pathways. We performed in vitro experiments in various cancer cell lines, investigating the effects of platinum chemotherapeutics on STAT phosphorylation and nuclear translocation, the expression of STAT-modulating proteins and downstream signaling pathways...
May 7, 2017: Oncotarget
https://www.readbyqxmd.com/read/28525386/prognostic-value-of-kras-mutation-in-advanced-non-small-cell-lung-cancer-treated-with-immune-checkpoint-inhibitors-a-metaanalysis-and-review
#6
Jung Han Kim, Hyeong Su Kim, Bum Jun Kim
Immune checkpoint inhibitors (ICIs) have emerged as a promising treatment option in the fight against advanced non-small-cell lung cancer (NSCLC). KRAS is the most frequently mutated oncogene in NSCLC. We performed this meta-analysis to investigate if KRAS mutation status affects survival benefits of ICIs in patients with advanced NSCLC. Electronic databases were searched for eligible studies. We included randomized trials with the data of overall survival stratified by KRAS mutation status. From 3 eligible studies, 138 patients with KRAS mutant NSCLC and 371 with KRAS wild-type tumor were included in the meta-analysis...
May 3, 2017: Oncotarget
https://www.readbyqxmd.com/read/28525382/sulfatase-1-overexpression-indicates-poor-prognosis-in-urothelial-carcinoma-of-the-urinary-bladder-and-upper-tract
#7
Hsiang-Ying Lee, Bi-Wen Yeh, Ti-Chun Chan, Kei-Fu Yang, Wei-Ming Li, Chun-Nung Huang, Hung-Lung Ke, Ching-Chia Li, Hsin-Chih Yeh, Peir-In Liang, Yow-Ling Shiue, Wen-Jeng Wu, Chien-Feng Li
Urothelial carcinoma (UC), arising from the urothelium of the urinary tract, can occur in the upper (UTUC) and the urinary bladder (UBUC). A representative molecular aberration for UC characteristics and prognosis remains unclear. Data mining of Gene Expression Omnibus focusing on UBUC, we identified sulfatase-1 (SULF1) upregulation is associated with UC progression. SULF1 controls the sulfation status of heparan sulfate proteoglycans and plays a role in tumor growth and metastasis, while its role is unexplored in UC...
May 3, 2017: Oncotarget
https://www.readbyqxmd.com/read/28525379/pdz-binding-kinase-regulated-by-foxm1-enhances-malignant-phenotype-via-activation-of-%C3%AE-catenin-signaling-in-hepatocellular-carcinoma
#8
Yu-Feng Yang, Ying-Hua Pan, Yun Cao, Jia Fu, Xia Yang, Mei-Fang Zhang, Qiu-Hong Tian
Deregulation of serine/threonine kinase contributes to the development and progression of human diseases. PDZ-binding kinase (PBK) has been implicated in the malignant process of cancers, but its role and clinical significance in hepatocellular carcinoma (HCC) remains unclear. Here we show that PBK expression is increased and associated with larger tumor size, presence of vascular invasion, lymph node metastasis and poor overall and disease-free survivals in two independent cohorts of 879 patients with HCC...
May 3, 2017: Oncotarget
https://www.readbyqxmd.com/read/28525372/overexpression-of-a-novel-candidate-oncogene-kif14-correlates-with-tumor-progression-and-poor-prognosis-in-prostate-cancer
#9
Yixiang Zhang, Yeqing Yuan, Pei Liang, Zhaoxia Zhang, Xiaojing Guo, Ligang Xia, Yingying Zhao, Xing-Sheng Shu, Shengkun Sun, Ying Ying, Yingduan Cheng
Prostate cancer (PCa) is the second leading cause of death from cancer in men. The mechanism underlying tumorigenesis and development of PCa is largely unknown. Here, we identified Kinesin family member 14 (KIF14) as a novel candidate oncogene in PCa. We found that KIF14 was overexpressed in multiple PCa cell lines and primary PCa tissues. Knockdown of KIF14 in DU145 and PC3 prostate cancer cells suppressed cell proliferation, induced cell cycle arrest and apoptosis. Transcriptome analysis by RNA-sequencing demonstrated that KIF4 suppression led to transcriptional changes of genes involved in p53 and TGF-beta signaling pathway...
May 2, 2017: Oncotarget
https://www.readbyqxmd.com/read/28525363/targeted-sequencing-of-tonsillar-and-base-of-tongue-cancer-and-human-papillomavirus-positive-unknown-primary-of-the-head-and-neck-reveals-prognostic-effects-of-mutated-fgfr3
#10
Cinzia Bersani, Lars Sivars, Linnea Haeggblom, Sebastian DiLorenzo, Michael Mints, Andreas Ährlund-Richter, Nikolaos Tertipis, Eva Munck-Wikland, Anders Näsman, Torbjörn Ramqvist, Tina Dalianis
BACKGROUND: Human papillomavirus positive (HPV+) tonsillar cancer (TSCC), base of tongue cancer (BOTSCC) and unknown primary cancer of the head and neck (HNCUP) have better outcome than corresponding HPV- cancers. To find predictive markers for response to treatment, and correlations and differences in mutated oncogenes and suppressor genes between HPV+ TSCC/BOTSSCC and HPV+ HNCUP and HPV- TSCC/BOTSCC targeted next-generation sequencing was performed of frequently mutated regions in 50 cancer related genes...
February 9, 2017: Oncotarget
https://www.readbyqxmd.com/read/28524659/synthesis-molecular-docking-molecular-dynamics-studies-and-biological-evaluation-of-4h-chromone-1-2-3-4-tetrahydropyrimidine-5-carboxylate-derivatives-as-potential-anti-leukemic-agents
#11
Zahra Dolatkhah, Shahrzad Javanshir, Ahmad Shahir Sadr, Jaber Hosseini, Soroush Sardari
Series of 4H-chromone-1,2,3,4-tetrahydropyrimidine-5-carboxylates derivatives were synthesized via a three component one-pot condensation of chromone-3-carbaldehyde, alkyl acetoacetate and urea or thiourea, using MCM-41-SO3H as an efficient Nano-catalysts, and evaluated for their anti-cancer activity using a combined in silico docking and molecular dynamics protocol to estimate the binding affinity of the title compounds with the Bcr-Abl oncogene. Two programs, AutoDock 4 and AutoDock Vina software were applied to dock the target protein with synthesized compounds and ATP...
May 19, 2017: Journal of Chemical Information and Modeling
https://www.readbyqxmd.com/read/28524356/association-between-yap-expression-in-neoplastic-and-non-neoplastic-breast-tissue-with-arsenic-urinary-levels
#12
Gladis Michel-Ramirez, Rogelio Recio-Vega, Guadalupe Ocampo-Gomez, Eduardo Palacios-Sanchez, Manuel Delgado-Macias, Manuel Delgado-Gaona, Robert Clark Lantz, Jay Gandolfi, Tania Gonzalez-Cortes
The Hippo pathway regulates cell proliferation and apoptosis and it has been noted that loss of critical components of this pathway can lead to uncontrolled cell growth. Yes-associated protein (YAP) is an important component of this Hippo pathway because YAP is the nuclear effector of the Hippo tumor suppressor pathway and it is crucial for the response to oxidative stress induced by cellular process and by different xenobiotics, including arsenic. It has been proposed that YAP dysregulation can contribute to a malignant cellular phenotype acting as both a tumor suppressor and an oncogene...
May 19, 2017: Journal of Applied Toxicology: JAT
https://www.readbyqxmd.com/read/28524162/targeted-sequencing-based-analyses-of-candidate-gene-variants-in-ulcerative-colitis-associated-colorectal-neoplasia
#13
Sanjiban Chakrabarty, Vinay Koshy Varghese, Pranoy Sahu, Pradyumna Jayaram, Bhadravathi M Shivakumar, Cannanore Ganesh Pai, Kapaettu Satyamoorthy
BACKGROUND: Long-standing ulcerative colitis (UC) leading to colorectal cancer (CRC) is one of the most serious and life-threatening consequences acknowledged globally. Ulcerative colitis-associated colorectal carcinogenesis showed distinct molecular alterations when compared with sporadic colorectal carcinoma. METHODS: Targeted sequencing of 409 genes in tissue samples of 18 long-standing UC subjects at high risk of colorectal carcinoma (UCHR) was performed to identify somatic driver mutations, which may be involved in the molecular changes during the transformation of non-dysplastic mucosa to high-grade dysplasia...
May 18, 2017: British Journal of Cancer
https://www.readbyqxmd.com/read/28524002/mirna-expression-in-bladder-cancer-and-their-potential-role-in-clinical-practice
#14
Ana Blanca, Liang Cheng, Rodolfo Montironi, Holger Moch, Francesco Massari, Michelangelo Fiorentino, Maria Rosaria Raspollini, Marina Scarpelli, Antonio Lopez-Beltran
To date more than 3000 miRNA sequences have been described in humans and reg¬istered at miRBase since their discovery. However, the functions of only a few of these miRNAs have been experimentally determined using deep sequencing technology. Aberrant miRNA expression has been associated with differentiation, invasion and metastasis in several cancers. In this context, recent reports have suggested that miRNAs play important roles in the regulation of target genes by binding to complementary regions of messenger transcripts to repress their translation or regulate degradation...
May 18, 2017: Current Drug Metabolism
https://www.readbyqxmd.com/read/28524001/brain-derived-neurotrophic-factor-promotes-growth-of-neurons-and-neural-stem-cells-possibly-by-triggering-the-phosphoinositide-3-kinase-akt-glycogen-synthase-kinase-3%C3%AE-%C3%AE-catenin-pathway
#15
Jin-Wei Yang, Zhang Liang, Shi-Kang Deng Deng, Wei Ma, Xian-Bin Wang, Xing-Tong Li, Tong-Tong Wang, Yun-Fei Dai, Jian-Hui Guo, Li-Yan Li
BACKGROUND: Brain-derived neurotrophic factor (BDNF) plays a crucial role in promoting survival and differentiation of neurons and neural stem cells (NSCs), but the downstream regulating mechanisms remain poorly understood. OBJECTIVE: We investigated whether BDNF exerts its effect by triggering the phosphoinositide 3-kinase (PI3K), protein kinase B, PKB (AKT), glycogen synthase kinase-3β (GSK-3β) and β-catenin signaling pathway in cultured neurons and NSCs derived from the rat embryonic spinal cord...
May 18, 2017: CNS & Neurological Disorders Drug Targets
https://www.readbyqxmd.com/read/28523736/hyper-activation-of-%C3%AE-catenin-signalling-induced-by-ikk%C3%AE%C2%B5-inhibition-thwarts-colorectal-cancer-cell-proliferation
#16
Jie Chen, Jun Zhao, Xuan Chen, Chengming Ding, Katie Lee, Zeming Jia, Yaoting Zhang, Yuzheng Zhou, Chaoying Wei, Jiantai He, Zanxian Xia, Jian Peng
OBJECTIVE: Aberrant activation of Wnt/β-catenin signalling contributes significantly to the development of human colorectal cancers and β-catenin is the key signalling molecule transducing canonical Wnt/β-catenin signalling. Therefore, β-catenin is a promising therapeutic target for cancer treatment. This study demonstrates that the oncogenic IKKε kinase phosphorylates β-catenin to restrain its hyper activation, therefore promoting colorectal cancer (CRC) cell proliferation. MATERIALS AND METHODS: IKKε and β-catenin expression levels in human colorectal cancer tissues and cell lines were analysed by immunohistochemical staining and Western blotting...
May 19, 2017: Cell Proliferation
https://www.readbyqxmd.com/read/28523344/role-of-g3bp1-in-glucocorticoid-receptor-mediated-microrna-15b-and-microrna-23a-biogenesis-in-endothelial-cells
#17
Hoi-Hin Kwok, Po-Ying Poon, Kylie Hin-Man Mak, Lin-Yao Zhang, Pei Liu, Huoming Zhang, Nai-Ki Mak, Patrick Ying-Kit Yue, Ricky Ngok-Shun Wong
MicroRNAs (miRNAs) are a family of non-coding RNAs that play crucial roles in regulating various normal cellular responses. Recent studies revealed that the canonical miRNA biogenesis pathway is subject to sophisticated regulation. Hormonal control of miRNA biogenesis by androgen and estrogen has been demonstrated, but the direct effects of the glucocorticoid receptor (GR) on miRNA biogenesis are unknown. This study revealed the role of GR in miRNA maturation. We showed that two GR agonists, dexamethasone and ginsenoside-Rg1 rapidly suppressed the expression of mature miR-15b, miR-23a, and miR-214 in human endothelial cells...
May 18, 2017: Cellular and Molecular Life Sciences: CMLS
https://www.readbyqxmd.com/read/28523248/the-keap1-nrf2-system-in-cancer
#18
REVIEW
Keiko Taguchi, Masayuki Yamamoto
Cancer cells first adapt to the microenvironment and then propagate. Mutations in tumor suppressor genes or oncogenes are frequently found in cancer cells. Comprehensive genomic analyses have identified somatic mutations and other alterations in the KEAP1 or NRF2 genes and in well-known tumor suppressor genes or oncogenes, such as TP53, CDKN2A, PTEN, and PIK3CA, in various types of cancer. Aberrant NRF2 activation in cancer cells occurs through somatic mutations in the KEAP1 or NRF2 gene as well as through other mechanisms that disrupt the binding of KEAP1 to NRF2...
2017: Frontiers in Oncology
https://www.readbyqxmd.com/read/28522860/involvement-of-fak-erk2-signaling-pathway-in-ckap2-induced-proliferation-and-motility-in-cervical-carcinoma-cell-lines
#19
Qi-Sang Guo, Yu Song, Ke-Qin Hua, Shu-Jun Gao
Cervical carcinoma is the fourth most common cause of death in woman, caused by human papillomavirus (HPV) infections and arising from the cervix. Cytoskeleton-associated protein 2 (CKAP2), also known as tumor-associated microtubule-associated protein, has been linked to tumorigenic effects. In the present study, we screened CKAP2 as a new candidate gene which promotes development of cervical carcinoma, in two independent datasets (TCGA and GSE27678). Results showed that CKAP2 expression was significantly up-regulated in cervical cancerous tissues compared with normal counterparts...
May 18, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28522754/met-exon-14-mutation-encodes-an-actionable-therapeutic-target-in-lung-adenocarcinoma
#20
Xinyuan Lu, Nir Peled, John Greer, Wei Wu, Peter Choi, Alice H Berger, Sergio Wong, Kuang-Yu Jen, Youngho Seo, Byron Hann, Angela Brooks, Matthew Meyerson, Eric A Collisson
Targeting somatically activated oncogenes has revolutionized the treatment of non-small cell lung cancer (NSCLC). Mutations in the gene mesenchymal-epithelial transition (MET) near the exon 14 splice sites are recurrent in lung adenocarcinoma and cause exon skipping (METΔ14). Here we analyzed 4,422 samples from 12 different malignancies to estimate the rate of said exon skipping. METΔ14 mutation and transcript were most common in lung adenocarcinoma. Endogenously expressed levels of METΔ14 transformed human epithelial lung cells in a Hepatocyte growth factor (HGF)-dependent manner...
May 18, 2017: Cancer Research
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