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https://www.readbyqxmd.com/read/28915722/correction-a-novel-highly-potent-trivalent-tgf-%C3%AE-receptor-trap-inhibits-early-stage-tumorigenesis-and-tumor-cell-invasion-in-murine-pten-deficient-prostate-glands
#1
Tai Qin, Lindsey Barron, Lu Xia, Haojie Huang, Maria M Villarreal, John Zwaagstra, Cathy Collins, Junhua Yang, Christian Zwieb, Ravindra Kodali, Cynthia S Hinck, Sun Kyung Kim, Robert L Reddick, Chang Shu, Maureen D O'Connor-McCourt, Andrew P Hinck, Lu-Zhe Sun
[This corrects the article DOI: 10.18632/oncotarget.13343.].
August 22, 2017: Oncotarget
https://www.readbyqxmd.com/read/28915692/biomarker-analysis-of-the-phase-3-torch-trial-for-first-line-erlotinib-versus-chemotherapy-in-advanced-non-small-cell-lung-cancer-patients
#2
Lucia Kim, Mauro Saieg, Massimo Di Maio, Ciro Gallo, Charles Butts, Fortunato Ciardiello, Ronald Feld, Dengxiao Cheng, Vittorio Gebbia, Marco Angelo Burgio, Yasmin Alam, Simona Signoriello, Antonio Rossi, Natasha Leighl, Paolo Maione, Alessandro Morabito, Geoffrey Liu, Ming-Sound Tsao, Francesco Perrone, Cesare Gridelli
BACKGROUND: The TORCH phase III trial compared the efficacy of first-line erlotinib followed by chemotherapy at progression (experimental arm) with the reverse sequence (standard arm) in unselected advanced non-small cell lung cancer (NSCLC) patients. Here we report biomarker analyses. METHODS: EGFR and KRAS mutation, expression of EGFR family members and of cMET and PTEN and EGFR and ABCG2 germline polymorphisms were tested on tumor tissue or blood samples to either confirm previously proposed predictive role or describe it in an explorative setting...
August 22, 2017: Oncotarget
https://www.readbyqxmd.com/read/28915623/inhibition-of-the-pi3k-akt-mtor-pathway-activates-autophagy-and-compensatory-ras-raf-mek-erk-signalling-in-prostate-cancer
#3
Dominika E Butler, Christopher Marlein, Hannah F Walker, Fiona M Frame, Vincent M Mann, Matthew S Simms, Barry R Davies, Anne T Collins, Norman J Maitland
The PI3K/AKT/mTOR pathway is frequently activated in advanced prostate cancer, due to loss of the tumour suppressor PTEN, and is an important axis for drug development. We have assessed the molecular and functional consequences of pathway blockade by inhibiting AKT and mTOR kinases either in combination or as individual drug treatments. In established prostate cancer cell lines, a decrease in cell viability and in phospho-biomarker expression was observed. Although apoptosis was not induced, a G1 growth arrest was observed in PTEN null LNCaP cells, but not in BPH1 or PC3 cells...
August 22, 2017: Oncotarget
https://www.readbyqxmd.com/read/28915599/copy-number-variations-of-circulating-cell-free-dna-in-urothelial-carcinoma-of-the-bladder-patients-treated-with-radical-cystectomy-a-prospective-study
#4
Armin Soave, Felix K-H Chun, Timo Hillebrand, Michael Rink, Lars Weisbach, Bettina Steinbach, Margit Fisch, Klaus Pantel, Heidi Schwarzenbach
The aim of the present study was to establish a rapid profiling method using multiplex ligation-dependent probe amplification (MLPA) and characterize copy number variations (CNV) in circulating, cell-free DNA (cfDNA) in 85 urothelial carcinoma of the bladder (UCB) patients treated with radical cystectomy (RC). MLPA was tested for the use of cfDNA extracted from serum and plasma by various commercial extraction kits. Eighteen probes served as reference to control denaturation, ligation and amplification efficiency...
August 22, 2017: Oncotarget
https://www.readbyqxmd.com/read/28911096/distinct-regulation-of-alternative-polyadenylation-and-gene-expression-by-nuclear-poly-a-polymerases
#5
Weimin Li, Wencheng Li, Rakesh S Laishram, Mainul Hoque, Zhe Ji, Bin Tian, Richard A Anderson
Polyadenylation of nascent RNA by poly(A) polymerase (PAP) is important for 3' end maturation of almost all eukaryotic mRNAs. Most mammalian genes harbor multiple polyadenylation sites (PASs), leading to expression of alternative polyadenylation (APA) isoforms with distinct functions. How poly(A) polymerases may regulate PAS usage and hence gene expression is poorly understood. Here, we show that the nuclear canonical (PAPα and PAPγ) and non-canonical (Star-PAP) PAPs play diverse roles in PAS selection and gene expression...
September 6, 2017: Nucleic Acids Research
https://www.readbyqxmd.com/read/28910982/exosomes-containing-mir-21-transfer-the-characteristic-of-cisplatin-resistance-by-targeting-pten-and-pdcd4-in-oral-squamous-cell-carcinoma
#6
Tao Liu, Gang Chen, Dawei Sun, Minghui Lei, Yongqiang Li, Changming Zhou, Xiaodong Li, Wei Xue, Hong Wang, Chunjun Liu, Jiang Xu
Resistance to chemotherapy remains a major obstacle for the effective treatment of oral squamous cell carcinoma (OSCC). Evidence for the involvement of exosomes as important regulators of cisplatin chemoresistance in OSCC is still poorly understood. Our objective of this study was to explore the roles for exosomes in modulating key cellular pathways mediating response to chemotherapy. We first developed the cisplatin-resistant cell lines (HSC-3-R and SCC-9-R) and found that the conditioned media from cisplatin-resistant OSCC cells enhanced the chemoresistance of parental OSCC cell...
September 1, 2017: Acta Biochimica et Biophysica Sinica
https://www.readbyqxmd.com/read/28910818/protein-expression-of-programmed-death-1-ligand-1-and-her2-in-gastric-carcinoma
#7
Eiji Oki, Shinji Okano, Hiroshi Saeki, Yuichiro Umemoto, Koji Teraishi, Yu Nakaji, Koji Ando, Yoko Zaitsu, Nami Yamashita, Masahiko Sugiyama, Yuichiro Nakashima, Kippei Ohgaki, Yoshinao Oda, Yoshihiko Maehara
OBJECTIVES: Programmed death 1 (PD-1) is an immunoinhibitory receptor and has been identified as a new target for immunotherapy in cancer. Here we report the expression of PD-1 ligand 1 (PD-L1) in surgically resected gastric cancer. MATERIALS AND METHODS: We examined formalin-fixed tumor samples from 144 gastric cancer patients with a primary diagnosis of gastric carcinoma. Immunohistochemistry was used to detect PD-L1. Human epidermal growth factor receptor 2 (HER2) expression and phosphatase and tensin homolog (PTEN) loss of heterozygosity were investigated in these patients...
September 15, 2017: Oncology
https://www.readbyqxmd.com/read/28903445/predicting-clinical-benefit-from-everolimus-in-patients-with-advanced-solid-tumors-the-cpct-03-study
#8
Fleur Weeber, Geert A Cirkel, Marlous Hoogstraat, Sander Bins, Christa G M Gadellaa-van Hooijdonk, Salo Ooft, Erik van Werkhoven, Stefan M Willems, Marijn van Stralen, Wouter B Veldhuis, Nicolle J M Besselink, Hugo M Horlings, Neeltje Steeghs, Maja J de Jonge, Marlies H G Langenberg, Lodewyk F A Wessels, Edwin P J G Cuppen, J H Schellens, Stefan Sleijfer, Martijn P Lolkema, Emile E Voest
BACKGROUND: In this study, our aim was to identify molecular aberrations predictive for response to everolimus, an mTOR inhibitor, regardless of tumor type. METHODS: To generate hypotheses about potential markers for sensitivity to mTOR inhibition, drug sensitivity and genomic profiles of 835 cell lines were analyzed. Subsequently, a multicenter study was conducted. Patients with advanced solid tumors lacking standard of care treatment options were included and underwent a pre-treatment tumor biopsy to enable DNA sequencing of 1,977 genes, derive copy number profiles and determine activation status of pS6 and pERK...
August 15, 2017: Oncotarget
https://www.readbyqxmd.com/read/28903364/kif7-attenuates-prostate-tumor-growth-through-lkb1-mediated-akt-inhibition
#9
Kai Yau Wong, Jing Liu, Kwok Wah Chan
This study investigated kinesin family member 7 (KIF7) expression and function in prostate cancer (PCa). Our results showed that KIF7 was significantly downregulated in PCa, compared with normal, benign prostatic hyperplasia and prostate intraepithelial neoplasia tissues, partially through promoter hypermethylation. We further investigated the effects of KIF7 coiled coil (CC) domain and motor domain (MD) on PCa development in vitro and in vivo. Our results showed that KIF7-CC but not KIF7-MD significantly attenuated proliferation and colony formation, impeded migration and invasion, induced apoptosis and sensitized PCa cells to paclitaxel...
August 15, 2017: Oncotarget
https://www.readbyqxmd.com/read/28901474/inhibition-of-mir-23a-increases-the-sensitivity-of-lung-cancer-stem-cells-to-erlotinib-through-pten-pi3k-akt-pathway
#10
Zhijun Han, Xiaoyun Zhou, Shanqing Li, Yingzhi Qin, Yeye Chen, Hongsheng Liu
Epidermal growth factor receptor-targeted tyrosine kinase inhibitors (EGFR-TKIs) have become first-line drugs used for non-small cell lung cancer (NSCLC) treatment. However, drug resistance to EGFR-TKIs will be developed inevitably due to the repeated use of these drugs. In the present study, we isolated cancer stem cells (CSCs) from the PC9 NSCLC cell line. We then observed that the PC9 CSCs showed significant resistance to erlotinib compared with the PC9 non-CSCs. Erlotinib failed to suppress the phosphorylation of PI3K and AKT in PC9 CSCs, although the EGFR was inhibited sufficiently...
September 4, 2017: Oncology Reports
https://www.readbyqxmd.com/read/28901447/microrna%C3%A2-146a-promotes-the-proliferation-of-rat-vascular-smooth-muscle-cells-by-downregulating-p53-signaling
#11
Yu Luo, Wei Xiong, Shaohong Dong, Feng Liu, Huadong Liu, Jianghua Li
The present study aimed to detect and verify gene expression profile differences for microRNA (miR)‑146a and its role in the proliferation of vascular smooth muscle cells (VSMCs). Artificially synthesized miR‑146a mimics, miR‑146 inhibitor, scramble‑miRNA or PBS was transfected into cultured primary rat VSMCs in vitro. Reverse transcription‑quantitative polymerase chain reaction confirmed that the miR‑146a expression level was significantly decreased in VSMCs treated with miR‑146a inhibitor (P<0...
September 12, 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28900506/combination-of-aav-trail-with-mir-221-zip-therapeutic-strategy-overcomes-the-resistance-to-trail-induced-apoptosis-in-liver-cancer
#12
Sisi Ma, Jiazeng Sun, Yabin Guo, Peng Zhang, Yanxin Liu, Dexian Zheng, Juan Shi
TNF-related apoptosis-inducing ligand (TRAIL) possesses the capacity to induce apoptosis in a wide variety of tumor cells without affecting most normal cells. However, it has now emerged that many primary cancer cells are resistant to TRAIL monotherapy. Overcoming the intrinsic or acquired TRAIL resistance is desirable for TRAIL-mediated cancer therapy. In this study, we found that the miR-221/222 cluster was up-regulated in TRAIL-resistant liver cancer cells. Specific inhibitors of miR-221 and/or miR-222, called sponge, TuD and miR-Zip were constructed, and their ability to overcome TRAIL resistance was compared...
2017: Theranostics
https://www.readbyqxmd.com/read/28900498/correlation-between-erg-fusion-protein-and-androgen-receptor-expression-by-immunohistochemistry-in-prostate-possible-role-in-diagnosis-and-therapy
#13
Amir Hassan Navaei, Beatriz A Walter, Vanessa Moreno, Svetlana D Pack, Peter Pinto, Maria J Merino
Background: Recent discovery of gene rearrangements have brought a new look to the molecular pathogenesis of cancer. Gene fusions occur in nearly 60% of prostate adenocarcinoma, being the TMPRSS2-ERG one of the most common. Evidence supports the role of ERG fusion in tumorigenesis, progression and invasion via effecting pathways such as WNT, MYC, uPA, PI3K/AKT/PTEN, RAS/RAF/MAPF, NKX3.1, GST-pi and androgen receptor (AR) mediated signaling. Most of the ERG fusions involve 5'-partners androgen responsive. Therefore, we aimed to evaluate AR and ERG fusion protein expression on prostate tissue to find clinicopathological applications and possible role in therapy...
2017: Journal of Cancer
https://www.readbyqxmd.com/read/28900482/study-on-inhibitory-effect-of-maimendong-decoction-and-weijing-decoction-combination-with-cisplatin-on-nci-a549-xenograft-in-nude-mice-and-its-mechanism
#14
Fei Xiong, Miao Jiang, Meijuan Chen, Xiaoxia Wang, Shiping Zhang, Jing Zhou, Ke Li, Yan Sheng, Lian Yin, Yuping Tang, Lihong Ye, Mianhua Wu, Haian Fu, Xu Zhang
MaiMenDong Decoction and WeiJing Decoction (Jin formula) is a traditional Chinese medication that consists of 8 medicinal plants, which recorded in the classical TCM literature Jin Kui Yao Lue and has been utilized in the treatment of lung diseases for hundreds of years in China. The present study aimed to determine the anti-tumor activity and the underlying mechanisms of Jin formula combined with cisplatin in the treatment of non-small cell lung cancer (NSCLC). Xenograft model of NCI-A549 was established in Balb/c nude mice...
2017: Journal of Cancer
https://www.readbyqxmd.com/read/28900085/-expression-of-mir-21-and-its-acat1-armcx1-and-pten-target-genes-in-liver-of-female-rats-treated-with-ddt-and-benzo-a-pyrene
#15
M D Chanyshev, D S Ushakov, L F Gulyaeva
MiR-21 is the most studied cancer-promoting oncomiR, which target numerous tumor suppressor genes associated with proliferation, apoptosis, and invasion. Here we have studied the synthesis of miR-21 and quantified the mRNA and protein levels for miR-21 potential target genes, i.e., Acat1, Armcx1, and Pten, in the livers of female Wistar rats after their treatment with either 1,1-trichloro-2,2-di(4-chlorophenyl)ethane (DDT) or benzo[a]pyrene (BP). The most important finding appears to be the significant decrease in the miR-21 level the day after treatment with DDT with subsequent rebound...
July 2017: Molekuliarnaia Biologiia
https://www.readbyqxmd.com/read/28899058/distinct-radiomic-phenotypes-define-glioblastoma-tp53-pten-egfr-mutational-landscape
#16
Pascal O Zinn, Sanjay K Singh, Aikaterini Kotrotsou, Srishti Abrol, Ginu Thomas, Jennifer Mosley, Ahmed Elakkad, Islam Hassan, Ashok Kumar, Rivka R Colen
No abstract text is available yet for this article.
September 1, 2017: Neurosurgery
https://www.readbyqxmd.com/read/28894028/mtorc1-regulates-both-general-autophagy-and-mitophagy-induction-after-oxidative-phosphorylation-uncoupling
#17
Alberto Bartolomé, Ana García-Aguilar, Shun-Ichiro Asahara, Yoshiaki Kido, Carlos Guillén, Utpal B Pajvani, Manuel Benito
The mechanistic target of rapamycin complex 1 (MTORC1) is a critical negative regulator of general autophagy. We hypothesized that MTORC1 may specifically regulate autophagic clearance of damaged mitochondria. To test this, we used cells lacking tuberous sclerosis complex 2 (TSC2 -/-), which show constitutive MTORC1 activation. TSC2 -/- cells show MTORC1-dependent impaired autophagic flux after chemical uncoupling of mitochondria, increased mitochondrial protein aging and accumulation of p62/SQSTM1 positive mitochondria...
September 11, 2017: Molecular and Cellular Biology
https://www.readbyqxmd.com/read/28891274/breast-cancer-risk-and-germline-genomic-profiling-of-women-with-neurofibromatosis-type-1-who-developed-breast-cancer
#18
Xia Wang, Jamie K Teer, Renee N Tousignant, Albert M Levin, David Boulware, Dhananjay A Chitale, Brandon M Shaw, Zhihua Chen, Yonghong Zhang, Jaishri O Blakeley, Maria T Acosta, Ludwine M Messiaen, Bruce R Korf, Michael A Tainsky
NF1 mutations predispose to neurofibromatosis type1 (NF1) and women with NF1 have a moderately elevated risk for breast cancer, especially under age 50. Germline genomic analysis may better define the risk so screening and prevention can be applied to the individuals who benefit the most. Survey conducted in several neurofibromatosis clinics in the United States has demonstrated a 17.2% lifetime risk of breast cancer in women affected with NF1. Cumulated risk to age 50 is estimated to be 9.27%. For genomic profiling, fourteen women with NF1 and a history of breast cancer were recruited and underwent whole exon sequencing (WES), targeted genomic DNA based and RNA based analysis of the NF1 gene...
September 10, 2017: Genes, Chromosomes & Cancer
https://www.readbyqxmd.com/read/28891157/pten-in-the-maintenance-of-genome-integrity-from-dna-replication-to-chromosome-segregation
#19
REVIEW
Sheng-Qi Hou, Meng Ouyang, Andrew Brandmaier, Hongbo Hao, Wen H Shen
Faithful DNA replication and accurate chromosome segregation are the key machineries of genetic transmission. Disruption of these processes represents a hallmark of cancer and often results from loss of tumor suppressors. PTEN is an important tumor suppressor that is frequently mutated or deleted in human cancer. Loss of PTEN has been associated with aneuploidy and poor prognosis in cancer patients. In mice, Pten deletion or mutation drives genomic instability and tumor development. PTEN deficiency induces DNA replication stress, confers stress tolerance, and disrupts mitotic spindle architecture, leading to accumulation of structural and numerical chromosome instability...
September 11, 2017: BioEssays: News and Reviews in Molecular, Cellular and Developmental Biology
https://www.readbyqxmd.com/read/28891094/regulation-of-the-tumor-suppressor-pten-by-natural-anticancer-compounds
#20
REVIEW
Do-Hee Kim, Jinyoung Suh, Young-Joon Surh, Hye-Kyung Na
The tumor suppressor phosphatase and tensin homologue (PTEN) has phosphatase activity, with phosphatidylinositol (3,4,5)-trisphosphate (PIP3), a product of phosphatidylinositol 3-kinase (PI3K), as one of the principal substrates. PTEN is a negative regulator of the Akt pathway, which plays a fundamental role in controlling cell growth, survival, and proliferation. Loss of PTEN function has been observed in many different types of cancer. Functional inactivation of PTEN as a consequence of germ-line mutations or promoter hypermethylation predisposes individuals to malignancies...
August 2017: Annals of the New York Academy of Sciences
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