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https://www.readbyqxmd.com/read/28087699/activation-of-c-abl-kinase-potentiates-the-anti-myeloma-drug-lenalidomide-by-promoting-dda1-recruitment-to-the-crl4-ubiquitin-ligase
#1
Shaobing Gao, Chenlu Geng, Tianyu Song, Xuanru Lin, Jiye Liu, Zhen Cai, Yong Cang
Cullin Ring Ligase 4 (CRL4), a complex of Cul4 and DDB1, regulates cell cycle, DNA damage repair, and chromatin replication by targeting a variety of substrates for ubiquitination. CRL4 is also hijacked by viral proteins or thalidomide-derived compounds to degrade host restriction factors. Here we report that the c-Abl non-receptor kinase phosphorylates DDB1 at residue Y316 to recruit a small regulatory protein DDA1, leading to increased substrate ubiquitination. Pharmacological inhibition or genetic ablation of the Abl-DDB1-DDA1 axis decreases the ubiquitination of CRL4 substrates, including IKZF1 and IKZF3 in lenalidomide-treated multiple myeloma cells...
January 13, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28087610/long-non-coding-rna-exchange-during-the-oocyte-to-embryo-transition-in-mice
#2
Rosa Karlic, Sravya Ganesh, Vedran Franke, Eliska Svobodova, Jana Urbanova, Yutaka Suzuki, Fugaku Aoki, Kristian Vlahovicek, Petr Svoboda
The oocyte-to-embryo transition (OET) transforms a differentiated gamete into pluripotent blastomeres. The accompanying maternal-zygotic RNA exchange involves remodeling of the long non-coding RNA (lncRNA) pool. Here, we used next generation sequencing and de novo transcript assembly to define the core population of 1,600 lncRNAs expressed during the OET (lncRNAs). Relative to mRNAs, OET lncRNAs were less expressed and had shorter transcripts, mainly due to fewer exons and shorter 5' terminal exons. Approximately half of OET lncRNA promoters originated in retrotransposons suggesting their recent emergence...
January 13, 2017: DNA Research: An International Journal for Rapid Publication of Reports on Genes and Genomes
https://www.readbyqxmd.com/read/28087488/cathepsin-k-targeted-sub-micron-particles-for-regenerative-repair-of-vascular-elastic-matrix
#3
Brenton Jennewine, Jonathan Fox, Anand Ramamurthi
: Abdominal Aortic Aneurysms (AAA) involve slow dilation and weakening of the aortic wall due to breakdown of structural matrix components, such as elastic fibers by chronically overexpressed matrix metalloproteinases (MMPs), primarily, MMPs-2 and -9. Auto-regenerative repair of disrupted elastic fibers by smooth muscle cells (SMCs) at the AAA site is intrinsically poor and together with chronic proteolysis prevents restoration of elastin homeostasis, necessary to enable AAA growth arrest or regression to a healthy state...
January 10, 2017: Acta Biomaterialia
https://www.readbyqxmd.com/read/28087475/immunohistochemical-approach-for-the-diagnosis-of-a-liver-mass-on-small-biopsy-specimens
#4
Won-Tak Choi, Rageshree Ramachandran, Sanjay Kakar
Well-differentiated hepatocellular carcinoma (HCC) shares overlapping histological features with benign hepatocellular lesions, including hepatocellular adenoma (HCA) and focal nodular hyperplasia (FNH) in non-cirrhotic liver, and with high-grade dysplastic nodule (HGDN) in cirrhotic liver. Several metastatic tumors, such as neuroendocrine tumor, renal cell carcinoma, adrenocortical carcinoma, melanoma, and epithelioid angiomyolipoma, can be indistinguishable from HCC on histologic grounds. Since this distinction has important therapeutic implications, judicious use of immunohistochemical markers plays an important role in establishing an accurate diagnosis, especially when limited material of tumor is available on cell block or a small core biopsy...
January 10, 2017: Human Pathology
https://www.readbyqxmd.com/read/28086896/fast-track-surgery-versus-conventional-perioperative-management-of-lung-cancer-associated-pneumonectomy-a-randomized-controlled-clinical-trial
#5
Qing Dong, Kai Zhang, Shouqiang Cao, Jian Cui
BACKGROUND: The aim of this study is to investigate the effects of fast-track surgery (FTS) on postoperative recovery, hospital stay, total medical costs, and the complications of pneumonectomy in patients with non-small cell lung cancer (NSCLC). METHODS: Studies were performed between June 2012 and March 2014 in 17 patients received FTS and 18 patients given conventional management (control) after pneumonectomy in the Department of Thoracic Surgery, the Fourth Affiliated Hospital of Harbin Medical University...
January 13, 2017: World Journal of Surgical Oncology
https://www.readbyqxmd.com/read/28086833/delta-like-4-notch-signaling-promotes-apc-min-tumor-initiation-through-angiogenic-and-non-angiogenic-related-mechanisms
#6
Marina Badenes, Alexandre Trindade, Hugo Pissarra, Luís Lopes-da-Costa, António Duarte
BACKGROUND: Delta like 4 (Dll4)/Notch signaling is a key regulator of tumor angiogenesis. Additionally, the role of Dll4 has been studied on tumor stem cells. However, as these cells are implicated in tumor angiogenesis, it is conceivable that the effect of Dll4 on these cells may be a consequence of its angiogenic function. Our aim was to evaluate the expression and dissect the functions of Dll4 in the Apc (Min/+) model of colorectal cancer. METHODS: We evaluated the protein expression pattern of Dll4 and other Notch members in the Apc (Min/+) tumors relatively to the normal gut and compared endothelial-specific with ubiquitous Dll4 knockout mice on an Apc (Min/+) background...
January 13, 2017: BMC Cancer
https://www.readbyqxmd.com/read/28081275/role-of-xrcc1-gene-polymorphisms-in-non-small-cell-lung-cancer-cisplatin-based-chemotherapy-and-their-effect-on-clinical-and-pathological-characteristics
#7
H F Liu, J S Liu, J H Deng, R R Wu
Non-small cell lung cancer (NSCLC) is the most common cancer globally. The XRCC1 protein interacts with ligase and poly(ADP-ribose) polymerase to repair cisplatin-induced DNA damage. The authors of previous studies have reported XRCC1 Arg399Gln, Arg280His, and Arg194Trp polymorphisms and advanced NSCLC prognosis, but the results are inconclusive. We investigated the association between clinical outcome and XRCC1 Arg399Gln, Arg280His, and Arg194Trp polymorphisms in advanced NSCLC patients treated with cisplatin...
December 23, 2016: Genetics and Molecular Research: GMR
https://www.readbyqxmd.com/read/28079302/molecular-basis-for-covalent-inhibition-of-glyceraldehyde-3-phosphate-dehydrogenase-by-a-2-phenoxy-1-4-naphthoquinone-small-molecule
#8
Stefano Bruno, Elisa Uliassi, Mirko Zaffagnini, Federica Prati, Christian Bergamini, Riccardo Amorati, Gianluca Paredi, Marilena Margiotta, Paola Conti, Maria Paola Costi, Marcel Kaiser, Andrea Cavalli, Romana Fato, Maria Laura Bolognesi
Glyceraldehyde-3-phosphate dehydrogenase (GAPDH) has recently gained attention as an anti-protozoan and anti-cancer drug target. We have previously identified 2-phenoxy-1,4-naphthoquinone as an inhibitor of both Trypanosoma brucei and human GAPDH. Herein, through multiple chemical, biochemical, and biological studies, and through the design of analogs, we confirmed the formation of a covalent adduct, we clarified the inhibition mechanism and we demonstrated antitrypanosomal, antiplasmodial and cytotoxic activities in cell cultures...
January 12, 2017: Chemical Biology & Drug Design
https://www.readbyqxmd.com/read/28079203/complexation-of-short-ds-rna-dna-oligonucleotides-with-gemini-micelles-a-time-resolved-saxs-and-computational-study
#9
Sara Falsini, Emanuela Di Cola, Martin In, Maria Giordani, Stefano Borocci, Sandra Ristori
Gene therapy is based on nucleic acid delivery to pathogenic cells in order to modulate their gene expression. The most used non viral vectors are lipid-based nanoaggregates, which are safer than viral carriers and have been shown to assemble easily with both DNA and RNA. However, the transfection efficiency of non viral carriers still needs to be improved before intensive practise in clinical trials can be implemented. For this purpose, the in depth characterization of the complexes formed by nucleic acids and their transporters is of great relevance...
January 12, 2017: Physical Chemistry Chemical Physics: PCCP
https://www.readbyqxmd.com/read/28079142/the-prognostic-role-of-egfr-tkis-for-patients-with-advanced-non-small-cell-lung-cancer
#10
Dan Zhao, Xuejing Chen, Na Qin, Dan Su, Lijuan Zhou, Quan Zhang, Xi Li, Xinyong Zhang, Mulan Jin, Jinghui Wang
Clinical trials have shown that epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) did not improve the survival of patients with EGFR-mutated non-small cell lung cancer (NSCLC) because of the high crossover of treatments. Realistically, the role of EGFR-TKIs in NSCLC with mutated EGFR is not well known. We retrospectively analysed data from patients with recurrent or metastatic NSCLC. Clinical prognostic factors were identified by Cox proportional hazards modelling. Among 503 patients, the median overall survival (OS) for all of patients was 11...
January 12, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28078993/mirnas-new-biomarkers-and-therapeutic-targets-in-dementia
#11
Ana Teresa de Bastos Viegas, Joana Ribeiro Guedes, Ana Rafaela Oliveira, Ana Maria Sequeira Cardoso, Ana Luísa Colaço Cardoso
BACKGROUND: Dementia is a complex pathological state that affects millions of individuals worldwide and is responsible for a huge socioeconomic burden, making it a major health concern of current times. Given the impact of dementia in both patients and caregivers, it is crucial to fully clarify the molecular mechanisms underlying dementia-associated disorders, since without this knowledge our ability to correctly diagnose and treat these diseases is severely hampered. METHODS: Epigenetic mechanisms, such as miRNA-mediated post-transcriptional regulation, have been reported to play a role in dementia pathogenesis...
January 10, 2017: Current Pharmaceutical Design
https://www.readbyqxmd.com/read/28078410/effects-of-direct-current-electric-fields-on-lung-cancer-cell-electrotaxis-in-a-pmma-based-microfluidic-device
#12
Yaping Li, Tao Xu, Xiaomei Chen, Shin Lin, Michael Cho, Dong Sun, Mengsu Yang
Tumor metastasis is the primary cause of cancer death. Numerous studies have demonstrated the electrotactic responses of various cancer cell types, and suggested its potential implications in metastasis. In this study, we used a microfluidic device to emulate endogenous direct current electric field (dcEF) environment, and studied the electrotactic migration of non-small cell lung cancer cell lines (H460, HCC827, H1299, and H1975) and the underlying mechanisms. These cell lines exhibited greatly different response in applied dcEFs (2-6 V/cm)...
January 11, 2017: Analytical and Bioanalytical Chemistry
https://www.readbyqxmd.com/read/28077810/increased-expression-of-long-non-coding-rna-bcar4-is-predictive-of-poor-prognosis-in-patients-with-non-small-cell-lung-cancer
#13
Jianhua Gong, Han Zhang, Li He, Lixin Wang, Jipeng Wang
Lung cancer is the most common human cancer, and the majority of lung cancer cases are categorized as non-small cell lung cancer (NSCLC). Long non-coding RNAs (lncRNAs) play key roles in the development and progression of human cancers. LncRNA breast cancer anti-estrogen resistance 4 (BCAR4) has been identified as an oncogenic lncRNA involved in the progression of breast cancer and osteosarcoma. However, the clinical significance of the lncRNA BCAR4 in NSCLC remains largely unclear. In the present study, real-time quantitative reverse transcriptase-polymerase chain reaction was used to examine the relative level of lncRNA BCAR4 in 68 cases of NSCLC tissues and their adjacent non-tumor tissues...
2017: Tohoku Journal of Experimental Medicine
https://www.readbyqxmd.com/read/28077790/flt3-activating-mutations-display-differential-sensitivity-to-multiple-tyrosine-kinase-inhibitors
#14
Bao Nguyen, Allen B Williams, David J Young, Hayley Ma, Li Li, Mark Levis, Patrick Brown, Donald Small
Fms-like tyrosine kinase-3 (FLT3) is a receptor tyrosine kinase that normally functions in hematopoietic cell survival, proliferation and differentiation. Constitutively activating mutations of FLT3 map predominately to the juxtamembrane domain (internal tandem duplications; ITD) or the activation loop (AL) of the kinase domain and are detected in about 1/3 of de novo acute myeloid leukemia (AML) patients. Small molecule tyrosine kinase inhibitors (TKI) effectively target FLT3/ITD mutations, but some activating mutations, particularly those on the AL, are relatively resistant to many FLT3 TKI...
January 6, 2017: Oncotarget
https://www.readbyqxmd.com/read/28077676/a-ptk7-targeted-antibody-drug-conjugate-reduces-tumor-initiating-cells-and-induces-sustained-tumor-regressions
#15
Marc Damelin, Alexander Bankovich, Jeffrey Bernstein, Justin Lucas, Liang Chen, Samuel Williams, Albert Park, Jorge Aguilar, Elana Ernstoff, Manoj Charati, Russell Dushin, Monette Aujay, Christina Lee, Hanna Ramoth, Milly Milton, Johannes Hampl, Sasha Lazetic, Virginia Pulito, Edward Rosfjord, Yongliang Sun, Lindsay King, Frank Barletta, Alison Betts, Magali Guffroy, Hadi Falahatpisheh, Christopher J O'Donnell, Robert Stull, Marybeth Pysz, Paul Escarpe, David Liu, Orit Foord, Hans Peter Gerber, Puja Sapra, Scott J Dylla
Disease relapse after treatment is common in triple-negative breast cancer (TNBC), ovarian cancer (OVCA), and non-small cell lung cancer (NSCLC). Therapies that target tumor-initiating cells (TICs) should improve patient survival by eliminating the cells that can drive tumor recurrence and metastasis. We demonstrate that protein tyrosine kinase 7 (PTK7), a highly conserved but catalytically inactive receptor tyrosine kinase in the Wnt signaling pathway, is enriched on TICs in low-passage TNBC, OVCA, and NSCLC patient-derived xenografts (PDXs)...
January 11, 2017: Science Translational Medicine
https://www.readbyqxmd.com/read/28077299/anaplastic-lymphoma-kinase-alk-inhibitors-in-the-treatment-of-alk-driven-lung-cancers
#16
REVIEW
Robert Roskoski
Anaplastic lymphoma kinase is expressed in two-thirds of the anaplastic large-cell lymphomas as an NPM-ALK fusion protein. Physiological ALK is a receptor protein-tyrosine kinase within the insulin receptor superfamily of proteins that participates in nervous system development. The EML4-ALK fusion protein and four other ALK-fusion proteins play a fundamental role in the development in about 5% of non-small cell lung cancers. The amino-terminal portions of the ALK fusion proteins result in dimerization and subsequent activation of the ALK protein kinase domain that plays a key role in the pathogenesis of various tumors...
January 8, 2017: Pharmacological Research: the Official Journal of the Italian Pharmacological Society
https://www.readbyqxmd.com/read/28077297/exosomes-key-mediators-of-metastasis-and-pre-metastatic-niche-formation
#17
REVIEW
Richard J Lobb, Luize G Lima, Andreas Möller
While tumour cells are classically known to communicate via direct cell-to-cell contact and the secretion of soluble protein-based factors such as cytokines and growth factors, alternative novel mechanisms that promote tumour progression have recently emerged. Now, new critical components of the secretome thought to be involved in tumour progression are exosomes, small vesicles of endocytic origin that carry a variety of bioactive molecules, including proteins, lipids, RNA, as well as DNA molecules. Cancer cell-derived exosomes have been shown to participate in crucial steps of metastatic spread of a primary tumour, ranging from oncogenic reprogramming of malignant cells to formation of pre-metastatic niches...
January 8, 2017: Seminars in Cell & Developmental Biology
https://www.readbyqxmd.com/read/28076844/sulforaphane-inhibits-cancer-stem-like-cell-properties-and-cisplatin-resistance-through-mir-214-mediated-downregulation-of-c-myc-in-non-small-cell-lung-cancer
#18
Qian-Qian Li, You-Ke Xie, Yue Wu, Lin-Lin Li, Ying Liu, Xiao-Bo Miao, Qiu-Zhen Liu, Kai-Tai Yao, Guang-Hui Xiao
We herein report that sulforaphane (SFN), a potent anti-cancer and well-tolerated dietary compound, inhibits cancer stem-like cell (CSC) properties and enhances therapeutic efficacy of cisplatin in human non-small cell lung cancer (NSCLC). SFN exerted these functions through upregulation of miR-214, which in turn targets the coding region of c-MYC. This finding was further corroborated by our observations that plasmid or lentiviral vector-mediated expression of 3'UTR-less c-MYC cDNA and cisplatin- or doxorubicin-induced endogenous c-MYC accumulation was similarly suppressed by either SFN or miR-214...
January 5, 2017: Oncotarget
https://www.readbyqxmd.com/read/28076327/mir-410-induces-stemness-by-inhibiting-gsk3%C3%AE-but-upregulating-%C3%AE-catenin-in-non-small-cells-lung-cancer
#19
Xixian Ke, Yue Yuan, Chenglin Guo, Yan Yang, Qiang Pu, Xueting Hu, Kui Tang, Xinmei Luo, Qianqian Jiang, Xiaolan Su, Lunxu Liu, Wen Zhu, Yuquan Wei
Our previous research indicated miR-410 played a critical role in promoting the tumorigenesis and development of NSCLC (non-small cells lung cancer). MiR-410 has been recently reported to be crucial for development and differentiation of embryonic stem cells. But it remains elusive whether miR-410 stimulates the stemness of cancer until now. Herein, we identify miR-410 induces the stemness and is associated with the progression of NSCLC. We demonstrate miR-410 increases the levels of stem cells marker Sox2, Oct4, Nanog, CXCR4 as well as lung cancer stem cells surface marker CD44 and CD166...
January 5, 2017: Oncotarget
https://www.readbyqxmd.com/read/28076323/clinical-outcome-of-tyrosine-kinase-inhibitors-alone-or-combined-with-radiotherapy-for-brain-metastases-from-epidermal-growth-factor-receptor-egfr-mutant-non-small-cell-lung-cancer-nsclc
#20
Qianqian Zhu, Yanan Sun, Yingying Cui, Ke Ye, Chengliang Yang, Daoke Yang, Jie Ma, Xiao Liu, Jinming Yu, Hong Ge
This study compared treatment outcomes between TKI monotherapy and TKI administration combined with brain radiotherapy (TKI + RT) in 133 non-small cell lung cancer (NSCLC) patients with brain metastasis (BM). We also evaluated the association of different epidermal growth factor receptor (EGFR) mutation subtypes with treatment outcome. To screen for potential variables affecting cranial progression free survival (PFS) and overall survival (OS), we performed univariate and multivariate analysis based on Cox proportional-hazards models...
January 5, 2017: Oncotarget
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