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https://www.readbyqxmd.com/read/28437065/a-macrocyclic-peptide-ligand-binds-the-oncogenic-microrna-21-precursor-and-suppresses-dicer-processing
#1
Matthew D Shortridge, Matthew J Walker, Tom Pavelitz, Yu Chen, Gabriele Varani
MicroRNAs (miRNAs) help orchestrate cellular growth and survival through post-transcriptional mechanisms. The dysregulation of miRNA biogenesis can lead to cellular growth defects, chemotherapeutic resistance and plays a direct role in the development of many chronic diseases. Among these RNAs, miR-21 is consistently overexpressed in most human cancers leading to the down regulation of key tumor suppressing and pro-apoptotic factors; suggesting that inhibition of miR-21 biogenesis could reverse these negative effects...
April 24, 2017: ACS Chemical Biology
https://www.readbyqxmd.com/read/28436987/genomic-consequences-of-aberrant-dna-repair-mechanisms-stratify-ovarian-cancer-histotypes
#2
Yi Kan Wang, Ali Bashashati, Michael S Anglesio, Dawn R Cochrane, Diljot S Grewal, Gavin Ha, Andrew McPherson, Hugo M Horlings, Janine Senz, Leah M Prentice, Anthony N Karnezis, Daniel Lai, Mohamed R Aniba, Allen W Zhang, Karey Shumansky, Celia Siu, Adrian Wan, Melissa K McConechy, Hector Li-Chang, Alicia Tone, Diane Provencher, Manon de Ladurantaye, Hubert Fleury, Aikou Okamoto, Satoshi Yanagida, Nozomu Yanaihara, Misato Saito, Andrew J Mungall, Richard Moore, Marco A Marra, C Blake Gilks, Anne-Marie Mes-Masson, Jessica N McAlpine, Samuel Aparicio, David G Huntsman, Sohrab P Shah
We studied the whole-genome point mutation and structural variation patterns of 133 tumors (59 high-grade serous (HGSC), 35 clear cell (CCOC), 29 endometrioid (ENOC), and 10 adult granulosa cell (GCT)) as a substrate for class discovery in ovarian cancer. Ab initio clustering of integrated point mutation and structural variation signatures identified seven subgroups both between and within histotypes. Prevalence of foldback inversions identified a prognostically significant HGSC group associated with inferior survival...
April 24, 2017: Nature Genetics
https://www.readbyqxmd.com/read/28435677/control-of-immune-cell-entry-through-the-tumour-vasculature-a-missing-link-in-optimising-melanoma-immunotherapy
#3
REVIEW
Lih Yin Tan, Carmela Martini, Zvi G Fridlender, Claudine S Bonder, Michael P Brown, Lisa M Ebert
Metastatic melanoma remains a fatal disease to many worldwide, even after the breakthrough introduction of targeted therapies such as BRAF inhibitors and immune checkpoint blockade therapies such as CTLA-4 and PD-1 inhibitors. With advances in our understanding of this disease, as well as the increasing data gathered from patient studies, the significance of the host immune response to cancer progression and response to treatment is becoming clear. More specifically, the presence of intratumoral CD8(+) cytotoxic T-cells correlates with better prognosis whereas the accumulation of monocytes/macrophages and neutrophils in the tumour is often associated with worse prognosis...
March 2017: Clinical & Translational Immunology
https://www.readbyqxmd.com/read/28435517/inhibition-of-the-platelet-derived-growth-factor-receptor-beta-pdgfrb-using-gene-silencing-crenolanib-besylate-or-imatinib-mesylate-hampers-the-malignant-phenotype-of-mesothelioma-cell-lines
#4
Ombretta Melaiu, Calogerina Catalano, Chiara De Santi, Monica Cipollini, Gisella Figlioli, Lucia Pellè, Elisa Barone, Monica Evangelista, Alice Guazzelli, Laura Boldrini, Elisa Sensi, Alessandra Bonotti, Rudy Foddis, Alfonso Cristaudo, Luciano Mutti, Gabriella Fontanini, Federica Gemignani, Stefano Landi
Malignant pleural mesothelioma (MPM) is a cancer of the pleural cavity resistant to chemotherapy. The identification of novel therapeutic targets is needed to improve its poor prognosis. Following a review of literature and a screening of specimens we found that platelet-derived growth factor receptor beta (PDGFRB) is over-expressed, but not somatically mutated, in MPM tissues. We aimed to ascertain whether PDGFRB is a MPM-cancer driver gene. The approaches employed included the use of gene silencing and the administration of small molecules, such as crenolanib and imatinib (PDGFR inhibitors) on MPM cell lines (IstMes2, Mero-14, Mero-25)...
January 2017: Genes & Cancer
https://www.readbyqxmd.com/read/28435466/design-of-tumor-acidity-responsive-sheddable-nanoparticles-for-fluorescence-magnetic-resonance-imaging-guided-photodynamic-therapy
#5
Feng Fan, Yue Yu, Fei Zhong, Meng Gao, Tianmeng Sun, Jiaxin Liu, Huimao Zhang, Haisheng Qian, Wei Tao, Xianzhu Yang
Imaging-guided cancer therapy, which integrates diagnostic and therapeutic functionalities into a single system, holds great promise to enhance the accuracy of diagnosis and improve the efficacy of therapy. Specifically, for photodynamic therapy (PDT), it is highly desirable to precisely focus laser light onto the tumor areas to generate reactive oxygen species (ROS) that are cytotoxic tumor cells and avoid light-associated side effects. Herein, a distinct three-layer nanostructured particle with tumor acidity-responsiveness (S-NP) that encapsulates the photosensitizer chlorin e6 (Ce6) and chelates Gd(3+) is successfully developed for fluorescence/magnetic resonance (MR) dual-model imaging-guided precision PDT...
2017: Theranostics
https://www.readbyqxmd.com/read/28435451/ahnak2-is-a-novel-prognostic-marker-and-oncogenic-protein-for-clear-cell-renal-cell-carcinoma
#6
Minglei Wang, Xuefeng Li, Jin Zhang, Qiong Yang, Wenqi Chen, Weilin Jin, Yi-Ran Huang, Ru Yang, Wei-Qiang Gao
Integrative database analysis was performed to identify novel candidate oncogene AHNAK2 overexpressed in clear cell renal cell carcinoma (ccRCC). However, the function of AHNAK2 in cancer cells is currently unknown. In this study, we first confirmed the upregulation of AHNAK2 in ccRCC tissues compared with adjacent normal tissues in 15 pairs of samples. Then we analyzed AHNAK2 expression in a large cohort of ccRCC patient samples (n = 355), and found that up-regulation of AHNAK2 was positively correlated with tumor progression and poor survival (p = 0...
2017: Theranostics
https://www.readbyqxmd.com/read/28435289/long-noncoding-rna-nbat-1-suppresses-tumorigenesis-and-predicts-favorable-prognosis-in-ovarian-cancer
#7
Changsheng Yan, Yi Jiang, Yicong Wan, Lin Zhang, Jinhui Liu, Shulin Zhou, Wenjun Cheng
Long noncoding RNA (lncRNA) has been proven to be involved in many biological processes in ovarian cancer (OC). However, the mechanism still remains unknown. In this study, we screened significantly downregulated NBAT-1, which has been proven to play a significant role in breast cancer, clear cell renal cell carcinoma, and neuroblastoma, but not in OC, in two independent datasets with relatively more samples (GSE18520 and GSE38666) from Gene Expression Omnibus. We found that lncRNA NBAT-1 was obviously downregulated in OC tissue compared to normal ovarian tissue (P<0...
2017: OncoTargets and Therapy
https://www.readbyqxmd.com/read/28435256/doxorubicin-loaded-cell-derived-nanovesicles-an-alternative-targeted-approach-for-anti-tumor-therapy
#8
Wei Jiang Goh, Choon Keong Lee, Shui Zou, Esther Cy Woon, Bertrand Czarny, Giorgia Pastorin
Cell-derived nanovesicles (CDNs) are an emerging class of biological drug delivery systems (DDS) that retain the characteristics of the cells they were derived from, without the need for further surface functionalization. CDNs are also biocompatible, being derived from natural sources and also take advantage of the enhanced permeability and retention effect due to their nanodimensions. Furthermore, CDNs derived from monocytes were shown to have an in vivo targeting effect, accumulating at the tumor site in a previous study conducted in a mouse tumor model...
2017: International Journal of Nanomedicine
https://www.readbyqxmd.com/read/28434400/role-of-modern-immunotherapy-in-gastrointestinal-malignancies-a-review-of-current-clinical-progress
#9
REVIEW
Zin W Myint, Gaurav Goel
Gastrointestinal (GI) cancers are a group of highly aggressive malignancies with a huge disease burden worldwide. There is clearly a significant unmet need for new drugs and therapies to further improve the treatment outcomes of GI malignancies. Immunotherapy is a novel treatment strategy that is emerging as an effective and promising treatment option against several types of cancers. CTLA-4 and PD-1 are critical immune checkpoint molecules that negatively regulate T cell activation via distinct mechanisms...
April 24, 2017: Journal of Hematology & Oncology
https://www.readbyqxmd.com/read/28433634/dual-sphingosine-kinase-inhibitor-ski-ii-enhances-sensitivity-to-5-fluorouracil-in-hepatocellular-carcinoma-cells-via-suppression-of-osteopontin-and-fak-igf-1r-signalling
#10
Petra Grbčić, Ivana Tomljanović, Marko Klobučar, Sandra Kraljević Pavelić, Ksenija Lučin, Mirela Sedić
Hepatocellular carcinoma (HCC) represents the third leading cause of cancer-related deaths globally. Although 5-Fluorouracil (5-FU) is used as the first choice treatment for advanced HCC, it exerts poor efficacy and is associated with acquired and intrinsic resistance. Sphingosine kinases (Sphk) 1 and 2 play tumour-promoting roles in different cancer types including HCC and thus represent promising pharmacological targets. In the present study, we have investigated for the first time the anticancer efficacy and underlying molecular mechanisms of combined administration of 5-FU and dual Sphk1/Sphk2 inhibitor SKI-II (4-[[4-(4-chlorophenyl)-1,3-thiazol-2-yl]amino]phenol) in HepG2 hepatocellular carcinoma cells...
April 19, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28433392/quantifying-rates-of-cell-migration-and-cell-proliferation-in-co-culture-barrier-assays-reveals-how-skin-and-melanoma-cells-interact-during-melanoma-spreading-and-invasion
#11
Parvathi Haridas, Catherine J Penington, Jacqui A McGovern, D L Sean McElwain, Matthew J Simpson
Malignant spreading involves the migration of cancer cells amongst other native cell types. For example, in vivo melanoma invasion involves individual melanoma cells migrating through native skin, which is composed of several distinct subpopulations of cells. Here, we aim to quantify how interactions between melanoma and fibroblast cells affect the collective spreading of a heterogeneous population of these cells in vitro. We perform a suite of circular barrier assays that includes: (i) monoculture assays with fibroblast cells; (ii) monoculture assays with SK-MEL-28 melanoma cells; and (iii) a series of co-culture assays initiated with three different ratios of SK-MEL-28 melanoma cells and fibroblast cells...
April 19, 2017: Journal of Theoretical Biology
https://www.readbyqxmd.com/read/28433219/importance-of-ground-glass-opacity-component-in-clinical-stage-ia-radiologic-invasive-lung-cancer
#12
Aritoshi Hattori, Takeshi Matsunaga, Kazuya Takamochi, Shiaki Oh, Kenji Suzuki
BACKGROUND: We evaluated the clinical significance of the presence of a ground glass opacity (GGO) component in clinical stage IA radiologic invasive non-small cell lung cancer (NSCLC). METHODS: We reviewed 497 surgically resected clinical stage IA radiologic invasive NSCLCs, which were then classified into two groups based on consolidation tumor ratio (CTR), that is part-solid (0.5 ≤ CTR < 1.0, n = 177) and pure-solid (CTR = 1.0, n = 320). The part-solid tumors were subdivided into GGO-predominant (0...
April 19, 2017: Annals of Thoracic Surgery
https://www.readbyqxmd.com/read/28432832/profiling-microrna-from-nephrectomy-and-biopsy-specimens-predictors-of-progression-and-survival-in-clear-cell-renal-cell-carcinoma
#13
Casey G Kowalik, Drew A Palmer, Travis B Sullivan, Patrick A Teebagy, John M Dugan, John A Libertino, Eric J Burks, David Canes, Kimberly M Rieger-Christ
OBJECTIVE: To identify miRNA characteristic of metastatic clear cell renal cell carcinoma (ccRCC) and those indicative of cancer specific survival in nephrectomy and biopsy specimens. We also sought to determine if a miRNA panel could differentiate benign from ccRCC tissue. MATERIALS AND METHODS: RNA was isolated from nephrectomy and kidney biopsy specimens (n=156; n=46 respectively). Samples were grouped: benign, non-progressive and progressive ccRCC. MiRNA were profiled by microarray and validated by qRT-PCR...
April 22, 2017: BJU International
https://www.readbyqxmd.com/read/28431926/multiple-repair-pathways-mediate-cellular-tolerance-to-resveratrol-induced-dna-damage
#14
Ying Liu, Xiaohua Wu, Xiaoqing Hu, Ziyuan Chen, Hao Liu, Shunichi Takeda, Yong Qing
Resveratrol (RSV) has been reported to exert health benefits for the prevention and treatment of many diseases, including cancer. The anticancer mechanisms of RSV seem to be complex and may be associated with genotoxic potential. To better understand the genotoxic mechanisms, we used wild-type (WT) and a panel of isogenic DNA-repair deficient DT40 cell lines to identify the DNA damage effects and molecular mechanisms of cellular tolerance to RSV. Our results showed that RSV induced significant formation of γ-H2AX foci and chromosome aberrations (CAs) in WT cells, suggesting direct DNA damage effects...
April 18, 2017: Toxicology in Vitro: An International Journal Published in Association with BIBRA
https://www.readbyqxmd.com/read/28431881/design-and-synthesis-of-1-2-3-triazolo-phenanthrene-hybrids-as-cytotoxic-agents
#15
Niggula Praveen Kumar, Shalini Nekkanti, S Sujana Kumari, Pankaj Sharma, Nagula Shankaraiah
A series of new 1,2,3-triazolo-phenanthrene hybrids has been synthesized by employing Cu(I)-catalyzed azide-alkyne cycloaddition (CuAAC) reaction. These compounds were evaluated for their in vitro cytotoxic potential against various human cancer cell lines viz. lung (A549), prostate (PC-3 and DU145), gastric (HGC-27), cervical (HeLa), triple negative breast (MDA-MB-231, MDA-MB-453) and breast (BT-549, 4T1) cells. Among the tested compounds, 7d displayed highest cytotoxicity against DU145 cells with IC50 value of 1...
April 7, 2017: Bioorganic & Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/28431404/upregulation-of-microrna-125b-by-g-csf-promotes-metastasis-in-colorectal-cancer
#16
Xinghua Zhang, Xiao Ma, Huaying An, Changqing Xu, Wenjo Cao, Wei Yuan, Jie Ma
Although there are reports of miR-125b being dysregulated in colorectal cancer (CRC) and associated with CRC progression, little is known about its intrinsic regulatory mechanisms. Here we detected the expression of miR-125b in CRC tissues, subsequently investigated the effect of miR-125b on the proliferation, apoptosis, cell cycle and metastasis on CRC cells. Our results showed that the expression of miR-125b was significantly decreased in CRC tissues comparing to adjacent tissues. However, with the stimulation of Granulocyte colony-stimulating factor (G-CSF), which was highly expressed in CRC tissues, the expression of miR-125b could be improved...
April 6, 2017: Oncotarget
https://www.readbyqxmd.com/read/28430163/long-non-coding-rnas-key-regulators-of-epithelial-mesenchymal-transition-tumour-drug-resistance-and-cancer-stem-cells
#17
REVIEW
Richard Heery, Stephen P Finn, Sinead Cuffe, Steven G Gray
Epithelial mesenchymal transition (EMT), the adoption by epithelial cells of a mesenchymal-like phenotype, is a process co-opted by carcinoma cells in order to initiate invasion and metastasis. In addition, it is becoming clear that is instrumental to both the development of drug resistance by tumour cells and in the generation and maintenance of cancer stem cells. EMT is thus a pivotal process during tumour progression and poses a major barrier to the successful treatment of cancer. Non-coding RNAs (ncRNA) often utilize epigenetic programs to regulate both gene expression and chromatin structure...
April 21, 2017: Cancers
https://www.readbyqxmd.com/read/28429085/the-role-of-rna-alternative-splicing-in-regulating-cancer-metabolism
#18
REVIEW
Itamar Kozlovski, Zahava Siegfried, Adi Amar-Schwartz, Rotem Karni
Tumor cells alter their metabolism by a wide array of mechanisms to promote growth and proliferation. Dysregulated expression and/or somatic mutations of key components of the glycolytic pathway/TCA cycle as well as other metabolic pathways allow tumor cells to improve their ability to survive harsh conditions such as hypoxia and the presence of reactive oxygen species, as well as the ability to obtain nutrients to increase lipids, protein, and nucleic acids biogenesis. Approximately 95% of the human protein encoding genes undergo alternative splicing (AS), a regulated process of gene expression that greatly diversifies the proteome by creating multiple proteins from a single gene...
April 20, 2017: Human Genetics
https://www.readbyqxmd.com/read/28428884/phase-i-clinical-trial-of-combination-imatinib-and-ipilimumab-in-patients-with-advanced-malignancies
#19
Matthew J Reilley, Ann Bailey, Vivek Subbiah, Filip Janku, Aung Naing, Gerald Falchook, Daniel Karp, Sarina Piha-Paul, Apostolia Tsimberidou, Siqing Fu, JoAnn Lim, Stacie Bean, Allison Bass, Sandra Montez, Luis Vence, Padmanee Sharma, James Allison, Funda Meric-Bernstam, David S Hong
BACKGROUND: Imatinib mesylate can induce rapid tumor regression, increase tumor antigen presentation, and inhibit tumor immunosuppressive mechanisms. CTLA-4 blockade and imatinib synergize in mouse models to reduce tumor volume via intratumoral accumulation of CD8+ T cells. We hypothesized that imatinib combined with ipilimumab would be tolerable and may synergize in patients with advanced cancer. METHODS: Primary objective of the dose-escalation study (3 + 3 design) was to establish the maximum tolerated dose (MTD) and recommended phase II dose...
2017: Journal for Immunotherapy of Cancer
https://www.readbyqxmd.com/read/28427506/recent-advances-in-genitourinary-tumors-a-review-focused-on-biology-and-systemic-treatment
#20
REVIEW
Aránzazu González Del Alba, José Ángel Arranz, Javier Puente, María José Méndez-Vidal, Enrique Gallardo, Enrique Grande, Begoña Pérez-Valderrama, Enrique González-Billalabeitia, Martín Lázaro-Quintela, Álvaro Pinto, Nuria Lainez, Josep M Piulats, Emilio Esteban, José Pablo Maroto Rey, Jorge A García, Cristina Suárez
Updated information published up to 2016 regarding major advances in renal cancer, bladder cancer, and prostate cancer is here presented. Based on an ever better understanding of the genetic and molecular alterations that govern the initial pathogenic mechanisms of tumor oncogenesis, an improvement in the characterization and treatment of urologic tumors has been achieved in the past year. According to the Cancer Genome Atlas (ATLAS) project, alterations in the MET pathway are characteristics of type 1 papillary renal cell carcinomas, and activation of NRF2-ARE pathway is associated with the biologically distinct type 2...
May 2017: Critical Reviews in Oncology/hematology
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