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https://www.readbyqxmd.com/read/29454008/temozolomide-affects-extracellular-vesicles-released-by-glioblastoma-cells
#1
Gwennan André-Grégoire, Nicolas Bidère, Julie Gavard
Glioblastoma multiforme (GBM) is the most aggressive primary tumour within the brain as well as the most common and lethal cerebral cancer, mainly because of treatment failure. Indeed, tumour recurrence is inevitable and fatal in a short period of time. Glioblastoma stem-like cells (GSCs) are thought to participate in tumour initiation, expansion, resistance to treatments, including to the alkylating chemotherapeutic agent temozolomide, and relapse. Here, we assessed whether extracellular vesicles (EVs) released by GSCs could disseminate factors involved in resistance mechanisms...
February 14, 2018: Biochimie
https://www.readbyqxmd.com/read/29453454/a-microvascularized-tumor-mimetic-platform-for-assessing-anti-cancer-drug-efficacy
#2
Shantanu Pradhan, Ashley M Smith, Charles J Garson, Iman Hassani, Wen J Seeto, Kapil Pant, Robert D Arnold, Balabhaskar Prabhakarpandian, Elizabeth A Lipke
Assessment of anti-cancer drug efficacy in in vitro three-dimensional (3D) bioengineered cancer models provides important contextual and relevant information towards pre-clinical translation of potential drug candidates. However, currently established models fail to sufficiently recapitulate complex tumor heterogeneity. Here we present a chip-based tumor-mimetic platform incorporating a 3D in vitro breast cancer model with a tumor-mimetic microvascular network, replicating the pathophysiological architecture of native vascularized breast tumors...
February 16, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29453318/integration-of-distinct-shca-signaling-complexes-promotes-breast-tumor-growth-and-tyrosine-kinase-inhibitor-resistance
#3
Jacqueline R Ha, Ryuhjin Ahn, Harvey W Smith, Valerie Sabourin, Steven Hėbert, Eduardo Cepeda Cañedo, Young Kyuen Im, Claudia Kleinman, William J Muller, Josie Ursini-Siegel
The commonality between most phospho-tyrosine signaling networks is their shared use of adaptor proteins to transduce mitogenic signals. ShcA (SHC1) is one such adaptor protein that employs two phospho-tyrosine binding domains (PTB and SH2) and key phospho-tyrosine residues to promote mammary tumorigenesis. Receptor tyrosine kinases (RTKs), such as ErbB2, engage the ShcA PTB domain to promote breast tumorigenesis by engaging Grb2 downstream of the ShcA tyrosine phosphorylation sites to activate AKT/mTOR signaling...
February 16, 2018: Molecular Cancer Research: MCR
https://www.readbyqxmd.com/read/29453286/chaperone-substrate-provides-missing-link-for-cancer-drug-discovery
#4
Katherine M Byrd, Brian S J Blagg
Both Hsp70 and Hsp90 chaperones are overexpressed in cancer, making them relevant targets for the development of cancer chemotherapeutics, but a lack of biomolecular readouts for Hsp70 inhibition has limited the pursuit of specific inhibitors for this enzyme. A new study from Cesa et al. identifies two inhibitors of apoptosis proteins (IAPs) as specific client substrates of Hsp70. These results establish biomarkers that can be utilized to monitor Hsp70 inhibition and provide a framework for future efforts to deconvolute chaperone networks...
February 16, 2018: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/29452772/metabolic-and-lipidomic-reprogramming-in-renal-cell-carcinoma-subtypes-reflects-regions-of-tumor-origin
#5
Elke Schaeffeler, Florian Büttner, Anna Reustle, Verena Klumpp, Stefan Winter, Steffen Rausch, Pascale Fisel, Jörg Hennenlotter, Stephan Kruck, Arnulf Stenzl, Judith Wahrheit, Denise Sonntag, Marcus Scharpf, Falko Fend, Abbas Agaimy, Arndt Hartmann, Jens Bedke, Matthias Schwab
BACKGROUND: Renal cell carcinoma (RCC) consists of prognostic distinct subtypes derived from different cells of origin (eg, clear cell RCC [ccRCC], papillary RCC [papRCC], and chromophobe RCC [chRCC]). ccRCC is characterized by lipid accumulation and metabolic alterations, whereas data on metabolic alterations in non-ccRCC are limited. OBJECTIVE: We assessed metabolic alterations and the lipid composition of RCC subtypes and ccRCC-derived metastases. Moreover, we elucidated the potential of metabolites/lipids for subtype classification and identification of therapeutic targets...
February 13, 2018: European Urology Focus
https://www.readbyqxmd.com/read/29452694/chitinase-3-like-1-chi3l1-promotes-vasculogenic-mimicry-formation-in-cervical-cancer
#6
Nipaporn Ngernyuang, Rong Shao, Komsun Suwannarurk, Temduang Limpaiboon
Vasculogenic mimicry (VM) is an alternative microvascular system which tumour cells orchestrate, independent of endothelial cell-mediated angiogenesis. VM develops tumour vascular networks that correlate with tumour growth, metastasis, and short survival time of patients with a number of cancers. However, little is known regarding VM in the vascularisation of cervical cancer. Chitinase 3 like 1 (CHI3L1) has been previously reported to display the ability to induce angiogenesis in cervical cancer. Here, we explored a pathological role of CHI3L1 in tumour cell-mediated vascularisation...
February 13, 2018: Pathology
https://www.readbyqxmd.com/read/29452595/fertility-preservation-healthcare-circuit-and-networks-in-cancer-patients-worldwide-what-are-the-issues
#7
REVIEW
Kathleen Melan, Frederic Amant, Jacqueline Veronique-Baudin, Clarisse Joachim, Eustase Janky
BACKGROUND: Fertility preservation (FP) is a major determinant of quality of life after cancer remission for women who may not have achieved their ideal family size. This article describes the FP services and strategy currently available, highlighting issues of oncofertility worldwide. For these patients in complex situations, health networks are essential to improve coordination of care, and the strengthening of this coordination is a major challenge to improve the performance of the health system...
February 17, 2018: BMC Cancer
https://www.readbyqxmd.com/read/29451304/distinct-methylation-profile-of-mucinous-ovarian-carcinoma-reveals-susceptibility-to-proteasome-inhibitors
#8
Phui-Ly Liew, Rui-Lan Huang, Yu-Chun Weng, Chia-Lang Fang, Tim Hui-Ming Huang, Hung-Cheng Lai
Mucinous type of epithelial ovarian cancer (MuOC) is a unique subtype with a poor survival outcome in recurrent and advanced stages. The role of type-specific epigenomics and its clinical significance remain uncertain. We analyzed the methylomic profiles of six benign mucinous adenomas, 24 MuOCs, 103 serous type of epithelial ovarian cancers (SeOCs), and 337 nonepithelial ovarian cancers. MuOC and SeOC exhibited distinct DNA methylation profiles comprising 101 genes, 81 of which exhibited low methylation in MuOC and were associated with the response to glucocorticoid, ATP hydrolysis-coupled proton transport, proteolysis involved in the cellular protein catabolic process, and ion transmembrane transport...
February 16, 2018: International Journal of Cancer. Journal International du Cancer
https://www.readbyqxmd.com/read/29451078/oncologists-perceptions-of-drug-affordability-using-nccn-evidence-blocks-results-from-a-national-survey
#9
Bijal Shah-Manek, William Wong, Arliene Ravelo, Marco DiBonaventura
BACKGROUND: The increasing prevalence of cancer coupled with approvals of new drugs and technologies used in therapy have brought increased scrutiny to the cost and value of treatments in oncology. To address the rising concern about oncology drug costs, several organizations have developed value frameworks to help assess the value of oncology regimens. The objective of this study was to assess oncologists' perceptions, awareness, and knowledge of all oncology value frameworks in the United States and to understand oncologists' perceptions of affordability in the context of National Comprehensive Cancer Network (NCCN) Evidence Blocks...
February 16, 2018: Journal of Managed Care & Specialty Pharmacy
https://www.readbyqxmd.com/read/29450843/detection-of-lung-contour-with-closed-principal-curve-and-machine-learning
#10
Tao Peng, Yihuai Wang, Thomas Canhao Xu, Lianmin Shi, Jianwu Jiang, Shilang Zhu
Radiation therapy plays an essential role in the treatment of cancer. In radiation therapy, the ideal radiation doses are delivered to the observed tumor while not affecting neighboring normal tissues. In three-dimensional computed tomography (3D-CT) scans, the contours of tumors and organs-at-risk (OARs) are often manually delineated by radiologists. The task is complicated and time-consuming, and the manually delineated results will be variable from different radiologists. We propose a semi-supervised contour detection algorithm, which firstly uses a few points of region of interest (ROI) as an approximate initialization...
February 15, 2018: Journal of Digital Imaging: the Official Journal of the Society for Computer Applications in Radiology
https://www.readbyqxmd.com/read/29450800/the-endogenous-subcellular-localisations-of-the-long-chain-fatty-acid-activating-enzymes-acsl3-and-acsl4-in-sarcoma-and-breast-cancer-cells
#11
Yassmeen Radif, Haarith Ndiaye, Vasiliki Kalantzi, Ruth Jacobs, Andrew Hall, Shane Minogue, Mark G Waugh
Fatty acid uptake and metabolism are often dysregulated in cancer cells. Fatty acid activation is a critical step that allows these biomolecules to enter cellular metabolic pathways such as mitochondrial β-oxidation for ATP generation or the lipogenic routes that generate bioactive lipids such as the inositol phospholipids. Fatty acid activation by the addition of coenzyme A is catalysed by a family of enzymes called the acyl CoA synthetase ligases (ACSL). Furthermore, enhanced expression of particular ACSL isoforms, such as ACSL4, is a feature of some more aggressive cancers and may contribute to the oncogenic phenotype...
February 15, 2018: Molecular and Cellular Biochemistry
https://www.readbyqxmd.com/read/29449933/a-simplified-characterization-of-s-adenosyl-l-methionine-consuming-enzymes-with-1-step-ez-mtase-a-universal-and-straightforward-coupled-assay-for-in-vitro-and-in-vivo-setting
#12
Emmanuel S Burgos, Ryan O Walters, Derek M Huffman, David Shechter
Methyltransferases use S -adenosyl-l-methionine (SAM) to deposit methyl marks. Many of these epigenetic 'writers' are associated with gene regulation. As cancer etiology is highly correlated with misregulated methylation patterns, methyltransferases are emerging therapeutic targets. Successful assignment of methyltransferases' roles within intricate biological networks relies on (1) the access to enzyme mechanistic insights and (2) the efficient screening of chemical probes against these targets. To characterize methyltransferases in vitro and in vivo , we report a highly-sensitive one-step deaminase-linked continuous assay where the S -adenosyl-l-homocysteine (SAH) enzyme-product is rapidly and quantitatively catabolized to S -inosyl-l-homocysteine (SIH)...
September 1, 2017: Chemical Science
https://www.readbyqxmd.com/read/29449773/potential-breast-anticancer-drug-targets-revealed-by-differential-gene-regulatory-network-analysis-and-molecular-docking-neoadjuvant-docetaxel-drug-as-a-case-study
#13
Adel Aloraini, Karim M ElSawy
Understanding gene-gene interaction and its causal relationship to protein-protein interaction is a viable route for understanding drug action at the genetic level, which is largely hindered by inability to robustly map gene regulatory networks. Here, we use biological prior knowledge of family-to-family gene interactions available in the KEGG database to reveal individual gene-to-gene interaction networks that underlie the gene expression profiles of 2 cell line data sets, sensitive and resistive to neoadjuvant docetaxel breast anticancer drug...
2018: Cancer Informatics
https://www.readbyqxmd.com/read/29448849/development-of-small-molecule-immune-checkpoint-inhibitors-of-pd-1-pd-l1-as-a-new-therapeutic-strategy-for-tumour-immunotherapy
#14
Kui Li, Tian Hongqi
Cancer immunotherapy has been increasingly utilized to treat advanced malignancies. The signalling network of immune checkpoints has attracted considerable attention. Immune checkpoint inhibitors are revolutionizing the treatment options and expectations for patients with cancer. The reported clinical success of targeting the T-cell immune checkpoint receptors PD-1/PD-L1 has demonstrated the importance of immune modulation. Indeed, antibodies binding to PD-1 or PD-L1 have shown remarkable efficacy. However, antibody drugs have many disadvantages, such as their production cost, stability, and immunogenicity, and therefore, small-molecule inhibitors of PD-1 and its ligand PD-L1 are being introduced...
February 16, 2018: Journal of Drug Targeting
https://www.readbyqxmd.com/read/29448055/proteomic-characterization-of-withaferin-a-targeted-protein-networks-for-the-treatment-of-monoclonal-myeloma-gammopathies
#15
Martin Dom, Fritz Offner, Wim Vanden Berghe, Xaveer Van Ostade
Withaferin A (WA), a natural steroid lactone from the plant Withania somnifera, is often studied because of its antitumor properties. Although many in vitro and in vivo studies have been performed, the identification of Withaferin A protein targets and its mechanism of antitumor action remain incomplete. We used quantitative chemoproteomics and differential protein expression analysis to characterize the WA antitumor effects on a multiple myeloma cell model. Identified relevant targets were further validated by Ingenuity Pathway Analysis and Western blot and indicate that WA targets protein networks that are specific for monoclonal gammopathy of undetermined significance (MGUS) and other closely related disorders, such as multiple myeloma (MM) and Waldenström macroglobulinemia (WM)...
February 12, 2018: Journal of Proteomics
https://www.readbyqxmd.com/read/29445424/promoter-methylation-of-dna-damage-repair-ddr-genes-in-human-tumor-entities-rbbp8-ctip-is-almost-exclusively-methylated-in-bladder-cancer
#16
Jolein Mijnes, Jürgen Veeck, Nadine T Gaisa, Eduard Burghardt, Tim C de Ruijter, Sonja Gostek, Edgar Dahl, David Pfister, Sebastian C Schmid, Ruth Knüchel, Michael Rose
Background: Genome-wide studies identified pan-cancer genes and shared biological networks affected by epigenetic dysregulation among diverse tumor entities. Here, we systematically screened for hypermethylation of DNA damage repair (DDR) genes in a comprehensive candidate-approach and exemplarily identify and validate candidate DDR genes as targets of epigenetic inactivation unique to bladder cancer (BLCA), which may serve as non-invasive biomarkers. Methods: Genome-wide DNA methylation datasets (2755 CpG probes of n = 7819 tumor and n = 659 normal samples) of the TCGA network covering 32 tumor entities were analyzed in silico for 177 DDR genes...
2018: Clinical Epigenetics
https://www.readbyqxmd.com/read/29445299/choosing-wisely-after-publication-of-level-i-evidence-in-breast-cancer-radiotherapy
#17
Joshua R Niska, Sameer R Keole, Barbara A Pockaj, Michele Y Halyard, Samir H Patel, Donald W Northfelt, Richard J Gray, Nabil Wasif, Carlos E Vargas, William W Wong
Background: Recent trials in early-stage breast cancer support hypofractionated whole-breast radiotherapy (WBRT) as part of breast-conserving therapy (BCT). Evidence also suggests that radiotherapy (RT) omission may be reasonable for some patients over 70 years. Among radiation-delivery techniques, intensity-modulated RT (IMRT) is more expensive than 3-dimensional conformal RT (3DCRT). Based on this evidence, in 2013, the American Society for Radiation Oncology (ASTRO) recommended hypofractionated schedules for women aged ≥50 years with early-stage breast cancer and avoiding routine use of IMRT for WBRT...
2018: Breast Cancer: Targets and Therapy
https://www.readbyqxmd.com/read/29445139/dynamic-network-biomarker-indicates-pulmonary-metastasis-at-the-tipping-point-of-hepatocellular-carcinoma
#18
Biwei Yang, Meiyi Li, Wenqing Tang, Weixin Liu, Si Zhang, Luonan Chen, Jinglin Xia
Developing predictive biomarkers that can detect the tipping point before metastasis of hepatocellular carcinoma (HCC), is critical to prevent further irreversible deterioration. To discover such early-warning signals or biomarkers of pulmonary metastasis in HCC, we analyse time-series gene expression data in spontaneous pulmonary metastasis mice HCCLM3-RFP model with our dynamic network biomarker (DNB) method, and identify CALML3 as a core DNB member. All experimental results of gain-of-function and loss-of-function studies show that CALML3 could indicate metastasis initiation and act as a suppressor of metastasis...
February 14, 2018: Nature Communications
https://www.readbyqxmd.com/read/29445084/the-carnitine-system-and-cancer-metabolic-plasticity
#19
REVIEW
Melone Mariarosa Anna Beatrice, Valentino Anna, Margarucci Sabrina, Galderisi Umberto, Giordano Antonio, Peluso Gianfranco
Metabolic flexibility describes the ability of cells to respond or adapt its metabolism to support and enable rapid proliferation, continuous growth, and survival in hostile conditions. This dynamic character of the cellular metabolic network appears enhanced in cancer cells, in order to increase the adaptive phenotype and to maintain both viability and uncontrolled proliferation. Cancer cells can reprogram their metabolism to satisfy the energy as well as the biosynthetic intermediate request and to preserve their integrity from the harsh and hypoxic environment...
February 14, 2018: Cell Death & Disease
https://www.readbyqxmd.com/read/29445031/the-perils-of-single-site-genetic-testing-for-hereditary-cancer-syndromes-in-the-era-of-next-generation-sequencing
#20
Nicole Casasanta, Elizabeth Stark, Allison McHenry, Tara Biagi, Rebecca Kaltman
A challenge in counseling patients with a family history suggesting a hereditary cancer syndrome is deciding which genetic tests or panels to order. In this article, we discuss the identification of multiple familial mutations through genetic counseling and panel testing. For patients meeting National Comprehensive Cancer Network criteria for clinical genetic testing, providers should consider expanded panels to provide a more complete assessment of one's genetic risk. The continued use of expanded panel testing in the clinical setting will help inform optimal management of cancer patients, as well as the management of their unaffected family members...
February 14, 2018: Oncologist
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