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https://www.readbyqxmd.com/read/28920959/targeting-mitochondrial-oxidative-phosphorylation-eradicates-therapy-resistant-chronic-myeloid-leukemia-stem-cells
#1
Elodie M Kuntz, Pablo Baquero, Alison M Michie, Karen Dunn, Saverio Tardito, Tessa L Holyoake, G Vignir Helgason, Eyal Gottlieb
Treatment of chronic myeloid leukemia (CML) with imatinib mesylate and other second- and/or third-generation c-Abl-specific tyrosine kinase inhibitors (TKIs) has substantially extended patient survival. However, TKIs primarily target differentiated cells and do not eliminate leukemic stem cells (LSCs). Therefore, targeting minimal residual disease to prevent acquired resistance and/or disease relapse requires identification of new LSC-selective target(s) that can be exploited therapeutically. Considering that malignant transformation involves cellular metabolic changes, which may in turn render the transformed cells susceptible to specific assaults in a selective manner, we searched for such vulnerabilities in CML LSCs...
September 18, 2017: Nature Medicine
https://www.readbyqxmd.com/read/28915579/microrna-profiling-associated-with-non-small-cell-lung-cancer-next-generation-sequencing-detection-experimental-validation-and-prognostic-value
#2
Sandra Gallach, Eloisa Jantus-Lewintre, Silvia Calabuig-Fariñas, David Montaner, Sergio Alonso, Rafael Sirera, Ana Blasco, Marta Usó, Ricardo Guijarro, Miguel Martorell, Carlos Camps
BACKGROUND: The average five-year survival for non-small cell lung cancer (NSCLC) patients is approximately 15%. Emerging evidence indicates that microRNAs (miRNAs) constitute a new class of gene regulators in humans that may play an important role in tumorigenesis. Hence, there is growing interest in studying their role as possible new biomarkers whose expression is aberrant in cancer. Therefore, in this study we identified dysregulated miRNAs by next generation sequencing (NGS) and analyzed their prognostic value...
August 22, 2017: Oncotarget
https://www.readbyqxmd.com/read/28915554/resistance-to-ctla-4-checkpoint-inhibition-reversed-through-selective-elimination-of-granulocytic-myeloid-cells
#3
Paul E Clavijo, Ellen C Moore, Jianhong Chen, Ruth J Davis, Jay Friedman, Young Kim, Carter Van Waes, Zhong Chen, Clint T Allen
PURPOSE: Local immunosuppression remains a critical problem that limits clinically meaningful response to checkpoint inhibition in patients with head and neck cancer. Here, we assessed the impact of MDSC elimination on responses to CTLA-4 checkpoint inhibition. EXPERIMENTAL DESIGN: Murine syngeneic carcinoma immune infiltrates were characterized by flow cytometry. Granulocytic MDSCs (gMDSCs) were depleted and T-lymphocyte antigen-specific responses were measured...
August 22, 2017: Oncotarget
https://www.readbyqxmd.com/read/28915493/in-situ-spectral-response-of-the-arabian-gulf-and-sea-of-oman-coastal-waters-to-bio-optical-properties
#4
Maryam R Al Shehhi, Imen Gherboudj, Hosni Ghedira
Mapping of Chlorophyll-a (Chl-a) over the coastal waters of the Arabian Gulf and the Sea of Oman using the satellite-based observations, such as MODIS (Moderate Resolution Imaging Spectro-radiometer), has shown inferior performance (Chl-a overestimation) than that of deep waters. Studies in the region have shown that this poor performance is due to three reasons: (i) water turbidity (sediments re-suspension), and the presence of colored dissolved organic matter (CDOM), (ii) bottom reflectance and (iii) incapability of the existing atmospheric correction models to reduce the effect of the aerosols from the water leaving radiance...
September 6, 2017: Journal of Photochemistry and Photobiology. B, Biology
https://www.readbyqxmd.com/read/28914135/hemodynamic-and-anatomic-predictors-of-renovisceral-stent-graft-occlusion-following-chimney-endovascular-repair-of-juxtarenal-aortic-aneurysms
#5
Rosamaria Tricarico, Yong He, Liza Laquian, Salvatore T Scali, Roger Tran-Son-Tay, Adam W Beck, Scott A Berceli
PURPOSE: To identify anatomic and hemodynamic changes associated with impending visceral chimney stent-graft occlusion after endovascular aneurysm repair (EVAR) with the chimney technique (chEVAR). METHODS: A retrospective evaluation was performed of computed tomography scans from 41 patients who underwent juxtarenal chEVAR from 2008 to 2012 to identify stent-grafts demonstrating conformational changes following initial placement. Six subjects (mean age 74 years; 3 men) were selected for detailed reconstruction and computational hemodynamic analysis; 4 had at least 1 occluded chimney stent-graft...
September 1, 2017: Journal of Endovascular Therapy
https://www.readbyqxmd.com/read/28912679/proteomic-differences-in-blood-plasma-associated-with-antidepressant-treatment-response
#6
Christoph W Turck, Paul C Guest, Giuseppina Maccarrone, Marcus Ising, Stefan Kloiber, Susanne Lucae, Florian Holsboer, Daniel Martins-de-Souza
The current inability of clinical psychiatry to objectively select the most appropriate treatment is a major factor contributing to the severity and clinical burden of major depressive disorder (MDD). Here, we have attempted to identify plasma protein signatures in 39 MDD patients to predict response over a 6-week treatment period with antidepressants. LC-MS/MS analysis showed that differences in the levels of 29 proteins at baseline were found in the group with a favorable treatment outcome. Most of these proteins were components of metabolism or immune response pathways as well as multiple components of the coagulation cascade...
2017: Frontiers in Molecular Neuroscience
https://www.readbyqxmd.com/read/28912571/comparative-global-immune-related-gene-profiling-of-somatic-cells-human-pluripotent-stem-cells-and-their-derivatives-implication-for-human-lymphocyte-proliferation
#7
Chia-Eng Wu, Chen-Wei Yu, Kai-Wei Chang, Wen-Hsi Chou, Chen-Yu Lu, Elisa Ghelfi, Fang-Chun Wu, Pey-Shynan Jan, Mei-Chi Huang, Patrick Allard, Shau-Ping Lin, Hong-Nerng Ho, Hsin-Fu Chen
Human pluripotent stem cells (hPSCs), including embryonic stem cells (ESCs) and induced PSCs (iPSCs), represent potentially unlimited cell sources for clinical applications. Previous studies have suggested that hPSCs may benefit from immune privilege and limited immunogenicity, as reflected by the reduced expression of major histocompatibility complex class-related molecules. Here we investigated the global immune-related gene expression profiles of human ESCs, hiPSCs and somatic cells and identified candidate immune-related genes that may alter their immunogenicity...
September 15, 2017: Experimental & Molecular Medicine
https://www.readbyqxmd.com/read/28905131/exploring-evidence-of-positive-selection-signatures-in-cattle-breeds-selected-for-different-traits
#8
Mengistie Taye, Wonseok Lee, Soomin Jeon, Joon Yoon, Tadelle Dessie, Olivier Hanotte, Okeyo Ally Mwai, Stephen Kemp, Seoae Cho, Sung Jong Oh, Hak-Kyo Lee, Heebal Kim
Since domestication, the genome landscape of cattle has been changing due to natural and artificial selection forces resulting in several general and specialized cattle breeds of the world. Identifying genomic regions affected due to these forces in livestock gives an insight into the history of selection for economically important traits and genetic adaptation to specific environments of the populations under consideration. This study explores the genes/genomic regions under selection in relation to the phenotypes of Holstein, Hanwoo, and N'Dama cattle breeds using Tajima's D, XP-CLR, and XP-EHH population statistical methods...
September 13, 2017: Mammalian Genome: Official Journal of the International Mammalian Genome Society
https://www.readbyqxmd.com/read/28904760/maintaining-genetic-integrity-of-coexisting-wild-and-domestic-populations-genetic-differentiation-between-wild-and-domestic-rangifer-with-long-traditions-of-intentional-interbreeding
#9
David G Anderson, Kjersti S Kvie, Vladimir N Davydov, Knut H Røed
This study investigates the genetic effect of an indigenous tradition of deliberate and controlled interbreeding between wild and domestic Rangifer. The results are interpreted in the context of conservation concerns and debates on the origin of domestic animals. The study is located in Northeastern Zabaĭkal'e, Russia at approximately 57 degrees North latitude. Blood and skin samples, collected from wild and domestic Rangifer, are analyzed for their mtDNA and microsatellite signatures. Local husbandry traditions are documented ethnographically...
September 2017: Ecology and Evolution
https://www.readbyqxmd.com/read/28904227/peptide-probes-detect-misfolded-transthyretin-oligomers-in-plasma-of-hereditary-amyloidosis-patients
#10
Joseph D Schonhoft, Cecilia Monteiro, Lars Plate, Yvonne S Eisele, John M Kelly, Daniel Boland, Christopher G Parker, Benjamin F Cravatt, Sergio Teruya, Stephen Helmke, Mathew Maurer, John Berk, Yoshiki Sekijima, Marta Novais, Teresa Coelho, Evan T Powers, Jeffery W Kelly
Increasing evidence supports the hypothesis that soluble misfolded protein assemblies contribute to the degeneration of postmitotic tissue in amyloid diseases. However, there is a dearth of reliable nonantibody-based probes for selectively detecting oligomeric aggregate structures circulating in plasma or deposited in tissues, making it difficult to scrutinize this hypothesis in patients. Hence, understanding the structure-proteotoxicity relationships driving amyloid diseases remains challenging, hampering the development of early diagnostic and novel treatment strategies...
September 13, 2017: Science Translational Medicine
https://www.readbyqxmd.com/read/28903376/improving-circulating-tumor-cells-enumeration-and-characterization-to-predict-outcome-in-first-line-chemotherapy-mcrpc-patients
#11
Luis León-Mateos, Helena Casas, Alicia Abalo, María Vieito, Manuel Abreu, Urbano Anido, Antonio Gómez-Tato, Rafael López, Miguel Abal, Laura Muinelo-Romay
INTRODUCTION: There is a critical need of new surrogate markers for improving the therapeutic selection and monitoring of metastatic prostate cancer patients. Nowadays clinical management of these patients is been driven by biochemical and clinical parameters without enough accuracy to allow a real personalized medicine. The present study was conducted to go insight the molecular profile of circulating tumor cells (CTCs) isolated from advanced metastatic castration-resistant prostate cancer (mCRPC) with the aim of identifying prognostic marker with potential utility for therapy selection and monitoring...
August 15, 2017: Oncotarget
https://www.readbyqxmd.com/read/28901136/tren-capped-hexaphyrin-zinc-complexes-interplaying-molecular-recognition-m%C3%A3-bius-aromaticity-and-chirality
#12
Hervé Ruffin, Gildas Nyame Mendendy Boussambe, Thierry Roisnel, Vincent Dorcet, Bernard Boitrel, Stéphane Le Gac
Over the last decade, the hexaphyrin skeleton has emerged as a multifaceted frame exhibiting strong interplay between topology, aromaticity and metal coordination, opening new research areas beyond porphyrins. Yet, molecular recognition with hexaphyrins has been under-explored, mainly due to the lack of general synthetic strategies leading to sophisticated molecular hosts. Here, we have developed a straightforward approach for capping the heteroannulene frame with tripodal units (e.g., tris(2-aminoethyl)amine [tren]), through the post-modification of a readily accessible meso-(2-aminophenyl) tris-substituted platform...
September 13, 2017: Journal of the American Chemical Society
https://www.readbyqxmd.com/read/28900812/radiomic-features-predict-ki-67-expression-level-and-survival-in-lower-grade-gliomas
#13
Yiming Li, Zenghui Qian, Kaibin Xu, Kai Wang, Xing Fan, Shaowu Li, Xing Liu, Yinyan Wang, Tao Jiang
To investigate the radiomic features associated with Ki-67 expression in lower grade gliomas and assess the prognostic values of these features. Patients with lower grade gliomas (n = 117) were randomly assigned into the training (n = 78) and validation (n = 39) sets. A total of 431 radiological features were extracted from each patient. Differential radiological features between the low and high Ki-67 expression groups were screened by significance analysis of microarrays. Then, generalized linear analysis was performed to select features that could predict the Ki-67 expression level...
September 12, 2017: Journal of Neuro-oncology
https://www.readbyqxmd.com/read/28900502/a-bap1-mutation-specific-microrna-signature-predicts-clinical-outcomes-in-clear-cell-renal-cell-carcinoma-patients-with-wild-type-bap1
#14
Yu-Zheng Ge, Lu-Wei Xu, Chang-Cheng Zhou, Tian-Ze Lu, Wen-Tao Yao, Ran Wu, You-Cai Zhao, Xiao Xu, Zhi-Kai Hu, Min Wang, Xiao-Bing Yang, Liu-Hua Zhou, Bing Zhong, Zheng Xu, Wen-Cheng Li, Jia-Geng Zhu, Rui-Peng Jia
Background: Clear cell renal cell carcinoma (ccRCC) is the most prevalent histologic subtype of kidney cancers in adults, which could be divided into two distinct subgroups according to the BRCA1 associated protein-1 (BAP1) mutation status. In the current study, we comprehensively analyzed the genome-wide microRNA (miRNA) expression profiles in ccRCC, with the aim to identify the differentially expressed miRNAs between BAP1 mutant and wild-type tumors, and generate a BAP1 mutation-specific miRNA signature for ccRCC patients with wild-type BAP1...
2017: Journal of Cancer
https://www.readbyqxmd.com/read/28900440/chlorophyll-fluorescence-imaging-uncovers-photosynthetic-fingerprint-of-citrus-huanglongbing
#15
Haiyan Cen, Haiyong Weng, Jieni Yao, Mubin He, Jingwen Lv, Shijia Hua, Hongye Li, Yong He
Huanglongbing (HLB) is one of the most destructive diseases of citrus, which has posed a serious threat to the global citrus production. This research was aimed to explore the use of chlorophyll fluorescence imaging combined with feature selection to characterize and detect the HLB disease. Chlorophyll fluorescence images of citrus leaf samples were measured by an in-house chlorophyll fluorescence imaging system. The commonly used chlorophyll fluorescence parameters provided the first screening of HLB disease...
2017: Frontiers in Plant Science
https://www.readbyqxmd.com/read/28900302/functional-dissection-of-hematopoietic-stem-cell-populations-with-a-stemness-monitoring-system-based-on-ns-gfp-transgene-expression
#16
Mohamed A E Ali, Kyoko Fuse, Yuko Tadokoro, Takayuki Hoshii, Masaya Ueno, Masahiko Kobayashi, Naho Nomura, Ha Thi Vu, Hui Peng, Ahmed M Hegazy, Masayoshi Masuko, Hirohito Sone, Fumio Arai, Atsushi Tajima, Atsushi Hirao
Hematopoietic stem cells (HSCs) in a steady state can be efficiently purified by selecting for a combination of several cell surface markers; however, such markers do not consistently reflect HSC activity. In this study, we successfully enriched HSCs with a unique stemness-monitoring system using a transgenic mouse in which green florescence protein (GFP) is driven by the promoter/enhancer region of the nucleostemin (NS) gene. We found that the phenotypically defined long-term (LT)-HSC population exhibited the highest level of NS-GFP intensity, whereas NS-GFP intensity was strongly downregulated during differentiation in vitro and in vivo...
September 12, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28900044/regulation-of-autophagy-nf-%C3%AE%C2%BAb-signaling-and-cell-viability-by-mir-124-in-kras-mutant-mesenchymal-like-nsclc-cells
#17
Anita K Mehta, Kevin Hua, William Whipple, Minh-Thuy Nguyen, Ching-Ti Liu, Johannes Haybaeck, Joanne Weidhaas, Jeff Settleman, Anurag Singh
KRAS mutant non-small cell lung cancer (NSCLC) may be classified into epithelial or mesenchymal subtypes. Despite having the same "driver" mutation, mesenchymal NSCLCs are less responsive than are epithelial NSCLCs to inhibition of the RAS pathway. Identifying alternative networks that promote survival specifically in mesenchymal NSCLC may lead to more effective treatments for this subtype. Through their numerous targets in cellular signaling pathways, noncoding microRNAs (miRNAs) often function as tumor suppressors or oncogenes...
September 12, 2017: Science Signaling
https://www.readbyqxmd.com/read/28899970/targeting-prostate-cancer-subtype-1-by-forkhead-box-m1-pathway-inhibition
#18
Kirsi Ketola, Ravi Sn Munuganti, Alastair Davies, Ka Mun Nip, Jennifer L Bishop, Amina Zoubeidi
PURPOSE: Prostate cancer was recently classified to three clinically relevant subtypes (PCS) demarcated by unique pathway activation and clinical aggressiveness. In this preclinical study, we investigated molecular targets and therapeutics for PCS1, the most aggressive and lethal subtype with no treatment options available in the clinic. EXPERIMENTAL DESIGN: We utilized the PCS1 gene set and our model of enzalutamide (ENZR) castration-resistant prostate cancer (CRPC) to identify targetable pathways and inhibitors for PCS1...
September 12, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28899518/relationship-between-obstructive-sleep-apnea-and-neuroimaging-signatures-of-cerebral-small-vessel-disease-in-community-dwelling-older-adults-the-atahualpa-project
#19
Oscar H Del Brutto, Robertino M Mera, Mauricio Zambrano, Pablo R Castillo
BACKGROUND/OBJECTIVES: Evidence of a relationship between obstructive sleep apnea (OSA) and neuroimaging signatures of cerebral small vessel disease (SVD) is limited. The present study aimed to evaluate this association in older adults living in rural Ecuador, where small vessel disease is a major pathogenetic mechanism underlying stroke. METHODS: A representative random sample of Atahualpa residents aged ≥60 years enrolled in the Atahualpa Project neuroimaging substudy underwent a single-night diagnostic polysomnography...
September 2017: Sleep Medicine
https://www.readbyqxmd.com/read/28899344/bacteriophages-are-the-major-drivers-of-shigella-flexneri-serotype-1c-genome-plasticity-a-complete-genome-analysis
#20
Pawan Parajuli, Marcin Adamski, Naresh K Verma
BACKGROUND: Shigella flexneri is the primary cause of bacillary dysentery in the developing countries. S. flexneri serotype 1c is a novel serotype, which is found to be endemic in many developing countries, but little is known about its genomic architecture and virulence signatures. We have sequenced for the first time, the complete genome of S. flexneri serotype 1c strain Y394, to provide insights into its diversity and evolution. RESULTS: We generated a high-quality reference genome of S...
September 12, 2017: BMC Genomics
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