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https://www.readbyqxmd.com/read/28092774/the-lonely-road-to-paranoia-a-path-analytic-investigation-of-loneliness-and-paranoia
#1
Fabian Lamster, Tania M Lincoln, Clara M Nittel, Winfried Rief, Stephanie Mehl
Loneliness and paranoia are related, but the mechanisms that link them to each other remain unclear. Systematic reviews on loneliness propose a social-cognitive model in which loneliness leads to negative evaluations of other persons and a lack of interpersonal trust. However, the data discussed in these reviews are based on healthy individuals. Building on this model, the present study investigated 1) whether negative interpersonal schemata mediate the association between loneliness and paranoia and 2) whether a low level of perceived social support and less frequent social contact are related to loneliness...
January 2, 2017: Comprehensive Psychiatry
https://www.readbyqxmd.com/read/28092685/precision-oncology-for-acute-myeloid-leukemia-using-a-knowledge-bank-approach
#2
Moritz Gerstung, Elli Papaemmanuil, Inigo Martincorena, Lars Bullinger, Verena I Gaidzik, Peter Paschka, Michael Heuser, Felicitas Thol, Niccolo Bolli, Peter Ganly, Arnold Ganser, Ultan McDermott, Konstanze Döhner, Richard F Schlenk, Hartmut Döhner, Peter J Campbell
Underpinning the vision of precision medicine is the concept that causative mutations in a patient's cancer drive its biology and, by extension, its clinical features and treatment response. However, considerable between-patient heterogeneity in driver mutations complicates evidence-based personalization of cancer care. Here, by reanalyzing data from 1,540 patients with acute myeloid leukemia (AML), we explore how large knowledge banks of matched genomic-clinical data can support clinical decision-making. Inclusive, multistage statistical models accurately predicted likelihoods of remission, relapse and mortality, which were validated using data from independent patients in The Cancer Genome Atlas...
January 16, 2017: Nature Genetics
https://www.readbyqxmd.com/read/28092680/utilizing-somatic-mutation-data-from-numerous-studies-for-cancer-research-proof-of-concept-and-applications
#3
D Amar, S Izraeli, R Shamir
Large cancer projects measure somatic mutations in thousands of samples, gradually assembling a catalog of recurring mutations in cancer. Many methods analyze these data jointly with auxiliary information with the aim of identifying subtype-specific results. Here, we show that somatic gene mutations alone can reliably and specifically predict cancer subtypes. Interpretation of the classifiers provides useful insights for several biomedical applications. We analyze the COSMIC database, which collects somatic mutations from The Cancer Genome Atlas (TCGA) as well as from many smaller scale studies...
January 16, 2017: Oncogene
https://www.readbyqxmd.com/read/28092679/genome-wide-analysis-of-p53-regulated-transcription-in-myc-driven-lymphomas
#4
C Tonelli, M J Morelli, A Sabò, A Verrecchia, L Rotta, T Capra, S Bianchi, S Campaner, B Amati
The tumour suppressor p53 is a transcription factor that controls cellular stress responses. Here, we dissected the transcriptional programmes triggered upon restoration of p53 in Myc-driven lymphomas, based on the integrated analysis of p53 genomic occupancy and gene regulation. p53 binding sites were identified at promoters and enhancers, both characterized by the pre-existence of active chromatin marks. Only a small fraction of these sites showed the 20 base-pair p53 consensus motif, suggesting that p53 recruitment to genomic DNA was primarily mediated through protein-protein interactions in a chromatin context...
January 16, 2017: Oncogene
https://www.readbyqxmd.com/read/28092678/6-phosphofructo-2-kinase-fructose-2-6-biphosphatase-4-is-essential-for-p53-null-cancer-cells
#5
S Ros, J Flöter, I Kaymak, C Da Costa, A Houddane, S Dubuis, B Griffiths, R Mitter, S Walz, S Blake, A Behrens, K M Brindle, N Zamboni, M H Rider, A Schulze
The bifunctional enzyme 6-phosphofructo-2-kinase/fructose-2,6-biphosphatase-4 (PFKFB4) controls metabolic flux through allosteric regulation of glycolysis. Here we show that p53 regulates the expression of PFKFB4 and that p53-deficient cancer cells are highly dependent on the function of this enzyme. We found that p53 downregulates PFKFB4 expression by binding to its promoter and mediating transcriptional repression via histone deacetylases. Depletion of PFKFB4 from p53-deficient cancer cells increased levels of the allosteric regulator fructose-2,6-bisphosphate, leading to increased glycolytic activity but decreased routing of metabolites through the oxidative arm of the pentose-phosphate pathway...
January 16, 2017: Oncogene
https://www.readbyqxmd.com/read/28092677/wnt-%C3%AE-catenin-signaling-regulates-mitochondrial-activity-to-alter-the-oncogenic-potential-of-melanoma-in-a-pten-dependent-manner
#6
K Brown, P Yang, D Salvador, R Kulikauskas, H Ruohola-Baker, A M Robitaille, A J Chien, R T Moon, V Sherwood
Aberrant regulation of WNT/β-catenin signaling has a crucial role in the onset and progression of cancers, where the effects are not always predictable depending on tumor context. In melanoma, for example, models of the disease predict differing effects of the WNT/β-catenin pathway on metastatic progression. Understanding the processes that underpin the highly context-dependent nature of WNT/β-catenin signaling in tumors is essential to achieve maximal therapeutic benefit from WNT inhibitory compounds. In this study, we have found that expression of the tumor suppressor, phosphatase and tensin homolog deleted on chromosome 10 (PTEN), alters the invasive potential of melanoma cells in response to WNT/β-catenin signaling, correlating with differing metabolic profiles...
January 16, 2017: Oncogene
https://www.readbyqxmd.com/read/28092676/intracellular-il-37b-interacts-with-smad3-to-suppress-multiple-signaling-pathways-and-the-metastatic-phenotype-of-tumor-cells
#7
C Luo, Y Shu, J Luo, D Liu, D-S Huang, Y Han, C Chen, Y-C Li, J-M Zou, J Qin, Y Wang, D Li, S-S Wang, G-M Zhang, J Chen, Z-H Feng
Multiple signaling pathways that promote tumor cell metastasis are differentially activated in low/non-metastatic and metastatic tumor cells, resulting in the differential expression of metastasis-related genes. The underlying mechanism may involve the alterations of the intrinsic negative regulation in tumor cells. Here we report that the differential expression of interleukin-37b (IL-37b) in tumor cells alters the intrinsic negative regulation of signaling pathways, resulting in the difference of metastatic capacity...
January 16, 2017: Oncogene
https://www.readbyqxmd.com/read/28092675/unbalancing-p53-mdm2-igf-1r-axis-by-mdm2-activation-restrains-the-igf-1-dependent-invasive-phenotype-of-skin-melanoma
#8
C Worrall, N Suleymanova, C Crudden, I Trocoli Drakensjö, E Candrea, D Nedelcu, S-I Takahashi, L Girnita, A Girnita
Melanoma tumors usually retain wild-type p53; however, its tumor-suppressor activity is functionally disabled, most commonly through an inactivating interaction with mouse double-minute 2 homolog (Mdm2), indicating p53 release from this complex as a potential therapeutic approach. P53 and the tumor-promoter insulin-like growth factor type 1 receptor (IGF-1R) compete as substrates for the E3 ubiquitin ligase Mdm2, making their relative abundance intricately linked. Hence we investigated the effects of pharmacological Mdm2 release from the Mdm2/p53 complex on the expression and function of the IGF-1R...
January 16, 2017: Oncogene
https://www.readbyqxmd.com/read/28092674/a-targetable-hb-egf-cited4-axis-controls-oncogenesis-in-lung-cancer
#9
C-H Hsieh, Y-T Chou, M-H Kuo, H-P Tsai, J-L Chang, C-W Wu
Aberrant epidermal growth factor (EGF) receptor (EGFR) signaling contributes to neoplastic initiation and progression in lung. Mutated EGFR has become as an important therapeutic target in lung cancer, whereas targeted treatment is not available for wild-type EGFR or its ligands. In this study, we found that heparin-binding (HB)-EGF, a member of the EGF family, was highly expressed in a subset of lung cancer, proliferation of which was dependent on HB-EGF signaling. Silencing of HB-EGF with RNA interference inhibited cell cycle progression in lung cancer cells...
January 16, 2017: Oncogene
https://www.readbyqxmd.com/read/28092673/irf7-regulates-the-development-of-granulocytic-myeloid-derived-suppressor-cells-through-s100a9-transrepression-in-cancer
#10
Q Yang, X Li, H Chen, Y Cao, Q Xiao, Y He, J Wei, J Zhou
Accumulation of myeloid-derived suppressor cells (MDSCs) is one of the major obstacles against achieving appropriate anti-tumor immune responses and successful tumor immunotherapy. Granulocytic MDSCs (G-MDSCs) are common in tumor-bearing hosts. However, the mechanisms regulating the development of MDSCs, especially G-MDSCs, remain poorly understood. In this report, we showed that interferon regulatory factor 7 (IRF7) plays an important role in the development of G-MDSCs, but not monocytic MDSCs. IRF7 deficiency caused significant elevation of G-MDSCs, and therefore enhanced tumor growth and metastasis in mice...
January 16, 2017: Oncogene
https://www.readbyqxmd.com/read/28092672/bpgap1-spatially-integrates-jnk-erk-signaling-crosstalk-in-oncogenesis
#11
T Jiang, C Q Pan, B C Low
Simultaneous hyperactivation of stress-activated protein kinase/c-Jun N-terminal protein kinase (SAPK/JNK) and mitogen-activated protein kinase kinase/extracellular signal-regulated kinase (MEK/ERK) signaling cascades has been reported in carcinogenesis. However, how they are integrated to promote oncogenesis remains unknown. By analyzing breast invasive carcinoma database (The Cancer Genome Altas), we found that the mRNA expression levels of both JNK1 and ERK2 are positively correlated with the mRNA level of EEA1, an endosome associated protein, indicating the potential JNK/ERK crosstalk at endosome...
January 16, 2017: Oncogene
https://www.readbyqxmd.com/read/28092671/pde4d-promotes-fak-mediated-cell-invasion-in-braf-mutated-melanoma
#12
J Delyon, A Servy, F Laugier, J André, N Ortonne, M Battistella, S Mourah, A Bensussan, C Lebbé, N Dumaz
The cyclic AMP (cAMP) signaling pathway is critical in melanocyte biology for regulating differentiation. It is downregulated by phosphodiesterase (PDE) enzymes, which degrade cAMP itself. In melanoma evidence suggests that inhibition of the cAMP pathway by PDE type 4 (PDE4) favors tumor progression. For example, in melanomas harboring RAS mutations, the overexpression of PDE4 is crucial for MAPK pathway activation and proliferation induced by oncogenic RAS. Here we showed that PDE4D is overexpressed in BRAF-mutated melanoma cell lines, constitutively disrupting the cAMP pathway activation...
January 16, 2017: Oncogene
https://www.readbyqxmd.com/read/28092670/neuropilin-1-is-upregulated-in-the-adaptive-response-of-prostate-tumors-to-androgen-targeted-therapies-and-is-prognostic-of-metastatic-progression-and-patient-mortality
#13
B W C Tse, M Volpert, E Ratther, N Stylianou, M Nouri, K McGowan, M L Lehman, S J McPherson, M Roshan-Moniri, M S Butler, J Caradec, C Y Gregory-Evans, J McGovern, R Das, M Takhar, N Erho, M Alshalafa, E Davicioni, E M Schaeffer, R B Jenkins, A E Ross, R J Karnes, R B Den, L Fazli, P A Gregory, M E Gleave, E D Williams, P S Rennie, R Buttyan, J H Gunter, L A Selth, P J Russell, C C Nelson, B G Hollier
Recent evidence has implicated the transmembrane co-receptor neuropilin-1 (NRP1) in cancer progression. Primarily known as a regulator of neuronal guidance and angiogenesis, NRP1 is also expressed in multiple human malignancies, where it promotes tumor angiogenesis. However, non-angiogenic roles of NRP1 in tumor progression remain poorly characterized. In this study, we define NRP1 as an androgen-repressed gene whose expression is elevated during the adaptation of prostate tumors to androgen-targeted therapies (ATTs), and subsequent progression to metastatic castration-resistant prostate cancer (mCRPC)...
January 16, 2017: Oncogene
https://www.readbyqxmd.com/read/28092669/interplay-between-epigenetics-and-metabolism-in-oncogenesis-mechanisms-and-therapeutic-approaches
#14
REVIEW
C C Wong, Y Qian, J Yu
Epigenetic and metabolic alterations in cancer cells are highly intertwined. Oncogene-driven metabolic rewiring modifies the epigenetic landscape via modulating the activities of DNA and histone modification enzymes at the metabolite level. Conversely, epigenetic mechanisms regulate the expression of metabolic genes, thereby altering the metabolome. Epigenetic-metabolomic interplay has a critical role in tumourigenesis by coordinately sustaining cell proliferation, metastasis and pluripotency. Understanding the link between epigenetics and metabolism could unravel novel molecular targets, whose intervention may lead to improvements in cancer treatment...
January 16, 2017: Oncogene
https://www.readbyqxmd.com/read/28092668/upregulation-of-ret-induces-perineurial-invasion-of-pancreatic-adenocarcinoma
#15
M Amit, S Na'ara, L Leider-Trejo, Y Binenbaum, N Kulish, E Fridman, A Shabtai-Orbach, R J Wong, Z Gil
Tumor spread along nerves, a phenomenon known as perineurial invasion, is common in various cancers including pancreatic ductal adenocarcinoma (PDAC). Neural invasion is associated with poor outcome, yet its mechanism remains unclear. Using the transgenic Pdx-1-Cre/KrasG12D /p53R172H (KPC) mouse model, we investigated the mechanism of neural invasion in PDAC. To detect tissue-specific factors that influence neural invasion by cancer cells, we characterized the perineurial microenvironment using a series of bone marrow transplantation (BMT) experiments in transgenic mice expressing single mutations in the Cx3cr1, GDNF and CCR2 genes...
January 16, 2017: Oncogene
https://www.readbyqxmd.com/read/28092667/oncogenic-braf-fusions-in-mucosal-melanomas-activate-the-mapk-pathway-and-are-sensitive-to-mek-pi3k-inhibition-or-mek-cdk4-6-inhibition
#16
H S Kim, M Jung, H N Kang, H Kim, C-W Park, S-M Kim, S J Shin, S H Kim, S G Kim, E K Kim, M R Yun, Z Zheng, K Y Chung, J Greenbowe, S M Ali, T-M Kim, B C Cho
Despite remarkable progress in cutaneous melanoma genomic profiling, the mutational landscape of primary mucosal melanomas (PMM) remains unclear. Forty-six PMMs underwent targeted exome sequencing of 111 cancer-associated genes. Seventy-six somatic nonsynonymous mutations in 42 genes were observed, and recurrent mutations were noted on eight genes, including TP53 (13%), NRAS (13%), SNX31 (9%), NF1 (9%), KIT (7%) and APC (7%). Mitogen-activated protein kinase (MAPK; 37%), cell cycle (20%) and phosphatidylinositol 3-kinase (PI3K)-mTOR (15%) pathways were frequently mutated...
January 16, 2017: Oncogene
https://www.readbyqxmd.com/read/28092594/adaptive-trajectory-tracking-of-nonholonomic-mobile-robots-using-vision-based-position-and-velocity-estimation
#17
Luyang Li, Yun-Hui Liu, Tianjiao Jiang, Kai Wang, Mu Fang
Despite tremendous efforts made for years, trajectory tracking control (TC) of a nonholonomic mobile robot (NMR) without global positioning system remains an open problem. The major reason is the difficulty to localize the robot by using its onboard sensors only. In this paper, a newly designed adaptive trajectory TC method is proposed for the NMR without its position, orientation, and velocity measurements. The controller is designed on the basis of a novel algorithm to estimate position and velocity of the robot online from visual feedback of an omnidirectional camera...
January 16, 2017: IEEE Transactions on Cybernetics
https://www.readbyqxmd.com/read/28092529/sub-category-classifiers-for-multiple-instance-learning-and-its-application-to-retinal-nerve-fiber-layer-visibility-classification
#18
Siyamalan Manivannan, Caroline Cobb, Stephen Burgess, Emanuele Trucco
We propose a novel multiple instance learning method to assess the visibility (visible/not visible) of the retinal nerve fiber layer (RNFL) in fundus camera images. Using only image-level labels, our approach learns to classify the images as well as to localize the RNFL visible regions. We transform the original feature space to a discriminative subspace, and learn a region-level classifier in that subspace. We propose a margin-based loss function to jointly learn this subspace and the region-level classifier...
January 16, 2017: IEEE Transactions on Medical Imaging
https://www.readbyqxmd.com/read/28092507/real-time-intravascular-ultrasound-and-photoacoustic-imaging
#19
Donald VanderLaan, Andrei B Karpiouk, Doug Yeager, Stanislav Emelianov
Combined intravascular ultrasound and intravascular photoacoustic (IVUS/IVPA) imaging is an emerging hybrid modality being explored as a means of improving the characterization of atherosclerotic plaque anatomical and compositional features. While initial demonstrations of the technique have been encouraging, they have been limited by catheter rotation and data acquisition, displaying, and processing rates on the order of several seconds per frame as well as the use of off-line image processing. Herein, we present a complete IVUS/IVPA imaging system and method capable of real-time IVUS/IVPA imaging, with online data acquisition, image processing, and display of both IVUS and IVPA images...
January 2017: IEEE Transactions on Ultrasonics, Ferroelectrics, and Frequency Control
https://www.readbyqxmd.com/read/28092496/the-effect-of-contrast-material-on-radiation-dose-at-ct-part-i-incorporation-of-contrast-material-dynamics-in-anthropomorphic-phantoms
#20
Pooyan Sahbaee, W Paul Segars, Daniele Marin, Rendon C Nelson, Ehsan Samei
Purpose To develop a method to incorporate the propagation of contrast material into computational anthropomorphic phantoms for estimation of organ dose at computed tomography (CT). Materials and Methods A patient-specific physiologically based pharmacokinetic (PBPK) model of the human cardiovascular system was incorporated into 58 extended cardiac-torso (XCAT) patient phantoms. The PBPK model comprised compartmental models of vessels and organs unique to each XCAT model. For typical injection protocols, the dynamics of the contrast material in the body were described according to a series of patient-specific iodine mass-balance differential equations, the solutions to which provided the contrast material concentration time curves for each compartment...
January 13, 2017: Radiology
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