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https://www.readbyqxmd.com/read/28549153/chippi-a-novel-method-for-mapping-chimeric-protein-protein-interactions-uncovers-selection-principles-of-protein-fusion-events-in-cancer
#1
Milana Frenkel-Morgenstern, Alessandro Gorohovski, Somnath Tagore, Vaishnovi Sekar, Miguel Vazquez, Alfonso Valencia
Fusion proteins, comprising peptides deriving from the translation of two parental genes, are produced in cancer by chromosomal aberrations. The expressed fusion protein incorporates domains of both parental proteins. Using a methodology that treats discrete protein domains as binding sites for specific domains of interacting proteins, we have cataloged the protein interaction networks for 11 528 cancer fusions (ChiTaRS-3.1). Here, we present our novel method, chimeric protein-protein interactions (ChiPPI) that uses the domain-domain co-occurrence scores in order to identify preserved interactors of chimeric proteins...
May 26, 2017: Nucleic Acids Research
https://www.readbyqxmd.com/read/28549108/longitudinal-associations-between-vitamin-d-metabolites-and-sarcopenia-in-older-australian-men-the-concord-health-and-aging-in-men-project
#2
Vasant Hirani, Robert G Cumming, Vasi Naganathan, Fiona Blyth, David G Le Couteur, Benjumin Hsu, David J Handelsman, Louise M Waite, Markus J Seibel
Background: To explore the associations between serum 25-hydroxyvitamin D (25D) and 1,25-dihydroxyvitamin D (1,25D) levels at baseline and incidence of sarcopenia over time in older Australian community-dwelling older men. Methods: Of the 1,705 men aged ≥70 years (2005-2007) participating in the Concord Health and Ageing in Men Project, those without sarcopenia at baseline (n = 1,312 for 25D and n = 1,231 for 1,25D), 2 years (n = 1,024 for 25D and n = 956 for 1,25D), and 5-year follow-up (n = 709 for 25D and n = 663 for 1,25D) were included in the study...
May 25, 2017: Journals of Gerontology. Series A, Biological Sciences and Medical Sciences
https://www.readbyqxmd.com/read/28548967/detection-of-activating-and-acquired-resistant-mutation-in-plasma-from-egfr-mutated-nsclc-patients-by-peptide-nucleic-acid-pna-clamping-assisted-fluorescence-melting-curve-analysis
#3
Chang Gon Kim, Hyo Sup Shim, Min Hee Hong, Yoon Jin Cha, Su Jin Heo, Hyung Soon Park, Jee Hung Kim, Jin Gu Lee, Chang Young Lee, Byoung Chul Cho, Hye Ryun Kim
This study was designed to prospectively examine whether peptide nucleic acid clamping-assisted fluorescence melting curve analysis (PANAMutyper™) is feasible for the detection of activating and acquired resistant epidermal growth factor receptor (EGFR) mutation in plasma. Patients with non-small cell lung cancer harboring activating EGFR mutations who were scheduled to undergo EGFR-tyrosine kinase inhibitors (EGFR-TKIs) were enrolled between September 2011 and March 2015. A total of 102 patients with EGFR-mutated lung cancer were enrolled, 53 had available plasma samples at disease progression, and 28 underwent serial plasma sampling during EGFR-TKI treatment...
May 10, 2017: Oncotarget
https://www.readbyqxmd.com/read/28548236/renal-functional-outcomes-in-patients-undergoing-percutaneous-cryoablation-or-partial-nephrectomy-for-a-solitary-renal-mass
#4
Ross J Mason, Thomas D Atwell, Christine Lohse, Bimal Bhindi, Adam Weisbrod, Stephen A Boorjian, Bradley C Leibovich, Grant D Schmit, R Houston Thompson
OBJECTIVES: To compare renal functional changes after percutaneous cryoablation (CA) or partial nephrectomy (PN). PATIENTS AND METHODS: Patients who underwent CA or PN for a solitary renal mass at a single institution were identified (2003-2013). Estimated glomerular filtration rates (eGFR) were calculated at baseline, discharge, and 3 months follow-up using the Chronic Kidney Disease Epidemiology Collaboration equation. Changes in renal function were compared between groups using 1:1 propensity score (PS) matching, adjustment for PS quintile, and inverse probability weighting (IPW)...
May 26, 2017: BJU International
https://www.readbyqxmd.com/read/28548166/biomass-involved-synthesis-of-n-substituted-benzofuro-2-3-d-pyrimidine-4-amines-and-biological-evaluation-as-novel-egfr-tyrosine-kinase-inhibitors
#5
Jianfei Sheng, Zhihong Liu, Ming Yan, Xuejing Zhang, Dejian Wang, Jun Xu, Ensheng Zhang, Yong Zou
Shikimic acid (1) is a renewable biomass which could be obtained sustainably through natural product isolation or metabolic engineering. Owing to its great potential in chemical conversion, the value-added utilization of this non-grain biomass has received much attention in recent years. Based on the established transformation route from shikimic acid (1) to methyl 3-dehydroshikimate (3-MDHS, 2) and to the multi-functionalized methyl 2-amino-3-cyanobenzofuran-5-carboxylate (3), we disclose a facile and transition metal-free method to access a series of N-substituted benzofuro[2,3-d]pyrimidine-4-amines in 63%-90% yields...
May 26, 2017: Organic & Biomolecular Chemistry
https://www.readbyqxmd.com/read/28548128/genomic-profiling-of-breast-secretory-carcinomas-reveals-distinct-genetics-from-other-breast-cancers-and-similarity-to-mammary-analog-secretory-carcinomas
#6
Gregor Krings, Nancy M Joseph, Gregory R Bean, David Solomon, Courtney Onodera, Eric Talevich, Iwei Yeh, James P Grenert, Elizabeth Hosfield, Emily D Crawford, Richard C Jordan, Annemieke van Zante, Charles Zaloudek, Sandra J Shin, Yunn-Yi Chen
Secretory carcinomas of the breast are rare tumors with distinct histologic features, recurrent t(12;15)(p13;q25) translocation resulting in ETV6-NTRK3 gene fusion and indolent clinical behavior. Mammary analog secretory carcinomas arising in other sites are histopathologically similar to the breast tumors and also harbor ETV6-NTRK3 fusions. Breast secretory carcinomas are often triple (estrogen and progesterone receptor, HER2) negative with a basal-like immunophenotype. However, genomic studies are lacking, and whether these tumors share genetic features with other basal and/or triple negative breast cancers is unknown...
May 26, 2017: Modern Pathology: An Official Journal of the United States and Canadian Academy of Pathology, Inc
https://www.readbyqxmd.com/read/28546520/-omic-approach-in-non-smoker-female-with-lung-squamous-cell-carcinoma-pinpoints-to-germline-susceptibility-and-personalized-medicine
#7
Margherita Baldassarri, Chiara Fallerini, Francesco Cetta, Marco Ghisalberti, Cristiana Bellan, Simone Furini, Ottavia Spiga, Sergio Crispino, Giuseppe Gotti, Francesca Ariani, Piero Paladini, Alessandra Renieri, Elisa Frullanti
Purpose: Lung cancer is strongly associated to tobacco smoking. However, global statistics estimate that in females the proportion of lung cancer cases that is unrelated to tobacco smoking reaches fifty percent, making questionable the etiology of the disease. Materials and Methods: A never-smoker female with primary EGFR/KRAS/ALK-negative squamous cell carcinoma of the lung and their normal sibs were subjected to a novel integrative "omic" approach using a pedigree-based model for discovering genetic factors leading to cancer in the absence of well-known environmental trigger...
May 26, 2017: Cancer Research and Treatment: Official Journal of Korean Cancer Association
https://www.readbyqxmd.com/read/28546442/post-transplant-hypophosphatemia-and-the-risk-of-death-censored-graft-failure-and-mortality-after-kidney-transplantation
#8
Marco van Londen, Brigitte M Aarts, Petronella E Deetman, Jessica van der Weijden, Michele F Eisenga, Gerjan Navis, Stephan J L Bakker, Martin H de Borst
BACKGROUND AND OBJECTIVES: Hypophosphatemia is common in the first year after kidney transplantation, but its clinical implications are unclear. We investigated the relationship between the severity of post-transplant hypophosphatemia and mortality or death-censored graft failure in a large cohort of renal transplant recipients with long-term follow-up. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: We performed a longitudinal cohort study in 957 renal transplant recipients who were transplanted between 1993 and 2008 at a single center...
May 25, 2017: Clinical Journal of the American Society of Nephrology: CJASN
https://www.readbyqxmd.com/read/28546440/albuminuria-proteinuria-and-renal-disease-progression-in-children-with-ckd
#9
Dana Y Fuhrman, Michael F Schneider, Katherine M Dell, Tom D Blydt-Hansen, Robert Mak, Jeffrey M Saland, Susan L Furth, Bradley A Warady, Marva M Moxey-Mims, George J Schwartz
BACKGROUND AND OBJECTIVES: The role of albuminuria as an indicator of progression has not been investigated in children with CKD in the absence of diabetes. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: Children were enrolled from 49 centers of the CKD in Children study between January of 2005 and March of 2014. Cross-sectional multivariable linear regression (n=647) was used to examine the relationship between urine protein-to-creatinine (UP/C [milligrams per milligram]) and albumin-to-creatinine (ACR [milligrams per gram]) with eGFR (milliliters per minute per 1...
May 25, 2017: Clinical Journal of the American Society of Nephrology: CJASN
https://www.readbyqxmd.com/read/28546016/timing-on-echocardiography-and-blood-laboratory-test-is-important-for-future-outcome-association-in-hospitalized-heart-failure-patients
#10
Li-Tan Yang, Yuichiro Kado, Yasufumi Nagata, Kyoko Otani, Yutaka Otsuji, Masaaki Takeuchi
BACKGROUND: We investigated whether both echocardiography and blood examination parameters obtained before discharge are more closely associated with adverse events than those obtained upon admission in hospitalized heart failure (HF) patients. METHODS: We retrospectively selected 267 hospitalized HF patients who underwent comprehensive transthoracic echocardiography (TTE) within 2 days of admission (n=223) and/or within 7 days of discharge (n=157). Blood test results were also collected at the same time window...
May 22, 2017: Journal of Cardiology
https://www.readbyqxmd.com/read/28545850/renal-response-to-intravascular-volume-expansion-in-euvolemic-heart-failure-patients-with-reduced-ejection-fraction-mechanistic-insights-and-clinical-implications
#11
Petra Nijst, Frederik H Verbrugge, Pieter Martens, Matthias Dupont, W H Wilson Tang, Wilfried Mullens
BACKGROUND: Untreated and preclinical heart failure patients with reduced ejection fraction (HFrEF) have an impaired ability to alleviate excess intravascular volume. OBJECTIVES: To investigate 1) the renal response to intravascular volume expansion in euvolemic and optimally treated HFrEF patients and 2) loop diuretic efficiency. METHODS: 14 healthy and 28 HFrEF patients underwent intravascular volume expansion with 1l hydroxyl ethyl starch 6% during 3h after which a loop diuretic was administered...
May 14, 2017: International Journal of Cardiology
https://www.readbyqxmd.com/read/28545627/impact-of-renal-function-on-survival-after-cardiac-resynchronization-therapy
#12
J Alvin Kpaeyeh, Laura Divoky, J Madison Hyer, David D Daly, Anbukarasi Maran, Ashley Waring, Michael R Gold
Chronic kidney disease (CKD) is associated with worse survival in patients with heart disease including those with implantable devices. Cardiac resynchronization therapy (CRT) can potentially improve renal function. To assess the relation between the change in renal function and survival with CRT, 238 patients undergoing initial CRT with defibrillator implantation between 2002 and 2011 were followed. The primary end point was all-cause mortality. The estimated glomerular filtration rate (eGFR), before implantation and 6 ± 3 months after CRT was calculated...
April 27, 2017: American Journal of Cardiology
https://www.readbyqxmd.com/read/28545469/age-related-terminal-duct-lobular-unit-involution-in-benign-tissues-from-chinese-breast-cancer-patients-with-luminal-and-triple-negative-tumors
#13
Changyuan Guo, Hyuna Sung, Shan Zheng, Jennifer Guida, Erni Li, Jing Li, Nan Hu, Joseph Deng, Jonine D Figueroa, Mark E Sherman, Gretchen L Gierach, Ning Lu, Xiaohong R Yang
BACKGROUND: Terminal duct lobular unit (TDLU) involution is a physiological process of breast tissue aging characterized by a reduction in the epithelial component. In studies of women with benign breast disease, researchers have found that age-matched women with lower levels of TDLU involution are at increased risk of developing breast cancer. We previously showed that breast cancer cases with core basal phenotype (CBP; estrogen receptor negative [ER(-)], progesterone receptor-negative [PR(-)], human epidermal growth factor receptor 2-negative [HER2(-)], cytokeratins (CK 5 or CK5/6)-positive [CK5/6(+)] and/or epidermal growth factor receptor-positive [EGFR(+)]) tumors had significantly reduced TDLU involution compared with cases with luminal A (ER(+) and/or PR(+), HER2(-), CK5/6(-), EGFR(-)) tumors from a population-based case-control study in Poland...
May 25, 2017: Breast Cancer Research: BCR
https://www.readbyqxmd.com/read/28544974/cetuximab-modified-collagen-scaffold-directs-neurogenesis-of-injury-activated-endogenous-neural-stem-cells-for-acute-spinal-cord-injury-repair
#14
Xing Li, Yannan Zhao, Shixiang Cheng, Sufang Han, Muya Shu, Bing Chen, Xuyi Chen, Fengwu Tang, Nuo Wang, Yue Tu, Bin Wang, Zhifeng Xiao, Sai Zhang, Jianwu Dai
Studies have shown that endogenous neural stem cells (NSCs) activated by spinal cord injury (SCI) primarily generate astrocytes to form glial scar. The NSCs do not differentiate into neurons because of the adverse microenvironment. In this study, we defined the activation timeline of endogenous NSCs in rats with severe SCI. These injury-activated NSCs then migrated into the lesion site. Cetuximab, an EGFR signaling antagonist, significantly increased neurogenesis in the lesion site. Meanwhile, implanting cetuximab modified linear ordered collagen scaffolds (LOCS) into SCI lesion sites in dogs resulted in neuronal regeneration, including neuronal differentiation, maturation, myelination, and synapse formation...
May 18, 2017: Biomaterials
https://www.readbyqxmd.com/read/28544778/differential-regulation-of-protein-tyrosine-kinase-signaling-by-dock-and-the-ptp61f-variants
#15
Lee F Willoughby, Jan Manent, Kirsten Allan, Han Lee, Marta Portela, Florian Wiede, Coral Warr, Tzu-Ching Meng, Tony Tiganis, Helena E Richardson
Tyrosine phosphorylation-dependent signalling is coordinated by the opposing actions of protein tyrosine kinases (PTKs) and protein tyrosine phosphatases (PTPs). There is a growing list of adaptor proteins that interact with PTPs and facilitate the dephosphorylation of substrates. The extent to which any given adaptor confers selectivity for any given substrate in vivo remains unclear. Here we have taken advantage of Drosophila melanogaster as a model organism to explore the influence of the SH3/SH2 adaptor protein Dock on the abilities of the membrane (PTP61Fm)- and nuclear (PTP61Fn)-targeted variants of PTP61F (the Drosophila othologue of the mammalian enzymes PTP1B and TCPTP respectively) to repress PTK signaling pathways in vivo...
May 23, 2017: FEBS Journal
https://www.readbyqxmd.com/read/28544624/pyrimidine-containing-epidermal-growth-factor-receptor-kinase-inhibitors-synthesis-and-biological-evaluation
#16
Gaurav Joshi, Himanshu Nayyar, Sourav Kalra, Praveen Sharma, Anjana Munshi, Sandeep Singh, Raj Kumar
Structure based design and synthesis of pyrimidine containing reversible epidermal growth factor receptor (EGFR) inhibitors 1a-d are reported. The compounds (1a-d) inhibited the EGFR kinase activity in vitro with IC50 range 740 nM to 3 μM. mRNA expression of EGFR downstream target genes i.e. twist, c-fos and aurora were found to be altered upon treatment with compounds 1a-d. The compounds 1a-d exhibited excellent anticancer activity at low micromolar level (3.2-9 μM) in lung, colon and breast cancer cell lines...
May 23, 2017: Chemical Biology & Drug Design
https://www.readbyqxmd.com/read/28544101/belatacept-combined-with-transient-calcineurin-inhibitor-therapy-prevents-rejection-and-promotes-improved-long-term-renal-allograft-function
#17
A B Adams, J Goldstein, C Garrett, R Zhang, R E Patzer, K A Newell, N A Turgeon, A S Chami, A Guasch, A D Kirk, S O Pastan, T C Pearson, C P Larsen
Belatacept, a T cell costimulation-blocker demonstrated superior renal function, lower cardiovascular risk, and improved graft/patient survival in renal transplant recipients. Despite the potential benefits, adoption of belatacept has been limited in part due to concerns regarding higher rates and grades of acute rejection in clinical trials. Since July 2011 we have utilized belatacept-based immunosuppression regimens in clinical practice. In this retrospective analysis of 745 patients undergoing renal transplantation at our center, we compared patients treated with belatacept (n=535) to a historical cohort receiving a tacrolimus-based protocol (n=205)...
May 23, 2017: American Journal of Transplantation
https://www.readbyqxmd.com/read/28544061/survival-difference-according-to-mutation-status-in-a-prospective-cohort-study-of-australian-patients-with-metastatic-non-small-cell-lung-carcinoma-nsclc
#18
Lavinia Tan, Marliese Alexander, Ann Officer, Michael MacManus, Linda Mileshkin, Ross Jennens, Dishan Herath, Richard de Boer, Stephen B Fox, David Ball, Benjamin Solomon
BACKGROUND AND OBJECTIVE: Non-small cell lung cancer (NSCLC) is a heterogeneous disease comprising not only different histologic subtypes but also different molecular subtypes. Our objective is to describe the frequency of oncogenic drivers in patients with metastatic NSCLC, the proportion of patients tested and survival difference according to mutation status in a single-institution study. METHODS: Metastatic NSCLC patients enrolled onto a prospective Thoracic Malignancies Cohort (TMC) Study between July 2012 and August 2016 were selected...
May 24, 2017: Internal Medicine Journal
https://www.readbyqxmd.com/read/28544031/ubiquitin-specific-protease-8-is-a-novel-prognostic-marker-in-early-stage-lung-adenocarcinoma
#19
Yunjung Kim, Aya Shiba-Ishii, Tomoki Nakagawa, Ryan Edbert Husni, Shingo Sakashita, Tomoyo Takeuchi, Masayuki Noguchi
Alterations of epidermal growth factor receptor (EGFR) expression frequently occur in early-stage lung adenocarcinoma. Ubiquitin-specific protease 8 (USP8) has been reported to stabilize EGFR protein at the plasma membrane through the recycling pathway. Here, we examined the correlation between USP8 expression and the expression or mutation status of EGFR, as well as the clinicopathological features of lung adenocarcinoma and patient outcome. Expression of EGFR and USP8 in surgically resected specimens of lung adenocarcinoma (82 cases) was examined by immunohistochemistry...
May 19, 2017: Pathology International
https://www.readbyqxmd.com/read/28542269/the-small-molecule-kinase-inhibitor-d11-counteracts-17-aag-mediated-up-regulation-of-hsp70-in-brain-cancer-cells
#20
Susanne Schaefer, Tina H Svenstrup, Barbara Guerra
Many types of cancer express high levels of heat shock proteins (HSPs) that are molecular chaperones regulating protein folding and stability ensuring protection of cells from potentially lethal stress. HSPs in cancer cells promote survival, growth and spreading even in situations of growth factors deprivation by associating with oncogenic proteins responsible for cell transformation. Hence, it is not surprising that the identification of potent inhibitors of HSPs, notably HSP90, has been the primary research focus, in recent years...
2017: PloS One
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