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https://www.readbyqxmd.com/read/28449027/lipoprotein-a-and-the-risk-of-cardiovascular-disease-in-the-european-population-results-from-the-biomarcare-consortium
#1
Christoph Waldeyer, Nataliya Makarova, Tanja Zeller, Renate B Schnabel, Fabian J Brunner, Torben Jørgensen, Allan Linneberg, Teemu Niiranen, Veikko Salomaa, Pekka Jousilahti, John Yarnell, Marco M Ferrario, Giovanni Veronesi, Paolo Brambilla, Stefano G Signorini, Licia Iacoviello, Simona Costanzo, Simona Giampaoli, Luigi Palmieri, Christa Meisinger, Barbara Thorand, Frank Kee, Wolfgang Koenig, Francisco Ojeda, Jukka Kontto, Ulf Landmesser, Kari Kuulasmaa, Stefan Blankenberg
Aims: As promising compounds to lower Lipoprotein(a) (Lp(a)) are emerging, the need for a precise characterization and comparability of the Lp(a)-associated cardiovascular risk is increasing. Therefore, we aimed to evaluate the distribution of Lp(a) concentrations across the European population, to characterize the association with cardiovascular outcomes and to provide high comparability of the Lp(a)-associated cardiovascular risk by use of centrally determined Lp(a) concentrations. Methods and results: Based on the Biomarkers for Cardiovascular Risk Assessment in Europe (BiomarCaRE)-project, we analysed data of 56 804 participants from 7 prospective population-based cohorts across Europe with a maximum follow-up of 24 years...
April 24, 2017: European Heart Journal
https://www.readbyqxmd.com/read/28448782/amcp-partnership-forum-driving-value-and-outcomes-in-oncology
#2
(no author information available yet)
Innovation in cancer treatment has provided a wealth of recently available therapeutic agents and a healthy drug pipeline that promises to change the way we approach this disease and the lives of those affected in the years to come. However, the majority of these new agents, many of which are targeted to specific genomic features of various tumors, may challenge the health care system's ability to afford cancer care. This innovation drives the need to focus on the value of the treatments provided to patients with cancer and on methods to optimize the efficiency of the dollars we spend, in addition to the clinical value itself...
May 2017: Journal of Managed Care & Specialty Pharmacy
https://www.readbyqxmd.com/read/28447703/conserved-effects-and-altered-trafficking-of-cetuximab-antibodies-conjugated-to-gold-nanoparticles-with-precise-control-of-their-number-and-orientation
#3
Lorena García-Fernández, Javier Garcia-Pardo, Olivia Tort, Ian Prior, Mathias Brust, Eudald Casals, Julia Lorenzo, Victor F Puntes
Gold nanoparticles (17 nm) have been functionalized with the antiangiogenic monoclonal antibody drug Cetuximab at a well-defined orientation and coverage density of antibodies. Functionalization has been carried out through site-directed chemistry via the selective oxidation of the carbohydrate moiety of antibodies linked to a thiolated hydrazide. A431 tumor cells have been exposed to these conjugates for in vitro evaluation of their effects. In addition to epithelial growth factor receptor blocking, trafficking and signaling alterations were also observed...
April 27, 2017: Nanoscale
https://www.readbyqxmd.com/read/28447447/nuclear-targeting-gold-nanorods-for-extremely-low-nir-activated-photothermal-therapy
#4
Limin Pan, Jianan Liu, Jianlin Shi
Photo-related nanomedicine is of particular interest as an emerging paradigm toward precise cancer therapy, as demonstrated by the recent developments of photothermal therapy (PTT), an emerging technique employing light converting agents to burn cancerous cells by over-dosed optical energy-converted heat. However, most of the laser irradiations needed for effective PTT significantly exceed the maximal permissible power density in human skin, which is likely to damage surrounding normal tissues. Herein, we report a strategy of intranuclear PTT of cancer enabled by nuclear-targeted delivery of gold nanorods of ~ 10...
April 27, 2017: ACS Applied Materials & Interfaces
https://www.readbyqxmd.com/read/28447115/human-genetics-as-a-model-for-target-validation-finding-new-therapies-for-diabetes
#5
REVIEW
Soren K Thomsen, Anna L Gloyn
Type 2 diabetes is a global epidemic with major effects on healthcare expenditure and quality of life. Currently available treatments are inadequate for the prevention of comorbidities, yet progress towards new therapies remains slow. A major barrier is the insufficiency of traditional preclinical models for predicting drug efficacy and safety. Human genetics offers a complementary model to assess causal mechanisms for target validation. Genetic perturbations are 'experiments of nature' that provide a uniquely relevant window into the long-term effects of modulating specific targets...
April 26, 2017: Diabetologia
https://www.readbyqxmd.com/read/28447000/8th-edition-ajcc-uicc-staging-of-cancers-of-the-esophagus-and-esophagogastric-junction-application-to-clinical-practice
#6
Thomas W Rice, Deepa T Patil, Eugene H Blackstone
The 8th edition of the American Joint Committee on Cancer (AJCC) staging of epithelial cancers of the esophagus and esophagogastric junction (EGJ) presents separate classifications for clinical (cTNM), pathologic (pTNM), and postneoadjuvant (ypTNM) stage groups. Histopathologic cell type markedly affects survival of clinically and pathologically staged patients, requiring separate groupings for each cell type, but ypTNM groupings are identical for both cell types. Clinical categories, typically obtained by imaging with minimal histologic information, are limited by resolution of each method...
March 2017: Annals of Cardiothoracic Surgery
https://www.readbyqxmd.com/read/28446439/pax3-foxo1-establishes-myogenic-super-enhancers-and-confers-bet-bromodomain-vulnerability
#7
Berkley E Gryder, Marielle E Yohe, Hsien-Chao Chou, Xiaohu Zhang, Joana Marques, Marco Wachtel, Beat Schaefer, Nirmalya Sen, Young K Song, Alberto Gualtieri, Silvia Pomella, Rossella Rota, Abigail Cleveland, Xinyu Wen, Sivasish Sindiri, Jun S Wei, Frederic G Barr, Sudipto Das, Thorkell Andresson, Rajarshi Guha, Madhu Lal-Nag, Marc Ferrer, Jack F Shern, Keji Zhao, Craig J Thomas, Javed Khan
Alveolar rhabdomyosarcoma is a life-threatening myogenic cancer of children and adolescent young adults, driven primarily by the chimeric transcription factor PAX3-FOXO1 (P3F). The mechanisms by which P3F dysregulates chromatin are unknown. We find P3F reprograms the cis-regulatory landscape by inducing (de novo) super enhancers (SEs). P3F uses SEs to setup auto-regulatory loops in collaboration with master transcription factors MYOG, MYOD and MYCN. This myogenic SE circuitry is consistent across cell lines and primary tumors...
April 26, 2017: Cancer Discovery
https://www.readbyqxmd.com/read/28446179/glycam1-negatively-regulates-monocyte-entry-into-the-optic-nerve-head-and-contributes-to-radiation-based-protection-in-glaucoma
#8
Pete A Williams, Catherine E Braine, Nicole E Foxworth, Kelly E Cochran, Simon W M John
BACKGROUND: We previously reported a profound long-term neuroprotection subsequent to a single radiation-therapy in the DBA/2J mouse model of glaucoma. This neuroprotection prevents entry of monocyte-like immune cells into the optic nerve head during glaucoma. Gene expression studies in radiation-treated mice implicated Glycam1 in this protection. Glycam1 encodes a proteoglycan ligand for L-selectin and is an excellent candidate to modulate immune cell entry into the eye. Here, we experimentally test the hypothesis that radiation-induced over-expression of Glycam1 is a key component of the neuroprotection...
April 26, 2017: Journal of Neuroinflammation
https://www.readbyqxmd.com/read/28444967/co-delivery-of-microrna-21-antisense-oligonucleotides-and-gemcitabine-using-nanomedicine-for-pancreatic-cancer-therapy
#9
Yaqing Li, Yinting Chen, Jiajia Li, Zuoquan Zhang, Chumei Huang, Guoda Lian, Kege Yang, Shaojie Chen, Ying Lin, Lingyun Wang, Kaihong Huang, Linjuan Zeng
Tumor metastasis occurs naturally in pancreatic cancer, and the efficacy of chemotherapy is usually poor. Precision medicine, combining down-regulation of target genes with chemotherapy drugs, is expected to improve the therapeutic effects. Therefore, we developed a combined therapy of microRNA-21 antisense oligonucleotides (ASO-miR-21) and Gemcitabine (Gem) using a targeted co-delivery nanoparticle (NP) carrier and investigated the synergistic inhibitory effects on pancreatic cancer cells metastasis and growth...
April 26, 2017: Cancer Science
https://www.readbyqxmd.com/read/28444740/chronic-lymphocytic-leukaemia-genomics-and-the-precision-medicine-era
#10
REVIEW
Hussein Ghamlouch, Florence Nguyen-Khac, Olivier A Bernard
Massive genomic analyses have underscored the diversity of chronic lymphocytic leukaemia (CLL) between patients. Genetic heterogeneity of tumour clones within a patient may fuel tumour evolution. Several recurrently deregulated intra-cellular pathways are candidates for targeted therapies that are very promising and are dramatically changing clinical patients' perspectives. In this review we present an overview of the genetic and epigenetic features of CLL and their clinical and biological implications.
April 25, 2017: British Journal of Haematology
https://www.readbyqxmd.com/read/28443327/acidity-triggered-tumor-retention-internalization-of-chimeric-peptide-for-enhanced-photodynamic-therapy-and-real-time-monitoring-of-therapeutic-effects
#11
Kai Han, Wei-Yun Zhang, Zhao-Yu Ma, Shi-Bo Wang, Lu-Ming Xu, Jia Liu, Xianzheng Zhang, Heyou Han
Photodynamic therapy (PDT) holds great promise in tumor treatment. Nevertheless, it remains highly desirable to develop easy-to-fabricated PDT systems with improved tumor accumulation/internalization and timely therapeutic feedback. Here, we report a tumor acidity responsive chimeric peptide for enhanced PDT and noninvasively real-time apoptosis imaging. Both in vitro and in vivo studies revealed that tumor mildly acidic microenvironment could trigger rapid protonation of carboxylate anion in chimeric peptide, which led to increased zeta potential, improved hydrophobicity, controlled size enlargement and precise morphology switch from sphere to spherocylinder shape of chimeric peptide...
April 26, 2017: ACS Applied Materials & Interfaces
https://www.readbyqxmd.com/read/28443282/imprecision-in-the-era-of-precision-medicine-in-non-small-cell-lung-cancer
#12
REVIEW
Raghav Sundar, Maxime Chénard-Poirier, Dearbhaile Catherine Collins, Timothy A Yap
Over the past decade, major advances have been made in the management of advanced non-small cell lung cancer (NSCLC). There has been a particular focus on the identification and targeting of putative driver aberrations, which has propelled NSCLC to the forefront of precision medicine. Several novel molecularly targeted agents have now achieved regulatory approval, while many others are currently in late-phase clinical trial testing. These antitumor therapies have significantly impacted the clinical outcomes of advanced NSCLC and provided patients with much hope for the future...
2017: Frontiers in Medicine
https://www.readbyqxmd.com/read/28442560/obesity-and-menopause-modify-the-epigenomic-profile-of-breast-cancer
#13
Ana B Crujeiras, Angel Díaz-Lagares, Olafur A Stefansson, Manuel Macias, Juan Sandoval, Juan Cueva, Rafael López-López, Sebastian Moran, Jon G Jonasson, Laufey Tryggvadottir, Elinborg Olafsdottir, Francisco J Tinahones, Marcos C Carreira, Felipe F Casanueva, Manel Esteller
Obesity is a high risk factor for breast cancer. This relationship could be marked by a specific methylome. The current work was aimed to explore the impact of obesity and menopausal status on variation in breast cancer methylomes. Data from Infinium 450K array-based methylomes of 64 breast tumor were coupled with information on BMI and menopausal status. Additionally, DNA methylation results were validated in 18 non-tumor and 81 tumor breast samples. Breast tumors arising in either pre- or postmenopausal women stratified by BMI or menopausal status alone were not associated with a specific DNA methylation pattern...
April 25, 2017: Endocrine-related Cancer
https://www.readbyqxmd.com/read/28442401/trib3-downregulation-enhances-doxorubicin-induced-cytotoxicity-in-gastric-cancer-cells
#14
I-Jung Wu, Rong-Jaan Lin, Hsin-Chiao Wang, Tein-Ming Yuan, Show-Mei Chuang
TRIB3, which is a pseudokinase known to regulate multiple pro-survival pathways, appears to be a potential therapeutic target for the treatment of human tumors. However, its precise role in cancer is controversial, as TRIB3 protein levels have been associated with both good and poor prognosis in cancer patients. Here, we investigated the significance of TRIB3 expression in the survival of gastric cancer cells exposed to anticancer drugs. We found that the tested anticancer drug, doxorubicin, induced cytotoxicity by decreasing TRIB3 transcription, which was followed by apoptotic cell death...
April 22, 2017: Archives of Biochemistry and Biophysics
https://www.readbyqxmd.com/read/28442071/observational-practice-of-incentive-spirometry-in-stroke-patients
#15
Íllia N D F Lima, Guilherme A F Fregonezi, Rêncio B Florêncio, Tânia F Campos, Gardênia H Ferreira
BACKGROUND: Stroke may lead to several health problems, but positive effects can be promoted by learning to perform physical therapy techniques correctly. OBJECTIVE: To compare two different types of observational practice (video instructions and demonstration by a physical therapist) during the use of incentive spirometry (IS). METHOD: A total of 20 patients with diagnosis of stroke and 20 healthy individuals (56±9.7 years) were allocated into two groups: one with observational practice with video instructions for the use of IS and the other with observational practice with demonstration by a physical therapist...
January 2017: Brazilian Journal of Physical Therapy
https://www.readbyqxmd.com/read/28439796/adjuvant-endocrine-therapy-in-breast-cancer-evolving-paradigms-in-premenopausal-women
#16
REVIEW
Lorenzo Rossi, Olivia Pagani
In the last few years, new adjuvant endocrine treatment options have become available in young women with early breast cancer, such as the addition of ovarian function suppression to tamoxifen or aromatase inhibitors. Treatment duration has been also adapted in the latest guidelines based on the individual risk of recurrence. The oncologist is therefore challenged to precisely assess the risk of recurrence according to currently available predictive and prognostic factors in order to offer the most appropriate therapeutic option to the individual patient, considering also potential side effects, quality of life, pregnancy planning and patients' preferences...
May 2017: Current Treatment Options in Oncology
https://www.readbyqxmd.com/read/28439535/a-murine-preclinical-syngeneic-transplantation-model-for-breast-cancer-precision-medicine
#17
Lorenzo Federico, Zechen Chong, Dong Zhang, Daniel J McGrail, Wei Zhao, Kang Jin Jeong, Christopher P Vellano, Zhenlin Ju, Mihai Gagea, Shuying Liu, Shreya Mitra, Jennifer B Dennison, Philip L Lorenzi, Robert Cardnell, Lixia Diao, Jing Wang, Yiling Lu, Lauren A Byers, Charles M Perou, Shiaw-Yih Lin, Gordon B Mills
We previously demonstrated that altered activity of lysophosphatidic acid in murine mammary glands promotes tumorigenesis. We have now established and characterized a heterogeneous collection of mouse-derived syngeneic transplants (MDSTs) as preclinical platforms for the assessment of personalized pharmacological therapies. Detailed molecular and phenotypic analyses revealed that MDSTs are the most heterogeneous group of genetically engineered mouse models (GEMMs) of breast cancer yet observed. Response of MDSTs to trametinib, a mitogen-activated protein kinase (MAPK) kinase inhibitor, correlated with RAS/MAPK signaling activity, as expected from studies in xenografts and clinical trials providing validation of the utility of the model...
April 2017: Science Advances
https://www.readbyqxmd.com/read/28439497/study-of-recombinant-human-interleukin-12-for-treatment-of-complications-after-radiotherapy-for-tumor-patients
#18
Na Guo, Wen-Qin Wang, Xiao-Jing Gong, Lei Gao, Li-Rong Yang, Wei-Na Yu, Hong-Yu Shen, Ling-Qin Wan, Xi-Feng Jia, Yi-Shan Wang, Yi Zhao
AIM: To evaluate the treatment effects of recombinant human interleukin-12 (rhIL-12) on radiotherapy complications, such as severe myelosuppression or pancytopenia, the decline or imbalance of immune function, etc. METHODS: The patients received high-dose and short-course precise radiotherapy, such as Cyber knife and image-guided radiotherapy (IGRT), which can cause myelosuppression or pancytopenia and immune function decline within a short time. One-hundred subjects were enrolled in the study, and 50 were randomized to a treatment group which used rhIL-12 and 50 were randomized to a control group which used symptomatic and supportive therapy after radiotherapy...
April 10, 2017: World Journal of Clinical Oncology
https://www.readbyqxmd.com/read/28439040/the-impact-of-membrane-phospholipid-alterations-in-escherichia-coli-on-cellular-function-and-bacterial-stress-adaptation
#19
Veronica W Rowlett, Venkata K P S Mallampalli, Anja Karlstaedt, William Dowhan, Heinrich Taegtmeyer, William Margolin, Heidi Vitrac
Bacteria have evolved multiple strategies to sense and rapidly adapt to challenging and ever-changing environmental conditions. The ability to alter membrane lipid composition, a key component of the cellular envelope, is crucial for bacterial survival and adaptation in response to environmental stress. However, the precise roles played by membrane phospholipids in bacterial physiology and stress adaptation are not fully elucidated. The goal of this study was to define the role of membrane phospholipids in adaptation to stress and maintenance of bacterial cell fitness...
April 24, 2017: Journal of Bacteriology
https://www.readbyqxmd.com/read/28438436/effects-of-dextran-sulfate-sodium-induced-experimental-colitis-on-cytochrome-p450-activity-in-rat-liver-kidney-and-intestine
#20
Nan Hu, Yanjuan Huang, Xuejiao Gao, Sai Li, Zhixiang Yan, Bin Wei, Ru Yan
Dextran sulfate sodium (DSS) induced experimental colitis presents a histologic resemblance to human ulcerative colitis (UC). Altered cytochrome P450s (CYPs) have been reported in this model and patients with UC. In this study, six CYPs activities were quantitatively determined in microsomes of liver (RLMs), kidney (RRMs) and intestine (RIMs) from rats with colitis at acute (5% DSS for 7 days, UCA) and remission (7-day DSS treatment followed by 7-day cessation, UCR) phases and compared with normal rats. Generally, CYPs activities varied with isoform, organ, and disease status...
April 21, 2017: Chemico-biological Interactions
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