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https://www.readbyqxmd.com/read/28733706/phage-display-selection-in-vitro-characterization-and-correlative-pet-imaging-of-a-novel-her3-peptide
#1
Benjamin M Larimer, Nicholas Phelan, Eric Wehrenberg-Klee, Umar Mahmood
PURPOSE: HER3 (ERBB3) is a receptor tyrosine kinase that is implicated in treatment resistance across multiple cancers, including those of the breast, lung, and prostate. Overexpression of HER3 following targeted therapy can occur rapidly and heterogeneously both within a single lesion and across sites of metastasis, making protein quantification by biopsy highly challenging. A global, non-invasive methodology such as positron emission tomography (PET) imaging can permit serial quantification of HER3, providing a useful approach to monitor HER3 expression across the entire tumor burden both prior to and following treatment...
July 21, 2017: Molecular Imaging and Biology: MIB: the Official Publication of the Academy of Molecular Imaging
https://www.readbyqxmd.com/read/28730484/analysis-of-phosphotyrosine-signaling-networks-in-lung-cancer-cell-lines
#2
Malgorzata Broncel, Paul H Huang
Robust isolation and identification of peptides phosphorylated at their tyrosine residues are key steps in deciphering complex signaling networks governed by protein tyrosine kinases, including kinases involved in oncogenesis. Phosphotyrosine (pY)-containing peptides are commonly isolated from cellular lysates by means of antibody and/or metal affinity-based enrichment followed by their identification by mass spectrometry. Herein, we describe robust two-stage isolation of phosphotyrosine peptides and mass spectrometry-aided identification of phosphosites to characterize basal signaling networks in unstimulated non-small cell lung cancer (NSCLC) cell lines...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/28727410/exosomes-mediate-epithelium-mesenchyme-crosstalk-in-organ-development
#3
Nan Jiang, Lusai Xiang, Ling He, Guodong Yang, Jinxuan Zheng, Chenglin Wang, Yimei Zhang, Sainan Wang, Yue Zhou, Tzong-Jen Sheu, Jiaqian Wu, Kenian Chen, Paulo G Coelho, Nicky M Tovar, Shin Hye Kim, Mo Chen, Yan-Heng Zhou, Jeremy J Mao
Organ development requires complex signaling by cells in different tissues. Epithelium and mesenchyme interactions are crucial for the development of the skin, hair follicles, kidney, lungs, prostate, major glands and the teeth. Despite myriad literature on cell-cell interactions and ligand-receptor binding, the roles extracellular vesicles in epithelium-mesenchyme interactions during organogenesis are poorly understood. Here, we discovered that ~100 nm exosomes were secreted by the epithelium and mesenchyme of a developing tooth organ, and diffused through the basement membrane...
July 20, 2017: ACS Nano
https://www.readbyqxmd.com/read/28726253/%C3%AE-9-and-%C3%AE-7-containing-receptors-mediate-the-pro-proliferative-effects-of-nicotine-in-the-a549-adenocarcinoma-cell-line
#4
Vanessa Mucchietto, Francesca Fasoli, Susanna Pucci, Milena Moretti, Roberta Benfante, Annalisa Maroli, Simona Di Lascio, Cristiano Bolchi, Marco Pallavicini, Cheryl Dowell, Michael McIntosh, Francesco Clementi, Cecilia Gotti
BACKGROUND AND PURPOSE: Tobacco smoke contains many classes of carcinogens and although nicotine is unable to initiate tumorigenesis in humans and rodents, it promotes tumour growth and metastasis in lung tumours by acting on neuronal nicotinic acetylcholine receptors (nAChRs). The aim of this study was to identify molecularly, biochemically and pharmacologically which nAChR subtypes are expressed and functionally activated by nicotine in lung cancer cell lines. EXPERIMENTAL APPROACH: We used A549 and H1975 adenocarcinoma cell lines derived from lung tumour to test the in vitro effects of nicotine, and nAChR subtype-specific peptides and compounds...
July 20, 2017: British Journal of Pharmacology
https://www.readbyqxmd.com/read/28725925/characterisation-of-peptide5-systemic-administration-for-treating-traumatic-spinal-cord-injured-rats
#5
Yilin Mao, Tara Nguyen, Ryan S Tonkin, Justin G Lees, Caitlyn Warren, Simon J O'Carroll, Louise F B Nicholson, Colin R Green, Gila Moalem-Taylor, Catherine A Gorrie
Systemic administration of a Connexin43 mimetic peptide, Peptide5, has been shown to reduce secondary tissue damage and improve functional recovery after spinal cord injury (SCI). This study investigated safety measures and potential off-target effects of Peptide5 systemic administration. Rats were subjected to a mild contusion SCI using the New York University impactor. One cohort was injected intraperitoneally with a single dose of fluorescently labelled Peptide5 and euthanised at 2 or 4 h post-injury for peptide distribution analysis...
July 19, 2017: Experimental Brain Research. Experimentelle Hirnforschung. Expérimentation Cérébrale
https://www.readbyqxmd.com/read/28715644/detection-and-identification-of-serum-protein-peak-at-6648%C3%A2-m-z-as-a-novel-indicator-in-breast-cancer-based-on-mass-spectrometry
#6
Dongjian Song, Lifang Yue, Yuxiao Zhan, Junjie Zhang, Zechen Yan, Yingzhong Fan, Heying Yang, Da Zhang, Qiuliang Liu, Ziqiang Xia, Pan Qin, Jia Jia, Ming Yue, Jiekai Yu, Shu Zheng, Fuquan Yang, Jiaxiang Wang
Breast cancer (BC) is the second-leading cause of cancer mortality after lung cancer in women owing partly to a lack of specific and sensitive tests for early screening and monitoring. The detection of novel specific BC serum indicators for screening purposes is an essential clinical need. A total of 437 serum specimens from 310 BC patients that were divided into mining and testing sets were collected in this study. In contrast with the conventional BC indicators through receiver operating characteristic, survival and hazard function curves, and multivariate Cox regression analyses, we intended to hunt for stable protein indicators from serum specimens and identify their diagnostic and prognostic potential for BC...
May 2017: Discovery Medicine
https://www.readbyqxmd.com/read/28715634/a-novel-strategy-utilizing-extracellular-cysteine-rich-domain-of-membrane-receptor-for-constructing-d-peptide-mediated-targeted-drug-delivery-systems-a-case-study-on-fn14
#7
Zhuoxuan Li, Jing Xie, Shan Peng, Sha Liu, Ying Wang, Weiyue Lu, Jie Shen, Chong Li
The development of proteolysis-resistant D-peptide ligands for targeted drug/gene delivery has been greatly limited, due to the challenge lies in the chemical synthesis of membrane receptors without altering their structures. In the present research, a novel strategy utilizing self-stabilized extracellular cysteine-rich domain (CRD) of membrane receptor was developed to construct D-peptide ligands and their mediated targeted drug delivery systems. Fibroblast growth factor-inducible 14 (Fn14), a cell surface receptor overexpressed in many cancers including pancreatic and triple-negative breast cancers, was selected as the model receptor...
July 17, 2017: Bioconjugate Chemistry
https://www.readbyqxmd.com/read/28714690/selective-affinity-enrichment-of-nitrotyrosine-containing-peptides-for-quantitative-analysis-in-complex-samples
#8
Yingxin Zhao, Yueqing Zhang, Hong Sun, Rosario Maroto, Allan R Brasier
Protein tyrosine nitration by oxidative and nitrate stress is important in the pathogenesis of many inflammatory or aging-related diseases. Mass spectrometry analysis of protein nitrotyrosine is very challenging because the non-nitrated peptides suppress the signals of the low-abundance nitrotyrosine (NT) peptides. No validated methods for enrichment of NT-peptides are currently available. Here we report an immunoaffinity enrichment of NT-peptides for proteomics analysis. The effectiveness of this approach was evaluated using nitrated protein standards and whole-cell lysates in vitro...
July 17, 2017: Journal of Proteome Research
https://www.readbyqxmd.com/read/28714174/immunological-properties-and-protective-efficacy-of-a-single-mycobacterial-antigen-displayed-on-polyhydroxybutyrate-beads
#9
Patricia Rubio-Reyes, Natalie A Parlane, Bryce M Buddle, D Neil Wedlock, Bernd H A Rehm
In 2015, there were an estimated 10.4 million new tuberculosis (TB) cases and 1.4 million deaths worldwide. Bacille Calmette-Guérin (BCG), an attenuated strain of Mycobacterium bovis, is the vaccine available against TB, but it is insufficient for global TB control. This study evaluated the immunogenicity of the Mycobacterium tuberculosis antigen Rv1626 in mice while assessing the effect of co-delivering either Cpe30 (immunostimulatory peptide), CS.T3378-395 (promiscuous T helper epitope) or flagellin (TLR5 agonist) or a combination of all three immunostimulatory agents...
July 17, 2017: Microbial Biotechnology
https://www.readbyqxmd.com/read/28710964/design-synthesis-and-biological-studies-of-a-library-of-nk1-receptor-ligands-based-on-a-5-arylthiosubstituted-2-amino-4-6-diaryl-3-cyano-4h-pyran-core-switch-from-antagonist-to-agonist-effect-by-chemical-modification
#10
Rocío Recio, Empar Vengut-Climent, Bernard Mouillac, Hélène Orcel, Miguel López-Lázaro, José Manuel Calderón-Montaño, Eleuterio Álvarez, Noureddine Khiar, Inmaculada Fernández
A library of 5-arylthiosubstituted 2-amino-4,6-diaryl-3-cyano-4H-pyrans has been synthesized as a new family of non-peptide NK1 receptor ligands by a one-pot cascade process. Their biological effects via interaction with the NK1 receptor were experimentally determined as percentage of inhibition (for antagonists) and percentage of activation (for agonists), compared to the substance P (SP) effect, in IPone assay. A set of these amino compounds was found to inhibit the action of SP, and therefore can be considered as a new family of SP-antagonists...
June 28, 2017: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28708592/a-peptidomimetic-with-a-chiral-switch-is-an-inhibitor-of-epidermal-growth-factor-receptor-heterodimerization
#11
Shanthi P Kanthala, Yong-Yu Liu, Sitanshu Singh, Rushikesh Sable, Sandeep Pallerla, Seetharama D Jois
Among different types of EGFR dimers, EGFR-HER2 and HER2-HER3 are well known in different types of cancers. Targeting dimerization of EGFR will have a significant impact on cancer therapies. A symmetric peptidomimetic was designed to inhibit the protein-protein interaction of EGFR. The peptidomimetic (Cyclo(1,10)PpR (R) Anapa-FDDF-(R)-Anapa)R, compound 18) was shown to exhibit antiproliferative activity with an IC50 of 194 nM in HER2-expressing breast cancer cell lines and 18 nM in lung cancer cell lines. The peptidomimetic has a Pro-Pro sequence in the structure to stabilize the β-turn and a β-amino acid, amino napthyl propionic acid...
July 5, 2017: Oncotarget
https://www.readbyqxmd.com/read/28706128/transcriptome-analysis-reveals-a-role-for-the-endothelial-anp-gc-a-signaling-in-interfering-with-pre-metastatic-niche-formation-by-solid-cancers
#12
Takashi Nojiri, Miki Arai, Yutaka Suzuki, Motofumi Kumazoe, Takeshi Tokudome, Koichi Miura, Jun Hino, Hiroshi Hosoda, Mikiya Miyazato, Meinoshin Okumura, Shinpei Kawaoka, Kenji Kangawa
Cancer establishes a microenvironment called the pre-metastatic niche in distant organs where disseminated cancer cells can efficiently metastasize. Pre-metastatic niche formation requires various genetic factors. Previous studies suggest that inhibiting a single niche-factor is insufficient to completely block pre-metastatic niche formation especially in human patients. Here we show that the atrial natriuretic peptide (ANP), an endogenous hormone produced by the heart, inhibits pre-metastatic niche formation and metastasis of murine solid cancer models when pharmacologically supplied in vivo...
May 25, 2017: Oncotarget
https://www.readbyqxmd.com/read/28700781/efficacy-and-safety-of-spironolactone-in-acute-heart-failure-the-athena-hf-randomized-clinical-trial
#13
Javed Butler, Kevin J Anstrom, G Michael Felker, Michael M Givertz, Andreas P Kalogeropoulos, Marvin A Konstam, Douglas L Mann, Kenneth B Margulies, Steven E McNulty, Robert J Mentz, Margaret M Redfield, W H Wilson Tang, David J Whellan, Monica Shah, Patrice Desvigne-Nickens, Adrian F Hernandez, Eugene Braunwald
Importance: Persistent congestion is associated with worse outcomes in acute heart failure (AHF). Mineralocorticoid receptor antagonists administered at high doses may relieve congestion, overcome diuretic resistance, and mitigate the effects of adverse neurohormonal activation in AHF. Objective: To assess the effect of high-dose spironolactone and usual care on N-terminal pro-B-type natriuretic peptide (NT-proBNP) levels compared with usual care alone. Design, Setting, and Participants: This double-blind and placebo (or low-dose)-controlled randomized clinical trial was conducted in 22 US acute care hospitals among patients with AHF who were previously receiving no or low-dose (12...
July 12, 2017: JAMA Cardiology
https://www.readbyqxmd.com/read/28699892/dpp-4-enzyme-deficiency-protects-kidney-from-acute-ischemia-reperfusion-injury-role-for-remote-intermittent-bowel-ischemia-reperfusion-preconditioning
#14
Yen-Ta Chen, Christopher Glenn Wallace, Chih-Chao Yang, Chih-Hung Chen, Kuan-Hung Chen, Pei-Hsun Sung, Yung-Lung Chen, Han-Tan Chai, Sheng-Ying Chung, Sarah Chua, Fan-Yen Lee, Sheung-Fat Ko, Mel S Lee, Hon-Kan Yip
We analyzed the effects of acute ischemia-reperfusion (KIR) injury on the status of kidney function and architecture in dipeptidyl peptidase4-difficient (DPP4D) rats and the effect of remote small bowel ischemia-reperfusion (BIR) preconditioning. DPP4-deficient (DPP4D) and normal Fischer344 (F344) rats were divided into 6 groups: (1) sham-F344, (2) sham-DPP4D, (3) KIR-F344 (4) KIR-DPP4D, (5) DPP4D-KIR-extendin-9-39 and (6) BIR-KIR-F344. Blood creatinine and urea nitrogen levels and the urinary protein-to-creatinine ratio was higher in KIR-F344 rats than BIR-KIR-F344 or KIR-DPP4D rats 72 h after acute KIR...
July 4, 2017: Oncotarget
https://www.readbyqxmd.com/read/28699258/cytotoxic-peptides-with-insulin-releasing-activities-from-skin-secretions-of-the-italian-stream-frog-rana-italica-ranidae
#15
J Michael Conlon, Vishal Musale, Samir Attoub, Maria Luisa Mangoni, Jérôme Leprince, Laurent Coquet, Thierry Jouenne, Yasser H A Abdel-Wahab, Peter R Flatt, Andrea C Rinaldi
Peptidomic analysis of norepinephrine-stimulated skin secretions from Italian stream frog Rana italica led to the purification and characterization of two host-defense peptides differing by a single amino acid residue belonging to the brevinin-1 family (brevinin-1ITa and -1ITb), a peptide belonging to the temporin family (temporin-ITa) and a component identified as prokineticin Bv8. The secretions contained relatively high concentrations of the methionine-sulphoxide forms of brevinin-1ITa and -1ITb suggesting that these peptides may have a role as antioxidants in the skin of this montane frog...
July 11, 2017: Journal of Peptide Science: An Official Publication of the European Peptide Society
https://www.readbyqxmd.com/read/28699173/porous-silicon-nanoparticle-delivery-of-tandem-peptide-anti-infectives-for-the-treatment-of-pseudomonas-aeruginosa-lung-infections
#16
Ester J Kwon, Matthew Skalak, Alessandro Bertucci, Gary Braun, Francesco Ricci, Erkki Ruoslahti, Michael J Sailor, Sangeeta N Bhatia
There is an urgent need for new materials to treat bacterial infections. In order to improve antibacterial delivery, an anti-infective nanomaterial is developed that utilizes two strategies for localization: i) a biodegradable nanoparticle carrier to localize therapeutics within the tissue, and ii) a novel tandem peptide cargo to localize payload to bacterial membranes. First, a library of antibacterial peptides is screened that combines a membrane-localizing peptide with a toxic peptide cargo and discovers a tandem peptide that displays synergy between the two domains and is able to kill Pseudomonas aeruginosa at sub-micromolar concentrations...
July 12, 2017: Advanced Materials
https://www.readbyqxmd.com/read/28695222/ratiometric-in-vivo-auditioning-of-targeted-silver-nanoparticles
#17
Kadri Toome, Anne-Mari A Willmore, Päärn Paiste, Allan Tobi, Kazuki N Sugahara, Kalle Kirsimäe, Erkki Ruoslahti, Gary B Braun, Tambet Teesalu
Attaching affinity ligands to nanoparticles (NPs) increases selectivity for targeting cells and tissues, and can result in improved sensitivity and reduced off-target toxicity in diagnostic and therapeutic systems. The decision over key features - NP size, shape, coating strategies and targeting ligands for clinical translation is often hampered by a lack of quantitative in vivo NP homing assays. Sensitive, internally controlled assays are needed which allow for quantitative comparisons (auditions) among various formulations of targeted NPs...
July 20, 2017: Nanoscale
https://www.readbyqxmd.com/read/28694161/cxcr4-targeted-dendrimer-for-anti-cancer-drug-delivery-and-breast-cancer-cell-migration-inhibition
#18
Chuda Chittasupho, Songyot Anuchapreeda, Narong Sarisuta
CXCR4 and its ligand CXCL12 play a critical role in the metastasis of various types of cancer including breast cancer. Breast tumors preferentially metastasize to the lung, bones and distant lymph nodes, secreting high levels of CXCL12. We hypothesized that targeted inhibition of CXCR4 in breast cancer cells should suppress CXCR4-positive tumor cells toward secondary metastatic sites. In the present study, the efficacy of CXCR4 targeted dendrimers carrying DOX (LFC131-DOX-D4) on cellular binding, cytotoxicity, and migration of BT-549-Luc and T47D breast cancer cells was investigated...
July 7, 2017: European Journal of Pharmaceutics and Biopharmaceutics
https://www.readbyqxmd.com/read/28694069/engineering-aglycosylated-igg-variants-with-wild-type-or-improved-binding-affinity-to-human-fc-gamma-riia-and-fc-gamma-riiias
#19
Tiffany F Chen, Stephen L Sazinsky, Damian Houde, David J DiLillo, Julie Bird, Kevin K Li, George T Cheng, Huawei Qiu, John R Engen, Jeffrey V Ravetch, K Dane Wittrup
The binding of human IgG1 to human Fc gamma receptors (hFcγRs) is highly sensitive to the presence of a single N-linked glycosylation site at asparagine 297 of the Fc, with deglycosylation resulting in a complete loss of hFcγR binding. Previously, we demonstrated that aglycosylated human IgG1 Fc variants can engage the human FcγRII class of the low-affinity hFcγRs, demonstrating that N-linked glycosylation of the Fc is not a strict requirement for hFcγR engagement. In the present study, we demonstrate that aglycosylated IgG variants can be engineered to productively engage with FcγRIIIA, as well as the human Fc gamma RII subset...
July 8, 2017: Journal of Molecular Biology
https://www.readbyqxmd.com/read/28693166/quantitative-analysis-and-clonal-characterization-of-t-cell-receptor-%C3%AE-repertoires-in-patients-with-advanced-non-small-cell-lung-cancer-treated-with-cancer-vaccine
#20
Tu Mai, Atsushi Takano, Hiroyuki Suzuki, Takashi Hirose, Takahiro Mori, Koji Teramoto, Kazuma Kiyotani, Yusuke Nakamura, Yataro Daigo
With the development of cancer immunotherapy that may activate T cells, a practical and quantitative method to improve monitoring and/or prediction of immunological response of patients as a predictive biomarker is of importance. To examine possible biomarkers for a therapeutic cancer vaccine containing a mixture of three epitope peptides derived from cell division-associated 1, lymphocyte antigen 6 complex locus K and insulin-like growth factor-II mRNA-binding protein 3, T-cell receptor β (TCRβ) repertoires of blood samples from 24 patients with human leukocyte antigen-A*2402-positive non-small cell lung cancer were characterized prior to and following 8 weeks of the cancer vaccine treatment, by applying a next-generation sequencing method...
July 2017: Oncology Letters
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