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https://www.readbyqxmd.com/read/28922848/aggressive-behavior-in-silent-subtype-iii-pituitary-adenomas-may-depend-on-suppression-of-local-immune-response-a-whole-transcriptome-analysis
#1
Timothy E Richardson, Zhong-Jian Shen, Mohammed Kanchwala, Chao Xing, Alexander Filatenkov, Ping Shang, Samuel Barnett, Zahidur Abedin, James S Malter, Jack M Raisanen, Dennis K Burns, Charles L White, Kimmo J Hatanpaa
Silent subtype III pituitary adenomas (SS-3) are clinically nonfunctional adenomas that are more aggressive in terms of invasion and risk of recurrence than their conventional null cell counterparts. We previously showed that these tumors can be distinguished by immunohistochemistry based on the identification of a markedly enlarged and fragmented Golgi apparatus. To understand the molecular correlates of differential aggressiveness, we performed whole transcriptome sequencing (RNAseq) on 4 SS-3 and 4 conventional null cell adenomas...
October 1, 2017: Journal of Neuropathology and Experimental Neurology
https://www.readbyqxmd.com/read/28922577/functional-n-formyl-peptide-receptor-2-fpr2-antagonists-based-on-ureidopropanamide-scaffold-have-potential-to-protect-against-inflammation-associated-oxidative-stress
#2
Madia Letizia Stama, Enza Lacivita, Liliya N Kirpotina, Mauro Niso, Roberto Perrone, Igor A Schepetkin, Mark T Quinn, Marcello Leopoldo
Formyl peptide receptor-2 (FPR2) is a G protein-coupled receptor belonging to the N-formyl peptide receptor (FPR) family that plays critical roles in peripheral and brain inflammatory responses. FPR2 has been proposed as a target for the development of drugs that could facilitate the resolution of chronic inflammatory reactions by enhancing endogenous anti-inflammation systems. Starting from the structure of the FPR2 agonists (R)- and (S)-4 and 2, we designed a new series of ureidopropanamide derivatives with the goal of converting functional activity from agonism to antagonism and to develop new FPR2 antagonists...
September 18, 2017: ChemMedChem
https://www.readbyqxmd.com/read/28922150/synthesis-radiosynthesis-and-preliminary-in-vitro-and-in-vivo-evaluation-of-the-fluorinated-ceramide-trafficking-inhibitor-hpa-12-for-brain-applications
#3
Simone M Crivelli, Andreas Paulus, Jozef Markus, Matthias Bauwens, Dusan Berkes, Helga E De Vries, Monique T Mulder, Jochen Walter, Felix M Mottaghy, Mario Losen, Pilar Martinez-Martinez
Ceramide levels are increased in blood and brain tissue of Alzheimer's disease (AD) patients. Since the ceramide transporter protein (CERT) is the only known protein able to mediate non-vesicular transfer of ceramide between organelle membranes, the modulation of CERT function may impact on ceramide accumulation. The competitive CERT inhibitor N-(3-hydroxy-1-hydroxymethyl-3-phenylpropyl) dodecanamide (HPA-12) interferes with ceramide trafficking. To understand the role of ceramide/CERT in AD, HPA-12 can be a useful tool to modulate ceramide trafficking...
September 8, 2017: Journal of Alzheimer's Disease: JAD
https://www.readbyqxmd.com/read/28921976/isolation-synthesis-and-biological-activity-of-chlorinated-alkylresorcinols-from-dictyostelium-cellular-slime-molds
#4
Haruhisa Kikuchi, Ikuko Ito, Katsunori Takahashi, Hirotaka Ishigaki, Kyoichi Iizumi, Yuzuru Kubohara, Yoshiteru Oshima
Eight chlorinated alkylresorcinols, monochasiol A-H (1-8), were isolated from the fruiting bodies of Dictyostelium monochasioides. Compounds 1-8 were synthesized to confirm their structures and to obtain sufficient material for performing biological tests. Monochasiol A (1) selectively inhibited the concanavalin A-induced interleukin-2 production in Jurkat cells, a human T lymphocyte cell line. Monochasiols were biogenetically synthesized by the combination of biosynthetic enzymes relating to the principal polyketides, MPBD and DIF-1, produced by Dictyostelium discoideum...
September 18, 2017: Journal of Natural Products
https://www.readbyqxmd.com/read/28921877/analysis-of-infantile-fibrosarcoma-reveals-extensive-t-cell-responses-within-tumors-implications-for-immunotherapy
#5
Hua Zhu, Song Gu, Minzhi Yin, Min Shi, Chao Xin, Jianmin Zhu, Jing Wang, Siqi Huang, Chenjie Xie, Jing Ma, Ci Pan, Jingyan Tang, Min Xu, Xue-Feng Bai
BACKGROUND: Infantile fibrosarcoma (IFS) is a rare pediatric malignancy with relatively good prognosis, but the risk of progression or recurrence after therapy exists. To understand the immune microenvironment of IFS and determine if immunotherapy is a potential treatment, we analyzed T-cell responses in IFS tumors. PROCEDURE: IFS tumors were analyzed by immunohistochemistry and multicolor flow cytometry to characterize immune cell infiltration and function. Tumor infiltrating lymphocytes (TILs) were expanded in vitro and evaluated for recognition of autologous tumor cells...
September 17, 2017: Pediatric Blood & Cancer
https://www.readbyqxmd.com/read/28921872/first-line-therapy-with-dacomitinib-an-orally-available-pan-her-tyrosine-kinase-inhibitor-for-locally-advanced-or-metastatic-penile-squamous-cell-carcinoma-results-of-an-open-label-single-arm-single-center-phase-2-study
#6
A Necchi, S Lo Vullo, F Perrone, D Raggi, P Giannatempo, G Calareso, N Nicolai, L Piva, D Biasoni, M Catanzaro, T Torelli, S Stagni, E Togliardi, M Colecchia, A Busico, A Gloghini, A Testi, L Mariani, R Salvioni
OBJECTIVE: To harness the frontline therapy in advanced penile squamous cell carcinoma (PSCC), for which chemotherapy exerts moderate activity but poor efficacy. Dacomitinib is an irreversible, pan-epidermal growth factor receptor (HER) inhibitor. PATIENTS AND METHODS: In a phase 2 study (NCT01728233), patients received dacomitinib 45 mg/day, orally, continuously. Inclusion criteria were SCC histology, clinical stage N2-3 or M1 (TNM 2009), and no prior chemotherapy administration...
September 16, 2017: BJU International
https://www.readbyqxmd.com/read/28921818/blinatumomab-activity-in-a-patient-with-down-syndrome-b-precursor-acute-lymphoblastic-leukemia
#7
Aman Wadhwa, Matthew A Kutny, Ana C Xavier
Persistent minimal residual disease (MRD) after consolidation may indicate chemotherapy insensitivity in B-precursor acute lymphoblastic leukemia (BP-ALL). Given the strong association of MRD and outcome in non-Down syndrome (non-DS) BP-ALL, it is likely that MRD levels are also of prognostic significance in DS BP-ALL. We report here the successful use of blinatumomab, a bispecific T-cell engager antibody construct, in a patient with DS BP-ALL and persistent MRD at the end of consolidation. Blinatumomab has been shown to have excellent results in patients with relapsed/refractory BP-ALL...
September 17, 2017: Pediatric Blood & Cancer
https://www.readbyqxmd.com/read/28921800/initial-testing-stage-1-of-m6620-formerly-vx-970-a-novel-atr-inhibitor-alone-and-combined-with-cisplatin-and-melphalan-by-the-pediatric-preclinical-testing-program
#8
Raushan T Kurmasheva, Dias Kurmashev, C Patrick Reynolds, Min Kang, Jianwrong Wu, Peter J Houghton, Malcolm A Smith
BACKGROUND: M6620 is a novel inhibitor of the DNA damage repair enzyme ATR, and has potentiated the activity of cisplatin and irinotecan in non-small cell lung cancer and colon cancer xenografts, respectively. PROCEDURES: M6620 was tested in vitro at concentrations ranging from 1.0 nM to 10.0 μM and at 75 nM in combination with cisplatin or melphalan. M6620 was tested against 24 solid tumor xenografts alone and in combination with cisplatin. Cisplatin was administered intraperitoneally on days 1 and 8 at a dose of 5 mg/kg...
September 17, 2017: Pediatric Blood & Cancer
https://www.readbyqxmd.com/read/28921767/expansion-of-cd4-phenotype-among-cd160-receptor-expressing-lymphocytes-in-murine-pregnancy
#9
Matyas Meggyes, Laszlo Szereday, Pal Jakso, Barbara Bogar, Agnes Bogdan, Jasper Nörenberg, Eva Miko, Aliz Barakonyi
PROBLEM: CD160, a cell surface co-receptor, is capable of up- or downregulating cell proliferation, cytotoxicity or cytokine production on lymphocytes. Our aim was to investigate CD160(+) lymphocytes in the periphery and at the maternal-foetal interface during murine pregnancy. METHOD OF STUDY: CD4(+) , CD8(+) and gamma/delta T-cell phenotype, TIM3 co-expression and cytotoxic activity of CD160(+) lymphocytes of pregnant BALB/c mice were analysed by flow cytometry...
September 16, 2017: American Journal of Reproductive Immunology: AJRI
https://www.readbyqxmd.com/read/28921734/the-extracellular-signal-regulated-kinase-1-2-triggers-angiogenesis-in-human-ectopic-endometrial-implants-by-inducing-angioblast-differentiation-and-proliferation
#10
Sefa Arlier, William Murk, Ozlem Guzeloglu-Kayisli, Nihan Semerci, Kellie Larsen, Mehmet S Tabak, Aydin Arici, Frederick Schatz, Charles J Lockwood, Umit A Kayisli
PROBLEM: The role of extracellular signal-regulated kinase (ERK)1/2-mediated angiogenesis during endometriotic nidation is unknown. We posit that ERK1/2-induced angioblast differentiation and proliferation promotes ectopic endometrial angiogenesis. METHODS OF STUDY: Human eutopic and ectopic endometria were immunostained for total- (T-) or phosphorylated- (P-) ERK1/2 or double-immunostained for P-ERK1/2-CD34 and PCNA-CD34. Estradiol (E2 ), cytokines, normal peritoneal fluid (NPF) or endometriotic peritoneal fluid (EPF) ±PD98059, an ERK1/2 inhibitor, treaded primary human endometrial endothelial cells (HEECs) were evaluated by T-/P-ERK1/2 immunoblotting, MTT viability and tube formation assays...
September 16, 2017: American Journal of Reproductive Immunology: AJRI
https://www.readbyqxmd.com/read/28921702/3d-analysis-of-mitosis-distribution-highlights-the-longitudinal-zonation-and-diarch-symmetry-in-proliferation-activity-of-the-arabidopsis-thaliana-root-meristem
#11
V V Lavrekha, T Pasternak, V B Ivanov, K Palme, V V Mironova
To date CYCB1;1 marker and cortex cell lengths are conventionally used to determine the proliferation activity of the Arabidopsis root meristem. By creating a 3D map of mitosis distribution we showed that these markers overlooked that stele and endodermis save their potency to divide longer than cortex and epidermis. Cessation of cell divisions is not a random process, so that the mitotic activity within the endodermis and stele shows a diarch pattern. Mitotic activity of all root tissues peaked at the same distance from the quiescent center (QC); however, different tissues stopped dividing at different distances, with cells of the protophloem exiting the cell cycle first and the procambial cells being the last...
September 16, 2017: Plant Journal: for Cell and Molecular Biology
https://www.readbyqxmd.com/read/28921638/graft-infiltrating-pd-l1-hi-cross-dressed-dendritic-cells-regulate-anti-donor-t-cell-responses-in-mouse-liver-transplant-tolerance
#12
Yoshihiro Ono, Angelica Perez-Gutierrez, Toshimasa Nakao, Helong Dai, Geoffrey Camirand, Osamu Yoshida, Shinichiro Yokota, Donna Beer Stolz, Mark A Ross, Adrian E Morelli, David A Geller, Angus W Thomson
While a key role of cross-dressing has been established in immunity to viral infection and more recently in the instigation of transplant rejection, its role in tolerance is unclear. Here, we investigated the role of intra-graft dendritic cells (DC) and cross-dressing in mouse major histocompatibility complex (MHC)-mismatched liver transplant tolerance that occurs without therapeutic immunosuppression. While donor interstitial DC diminished rapidly following transplantation, they were replaced in the liver by host DC that peaked on postoperative day (POD) 7 and persisted indefinitely...
September 16, 2017: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
https://www.readbyqxmd.com/read/28921473/the-development-and-diversity-of-ilcs-nk-cells-and-their-relevance-in-health-and-diseases
#13
Yuxia Zhang, Bing Huang
Next to T and B cells, natural killer (NK) cells are the third largest lymphocyte population. They are recently re-categorized as innate lymphocytes (ILCs), which also include ILC1, ILC2, ILC3, and the lymphoid tissue inducer (LTi) cells. Both NK cells and ILC1 cells are designated as group 1 ILCs because they secrete interferon-γ (IFN-γ) and tumor necrosis factor (TNF). However, in contrast to ILC1 and all other ILCs, NK cells possess potent cytolytic functions that resemble cytotoxic T lymphocytes (CTL)...
2017: Advances in Experimental Medicine and Biology
https://www.readbyqxmd.com/read/28921388/immunomodulatory-potential-of-nanocurcumin-based-formulation
#14
Mahendra Kumar Trivedi, Sambhu Charan Mondal, Mayank Gangwar, Snehasis Jana
Vitamins, minerals, and nanocurcumin play a substantial role in various nutraceutical/pharmaceutical formulations that are widely used in therapeutics, cosmetics, and dietary supplements. The current study aimed to investigate the comparative in vitro immunomodulatory effect of a novel nanocurcumin-based formulation with curcumin in LPS-induced cytokine expression, NK cells' activity, and phagocytosis. The proinflammatory cytokines (TNF-α, IL-1β, and MIP-1α) and NK cells' activity were measured in cell supernatants using ELISA assay; however, phagocytosis activity was performed using colorimetric analysis...
September 18, 2017: Inflammopharmacology
https://www.readbyqxmd.com/read/28920934/esr1-cells-in-the-ventromedial-hypothalamus-control-female-aggression
#15
Koichi Hashikawa, Yoshiko Hashikawa, Robin Tremblay, Jiaxing Zhang, James E Feng, Alexander Sabol, Walter T Piper, Hyosang Lee, Bernardo Rudy, Dayu Lin
As an essential means of resolving conflicts, aggression is expressed by both sexes but often at a higher level in males than in females. Recent studies suggest that cells in the ventrolateral part of the ventromedial hypothalamus (VMHvl) that express estrogen receptor-α (Esr1) and progesterone receptor are essential for male but not female mouse aggression. In contrast, here we show that VMHvl(Esr1+) cells are indispensable for female aggression. This population was active when females attacked naturally...
September 18, 2017: Nature Neuroscience
https://www.readbyqxmd.com/read/28920925/expression-of-piwi-protein-miwi2-defines-a-distinct-population-of-multiciliated-cells
#16
Gregory A Wasserman, Aleksander D Szymaniak, Anne C Hinds, Kazuko Yamamoto, Hirofumi Kamata, Nicole Ms Smith, Kristie L Hilliard, Claudia Carrieri, Adam T Labadorf, Lee J Quinton, Xingbin Ai, Xaralabos Varelas, Felicia Chen, Joseph P Mizgerd, Alan Fine, Dónal O'Carroll, Matthew R Jones
P-element-induced wimpy testes (Piwi) proteins are known for suppressing retrotransposon activation in the mammalian germline. However, whether Piwi protein or Piwi-dependent functions occur in the mammalian soma is unclear. Contrary to germline-restricted expression, we observed that Piwi-like Miwi2 mRNA is indeed expressed in epithelial cells of the lung in adult mice and that it is induced during pneumonia. Further investigation revealed that MIWI2 protein localized to the cytoplasm of a discrete population of multiciliated airway epithelial cells...
September 18, 2017: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/28920922/g%C3%AE-13-ablation-reprograms-myofibers-to-oxidative-phenotype-and-enhances-whole-body-metabolism
#17
Ja Hyun Koo, Tae Hyun Kim, Shi-Young Park, Min Sung Joo, Chang Yeob Han, Cheol Soo Choi, Sang Geon Kim
Skeletal muscle is a key organ in energy homeostasis owing to its high requirement for nutrients. Heterotrimeric G proteins converge signals from cell-surface receptors to potentiate or blunt responses against environmental changes. Here, we show that muscle-specific ablation of Gα13 in mice promotes reprogramming of myofibers to the oxidative type, with resultant increases in mitochondrial biogenesis and cellular respiration. Mechanistically, Gα13 and its downstream effector RhoA suppressed nuclear factor of activated T cells 1 (NFATc1), a chief regulator of myofiber conversion, by increasing Rho-associated kinase 2-mediated (Rock2-mediated) phosphorylation at Ser243...
September 18, 2017: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/28920919/age-dependent-human-%C3%AE-cell-proliferation-induced-by-glucagon-like-peptide-1-and-calcineurin-signaling
#18
Chunhua Dai, Yan Hang, Alena Shostak, Greg Poffenberger, Nathaniel Hart, Nripesh Prasad, Neil Phillips, Shawn E Levy, Dale L Greiner, Leonard D Shultz, Rita Bottino, Seung K Kim, Alvin C Powers
Inadequate pancreatic β cell function underlies type 1 and type 2 diabetes mellitus. Strategies to expand functional cells have focused on discovering and controlling mechanisms that limit the proliferation of human β cells. Here, we developed an engraftment strategy to examine age-associated human islet cell replication competence and reveal mechanisms underlying age-dependent decline of β cell proliferation in human islets. We found that exendin-4 (Ex-4), an agonist of the glucagon-like peptide 1 receptor (GLP-1R), stimulates human β cell proliferation in juvenile but not adult islets...
September 18, 2017: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/28920716/transposons-moving-forward-from-preclinical-studies-to-clinical-trials
#19
Jaitip Tipanee, Thierry VandenDriessche, Marinee K Chuah
Transposons have emerged as promising vectors for gene therapy that can potentially overcome some of the limitations of commonly used viral vectors. Transposons stably integrate into the target cell genome, enabling persistent expression of therapeutic genes. Transposons have evolved from being used as basic tools in biomedical research to bona fide therapeutics. Currently, the most promising transposons for gene therapy applications are derived from Sleeping Beauty (SB) or piggyBac (PB). Stable transposition requires co-delivery of the transposon DNA with the corresponding transposase gene, mRNA, or protein...
August 22, 2017: Human Gene Therapy
https://www.readbyqxmd.com/read/28920671/development-of-a-multifunctional-nanobiointerface-based-on-self-assembled-fusion-protein-rsbpa-zz-for-blood-cell-enrichment-and-phenotyping
#20
Mario Rothbauer, Martin Frauenlob, Karoline Gutkas, Michael B Fischer, Eva Kathrin Sinner, Seta Küpcü, Peter Ertl
We present a multifunctional nanobiointerface for blood cell capture and phenotyping applications that features both excellent antifouling properties and high antibody activity. Multifunctionality is accomplished by modifying polymeric materials using self-assembled S-layer fusion-protein rSbpA/ZZ to immobilize high density antibodies at the two protein A binding sites of the rSbpA/ZZ nanolattice structure. Controlled orientation and alignment of the antibodies reduced antibody consumption 100-fold and increased cell capture efficiency 4-fold over standard methodologies...
September 18, 2017: ACS Applied Materials & Interfaces
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