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Erika Heninger, Timothy E G Krueger, Stephanie M Thiede, Jamie M Sperger, Brianna L Byers, Madison R Kircher, David Kosoff, Bing Yang, David F Jarrard, Douglas G McNeel, Joshua M Lang
Immune tolerance to self-antigens can limit robust anti-tumor immune responses in the use of tumor vaccines. Expression of novel tumor associated antigens can improve immune recognition and lysis of tumor cells. The cancer-testis antigen (CTA) family of proteins has been hypothesized to be an ideal class of antigens due to tumor-restricted expression, a subset of which have been found to induce antibody responses in patients with prostate disease. We demonstrate that CTA expression is highly inducible in five different Prostate Cancer (PC) cell lines using a hypomethylating agent 5-Aza-2'-deoxycytidine (5AZA) and/or a histone deacetylase inhibitor LBH589...
October 17, 2016: Oncotarget
Jessica A Flynn, Eberhard Durr, Ryan Swoyer, Pedro J Cejas, Melanie S Horton, Jennifer D Galli, Scott A Cosmi, Amy S Espeseth, Andrew J Bett, Lan Zhang
Infection with Respiratory Syncytial Virus (RSV) causes both upper and lower respiratory tract disease in humans, leading to significant morbidity and mortality in both young children and older adults. Currently, there is no licensed vaccine available, and therapeutic options are limited. During the infection process, the type I viral fusion (F) glycoprotein on the surface of the RSV particle rearranges from a metastable prefusion conformation to a highly stable postfusion form. In people naturally infected with RSV, most potent neutralizing antibodies are directed to the prefusion form of the F protein...
2016: PloS One
Sirong Chen, Shing Kee Cheung, Ka-Nin Wong, Kwok Kee Wong, Chi-Lai Ho
A bedridden 90-year-old man with fever and elevated prostate-specific antigen (PSA) (49 ng/mL) was referred for differentiation between infection and tumor. F-FDG PET/CT was negative for infection, but Ga-PSMA PET/CT showed multiple lesions in prostate gland with infiltration to bladder wall and seminal vesicle, consistent with locally advanced prostate cancer. The lesion with the highest Ga-PSMA uptake was strongly avid for Ga-DOTATOC, suggesting neuroendocrine tumor differentiation. After hormonal therapy, PSA normalized, but chromogranin-A increased (from 251 to 398 ng/mL), inferring progression of neuroendocrine tumor differentiation...
October 18, 2016: Clinical Nuclear Medicine
Carsten-O Sahlmann, Kia Homayounfar, Martin Niessner, Jerzy Dyczkowski, Lena-Christin Conradi, Friederike Braulke, Birgit Meller, Tim Beißbarth, B Michael Ghadimi, Johannes Meller, David M Goldenberg, Torsten Liersch
BACKGROUND: In previous work, a single administration of anticarcinoembryonic antigen (anti-CEA) (131) I-labetuzumab radioimmunotherapy (RIT) after complete resection of colorectal liver metastases was well tolerated and significantly improved survival compared with controls. In the current phase 2 trial, the authors studied repeated RIT in the same setting, examining safety, feasibility, and efficacy. METHODS: Sixty-three patients (median age, 64.5 years) received RIT at 40 to 50 millicuries/m(2) per dose...
October 20, 2016: Cancer
I Mancini, I Ricaño-Ponce, E Pappalardo, A Cairo, M M Gorski, G Casoli, B Ferrari, M Alberti, D Mikovic, M Noris, C Wijmenga, F Peyvandi
BACKGROUND: Acquired thrombotic thrombocytopenic purpura (TTP) is a rare, life-threatening thrombotic microangiopathy associated with the development of autoantibodies against the von Willebrand factor cleaving protease, ADAMTS13. Similarly to other autoimmune disorders, evidences of a genetic contribution have been reported, including the association of the human leukocyte antigen (HLA) class II complex with disease risk OBJECTIVE: To identify novel genetic risk factors in acquired TTP...
October 20, 2016: Journal of Thrombosis and Haemostasis: JTH
M Voigtlaender, K Holstein, B Spath, C Bokemeyer, F Langer
INTRODUCTION: Despite similar residual factor VIII activity, patients with haemophilia A (HA) show significant interindividual variability with regard to bleeding frequency and severity, suggesting that additional factors modulate thrombin generation and fibrin deposition. Protein disulphide isomerase (PDI) is an abundant oxidoreductase that exerts pleiotropic effects in primary and secondary haemostasis and contributes to thrombosis and vascular inflammation. AIM: We conducted a pilot study to explore a potential role of platelet PDI in patients with HA...
October 20, 2016: Haemophilia: the Official Journal of the World Federation of Hemophilia
Margaret M Brosnahan, Emily J Silvela, Jessica Crumb, Donald C Miller, Hollis N Erb, Douglas F Antczak
Invasive trophoblast from Day-34 horse conceptuses survives in extra-uterine sites in allogeneic recipients that are immunologically naïve to donor major histocompatibility complex class I antigens. The ectopic trophoblast retains its in utero characteristics, including similar lifespan, physiologic effect of its secreted product (equine chorionic gonadotrophin) upon the recipient's ovaries, and induction of host immune responses. Immunologic memory has not been considered previously in this experimental system...
October 19, 2016: Biology of Reproduction
N C Knox, K A Weedmark, J Conly, A W Ensminger, F S Hosein, S J Drews
An outbreak of Legionnaires' disease occurred in an inner city district in Calgary, Canada. This outbreak spanned a 3-week period in November-December 2012, and a total of eight cases were identified. Four of these cases were critically ill requiring intensive care admission but there was no associated mortality. All cases tested positive for Legionella pneumophila serogroup 1 (LP1) by urinary antigen testing. Five of the eight patients were culture positive for LP1 from respiratory specimens. These isolates were further identified as Knoxville monoclonal subtype and sequence subtype ST222...
October 20, 2016: Epidemiology and Infection
M L V Azevedo, N B Bonan, G Dias, F Brehm, T M Steiner, W M Souza, A E M Stinghen, F C Barreto, Selene Elifio-Esposito, R Pecoits-Filho, A N Moreno-Amaral
Immune system dysfunction is a common condition in chronic kidney disease (CKD). The present study investigated the effect of p-Cresyl sulfate (pCS) on human cell line U937 monocyte-derived macrophages (MDM) activity. MDM (1×10(6) cells/mL) were incubated with pCS (10, 25, or 50μg/mL), with or without lipopolysaccharide (LPS; 25ng/mL) and then evaluated NO production, phagocytosis and antigen-presenting molecules expression (HLA-ABC, HLA-DR, CD80 and CD86). All analyses were performed by flow cytometry. All pCS concentrations were able to increase NO production (49±12...
October 16, 2016: Toxicology Letters
Rosario Gajardo-Gómez, Valeria C Labra, Carola J Maturana, Kenji F Shoji, Cristian A Santibañez, Juan C Sáez, Christian Giaume, Juan A Orellana
The mechanisms involved in Alzheimer's disease are not completely understood and how astrocytes and their gliotransmission contribute to this neurodegenerative disease remains to be fully elucidated. Previous studies have shown that amyloid-β peptide (Aβ) induces neuronal death by a mechanism that involves the excitotoxic release of ATP and glutamate associated to astroglial hemichannel opening. We have demonstrated that synthetic and endogenous cannabinoids (CBs) reduce the opening of astrocyte Cx43 hemichannels evoked by activated microglia or inflammatory mediators...
October 19, 2016: Glia
S F Lax, K F Tamussino, P F Lang
Malignancies of the uterus metastasize by direct invasion of neighboring structures, lymphatically or hematogenously. Endometrial and cervical cancers lymphatically spread to the pelvic and para-aortic lymph nodes. For endometrial cancer the depth of myometrial invasion, lymphosvascular space involvement (LVSI) and a microcystic, elongated and fragmented (MELF) glandular invasion pattern are predictors for lymph node metastases. Metastases to the pelvic lymph nodes occur in approximately 10 % of endometrial cancer patients and in 30 % of these cases the para-aortic lymph nodes are also involved...
October 18, 2016: Der Pathologe
Debasish Sen, Stephen M Jones, Erin M Oswald, Henry Pinkard, Kaitlin Corbin, Matthew F Krummel
Myeloid-derived cells such as monocytes, dendritic cells (DCs), and macrophages are at the heart of the immune effector function in an inflammatory response. But because of the lack of an efficient imaging system to trace these cells live during their migration and maturation in their native environment at sub-cellular resolution, our knowledge is limited to data available from specific time-points analyzed by flow cytometry, histology, genomics and other immunological methods. Here, we have developed a ratiometric imaging method for measuring monocyte maturation in inflamed mouse lungs in situ using real-time using 2-photon imaging and complementary methods...
2016: PloS One
Risa Ramadhiani, Muhammad Saifur Rohman, Nashi Widodo, Valerinna Y S Putri, Mifetika Lukitasari, Jayarani F Putri, Didik H Utomo
OBJECTIVE: To investigate whether the angiotensinogen (AGT) G-217A polymorphism affects blood pressure response of telmisartan and valsartan in hypertensive patients. DESIGN AND METHOD: A total of 46 primary hypertensive patients, 23 patients received telmisartan 80 mg and 23 patients received valsartan 160 mg, were observed and followed up for 4 months. The AGT G-217A polymorphism was determined by PCR-RFLP and direct sequencing method. Blood pressure response was measured daytime (6 am - 10 pm), night-time (10 pm - 6 am), and 24 hours using twenty-four hours ambulatory blood pressure monitoring (ABPM)...
September 2016: Journal of Hypertension
Dawid Walas, Karol Nowicki-Osuch, Dominic Alibhai, Julian Paton
OBJECTIVE: Cerebrovascular remodeling in the SHR may be causative to the known brainstem hypoperfusion. Using RNA sequencing, we examined age-related processes that may govern remodeling of the cerebral arteries in the SHR. DESIGN AND METHOD: In SHR and their progenitor (normotensive) control (Wistar Kyoto, WKY), RNA-seq was performed at three ages: 5, 9, 13 weeks old. Cerebral arteries were flushed and peeled off the brain, stripped of meninges, snap frozen and RNA extracted...
September 2016: Journal of Hypertension
Pavel Hanč, Oliver Schulz, Hanna Fischbach, Stephen R Martin, Svend Kjær, Caetano Reis E Sousa
DNGR-1 is receptor expressed by certain dendritic cell (DC) subsets and by DC precursors in mouse. It possesses a C-type lectin-like domain (CTLD) followed by a poorly characterized neck region coupled to a transmembrane region and short intracellular tail. The CTLD of DNGR-1 binds F-actin exposed by dead cell corpses and causes the receptor to signal and potentiate cross-presentation of dead cell-associated antigens by DCs. Here, we describe a conformational change that occurs in the neck region of DNGR-1 in a pH- and ionic strength-dependent manner and that controls cross-presentation of dead cell-associated antigens...
October 17, 2016: EMBO Journal
E C Martino, G Misso, P Pastina, S Costantini, F Vanni, C Gandolfo, C Botta, F Capone, A Lombardi, L Pirtoli, P Tassone, C Ulivieri, P Tagliaferri, M G Cusi, M Caraglia, P Correale
The mPEBev is an anticancer regimen which combines a chemotherapy doublet, based on cisplatin and oral etoposide (mPE), with bevacizumab (mPEBev), a mAb targeting the vasculo-endothelial growth factor (VEGF). In previous studies, this regimen showed powerful anti-angiogenetic effects and significant antitumor activity in metastatic non-small-cell lung cancer (mNSCLC) patients. We also recorded the best benefit in patients exhibiting low-systemic inflammatory profile at baseline. On these bases, we hypothesized that mPEBev antitumor activity could be partially related to bevacizumab-associated immunological effects...
2016: Cell Death Discovery
X R Feng, M L Liu, F Liu, Y Fan, Q P Tian
OBJECTIVE: To assess the consequences of switching aspirin dosage from 100 mg/d to 40 mg/d on cardiovascular benefit, bleeding risk and platelet aggregation in very elderly patients. METHODS: Arachidonic acid induced platelet aggregation(AA-Ag) was measured in 537 patients aged 80 or older treated with aspirin (100 mg/d). In the study, 100 patients with low on-treatment platelet aggregation and at high risk of bleeding and low risk of cardiovascular events, were switched to aspirin (40 mg/d) and their platelet aggregation was measured again 7 days later...
October 18, 2016: Beijing da Xue Xue Bao. Yi Xue Ban, Journal of Peking University. Health Sciences
C Tonus, D Connan, O Waroux, B Vandenhove, J Wayet, L Gillet, D Desmecht, N Antoine, F J Ectors, L Grobet
In the present study, we compare a classical slow freezing (SLF) method and an aseptic vitrification (Vitrif) technique to cryopreserve a stable primordial germ cell (PGCs) line issued from the Ardennaise chicken breed. Viability immediately after warming was close to 80% and did not differ between the two cryopreservation methods. Proliferation tended to be slower for both cryopreservation methods compared with controls, but the difference was significant only for Vitrif. No difference was found between the two methods after flow cytometry analysis of stage-specific embryonic antigen-1 expression and reverse transcription-polymerase chain reaction on several factors related to PGC phenotype...
September 21, 2016: Theriogenology
Corina Lesseur, Brenda Diergaarde, Andrew F Olshan, Victor Wünsch-Filho, Andrew R Ness, Geoffrey Liu, Martin Lacko, José Eluf-Neto, Silvia Franceschi, Pagona Lagiou, Gary J Macfarlane, Lorenzo Richiardi, Stefania Boccia, Jerry Polesel, Kristina Kjaerheim, David Zaridze, Mattias Johansson, Ana M Menezes, Maria Paula Curado, Max Robinson, Wolfgang Ahrens, Cristina Canova, Ariana Znaor, Xavier Castellsagué, David I Conway, Ivana Holcátová, Dana Mates, Marta Vilensky, Claire M Healy, Neonila Szeszenia-Dąbrowska, Eleonóra Fabiánová, Jolanta Lissowska, Jennifer R Grandis, Mark C Weissler, Eloiza H Tajara, Fabio D Nunes, Marcos B de Carvalho, Steve Thomas, Rayjean J Hung, Wilbert H M Peters, Rolando Herrero, Gabriella Cadoni, H Bas Bueno-de-Mesquita, Annika Steffen, Antonio Agudo, Oxana Shangina, Xiangjun Xiao, Valérie Gaborieau, Amélie Chabrier, Devasena Anantharaman, Paolo Boffetta, Christopher I Amos, James D McKay, Paul Brennan
We conducted a genome-wide association study of oral cavity and pharyngeal cancer in 6,034 cases and 6,585 controls from Europe, North America and South America. We detected eight significantly associated loci (P < 5 × 10(-8)), seven of which are new for these cancer sites. Oral and pharyngeal cancers combined were associated with loci at 6p21.32 (rs3828805, HLA-DQB1), 10q26.13 (rs201982221, LHPP) and 11p15.4 (rs1453414, OR52N2-TRIM5). Oral cancer was associated with two new regions, 2p23.3 (rs6547741, GPN1) and 9q34...
October 17, 2016: Nature Genetics
Thorsten Derlin, Desiree Weiberg, Jan M Sohns
Paget disease is a chronic disorder resulting in enlarged and misshapen bones, and is caused by disorganized bone remodeling. We present the case of an 85-year-old man with prostatic adenocarcinoma and known Paget disease of the right iliac bone who underwent Ga-prostate-specific membrane antigen ligand, C-acetate, and F-fluoride PET/CT for restaging of cancer. On all PET scans, increased tracer accumulation was observed in Paget disease of bone. Besides that Paget disease may mimic metastases on PET/CT using various radiotracers, including Ga-prostate-specific membrane antigen ligands and C-acetate, this case highlights the potential of multiparametric disease characterization on PET...
October 5, 2016: Clinical Nuclear Medicine
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