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https://www.readbyqxmd.com/read/28916527/demethylation-therapy-as-a-targeted-treatment-for-human-papilloma-virus-associated-head-and-neck-cancer
#1
Asel K Biktasova, Michael Hajek, Andrew B Sewell, Cyril S Gary, Gary Bellinger, Hari Deshpande, Aarti K Bhatia, Barbara A Burtness, Benjamin L Judson, Saral Mehra, Wendell G Yarbrough, Natalia Issaeva
PURPOSE: DNA methylation in human papillomavirus-associated (HPV+) head and neck squamous cell carcinoma (HNSCC) may have importance for continuous expression of HPV oncogenes, tumor cell proliferation and survival. Here, we determined activity of a global DNA demethylating agent, 5-azacytidine (5-aza), against HPV+ HNSCC in pre-clinical models and explored it as a targeted therapy in a window trial enrolling patients with HPV+ HNSCC. EXPERIMENTAL DESIGN: Sensitivity of HNSCC cells to 5-aza treatment was determined, then 5-aza activity was tested in vivo using xenografted tumors in a mouse model...
September 15, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28916314/immunization-with-recombinant-gntr-plasmid-confers-protection-against-brucella-challenge-in-balb-c-mice
#2
Zhiqiang Li, Shuli Wang, Hui Zhang, Li Xi, Jinliang Zhang, Xiaogen Zhang, Jincheng Han, Junbo Zhang
It is essential to improve animal vaccine for brucellosis since conventional vaccines are residual virulent and poor protective effect, limit their applications. To solve these problems, the recombinant DNA vaccines were appeared, which could improve protective immunity and were attenuated to animals. In current research, the recombinant DNA vaccine (pVGntR) based on transcriptional regulator GntR of Brucella abortus (B. abortus) was constructed. The results show that pVGntR is significantly more protective than the conventional RB51 vaccine...
September 12, 2017: Microbial Pathogenesis
https://www.readbyqxmd.com/read/28916184/role-of-the-il-12-il-35-balance-in-sj%C3%A3-gren-s-syndrome
#3
Olivier Fogel, Elodie Rivière, Raphaèle Seror, Gaetane Nocturne, Saida Boudaoud, Bineta Ly, Jacques-Eric Gottenberg, Véronique Le Guern, Jean-Jacques Dubost, Joanne Nititham, Kimberly E Taylor, Philippe Chanson, Philippe Dieudé, Lindsey A Criswell, Bernd Jagla, Alice Thai, Michael Mingueneau, Xavier Mariette, Corinne Miceli-Richard
BACKGROUND: An interferon (IFN) signature is involved in the pathogenesis of primary Sjögren's syndrome (pSS), but whether the signature is type 1 or 2 remains controversial. Mouse models and genetic studies suggested the involvement of T helper 1 and type 2 IFN pathways. Likewise, polymorphisms of interleukin 12A gene (IL-12A), which encodes for IL-12p35, have been associated with pSS. IL-12p35 subunit is shared by 2 heterodimers, IL-12 and IL-35. OBJECTIVE: To confirm the genetic association of IL-12A polymorphism and pSS and elucidate the involvement of the IL-12/IL-35 balance in pSS by functional studies...
September 12, 2017: Journal of Allergy and Clinical Immunology
https://www.readbyqxmd.com/read/28915824/fucoidan-from-fucus-vesiculosus-suppresses-hepatitis-b-virus-replication-by-enhancing-extracellular-signal-regulated-kinase-activation
#4
Huifang Li, Junru Li, Yuan Tang, Lin Lin, Zhanglian Xie, Jia Zhou, Liyun Zhang, Xiaoyong Zhang, Xiaoshan Zhao, Zhengliang Chen, Daming Zuo
BACKGROUND: Hepatitis B virus (HBV) infection is a serious public health problem leading to cirrhosis and hepatocellular carcinoma. As the clinical utility of current therapies is limited, the development of new therapeutic approaches for the prevention and treatment of HBV infection is imperative. Fucoidan is a natural sulfated polysaccharide that extracted from different species of brown seaweed, which was reported to exhibit various bioactivities. However, it remains unclear whether fucoidan influences HBV replication or not...
September 16, 2017: Virology Journal
https://www.readbyqxmd.com/read/28913840/loss-of-regulatory-characteristics-in-cd4-cd25-hi-t-cells-induced-by-impaired-transforming-growth-factor-beta-secretion-in-pneumoconiosis
#5
Lu-Qin Bian, Ling Mao, Ying Bi, Shao-Wei Zhou, Zi-Dan Chen, Jun Wen, Jin Shi, Ling Wang
Pneumoconiosis is caused by the accumulation of airborne dust in the lung, which stimulates a progressive inflammatory response that ultimately results in lung fibrosis and respiratory failure. It is possible that regulatory cells in the immune system could function to suppress inflammation and possibly slow or reverse disease progression. However, results in this study suggest that in pneumoconiosis patients, the regulatory T cells (Tregs) and B cells are functionally impaired. First, we found that pneumoconiosis patients presented an upregulation of CD4(+) CD25(+) T cells compared to controls, whereas the CD4(+) CD25(+) and CD4(+) CD25(hi) T cells were enriched with Th1- and Th17-like cells but not Foxp3-expressing Treg cells and evidenced by significantly higher T-bet, interferon (IFN)-γ, and interleukin (IL)-17 expression but lower Foxp3 and transforming growth factor (TGF)-β expression...
September 15, 2017: APMIS: Acta Pathologica, Microbiologica, et Immunologica Scandinavica
https://www.readbyqxmd.com/read/28913367/efficacy-of-tumor-infiltrating-lymphocytes-combined-with-ifn-%C3%AE-in-chinese-resected-stage-iii-malignant-melanoma
#6
Wei Li, Linping Xu, Yaomei Wang, Lingdi Zhao, Daniel B Kellner, Quanli Gao
BACKGROUND: This study aims to explore the efficacy of tumor-infiltrating lymphocytes (TIL) along with interferon-α (IFN-α) to treat stage III malignant melanoma (MM) patients in China. METHODS: Between May 2010 and October 2014, 77 patients of stage III MM who underwent surgery were collected in this study. These patients were divided into two groups: patients who received TIL + IFN-α ± RetroNectin-activated cytokine-induced killer cells (R-CIK) in Arm 1 (n = 27) and IFN-α ± R-CIK in Arm 2 (n = 50) as adjuvant therapy...
2017: Journal of Immunology Research
https://www.readbyqxmd.com/read/28912267/antitumor-immunity-is-defective-in-t-cell-specific-microrna-155-deficient-mice-and-is-rescued-by-immune-checkpoint-blockade
#7
Thomas B Huffaker, Soh-Hyun Lee, William W Tang, Jared A Wallace, Margaret Alexander, Marah C Runtsch, Dane K Larsen, Jacob Thompson, Andrew G Ramstead, Warren P Voth, Ruozhen Hu, June L Round, Matthew A Williams, Ryan M O'Connell
MicroRNA-155 (miR-155) regulates antitumor immune responses. However, its specific functions within distinct immune cell types have not been delineated in conditional knockout (KO) mouse models. In this study, we investigated the role of miR-155 specifically within T cells during the immune response to syngeneic tumors. We found that miR-155 expression within T cells is required to limit syngeneic tumor growth and promote interferon gamma (IFNγ) production by T cells within the tumor microenvironment. Consequently, we found that miR-155 expression by T cells is necessary for proper tumor-associated macrophage (TAM) expression of IFNγ-inducible genes...
September 14, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28912017/indoleamine-2-3-dioxygenase-1-increased-in-human-gastric-pre-neoplasia-promotes-inflammation-and-metaplasia-in-mice-and-is-associated-with-type-ii-hypersensitivity-autoimmunity
#8
Mohamad El-Zaatari, Adam J Bass, Reanne Bowlby, Min Zhang, Li-Jyun Syu, Yitian Yang, Helmut Grasberger, Andrew Shreiner, Bei Tan, Shrinivas Bishu, Wai K Leung, Andrea Todisco, Nobuhiko Kamada, Marilia Cascalho, Andrzej A Dlugosz, John Y Kao
BACKGROUND & AIMS: Chronic gastrointestinal inflammation increases the risk of cancer by mechanisms that are not well understood. Indoleamine-2,3-dioxygenase 1 (IDO1) is a heme-binding enzyme that regulates the immune response via catabolization and regulation of tryptophan availability for immune cell uptake. IDO1 expression is increased during the transition from chronic inflammation to gastric metaplasia. We investigated whether IDO1 contributes to the inflammatory response that mediates loss of parietal cells leading to metaplasia...
September 11, 2017: Gastroenterology
https://www.readbyqxmd.com/read/28911151/expanding-the-phenotypic-and-genotypic-landscape-of-autoimmune-polyendocrine-syndrome-type-1
#9
Elizaveta M Orlova, Leila S Sozaeva, Maria A Kareva, Bergithe E Oftedal, Anette S B Wolff, Lars Breivik, Ekaterina Y Zakharova, Olga N Ivanova, Olle Kämpe, Ivan I Dedov, Per M Knappskog, Valentina A Peterkova, Eystein S Husebye
Context: Autoimmune polyendocrine syndrome type 1 (APS-1) is a rare monogenic autoimmune disease caused by mutations in the autoimmune regulator (AIRE) gene and characterized by chronic mucocutaneous candidiasis, hypoparathyroidism, and primary adrenal insufficiency. Comprehensive characterizations of large patient cohorts are rare. Objective: To perform an extensive clinical, immunological, and genetic characterization of a large nationwide Russian APS-1 cohort...
September 1, 2017: Journal of Clinical Endocrinology and Metabolism
https://www.readbyqxmd.com/read/28910635/gestational-stage-and-ifn-%C3%AE-signaling-regulate-zikv-infection-in-utero
#10
Brett W Jagger, Jonathan J Miner, Bin Cao, Nitin Arora, Amber M Smith, Attila Kovacs, Indira U Mysorekar, Carolyn B Coyne, Michael S Diamond
Although Zika virus (ZIKV)-induced congenital disease occurs more frequently during early stages of pregnancy, its basis remains undefined. Using established type I interferon (IFN)-deficient mouse models of ZIKV transmission in utero, we found that the placenta and fetus were more susceptible to ZIKV infection at earlier gestational stages. Whereas ZIKV infection at embryonic day 6 (E6) resulted in placental insufficiency and fetal demise, infections at midstage (E9) resulted in reduced cranial dimensions, and infection later in pregnancy (E12) caused no apparent fetal disease...
September 13, 2017: Cell Host & Microbe
https://www.readbyqxmd.com/read/28906152/relapse-outcomes-safety-and-treatment-patterns-in-patients-diagnosed-with-relapsing-remitting-multiple-sclerosis-and-initiated-on-subcutaneous-interferon-%C3%AE-1a-or-dimethyl-fumarate-a-real-world-study
#11
Frank R Ernst, Peri Barr, Riad Elmor, Schiffon L Wong
OBJECTIVE: To estimate real-world treatment patterns, safety, and relapse outcomes of subcutaneous (sc) interferon (IFN) β-1a (Rebif®) versus dimethyl fumarate (DMF; Tecfidera(®)), to treat relapsing-remitting multiple sclerosis (RRMS). METHODS: A U.S. retrospective chart review of 450 randomly selected adults newly diagnosed with RRMS who received sc IFN β-1a (n = 143) or DMF (n = 307) was conducted. Patients were either (a) treatment-naïve, initiating first-line treatment with sc IFN β-1a or DMF, or (b) previously treated, switching to sc IFN β-1a or DMF...
September 14, 2017: Current Medical Research and Opinion
https://www.readbyqxmd.com/read/28904198/type-1-interferon-signalling-to-dendritic-cells-limits-murid-herpesvirus-4-spread-from-the-olfactory-epithelium
#12
Clara Lawler, Philip G Stevenson
Murid Herpesvirus-4 (MuHV-4) is a B cell-tropic gamma-herpesvirus that can be studied in vivo Despite viral evasion, type 1 interferons (IFN-I) limit its spread. After MuHV-4 inoculation into footpads, IFN-I protect lymph node subcapsular sinus macrophages (SSM) against productive infection; after peritoneal inoculation, they protect splenic marginal zone macrophages; and they limit MuHV-4 replication in the lungs. While invasive infections can test specific aspects of host colonization, it is important also to understand natural infection...
September 13, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28904192/the-role-of-herpes-simplex-virus-type-1-%C3%AE-34-5-in-the-regulation-of-irf3-signaling
#13
Richard Manivanh, Jesse Mehrbach, David M Knipe, David A Leib
During viral infection, pattern recognition receptors (PRRs) and their associated adaptors recruit TANK-binding kinase 1 (TBK1) to activate interferon regulatory factor 3 (IRF3), resulting in production of type I interferons (IFNs). ICP0 and ICP34.5 are amongst the proteins encoded by herpes simplex virus 1 (HSV-1) that modulate type I IFN signaling. We constructed a recombinant virus (ΔXX) which lacks amino acids 87 - 106, a portion of the previously described TBK1-binding domain of the γ34.5 gene (D. Verpooten, Y...
September 13, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28903508/effect-of-paritaprevir-ritonavir-ombitasvir-dasabuvir-and-ledipasvir-sofosbuvir-regimens-on-survival-compared-with-untreated-hepatitis-c-virus-infected-persons-results-from-erchives
#14
Adeel Ajwad Butt, Peng Yan, Tracey G Simon, Abdul-Badi Abou-Samra
Background: Interferon-based regimens are associated with a substantial survival benefit for persons infected with hepatitis C virus (HCV). Survival data with direct-acting antiviral agents are not available. We conducted this study to quantify the effect of paritaprevir/ritonavir, ombitasvir, dasabuvir (PrOD) and ledipasvir/sofosbuvir (LDV/SOF) regimens upon mortality. Methods: In the Electronically Retrieved Cohort of HCV Infected Veterans (ERCHIVES), a well-established national cohort of HCV-infected Veterans, we identified HCV-infected persons initiated on PrOD or LDV/SOF, excluding those with human immunodeficiency virus, hepatitis B surface antigen positivity, hepatocellular carcinoma, or missing HCV RNA or FIB-4 scores...
September 15, 2017: Clinical Infectious Diseases: An Official Publication of the Infectious Diseases Society of America
https://www.readbyqxmd.com/read/28903381/tumor-location-impacts-immune-response-in-mouse-models-of-colon-cancer
#15
Xianda Zhao, Lihua Li, Timothy K Starr, Subbaya Subramanian
Existing preclinical models of human colorectal cancer (CRC) that rely on syngeneic subcutaneous grafts are problematic, because of increasing evidence that the immune microenvironment in subcutaneous tissue is significantly different from the gastrointestinal tract. Similarly, existing orthotopic models that use a laparotomy for establishing grafts are also problematic, because the surgical procedure results in extensive inflammation, thereby creating a nonphysiologic tumor microenvironment. To facilitate the bench-to-bedside translation of CRC immunotherapy strategies, we developed a novel orthotopic model in mice that uses endoscopy-guided microinjection of syngeneic cancer cells...
August 15, 2017: Oncotarget
https://www.readbyqxmd.com/read/28901958/pilot-study-of-the-tart-cherry-juice-for-the-treatment-of-insomnia-and-investigation-of-mechanisms
#16
Jack N Losso, John W Finley, Namrata Karki, Ann G Liu, Alfredo Prudente, Russell Tipton, Ying Yu, Frank L Greenway
BACKGROUND: Insomnia is common in the elderly and is associated with chronic disease, but use of hypnotics increases the incidence of falls. Montmorency tart cherry juice has improved insomnia by self-report questionnaire. STUDY QUESTION: Is insomnia confirmed by polysomnography and is tryptophan availability a potential mechanism for treating insomnia? STUDY DESIGN: A placebo-controlled balanced crossover study with subjects older than 50 years and insomnia were randomized to placebo (2 weeks) or cherry juice (2 weeks) (240 mL 2 times/d) separated by a 2-week washout...
March 27, 2017: American Journal of Therapeutics
https://www.readbyqxmd.com/read/28901485/a-novel-non%C3%A2-contact-communication-between-human-keratinocytes-and-t-cells-exosomes-derived-from-keratinocytes-support-superantigen%C3%A2-induced-proliferation-of-resting-t-cells
#17
Xiao-Wei Cai, Rong Zhu, Lei Ran, Yi-Qian Li, Ke Huang, Jing Peng, Wei He, Chun-Li Zhou, Ru-Peng Wang
It is widely accepted that keratinocytes act as non‑professional antigen‑presenting cells and support superantigen‑induced proliferation of resting T cells; however, it remains unknown whether keratinocytes function in situ with T cells via a non‑contact mechanism. The current study used a transwell co‑culture system and demonstrated, for the first time to the best of the authors' knowledge, that HaCaT cells (the human keratinocyte cell line) did induce T cell proliferation via indirect contact. The data further indicated that exosomes, small membrane vesicles that transfer antigens to recipient cells, are also involved in the superantigen‑associated immunity of keratinocytes...
September 13, 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28899409/alcohol-consumption-and-breast-tumor-gene-expression
#18
Jun Wang, Yujing J Heng, A Heather Eliassen, Rulla M Tamimi, Aditi Hazra, Vincent J Carey, Christine B Ambrosone, Victor P de Andrade, Adam Brufsky, Fergus J Couch, Tari A King, Francesmary Modugno, Celine M Vachon, David J Hunter, Andrew H Beck, Susan E Hankinson
BACKGROUND: Alcohol consumption is an established risk factor for breast cancer and the association generally appears stronger among estrogen receptor (ER)-positive tumors. However, the biological mechanisms underlying this association are not completely understood. METHODS: We analyzed messenger RNA (mRNA) microarray data from both invasive breast tumors (N = 602) and tumor-adjacent normal tissues (N = 508) from participants diagnosed with breast cancer in the Nurses' Health Study (NHS) and NHSII...
September 12, 2017: Breast Cancer Research: BCR
https://www.readbyqxmd.com/read/28895871/type-i-interferons-in-the-pathogenesis-and-treatment-of-canine-diseases
#19
REVIEW
Daniela Klotz, Wolfgang Baumgärtner, Ingo Gerhauser
Type I interferons (IFNs) such as IFN-α, IFN-β, IFN-ε, IFN-κ, and IFN-ω represent cytokines, which are deeply involved in the regulation and activation of innate and adaptive immune responses. They possess strong antiviral, antiproliferative, and immunomodulatory activities allowing their use in the therapy of different viral diseases, neoplasms, and immune-mediated disorders, respectively. Initially, treatment strategies were based on nonspecific inducers of type I IFNs, which were soon replaced by different recombinant proteins...
September 2017: Veterinary Immunology and Immunopathology
https://www.readbyqxmd.com/read/28895584/effects-of-lobeglitazone-a-novel-thiazolidinedione-on-adipose-tissue-remodeling-and-brown-and-beige-adipose-tissue-development-in-db-db-mice
#20
G Kim, Y-H Lee, M R Yun, J-Y Lee, E G Shin, B-W Lee, E S Kang, B-S Cha
BACKGROUND/OBJECTIVES: We investigated the effect of long-term treatment with lobeglitazone, a novel thiazolidinedione-based activator of PPARγ, on adipose tissue (AT), focusing on its effects on insulin resistance in obese db/db mice. METHODS: Seven-week-old male db/db mice were assigned to either a vehicle-treated (n=8) or lobeglitazone-treated (n=8) group. Lobeglitazone (1 mg/kg daily) was injected intraperitoneally for 20 weeks. RESULTS: Lobeglitazone treatment for 20 weeks resulted in a remarkably improved glycemic index, including significantly decreased glucose levels, enhanced insulin sensitivity, and preserved pancreatic beta cells...
September 12, 2017: International Journal of Obesity: Journal of the International Association for the Study of Obesity
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