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https://www.readbyqxmd.com/read/29055015/small-molecule%C3%A2-inhibition-of-pd-1-transcription-is-an-effective-alternative-to-antibody-blockade-in-cancer-therapy
#1
Alison Taylor, David Rothstein, Christopher Rudd
The impact of PD-1 immune checkpoint therapy prompts exploration of other strategies to downregulate PD-1 for cancer therapy. We previously showed that the serine/threonine kinase, glycogen synthase kinase GSK-3α/β, is a central regulator of PD-1 transcription in CD8+ T cells. Here, we show that the use of small molecule inhibitors of GSK-3α/β (GSK-3i) to reduce pcdc1 (PD-1) transcription and expression was as effective as anti-PD-1 and PDL-1 blocking antibodies in the control of B16 melanoma, or EL4 lymphoma, in primary tumor and metastatic settings...
October 20, 2017: Cancer Research
https://www.readbyqxmd.com/read/29054968/pivotal-neuroinflammatory-and-therapeutic-role-of-high-mobility-group-box-1-in-ischemic-stroke
#2
Seidu A Richard, Marian Sackey, Zhaoliang Su, Huaxi Xu
Stroke is a major cause of mortality and disability worldwide. Stroke is a frequent and severe neurovascular disorder. The main cause of stroke is atherosclerosis, and the most common risk factor for atherosclerosis is hypertension. Therefore, prevention and treatment of stroke are crucial issues in humans. High mobility group box 1 (HMGB1) is non-histone nuclear protein that is currently one of the crucial pro-inflammatory alarmin in ischemic stroke (IS). It is instantly released from necrotic cells in the ischemic core and activates an early inflammatory response...
October 20, 2017: Bioscience Reports
https://www.readbyqxmd.com/read/29054947/a-case-of-tuberculous-gumma-there-is-more-to-it-than-meets-the-eye
#3
Srikant Mohta, Arvind Kumar, Nayani Singh, Naveet Wig
We present a case of a young girl who presented with multiple cutaneous abscesses over 2 years at different sites. She had no constitutional symptoms or history of tuberculosis. On investigation, she was found to have rifampicin-sensitive tuberculosis presenting as tubercular gumma, a rare form of cutaneous tuberculosis which occurs due to haematogenous spread of the bacilli. She had disseminated disease involving the spinal column with associated psoas abscess. A thorough evaluation was done for immune-deficiency workup but was all negative...
October 19, 2017: BMJ Case Reports
https://www.readbyqxmd.com/read/29054890/natural-killer-t-cell-immunotherapy-in-combination-with-chemotherapy-induced-immunogenic-cell-death-targets-metastatic-breast-cancer
#4
Simon Gebremeskel, Lynnea Lobert, Kaitlyn Tanner, Brynn Walker, Tora Oliphant, Livia E Clarke, Graham Dellaire, Brent Johnston
Natural killer T (NKT) cells are glycolipid-reactive lymphocytes that promote cancer control. In previous studies, NKT-cell activation improved survival and antitumor immunity in a post-surgical mouse model of metastatic breast cancer. Herein, we investigated whether NKT-cell activation could be combined with chemotherapeutic agents to augment therapeutic outcomes. Gemcitabine and cyclophosphamide analogs enhanced the potential immunogenicity of 4T1 mammary carcinoma cells by increasing the expression of antigen-presenting molecules (MHC-I, MHC-II, and CD1d) and promoting exposure or release of immunogenic cell death markers (calreticulin, HMGB1 and ATP)...
October 20, 2017: Cancer Immunology Research
https://www.readbyqxmd.com/read/29054858/mirna-directed-cancer-therapies-implications-in-melanoma-intervention
#5
Anita Thyagarajan, Ahmed Shaban, Ravi P Sahu
Acquired tumor resistance to cancer therapies pose major challenges in the treatment of cancers including melanoma. Among several signaling pathways or factors that affect neocarcinogenesis, cancer progression and therapies, altered microRNAs (miRNAs) expression has been identified as crucial players in modulating the key pathways governing these events. While studies on miRNA field has grown exponentially in the last decade, much remains to be discovered, particularly with respect to their roles in cancer therapies...
October 20, 2017: Journal of Pharmacology and Experimental Therapeutics
https://www.readbyqxmd.com/read/29054828/cloning-and-expression-study-of-an-irf4a-gene-and-its-two-transcript-variants-in-turbot-scophthalmus-maximus
#6
Song Li, Guobin Hu, Zhipeng Chen, Lianfei Song, Guanjie Wang, Dahai Liu, Qiuming Liu
Interferon regulatory factor 4 (IRF4) is known to be involved in antiviral response as well as regulation of functional and developmental processes in lymphomyeloid cell lineages in mammals. In this study, the gene of IRF4a and its two transcript variants (named IRF4a1 and -2) were cloned from turbot, Scophthalmus maximus, the tissue distributions and in vivo immune responsive expression patterns of the two transcripts were subsequently examined. The Scophthalmus maximus (Sm)IRF4a gene is 8367 nucleotide (nt) in length, consisting of eight exons and seven introns...
October 17, 2017: Fish & Shellfish Immunology
https://www.readbyqxmd.com/read/29054784/developing-a-xenograft-human-tumor-model-in-immunocompetent-mice
#7
Matthew T Basel, Sanjeev Narayanan, Chanran Ganta, Tej B Shreshta, Alejandro Marquez, Marla Pyle, Jennifer Hill, Stefan H Bossmann, Deryl L Troyer
Animal models are essential to cancer research, but current xenograft models are limited in their utility especially due to the lack of an immune system. Here we demonstrate that a xenograft tumor model can be developed in immunocompetent mice by tolerizing murine fetuses to human tumor cells. A375 human melanoma cells were injected into day E14 fetuses and after birth mice were challenged with A375 cells to determine their ability to develop tumors. Intravenous injections of cells resulted in metastatic-like lung tumors, which were verified to be human in origin by immunohistochemistry and PCR...
October 17, 2017: Cancer Letters
https://www.readbyqxmd.com/read/29054692/plasmacytoid-dendritic-cells-drive-acute-exacerbations-of-asthma
#8
Aikaterini-Dimitra Chairakaki, Maria-Ioanna Saridaki, Katerina Pyrillou, Marios-Angelos Mouratis, Ourania Koltsida, Ross P Walton, Nathan W Bartlett, Athanasios Stavropoulos, Louis Boon, Nikoletta Rovina, Nikolaos G Papadopoulos, Sebastian L Johnston, Evangelos Andreakos
BACKGROUND: Although acute exacerbations, mostly triggered by viruses, account for the majority of hospitalizations in asthma, there is still very little known about the pathophysiological mechanisms involved. Plasmacytoid DCs (pDCs), prominent cells of antiviral immunity, exhibit pro-inflammatory or tolerogenic functions depending on the context, yet their involvement in asthma exacerbations remains unexplored. OBJECTIVES: We sought to investigate the role of pDCs in allergic airway inflammation and acute exacerbations of asthma...
October 17, 2017: Journal of Allergy and Clinical Immunology
https://www.readbyqxmd.com/read/29054595/the-n-acylethanolamine-acid-amidase-inhibitor-arn077-suppresses-inflammation-and-pruritus-in-a-mouse-model-of-allergic-dermatitis
#9
O Sasso, M Summa, A Armirotti, S Pontis, C De Mei, D Piomelli
N-acylethanolamine acid amidase (NAAA), a cysteine hydrolase highly expressed in macrophages and B-lymphocytes, catalyzes the degradation of palmitoylethanolamide (PEA). PEA is an agonist of peroxisome proliferator-activated receptor-α (PPAR-α) and an important regulator of pain and innate immunity. In the present study, we investigated the properties of the NAAA inhibitor, ARN077, in a mouse model of allergic contact dermatitis. Acute topical applications of ARN077 attenuated key signs of DNFB-induced dermatitis in a dose-dependent manner...
October 17, 2017: Journal of Investigative Dermatology
https://www.readbyqxmd.com/read/29054527/chitosan-based-particulate-systems-for-the-delivery-of-mucosal-vaccines-against-infectious-diseases
#10
REVIEW
Bijay Singh, Sushila Maharjan, Ki-Hyun Cho, LianHua Cui, In-Kyu Park, Yun-Jaie Choi, Chong-Su Cho
Given that most pathogens enter the body at mucosal surfaces for infection and mucosal immune responses act as the first line of defense against the invading pathogens, mucosal vaccination is the most effective method to prevent infectious diseases. However, the development of mucosal vaccines requires an efficient antigen delivery system which should protect the antigens from physical elimination and enzymatic degradation, target mucosal inductive sites, and appropriately stimulate the mucosal and systemic immunity...
October 17, 2017: International Journal of Biological Macromolecules
https://www.readbyqxmd.com/read/29054496/cancer-immunotherapy-a-paradigm-shift-in-the-treatment-of-advanced-urologic-cancers
#11
REVIEW
David M Gill, Neeraj Agarwal
The recent resurgence of immunotherapy has transformed the therapeutic field of advanced urologic cancers. In this seminars issue, we evaluate the role of emerging and recently approved immunotherapeutic agents in advanced prostate, urothelial, and renal cell carcinoma. In each of these fields, we discuss recent regulatory approvals as well as promising ongoing clinical trials. Finally, we discuss incidence and management of immune related adverse events specifically associated with PD-1/PD-L1 inhibitors.
October 17, 2017: Urologic Oncology
https://www.readbyqxmd.com/read/29054459/lymphocyte-subset-analysis-in-quantiferon-tb-gold-plus-and-t-spot-tb-for-latent-tuberculosis-infection-in-rheumatoid-arthritis
#12
Hidetoshi Igari, Satoru Ishikawa, Takuya Nakazawa, Yoshihiro Oya, Hidekazu Futami, Mizue Tsuyuzaki, Kiminori Suzuki, Ryutaro Matsumura
Rheumatoid arthritis (RA) is an immune mediated inflammatory disorder, and immune suppressive drugs are prescribed. RA patients receiving treatments are in a kind of immunosuppressive condition that presents increased risk of developing active tuberculosis. Accurate diagnosis of latent tuberculosis infection (LTBI) is recommended for RA. QuantiFERON(®)-TB Gold Plus (QFT-Plus), a novel IGRA, has two tubes (TB1 and TB2). TB2 is designed to elicit both CD4 and CD8 T-cell responses, with expected increased sensitivity...
October 18, 2017: Journal of Infection and Chemotherapy: Official Journal of the Japan Society of Chemotherapy
https://www.readbyqxmd.com/read/29054421/selenocompounds-in-cancer-therapy-an-overview
#13
Desirée Bartolini, Luca Sancineto, Andreza Fabro de Bem, Kenneth D Tew, Claudio Santi, Rafael Radi, Pierangelo Toquato, Francesco Galli
In vitro and in vivo experimental models clearly demonstrate the efficacy of Se compounds as anticancer agents, contingent upon chemical structures and concentrations of test molecules, as well as on the experimental model under investigation that together influence cellular availability of compounds, their molecular dynamics and mechanism of action. The latter includes direct and indirect redox effects on cellular targets by the activation and altered compartmentalization of molecular oxygen, and the interaction with protein thiols and Se proteins...
2017: Advances in Cancer Research
https://www.readbyqxmd.com/read/29054417/the-regulation-of-pathways-of-inflammation-and-resolution-in-immune-cells-and-cancer-stem-cells-by-selenium
#14
Bastihalli T Diwakar, Arvind M Korwar, Robert F Paulson, K Sandeep Prabhu
Cancer is a complex disease where cancer stem cells (CSCs) maintain unlimited replicative potential, but evade chemotherapy drugs through cellular quiescence. CSCs are able to give rise to bulk tumor cells that have the capability to override antiproliferative signals and evade apoptosis. Numerous pathways are dysregulated in tumor cells, where increased levels of prooxidant reactive oxygen and nitrogen species can lead to localized inflammation to exacerbate all three stages of tumorigenesis: initiation, progression, and metastasis...
2017: Advances in Cancer Research
https://www.readbyqxmd.com/read/29054397/tolerance-in-clinical-liver-transplantation
#15
REVIEW
Josh Levitsky, Sandy Feng
While advances in immunosuppressive therapy have lowered the rate of acute rejection following liver transplantation, the consequence has been an increase in morbidity and mortality related to the lifelong need for maintenance immunosuppression. These complications include an increased risk of malignancy, infection, metabolic disorders, and chronic kidney disease, as well as high health care costs associated with these therapies and the required drug monitoring. Given these issues, most clinicians attempt trial and error dose minimization with variable success rates, and there has been significant interest in full drug withdrawal in select patients through research protocols...
October 17, 2017: Human Immunology
https://www.readbyqxmd.com/read/29054354/strategies-to-reduce-ischemia-reperfusion-injury-in-vascularized-composite-allotransplantation-of-the-limb
#16
REVIEW
Kavit R Amin, Jason K F Wong, James E Fildes
An important and often underinvestigated contributor to solid organ transplant rejection is ischemia reperfusion injury. This pathophysiological response releases damaging reactive oxygen species and cell stress signals that initiate inflammation, which has a critical role in priming the immune system for allorecognition. In time, this renders graft dysfunction and how this response is mediated in composite tissues remains unknown. Current protocols are drawn from solid organ transplantation with little scientific basis as to how this informs current hand transplantation practices...
October 18, 2017: Journal of Hand Surgery
https://www.readbyqxmd.com/read/29054268/saliva-exosomics-in-cancer-molecular-characterization-of-cancer-derived-exosomes-in-saliva
#17
Taichiro Nonaka, David T W Wong
Exosomes are small membrane vesicles of endocytic origin that are secreted by most cells and detected in saliva. Pathophysiological roles for salivary exosomes are beginning to be recognized in diseases including cancer, highlighting potential biomarkers and biological functions. Since early detection of cancer is vital for successful treatment, salivary exosomes would be advantageous in achieving a better survival rate due to their ready availability and noninvasiveness. The use of salivary exosomes may therefore be promising in the accurate detection of premalignant lesions and early-stage cancers, also for better our understanding of the molecular basis of tumorigenesis...
2017: Enzymes
https://www.readbyqxmd.com/read/29054249/hiv-1-infected-t-cells-dynamics-and-prognosis-an-evolutionary-game-model
#18
Bahareh Khazaei, Javad Salimi Sartakhti, Mohammad Hossein Manshaei, Quanyan Zhu, Mehdi Sadeghi, Seyed Rasoul Mousavi
BACKGROUND AND OBJECTIVE: Understanding the dynamics of human immunodeficiency virus (HIV) is essential for depicting, developing, and investigating effective treatment strategies. HIV infects several types of immune cells, but its main target is to destroy helper T-cells. In the lymph nodes, the infected T-cells interact with each other and their environment to obtain more resources. According to infectivity and replicative capacity of T-cells in the HIV infection process, they can be divided into four phenotypes...
December 2017: Computer Methods and Programs in Biomedicine
https://www.readbyqxmd.com/read/29054140/acetaminophen-toxicity-novel-insights-into-mechanisms-and-future-perspectives
#19
Anup Ramachandran, Hartmut Jaeschke
Acetaminophen (APAP) overdose is the most common cause of acute liver failure in the United States and decades of intense study of its pathogenesis resulted in development of the antidote Nacetylcysteine, which facilitates scavenging of the reactive metabolite and is the only treatment in clinical use. However, the narrow therapeutic window of this intervention necessitates a better understanding of the intricacies of APAP-induced liver injury for development of additional therapeutic approaches which can benefit late presenting patients...
October 20, 2017: Gene Expression
https://www.readbyqxmd.com/read/29054075/evaluation-of-immunological-markers-of-ovine-vaginal-irritation-implications-for-preclinical-assessment-of-non-vaccine-hiv-preventive-agents
#20
Gregg N Milligan, Gracie Vargas, Kathleen L Vincent, Yong Zhu, Nigel Bourne, Massoud Motamedi
The presence of genital inflammatory responses and a compromised vaginal epithelial barrier have been linked to an increased risk of HIV acquisition. It is important to assure that application of candidate microbicides designed to limit HIV transmission will not cause these adverse events. We previously developed high resolution in vivo imaging methodologies in sheep to assess epithelial integrity following vaginal application of a model microbicide, however characterization of genital inflammation in sheep has not been previously possible...
October 13, 2017: Journal of Reproductive Immunology
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