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programmed death-1

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https://www.readbyqxmd.com/read/28643391/fatal-orthotopic-liver-transplant-organ-rejection-induced-by-a-checkpoint-inhibitor-in-two-patients-with-refractory-metastatic-hepatocellular-carcinoma
#1
Brian D Friend, Robert S Venick, Sue V McDiarmid, Xiaoyan Zhou, Bita Naini, Hanlin Wang, Douglas G Farmer, Ronald W Busuttil, Noah Federman
Although checkpoint inhibitor therapies have demonstrated significant efficacy in many malignancies, they have not been well studied in patients with a history of solid organ transplant. We describe two patients with recurrent, refractory, and progressive advanced fibrolamellar hepatocellular carcinoma (HCC) following orthotopic liver transplantation who received programmed cell death protein 1 (PD-1) inhibitor, nivolumab, on a patient access, off-label basis. Both rapidly developed irreversible acute liver rejection shortly after starting therapy, and ultimately died...
June 23, 2017: Pediatric Blood & Cancer
https://www.readbyqxmd.com/read/28643244/durvalumab-first-global-approval
#2
Yahiya Y Syed
Intravenous durvalumab (Imfinzi™; AstraZeneca) is a fully human monoclonal antibody that blocks programmed cell death ligand-1 binding to its receptors (PD-1 and CD80), resulting in enhanced T-cell responses against cancer cells. The US FDA has granted durvalumab accelerated approval for the treatment of patients with locally advanced or metastatic urothelial carcinoma who have disease progression during or following platinum-containing chemotherapy, or within 12 months of neoadjuvant or adjuvant platinum-containing chemotherapy...
June 22, 2017: Drugs
https://www.readbyqxmd.com/read/28643044/pd-1-signaling-and-inhibition-in-aml-and-mds
#3
REVIEW
Faysal Haroun, Sade A Solola, Samah Nassereddine, Imad Tabbara
Acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS) are clinically and molecularly heterogeneous clonal myeloid disorders with a poor prognosis especially in the relapsed refractory setting and in patients above the age of 60. While allogeneic hematopoietic stem cell transplantation (ASCT) is a potentially curative approach, high relapse, morbidity, and mortality rates necessitate the development of alternative therapies. Immune checkpoint inhibitors unmask tumoral immune tolerance and have demonstrated efficacy in the treatment of chemotherapy-resistant hematologic and solid malignancies...
June 22, 2017: Annals of Hematology
https://www.readbyqxmd.com/read/28643032/fall-from-heights-does-height-really-matter
#4
G Alizo, J D Sciarretta, S Gibson, K Muertos, A Romano, J Davis, A Pepe
INTRODUCTION: Fall from heights is high energy injuries and constitutes a fraction of all fall-related trauma evaluations while bearing an increase in morbidity and mortality. We hypothesize that despite advancements in trauma care, the overall survivability has not improved in this subset of trauma patients. METHODS: All adult trauma patients treated after sustaining a fall from heights during a 40-month period were retrospectively reviewed. Admission demographics, clinical data, fall height (ft), injury patterns, ISS, GCS, length of stay, and mortality were reviewed...
June 22, 2017: European Journal of Trauma and Emergency Surgery: Official Publication of the European Trauma Society
https://www.readbyqxmd.com/read/28643011/prevalence-and-risk-factors-for-cardiac-arrest-and-myocardial-infarction-after-pelvic-reconstructive-surgery-a-national-multi-institutional-surgical-database-study
#5
David Sheyn, Sangeeta Mahajan, Sherif El-Nashar, Adonis Hijaz, Xiao-Yu Wang, Jeff Mangel
INTRODUCTION AND HYPOTHESIS: There is limited data available regarding the risk for perioperative cardiac morbidity following pelvic reconstructive surgery (PRS). We sought to determine the incidence of cardiac arrest and myocardial infarction within 30 days of pelvic organ prolapse (POP) surgery and determine which factors may contribute to an increased risk of these complications. METHODS: Using the American College of Surgeons National Quality Improvement Program (NSQIP) database, we identified patients who underwent PRS procedures between 2010 to 2015 using Current Procedural Terminology (CPT) codes...
June 22, 2017: International Urogynecology Journal
https://www.readbyqxmd.com/read/28642997/pd-1-and-cancer-molecular-mechanisms-and-polymorphisms
#6
REVIEW
Arash Salmaninejad, Vahid Khoramshahi, Alireza Azani, Ehsan Soltaninejad, Saeed Aslani, Mohammad Reza Zamani, Masoud Zal, Abolfazl Nesaei, Sayed Mostafa Hosseini
The programmed cell death protein 1 (PD-1) is expressed by activated T cells that act as an immunoregulatory molecule, and are responsible for the negative regulation of T cell activation and peripheral tolerance. The PD-1 gene also encodes an inhibitory cell surface receptor involved in the regulation of T cell functions during immune responses/tolerance. Beyond potent inhibitory effects on T cells, PD-1 also has a role in regulating B cell and monocyte responses. An overexpression of PD-1 has been reported to contribute to immune system avoidance in different cancers...
June 22, 2017: Immunogenetics
https://www.readbyqxmd.com/read/28641702/-prospect-and-current-situation-of-immune-checkpoint-inhibitors-%C3%A2-in-first-line-treatment-in-advanced-non-small-cell-lung-cancer-patients
#7
Haiyang Wang, Xiaoqing Yu, Yun Fan
With the breakthroughs achieved of programmed death-1 (PD-1)/PD-L1 inhibitors monotherapy as first-line and second-line treatment in advanced non-small cell lung cancer (NSCLC), the treatment strategy is gradually evolving and optimizing. Immune combination therapy expands the benefit population and improves the curative effect. A series of randomized phase III trials are ongoing. In this review, we discuss the prospect and current situation of immune checkpoint inhibitors in first-line treatment in advanced NSCLC patients...
June 20, 2017: Zhongguo Fei Ai za Zhi, Chinese Journal of Lung Cancer
https://www.readbyqxmd.com/read/28641163/6-shogaol-induces-autophagic-cell-death-then-triggered-apoptosis-in-colorectal-adenocarcinoma-ht-29-cells
#8
Ting-Yi Li, Been-Huang Chiang
6-shogaol is a phytochemical of dietary ginger, we found that 6-shogaol could induced both autophagic and apoptotic death in human colon adenocarcinoma (HT-29) cells. Results of this study showed that 6-shogal induced cell cycle arrest, autophagy, and apoptosis in HT-29 cells in a time sequence. After 6h, 6-shogal induced apparent G2/M arrest, then the HT-29 cells formed numerous autophagosomes in each phase of the cell cycle. After 18h, increases in acidic vesicles and LAMP-1 (Lysosome-associated membrane proteins 1) showed that 6-shogaol had caused autophagic cell death...
June 19, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28640823/estimating-the-number-of-secondary-ebola-cases-resulting-from-an-unsafe-burial-and-risk-factors-for-transmission-during-the-west-africa-ebola-epidemic
#9
Amanda Tiffany, Benjamin D Dalziel, Hilary Kagume Njenge, Ginger Johnson, Roselyn Nugba Ballah, Daniel James, Abdoulaye Wone, Juliet Bedford, Amanda McClelland
BACKGROUND: Safely burying Ebola infected individuals is acknowledged to be important for controlling Ebola epidemics and was a major component of the 2013-2016 West Africa Ebola response. Yet, in order to understand the impact of safe burial programs it is necessary to elucidate the role of unsafe burials in sustaining chains of Ebola transmission and how the risk posed by activities surrounding unsafe burials, including care provided at home prior to death, vary with human behavior and geography...
June 2017: PLoS Neglected Tropical Diseases
https://www.readbyqxmd.com/read/28640005/intussusception-related-hospitalizations-among-infants-before-and-after-private-market-licensure-of-rotavirus-vaccines-in-taiwan-2001-2013
#10
Catherine Yen, Shu-Man Shih, Jacqueline E Tate, Fang-Tzy Wu, Yhu-Chering Huang, Umesh D Parashar, Chao A Hsiung
INTRODUCTION: Rotavirus is a leading cause of acute gastroenteritis among Taiwanese children. Two globally licensed rotavirus vaccines recommended for inclusion in routine immunization programs that have been available for private market use in Taiwan since 2006 have been associated with a low risk of intussusception in post-marketing studies conducted in several countries. Our objective was to examine trends and characteristics of intussusception hospitalizations in Taiwan among children aged <12 months before and after rotavirus vaccine licensure to provide updated baseline and early post-licensure data...
June 17, 2017: Pediatric Infectious Disease Journal
https://www.readbyqxmd.com/read/28638792/immunotherapy-in-pancreatic-cancer-unleash-its-potential-through-novel-combinations
#11
REVIEW
Songchuan Guo, Merly Contratto, George Miller, Lawrence Leichman, Jennifer Wu
Pancreatic cancer is the third leading cause of cancer mortality in both men and women in the United States, with poor response to current standard of care, short progression-free and overall survival. Immunotherapies that target cytotoxic T lymphocyte antigen-4, programmed cell death protein-1, and programmed death-ligand 1 checkpoints have shown remarkable activities in several cancers such as melanoma, renal cell carcinoma, and non-small cell lung cancer due to high numbers of somatic mutations, combined with cytotoxic T-cell responses...
June 10, 2017: World Journal of Clinical Oncology
https://www.readbyqxmd.com/read/28638740/tumor-cells-pd-l1-expression-as-a-favorable-prognosis-factor-in-nasopharyngeal-carcinoma-patients-with-pre-existing-intratumor-infiltrating-lymphocytes
#12
Qian Zhu, Mu-Yan Cai, Chang-Long Chen, Hao Hu, Huan-Xin Lin, Min Li, De-Sheng Weng, Jing-Jing Zhao, Ling Guo, Jian-Chuan Xia
Programmed death ligand 1 (PD-L1) expression represents a mechanism of immune escape by inhibiting T cell immunity. This study systematically evaluated the expression of PD-L1, spatial distribution of CD3(+) immune cells and the relationship of both factors to survival in nasopharyngeal carcinoma (NPC) patients. A total of 209 NPC patients treated between 1991 and 2000 were included. Pairs of TMAs were immunohistochemically stained with PD-L1 and CD3. Survival analysis was evaluated according to PD-L1 status and the spatial distribution of CD3(+) immune cells in the primary lesion microenvironment...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/28638732/serum-levels-of-soluble-programmed-death-protein-1-spd-1-and-soluble-programmed-death-ligand-1-spd-l1-in-advanced-pancreatic-cancer
#13
Stephan Kruger, Marie-Louise Legenstein, Verena Rösgen, Michael Haas, Dominik Paul Modest, Christoph Benedikt Westphalen, Steffen Ormanns, Thomas Kirchner, Volker Heinemann, Stefan Holdenrieder, Stefan Boeck
Up to now, the efficacy of programmed death protein 1/programmed death ligand 1 (PD-1/PD-L1) blockade in pancreatic cancer (PC) remains uncertain. Serum levels of soluble PD-1 and PD-L1 (sPD-1/sPD-L1) have been reported to be independent prognostic factors in solid tumors susceptible to checkpoint blockade. Provenience, regulation and immunologic function of sPD-1 and sPD-L1 in cancer are poorly understood. To the best of our knowledge, sPD-1 and sPD-L1 have not been measured conjointly in any cancer type yet...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/28638727/identification-of-an-immunogenic-neo-epitope-encoded-by-mouse-sarcoma-using-cxcr3-ligand-mrnas-as-sensors
#14
Keisuke Fujii, Yoshihiro Miyahara, Naozumi Harada, Daisuke Muraoka, Mitsuhiro Komura, Rui Yamaguchi, Hideo Yagita, Junko Nakamura, Sahoko Sugino, Satoshi Okumura, Seiya Imoto, Satoru Miyano, Hiroshi Shiku
The CXCR3 ligands CXCL9, 10, and 11 play critical roles in the amplification of immune responses by recruiting CXCR3(+) immune effector cells to the tumor site. Taking advantage of this property of CXCR3 ligands, we aimed to establish a novel approach to identify immunogenic mutated-antigens. We examined the feasibility of using CXCR3 ligand mRNAs as sensors for detection of specific immune responses in human and murine systems. We further investigated whether this approach is applicable for the identification of immunogenic mutated-antigens by using murine sarcoma lines...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/28638381/anti-bovine-programmed-death-1-rat-bovine-chimeric-antibody-for-immunotherapy-of-bovine-leukemia-virus-infection-in-cattle
#15
Tomohiro Okagawa, Satoru Konnai, Asami Nishimori, Naoya Maekawa, Ryoyo Ikebuchi, Shinya Goto, Chie Nakajima, Junko Kohara, Satoshi Ogasawara, Yukinari Kato, Yasuhiko Suzuki, Shiro Murata, Kazuhiko Ohashi
Blockade of immunoinhibitory molecules, such as programmed death-1 (PD-1)/PD-ligand 1 (PD-L1), is a promising strategy for reinvigorating exhausted T cells and preventing disease progression in a variety of chronic infections. Application of this therapeutic strategy to cattle requires bovinized chimeric antibody targeting immunoinhibitory molecules. In this study, anti-bovine PD-1 rat-bovine chimeric monoclonal antibody 5D2 (Boch5D2) was constructed with mammalian expression systems, and its biochemical function and antiviral effect were characterized in vitro and in vivo using cattle infected with bovine leukemia virus (BLV)...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28637876/monocyte-derived-dendritic-cells-with-silenced-pd-1-ligands-and-transpresenting-interleukin-15-stimulate-strong-tumor-reactive-t-cell-expansion
#16
Johan Mj Van den Bergh, Evelien Ljm Smits, Zwi N Berneman, Tim Ja Hutten, Hans De Reu, Viggo Fi Van Tendeloo, Harry Dolstra, Eva Lion, Willemijn Hobo
Although allogeneic stem cell transplantation (allo-SCT) can elicit graft-versus-tumor (GVT) immunity, patients often relapse due to residual tumor cells. As essential orchestrators of the immune system, vaccination with dendritic cells (DCs) is an appealing strategy to boost the GVT-response. Nevertheless, durable clinical responses after DC vaccination are still limited, stressing the need to improve current DC vaccines. Aiming to empower DC potency, we engineered monocyte-derived DCs to deprive them of ligands for the immune checkpoint regulated by programmed death 1 (PD-1)...
June 21, 2017: Cancer Immunology Research
https://www.readbyqxmd.com/read/28636985/changes-in-programmed-death-ligand-1-expression-during-cisplatin-treatment-in-patients-with-head-and-neck-squamous-cell-carcinoma
#17
Chan-Young Ock, Sehui Kim, Bhumsuk Keam, Soyeon Kim, Yong-Oon Ahn, Eun-Jae Chung, Jin-Ho Kim, Tae Min Kim, Seong Keun Kwon, Yoon Kyung Jeon, Kyeong Chun Jung, Dong-Wan Kim, Hong-Gyun Wu, Myung-Whun Sung, Dae Seog Heo
Programmed death-ligand 1 (PD-L1) expression is regarded as a predictive marker for anti-PD-1/PD-L1 therapy. The purpose of study was to explore the changes in PD-L1 expression in head and neck squamous cell carcinoma (HNSCC) during treatment. Paired HNSCC tissues prior to and after cisplatin-based treatment were evaluated to determine PD-L1 protein expression by immunohistochemistry. Among the 35 HNSCC patient samples, PD-L1 expression status changed after treatment in 37.1% (13/35) of samples. Among the 13 patients whose baseline PD-L1 was negative, PD-L1 expression was increased in 9 cases (69...
June 16, 2017: Oncotarget
https://www.readbyqxmd.com/read/28636851/first-line-nivolumab-in-stage-iv-or-recurrent-non-small-cell-lung-cancer
#18
COMMENT
David P Carbone, Martin Reck, Luis Paz-Ares, Benjamin Creelan, Leora Horn, Martin Steins, Enriqueta Felip, Michel M van den Heuvel, Tudor-Eliade Ciuleanu, Firas Badin, Neal Ready, T Jeroen N Hiltermann, Suresh Nair, Rosalyn Juergens, Solange Peters, Elisa Minenza, John M Wrangle, Delvys Rodriguez-Abreu, Hossein Borghaei, George R Blumenschein, Liza C Villaruz, Libor Havel, Jana Krejci, Jesus Corral Jaime, Han Chang, William J Geese, Prabhu Bhagavatheeswaran, Allen C Chen, Mark A Socinski
BACKGROUND: Nivolumab has been associated with longer overall survival than docetaxel among patients with previously treated non-small-cell lung cancer (NSCLC). In an open-label phase 3 trial, we compared first-line nivolumab with chemotherapy in patients with programmed death ligand 1 (PD-L1)-positive NSCLC. METHODS: We randomly assigned, in a 1:1 ratio, patients with untreated stage IV or recurrent NSCLC and a PD-L1 tumor-expression level of 1% or more to receive nivolumab (administered intravenously at a dose of 3 mg per kilogram of body weight once every 2 weeks) or platinum-based chemotherapy (administered once every 3 weeks for up to six cycles)...
June 22, 2017: New England Journal of Medicine
https://www.readbyqxmd.com/read/28636620/risk-of-ischemic-stroke-after-atrial-fibrillation-diagnosis-a-national-sample-cohort
#19
Mi Kyoung Son, Nam-Kyoo Lim, Hyung Woo Kim, Hyun-Young Park
Atrial fibrillation (AF) is a major risk factor for ischemic stroke and associated with a 5-fold higher risk of stroke. In this retrospective cohort study, the incidence of and risk factors for ischemic stroke in patients with AF were identified. All patients (≥30 years old) without previous stroke who were diagnosed with AF in 2007-2013 were selected from the National Health Insurance Service-National Sample Cohort. To identify factors that influenced ischemic stroke risk, Cox proportional hazard regression analysis was conducted...
2017: PloS One
https://www.readbyqxmd.com/read/28635644/pd-1-pd-l1-blockade-therapy-for-tumors-with-downregulated-mhc-class-i-expression
#20
REVIEW
Michal Šmahel
The therapy of different advanced-stage malignancies with monoclonal antibodies blocking programmed cell death protein 1 (PD-1)/PD-1 ligand 1 (PD-L1) signaling has had an impressive long-lasting effect in a portion of patients, but in most cases, this therapy was not successful, or a secondary resistance developed. To enhance its efficacy in treated patients, predictive biomarkers are searched for and various combination treatments are intensively investigated. As the downregulation of major histocompatibility complex (MHC) class I molecules is one of the most frequent mechanisms of tumor escape from the host's immunity, it should be considered in PD-1/PD-L1 checkpoint inhibition...
June 21, 2017: International Journal of Molecular Sciences
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