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Programmed Cell death AND disease

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https://www.readbyqxmd.com/read/28813164/pembrolizumab-in-patients-with-extensive-stage-small-cell-lung-cancer-results-from-the-phase-ib-keynote-028-study
#1
Patrick A Ott, Elena Elez, Sandrine Hiret, Dong-Wan Kim, Anne Morosky, Sanatan Saraf, Bilal Piperdi, Janice M Mehnert
Purpose The safety and efficacy of pembrolizumab, a humanized monoclonal antibody against programmed death 1 (PD-1), were assessed in patients with programmed death ligand 1 (PD-L1)-expressing extensive-stage small-cell lung cancer (SCLC) in the multicohort, phase Ib open-label KEYNOTE-028 study ( ClinicalTrials.gov identifier: NCT02054806). Methods Patients with SCLC received pembrolizumab 10 mg/kg every 2 weeks for 24 months or until disease progression or intolerable toxicity occurred. PD-L1 expression was assessed by immunohistochemistry...
August 16, 2017: Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology
https://www.readbyqxmd.com/read/28808573/osimertinib-induced-interstitial-lung-disease-in-a-patient-with-non-small-cell-lung-cancer-pretreated-with-nivolumab-a-case-report
#2
Osamu Takakuwa, Tetsuya Oguri, Takehiro Uemura, Kazuki Sone, Satoshi Fukuda, Minami Okayama, Yoshihiro Kanemitsu, Hirotsugu Ohkubo, Masaya Takemura, Yutaka Ito, Ken Maeno, Akio Niimi
Osimertinib (AZD9291) is a third-generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor approved for EGFR-T790M-positive non-small cell lung cancer. A high incidence of interstitial lung disease (ILD) during combination treatment with osimertinib and anti-programmed cell death-ligand 1 (PD-L1) inhibitor has been reported. The current study presents a case of ILD development during osimertinib treatment following nivolumab (an anti-PD-1 antibody) treatment. The 59-year-old female was diagnosed with stage IV lung adenocarcinoma harboring a deletion in exon 19 of the EGFR gene...
September 2017: Molecular and Clinical Oncology
https://www.readbyqxmd.com/read/28807004/predictive-role-of-pd-l1-expression-in-the-response-of-renal-medullary-carcinoma-to-pd-1-inhibition
#3
Quaovi Sodji, Kandy Klein, Kavuri Sravan, Jigarkumar Parikh
BACKGROUND: Renal medullary carcinoma is one of the rarest malignancies arising from the kidney. Despite various aggressive therapeutic regimens, mortality remains significantly high (95%) with a median overall survival of 5 months. Furthermore, the scarcity of this malignancy renders randomized clinical trials impossible. We examined the expression of programmed death ligand 1 (PD-L1) in two new renal medullary carcinoma cases, investigated their responses to the PD-L1 inhibitor nivolumab and explored the predictive role of the rate of PD-L1 expression in such response...
August 15, 2017: Journal for Immunotherapy of Cancer
https://www.readbyqxmd.com/read/28806116/systemic-therapy-for-stage-iv-non-small-cell-lung-cancer-american-society-of-clinical-oncology-clinical-practice-guideline-update
#4
Nasser Hanna, David Johnson, Sarah Temin, Sherman Baker, Julie Brahmer, Peter M Ellis, Giuseppe Giaccone, Paul J Hesketh, Ishmael Jaiyesimi, Natasha B Leighl, Gregory J Riely, Joan H Schiller, Bryan J Schneider, Thomas J Smith, Joan Tashbar, William A Biermann, Gregory Masters
Purpose Provide evidence-based recommendations updating the 2015 ASCO guideline on systemic therapy for patients with stage IV non-small-cell lung cancer (NSCLC). Methods The ASCO NSCLC Expert Panel made recommendations based on a systematic review of randomized controlled trials from February 2014 to December 2016 plus the Cancer Care Ontario Program in Evidence-Based Care's update of a previous ASCO search. Results This guideline update reflects changes in evidence since the previous guideline update. Fourteen randomized controlled trials provide the evidence base; earlier phase trials also informed recommendation development...
August 14, 2017: Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology
https://www.readbyqxmd.com/read/28798088/immune-checkpoint-inhibitors-associated-with-interstitial-lung-disease-in-cancer-patients
#5
Myriam Delaunay, Jacques Cadranel, Amélie Lusque, Nicolas Meyer, Valérie Gounaut, Denis Moro-Sibilot, Jean-Marie Michot, Judith Raimbourg, Nicolas Girard, Florian Guisier, David Planchard, Anne-Cécile Metivier, Pascale Tomasini, Eric Dansin, Maurice Pérol, Marion Campana, Oliver Gautschi, Martin Früh, Jean-David Fumet, Clarisse Audigier-Valette, Sébastien Couraud, Stéphane Dalle, Marie-Thérèse Leccia, Marion Jaffro, Samia Collot, Grégoire Prévot, Julie Milia, Julien Mazieres
Immunotherapy is becoming a standard of care for many cancers. Immune-checkpoint inhibitors (ICI) can generate immune-related adverse events. Interstitial lung disease (ILD) has been identified as a rare but potentially severe event.Between December 2015 and April 2016, we conducted a retrospective study in centres experienced in ICI use. We report the main features of ICI-ILD with a focus on clinical presentation, radiological patterns and therapeutic strategies.We identified 64 (3.5%) out of 1826 cancer patients with ICI-ILD...
August 2017: European Respiratory Journal: Official Journal of the European Society for Clinical Respiratory Physiology
https://www.readbyqxmd.com/read/28797000/new-molecular-biological-and-immunological-agents-inducing-hypophysitis
#6
Anna Angelousi, Eleftherios Chatzellis, Gregory Kaltsas
<br>Hypophysitis is a relatively rare disease that exerts a strong autoimmune component encompassing different aetiologies. Immunomodulatory drugs, such as interferon-α, are known to rarely induce hypophysitis. In recent years a large number of new biological and immunomodulatory agents have been introduced into clinical practice. Although immune suppressing agents used for the treatment of autoimmune disorders only rarely are associated with hypophysitis, it is commonly encountered with immunomodulatory agents used for the treatment of cancer...
August 8, 2017: Neuroendocrinology
https://www.readbyqxmd.com/read/28791012/extracellular-vesicles-transfer-the-receptor-programmed-death-1-in-rheumatoid-arthritis
#7
Stinne R Greisen, Yan Yan, Aida S Hansen, Morten T Venø, Jens R Nyengaard, Søren K Moestrup, Malene Hvid, Gordon J Freeman, Jørgen Kjems, Bent Deleuran
INTRODUCTION: Extracellular vesicles (EVs) have been recognized as route of communication in the microenvironment. They transfer proteins and microRNAs (miRNAs) between cells, and possess immunoregulatory properties. However, their role in immune-mediated diseases remains to be elucidated. We hypothesized a role for EVs in the rheumatoid arthritis (RA) joint, potentially involving the development of T cell exhaustion and transfer of the co-inhibitory receptor programmed death 1 (PD-1)...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28782624/post-translational-modifications-of-the-mitochondrial-f1fo-atpase
#8
REVIEW
Salvatore Nesci, Fabiana Trombetti, Vittoria Ventrella, Alessandra Pagliarani
BACKGROUND: The mitochondrial F1FO-ATPase has the main role in synthesizing most of ATP, thus providing energy to living cells, but it also works in reverse and hydrolyzes ATP, depending on the transmembrane electrochemical gradient. Within the same complex the vital role of the enzyme of life coexists with that of molecular switch to trigger programmed cell death. The two-faced vital/lethal role makes the enzyme complex an intriguing biochemical target to fight pathogens resistant to traditional therapies and diseases linked to mitochondrial dysfunctions...
August 4, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28781814/expression-of-programmed-death-ligand-1-predicts-poor-outcome-in-nasopharyngeal-carcinoma
#9
Ying-Fei Li, Jian-Wu Ding, Ling-Min Liao, Zhi-Lin Zhang, Shou-Sheng Liao, Ying Wu, Dan-Yang Zhou, An-Wen Liu, Long Huang
Programmed death ligand-1 (PD-L1) is a potentially important tumor immunotherapy target. However, whether PD-L1 expression is associated with survival in nasopharyngeal carcinoma (NPC) remains controversial. The aim of the present study was to investigate the association between PD-L1 expression and prognosis in NPC. The expression of PD-L1 was assessed in tumor specimens from 120 patients with NPC using immunohistochemistry. Staining was evaluated using the H-score method. The associations between PD-L1 expression and clinical characteristics and prognosis were analyzed...
September 2017: Molecular and Clinical Oncology
https://www.readbyqxmd.com/read/28774167/geographic-distribution-of-the-incidence-of-colorectal-cancer-in-iran-a-population-based-study
#10
Fatemeh Khosravi Shadmani, Erfan Ayubi, Salman Khazaei, Mohadeseh Sani, Shiva Mansouri Hanis, Somayeh Khazaei, Mokhtar Soheylizad, Kamyar Mansori
OBJECTIVES: Colorectal cancer (CRC) is the third most common cancer and the fourth most common cause of cancer death in the world. The aim of this study was to investigate the provincial distribution of the incidence of CRC across Iran. METHODS: This epidemiologic study used data from the National Cancer Registry of Iran and the Center for Disease Control and Prevention of the Ministry of Health and Medical Education of Iran. The average annual age-standardized rate (ASR) for the incidence of CRC was calculated for each province...
2017: Epidemiology and Health
https://www.readbyqxmd.com/read/28771957/bridging-pharmaceutical-chemistry-with-drug-and-nanoparticle-targeting-to-investigate-the-role-of-the-18-kda-translocator-protein-tspo
#11
REVIEW
Rosa Maria Iacobazzi, Antonio Lopalco, Annalisa Cutrignelli, Valentino Laquintana, Angela Lopedota, Massimo Franco, Nunzio Denora
An interesting mitochondrial biomarker is the 18-kDa mitochondrial translocator protein (TSPO). Decades of study have shown that this protein plays an important role in a wide range of cellular functions, including opening of the mitochondrial permeability transition pore as well as programmed cell death and proliferation. Variations in TSPO expression have been correlated to different diseases, from tumors to endocrine and neurological disorders. TSPO has therefore become an appealing target for both early diagnosis and selective mitochondrial drug delivery...
August 3, 2017: ChemMedChem
https://www.readbyqxmd.com/read/28768724/pd-l2-regulates-b-1-cell-antibody-production-against-phosphorylcholine-through-an-il-5-dependent-mechanism
#12
Jerome T McKay, Marcela A Haro, Christina A Daly, Rama D Yammani, Bing Pang, W Edward Swords, Karen M Haas
B-1 cells produce natural Abs which provide an integral first line of defense against pathogens while also performing important homeostatic housekeeping functions. In this study, we demonstrate that programmed cell death 1 ligand 2 (PD-L2) regulates the production of natural Abs against phosphorylcholine (PC). Naive PD-L2-deficient (PD-L2(-/-)) mice produced significantly more PC-reactive IgM and IgA. This afforded PD-L2(-/-) mice with selectively enhanced protection against PC-expressing nontypeable Haemophilus influenzae, but not PC-negative nontypeable Haemophilus influenzae, relative to wild-type mice...
August 2, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28767147/programmed-death-1-is-highly-expressed-on-cd8-cd57-t-cells-in-patients-with-stable-multiple-sclerosis-and-inhibits-their-cytotoxic-response-to-ebv
#13
Maria T Cencioni, Roberta Magliozzi, Richard Nicholas, Rehiana Ali, Omar Malik, Richard Reynolds, Giovanna Borsellino, Luca Battistini, Paolo Muraro
Growing evidence points to a deregulated response to Epstein-Barr virus (EBV) in the CNS of patients with Multiple Sclerosis (pwMS) as a possible cause of disease. In this study, we have investigated the response of a subpopulation of effector CD8+ T cells to EBV in 36 healthy donors and in 35 pwMS in active and inactive disease. We have measured the expression of markers of degranulation, the release of cytokines, cytotoxicity and the regulation of effector functions by inhibitory receptors, such as programmed death-1 (PD-1) and human inhibitor receptor Ig-like transcript 2 (ILT2)...
August 2, 2017: Immunology
https://www.readbyqxmd.com/read/28765602/arc-is-essential-for-maintaining-pancreatic-islet-structure-and-%C3%AE-cell-viability-during-type-2-diabetes
#14
Wendy M McKimpson, Min Zheng, Streamson C Chua, Jeffrey E Pessin, Richard N Kitsis
Pancreatic β-cell loss through apoptosis is an important disease mechanism in type 2 diabetes. Apoptosis Repressor with CARD (ARC) is a cell death inhibitor that antagonizes multiple death programs. We previously reported that ARC is abundant in pancreatic β-cells and modulates survival of these cells in vitro. Herein we assessed the importance of endogenous ARC in maintaining islet structure and function in vivo. While generalized loss of ARC did not result in detectable abnormalities, its absence in ob/ob mice, a model of type 2 diabetes, induced a striking pancreatic phenotype: marked β-cell death, loss of β-cell mass, derangements of islet architecture, and impaired glucose-stimulated insulin secretion in vivo...
August 1, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28765287/genetic-inhibition-of-receptor-interacting-protein-kinase-1-reduces-cell-death-and-improves-functional-outcome-after-intracerebral-hemorrhage-in-mice
#15
Sevda Lule, Limin Wu, Lauren M McAllister, William J Edmiston, Joon Yong Chung, Emily Levy, Yi Zheng, Peter J Gough, John Bertin, Alexei Degterev, Eng H Lo, Michael J Whalen
BACKGROUND AND PURPOSE: Recent studies using cultured cells and rodent intracerebral hemorrhage (ICH) models have implicated RIPK1 (receptor interacting protein kinase-1) as a driver of programmed necrosis and secondary injury based on use of chemical inhibitors. However, these inhibitors have off-target effects and cannot be used alone to prove a role for RIPK1. The aim of the current study was to examine the effect of genetic inhibition of the kinase domain of RIPK1 in a mouse ICH model...
August 1, 2017: Stroke; a Journal of Cerebral Circulation
https://www.readbyqxmd.com/read/28763140/necroptosis-in-the-periodontal-homeostasis-signals-emanating-from-dying-cells
#16
REVIEW
Jiao Li, XiaoJing Ke, Fuhua Yan, Lang Lei, Houxuan Li
Periodontal tissues are constantly exposed to microbial stimuli. The equilibrium between microbes and host defense system helps maintain the homeostasis in the periodontal microenvironment. Growth of pathogenic bacteria in dental biofilms may induce proinflammatory cytokine production to recruit sentinel cells, mainly neutrophils and monocytes into the gingival sulcus or the periodontal pocket. Moreover,dybiosis with over-growth of anaerobic pathogens, such as Porphyromonas gingivalis and Tannerella forsythia, may induce death of both immune cells and host resident cells...
August 1, 2017: Oral Diseases
https://www.readbyqxmd.com/read/28754154/prognostic-value-of-programmed-death-1-programmed-death-ligand-1-programmed-death-ligand-2-expression-and-cd8-t-cell-density-in-primary-tumors-and-metastatic-lymph-nodes-from-patients-with-stage-t1-4n-m0-gastric-adenocarcinoma
#17
Yuan Gao, Su Li, Dazhi Xu, Shangxiang Chen, Yuchen Cai, Wenqi Jiang, Xinke Zhang, Jin Sun, Kefeng Wang, Boyang Chang, Fenghua Wang, Minghuang Hong
BACKGROUND: Anti-programmed death-1/programmed death-ligand 1 (PD-1/PD-L1) immunotherapy has been proved to be effective on gastric cancer in ongoing clinical trials. However, the value of PD-L1 in predicting responses of patients with gastric cancer to anti-PD-1/PD-L1 immunotherapy is controversial. Some studies suggested that intra- and inter-tumoral heterogeneity of PD-L1 expression might explain the controversy. This study aimed to analyze the expression of PD-L1, PD-L2, and PD-1 as well as CD8(+) T-cell density in primary tumors and lymph nodes from patients with stage T1-4N+M0 gastric adenocarcinoma to explore the heterogeneity of PD-1 signaling pathway molecules...
July 29, 2017: Chinese Journal of Cancer
https://www.readbyqxmd.com/read/28754096/successful-treatment-with-anti-programmed-death-1-antibody-in-a-relapsed-natural-killer-t-cell-lymphoma-patient-with-multi-line-resistance-a-case-report
#18
Jianping Lai, Peng Xu, Xiaoliu Jiang, Shan Zhou, Anwen Liu
BACKGROUND: Extranodal natural killer/T-cell lymphoma (NKTCL), nasal type, is an aggressive malignancy with poor prognosis. Currently, there is no recommended standard therapy for relapsed NKTCL. CASE PRESENTATION: A 37-year-old woman with lymphadenopathy was diagnosed with NKTCL by biopsy of an enlarged lymph node on the right side of her neck. Enhanced computed tomography revealed no metastasis. For this patient, we performed continuous chemotherapy followed by radiotherapy; however, nodule biopsy showed metastases in her lower limbs 3 months after radiotherapy, which confirmed disease progression...
July 28, 2017: BMC Cancer
https://www.readbyqxmd.com/read/28751313/5-aminolevulinic-acid-dehydratase-gene-dosage-affects-programmed-cell-death-and-immunity
#19
Qichao Chai, Xiaoguang Shang, Shuang Wu, Guozhong Zhu, Chaoze Cheng, Caiping Cai, Xinyu Wang, Wangzhen Guo
Programmed cell death (PCD) is an important form to protect plants from pathogen attack. However, plants must precisely control the PCD process under microbe attacks to avoid detrimental effects. The complexity of how plants balance the defense activation and PCD requires further clarification. Lesion mimic mutants constitute an excellent material to study the crosstalk between them. Here, we identified a Gossypium hirsutum lesion mimic mutant (Ghlmm), which exhibits necrotic leaf damage and enhanced disease resistance...
July 27, 2017: Plant Physiology
https://www.readbyqxmd.com/read/28749918/immunotherapy-in-urothelial-cancer-part-2-adjuvant-neoadjuvant-and-adjunctive-treatment
#20
Steven S Yu, Leslie K Ballas, Eila C Skinner, Tanya B Dorff, Sarmad Sadeghi, David I Quinn
Urothelial cancer, which is predominantly seen in men, is common throughout the world. Most disease presents as non-muscle invasive bladder cancer (NMIBC), with cancer recurring or progressing to muscle invasive disease in more than 50% of patients after initial therapy. NMIBC is an immune responsive disease, as indicated by the use of intravesical bacillus Calmette-Guérin as treatment for more than 3 decades. The advent of T-cell checkpoint inhibitors, especially those directed at programmed death 1 (PD-1) and its ligand (PD-L1), has had a significant impact on the therapy of advanced urothelial cancer...
July 2017: Clinical Advances in Hematology & Oncology: H&O
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