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Programmed Cell death AND disease

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https://www.readbyqxmd.com/read/29348848/pd-l1-expression-in-tumor-tissue-and-peripheral-blood-of-patients-with-oral-squamous-cell-carcinoma
#1
Manuel Weber, Falk Wehrhan, Christoph Baran, Abbas Agaimy, Maike Büttner-Herold, Raimund Preidl, Friedrich W Neukam, Jutta Ries
Background: Immune checkpoints like programmed cell death-1 (PD-1) and its ligand PD-L1 are involved in immune escape mechanisms of solid tumors including oral squamous cell carcinoma (OSCC). Inhibitors of the pathway are successfully used for treating especially advanced disease. However, the physiological relevance of PD-1/PD-L1-signaling in OSCC is insufficiently understood. The aim of the study was to analyze if PD-L1 expression in tumor tissue and peripheral blood samples of OSCC patients is associated with histomorphological tumor parameters and if PD-L1 expression in patients is different from controls...
December 22, 2017: Oncotarget
https://www.readbyqxmd.com/read/29348830/inactivation-deficiency-of-dhodh-induces-cell-cycle-arrest-and-programed-cell-death-in-melanoma
#2
Lichao Liu, Zhen Dong, Qian Lei, Jie Yang, Huanrong Hu, Qian Li, Yacong Ji, Leiyang Guo, Yanli Zhang, Yaling Liu, Hongjuan Cui
Malignant melanoma (MM) is one of the most malignant tumors and has a very poor prognosis. However, there are no effective drugs to treat this disease. As a kind of iron flavin dependent enzyme, dihydroorotate dehydrogenase (DHODH, EC 1.3.3.1) is the fourth and a key enzyme in the de novo biosynthesis of pyrimidines. Herein, we found that DHODH inactivation/deficiency inhibited melanoma cell proliferation, induced cell cycle arrest at S phase and lead to autophagy in human melanoma cells. Meanwhile, leflunomide treatment induced cell apoptosis and deficiency of DHODH sensitized cells to drug-induced apoptosis in BCL-2 deficient melanoma cells, while not in BCL-2 abundant melanoma cells...
December 22, 2017: Oncotarget
https://www.readbyqxmd.com/read/29347993/updated-efficacy-of-avelumab-in-patients-with-previously-treated-metastatic-merkel-cell-carcinoma-after-%C3%A2-1%C3%A2-year-of-follow-up-javelin-merkel-200-a-phase-2-clinical-trial
#3
Howard L Kaufman, Jeffery S Russell, Omid Hamid, Shailender Bhatia, Patrick Terheyden, Sandra P D'Angelo, Kent C Shih, Céleste Lebbé, Michele Milella, Isaac Brownell, Karl D Lewis, Jochen H Lorch, Anja von Heydebreck, Meliessa Hennessy, Paul Nghiem
BACKGROUND: Merkel cell carcinoma (MCC) is a rare, aggressive skin cancer associated with poor survival outcomes in patients with distant metastatic disease (mMCC). In an initial analysis from JAVELIN Merkel 200, a phase 2, prospective, open-label, single-arm trial in mMCC, avelumab-a human anti-programmed death-ligand 1 (PD-L1) monoclonal antibody-showed promising efficacy and a safety profile that was generally manageable and tolerable. Here, we report the efficacy of avelumab after ≥1 year of follow-up in patients with distant mMCC that had progressed following prior chemotherapy for metastatic disease...
January 19, 2018: Journal for Immunotherapy of Cancer
https://www.readbyqxmd.com/read/29345842/pd-l1-is-a-promising-blood-marker-for-predicting-tumor-progression-and-prognosis-in-patients-with-gastric-cancer
#4
Masahiko Amatatsu, Takaaki Arigami, Yoshikazu Uenosono, Shigehiro Yanagita, Yasuto Uchikado, Yuko Kijima, Hiroshi Kurahara, Yoshiaki Kita, Shinichiro Mori, Ken Sasaki, Itaru Omoto, Kosei Maemura, Sumiya Ishigami, Shoji Natsugoe
Immune checkpoint inhibitor therapy has been clinically introduced for several malignancies, and its effectiveness has been confirmed by clinical trials. In particular, programmed cell death protein 1 (PD-1) and programmed death-ligand 1 (PD-L1) are widely known as important immune checkpoint molecules associated with the mechanisms of immune escape by malignant tumor cells. On the other hand, liquid biopsy of blood specimens has the clinical benefit of providing a simple, repeatable sampling tool. Non-invasive liquid biopsy has recently been spotlighted as a promising approach to predicting tumor progression and prognosis...
January 18, 2018: Cancer Science
https://www.readbyqxmd.com/read/29345343/mycobacterium-tuberculosis-rewiring-host-cell-signaling-to-promote-infection
#5
REVIEW
Michael D Stutz, Michelle P Clark, Marcel Doerflinger, Marc Pellegrini
The ability of Mycobacterium tuberculosis to cause disease hinges upon successfully thwarting the innate defenses of the macrophage host cell. The pathogen's trump card is its armory of virulence factors that throw normal host cell signaling into disarray. This process of subverting the macrophage begins upon entry into the cell, when M. tuberculosis actively inhibits the fusion of the bacilli-laden phagosomes with lysosomes. The pathogen then modulates an array of host signal transduction pathways, which dampens the macrophage's host-protective cytokine response, while simultaneously adapting host cell metabolism to stimulate lipid body accumulation...
December 15, 2017: Journal of Leukocyte Biology
https://www.readbyqxmd.com/read/29339209/extratumoral-pd-1-blockade-does-not-perpetuate-obesity-associated-inflammation-in-esophageal-adenocarcinoma
#6
Karen C Galvin, Melissa J Conroy, Suzanne L Doyle, Margaret R Dunne, Ronan Fahey, Emma Foley, Katie E O'Sullivan, Derek G Doherty, Justin G Geoghegan, Narayanasamy Ravi, Cliona O'Farrelly, John V Reynolds, Joanne Lysaght
Checkpoint inhibitors, such as anti-PD-1 (Programmed death-1), are transforming cancer treatment for inoperable or advanced disease. As the incidence of obesity-associated malignancies, including esophageal adenocarcinoma (EAC) continue to increase and treatment with checkpoint inhibitors are being FDA approved for a broader range of cancers, it is important to assess how anti-PD-1 treatment might exacerbate pre-existing inflammatory processes at other sites. Outside the EAC tumor, the omentum and liver were found to be enriched with substantial populations of PD-1 expressing T cells...
January 12, 2018: Cancer Letters
https://www.readbyqxmd.com/read/29337640/molecular-determinants-of-response-to-anti-programmed-cell-death-pd-1-and-anti-programmed-death-ligand-pd-l-ligand-1-blockade-in-patients-with-non-small-cell-lung-cancer-profiled-with-targeted-next-generation-sequencing
#7
Hira Rizvi, Francisco Sanchez-Vega, Konnor La, Walid Chatila, Philip Jonsson, Darragh Halpenny, Andrew Plodkowski, Niamh Long, Jennifer L Sauter, Natasha Rekhtman, Travis Hollmann, Kurt A Schalper, Justin F Gainor, Ronglai Shen, Ai Ni, Kathryn C Arbour, Taha Merghoub, Jedd Wolchok, Alexandra Snyder, Jamie E Chaft, Mark G Kris, Charles M Rudin, Nicholas D Socci, Michael F Berger, Barry S Taylor, Ahmet Zehir, David B Solit, Maria E Arcila, Marc Ladanyi, Gregory J Riely, Nikolaus Schultz, Matthew D Hellmann
Purpose Treatment of advanced non-small-cell lung cancer with immune checkpoint inhibitors (ICIs) is characterized by durable responses and improved survival in a subset of patients. Clinically available tools to optimize use of ICIs and understand the molecular determinants of response are needed. Targeted next-generation sequencing (NGS) is increasingly routine, but its role in identifying predictors of response to ICIs is not known. Methods Detailed clinical annotation and response data were collected for patients with advanced non-small-cell lung cancer treated with anti-programmed death-1 or anti-programmed death-ligand 1 [anti-programmed cell death (PD)-1] therapy and profiled by targeted NGS (MSK-IMPACT; n = 240)...
January 16, 2018: Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology
https://www.readbyqxmd.com/read/29336323/nivolumab-for-recurrent-cutaneous-squamous-cell-carcinoma-three-cases
#8
Veronika Blum, Beat Müller, Silvia Hofer, Esther Pardo, Kristin Zeidler, Joachim Diebold, Klaus Strobel, Christoph Brand, Stefan Aebi, Oliver Gautschi
Programmed cell death ligand 1 (PD-L1) is frequently expressed in cutaneous squamous cell cancer (CSCC) and preliminary data from an ongoing clinical trial suggest that programmed death receptor 1 (PD-1) checkpoint inhibitors may be useful to treat patients with metastatic non-melanoma skin cancer. To report a series of three patients with advanced CSCC treated with nivolumab, showing that commercially available PD-1 checkpoint inhibitors may be useful in non-melanoma skin cancer patients without access to a clinical trial...
January 16, 2018: European Journal of Dermatology: EJD
https://www.readbyqxmd.com/read/29335088/-role-of-programmed-death-1-in-viral-infectious-diseases
#9
Fu-Ce Lu, Guang-Min Nong
The research on the immunoregulatory effect of programmed death-1 (PD-1) in infectious diseases mainly focuses on chronic viral infection, but there are few studies on acute viral infection. In chronic viral infection, PD-1 is highly expressed on the surface of CD8+ T cells, which is a sign of CD8+ T cell depletion. Recent studies have shown that in chronic viral infection, PD-1 is also highly expressed on the surface of regulatory T cells and binds to programmed death-ligand 1 (PD-L1) on the surface of exhausted CD8+ T cells, resulting in a stronger inhibitory effect on CD8+ T cell immunity...
January 2018: Zhongguo Dang Dai Er Ke za Zhi, Chinese Journal of Contemporary Pediatrics
https://www.readbyqxmd.com/read/29332300/long-term-exposure-to-cell-phone-frequencies-900-and-1800%C3%A2-mhz-induces-apoptosis-mitochondrial-oxidative-stress-and-trpv1-channel-activation-in-the-hippocampus-and-dorsal-root-ganglion-of-rats
#10
Kemal Ertilav, Fuat Uslusoy, Serdar Ataizi, Mustafa Nazıroğlu
Mobile phone providers use electromagnetic radiation (EMR) with frequencies ranging from 900 to 1800 MHz. The increasing use of mobile phones has been accompanied by several potentially pathological consequences, such as neurological diseases related to hippocampal (HIPPON) and dorsal root ganglion neuron (DRGN). The TRPV1 channel is activated different stimuli, including CapN, high temperature and oxidative stress. We investigated the contribution TRPV1 to mitochondrial oxidative stress and apoptosis in HIPPON and DRGN following long term exposure to 900 and 1800 MHz in a rat model...
January 13, 2018: Metabolic Brain Disease
https://www.readbyqxmd.com/read/29332285/immunity-associated-programmed-cell-death-as-a-tool-for-the-identification-of-genes-essential-for-plant-innate-immunity
#11
Bangjun Zhou, Lirong Zeng
Plants have evolved a sophisticated innate immune system to contend with potential infection by various pathogens. Understanding and manipulation of key molecular mechanisms that plants use to defend against various pathogens are critical for developing novel strategies in plant disease control. In plants, resistance to attempted pathogen infection is often associated with hypersensitive response (HR), a form of rapid programmed cell death (PCD) at the site of attempted pathogen invasion. In this chapter, we describe a method for rapid identification of genes that are essential for plant innate immunity...
2018: Methods in Molecular Biology
https://www.readbyqxmd.com/read/29332281/programmed-cell-death-in-plants-an-overview
#12
Vittoria Locato, Laura De Gara
Programmed cell death (PCD) is a controlled mechanism that eliminates specific cells under developmental or environmental stimuli. All organisms-from bacteria to multicellular eukaryotes-have the ability to induce PCD in selected cells. Although this process was first identified in plants, the interest in deciphering the signaling pathways leading to PCD strongly increased when evidence came to light that PCD may be involved in several human diseases. In plants, PCD activation ensures the correct occurrence of growth and developmental processes, among which embryogenesis and differentiation of tracheary elements...
2018: Methods in Molecular Biology
https://www.readbyqxmd.com/read/29331748/safety-and-efficacy-of-anti-programmed-death-1-antibodies-in-patients-with-cancer-and-pre-existing-autoimmune-or-inflammatory-disease
#13
François-Xavier Danlos, Anne-Laure Voisin, Valérie Dyevre, Jean-Marie Michot, Emilie Routier, Laurent Taillade, Stéphane Champiat, Sandrine Aspeslagh, Julien Haroche, Laurence Albiges, Christophe Massard, Nicolas Girard, Stéphane Dalle, Benjamin Besse, Salim Laghouati, Jean-Charles Soria, Christine Mateus, Caroline Robert, Emilie Lanoy, Aurélien Marabelle, Olivier Lambotte
OBJECTIVE: Patients with autoimmune or inflammatory disease (AID) are susceptible to immune-related adverse events (irAEs) when treated with immune check-point inhibitors (ICIs). We decided to analyse the safety and effectiveness of anti-PD-1 antibodies in AID patients and look for an association between the presence of pre-existing AID and the clinical outcome. METHODS: In a prospective study of the REISAMIC registry of grade ≥2 irAEs occurring in ICI-treated patients, we studied the associations between pre-existing AID on one hand and irAE-free survival, overall survival and best objective response rate on the other...
January 10, 2018: European Journal of Cancer
https://www.readbyqxmd.com/read/29330929/adipocytes-affect-castration-resistant-prostate-cancer-cells-to-develop-the-resistance-to-cytotoxic-action-of-nk-cells-with-alterations-of-pd-l1-nkg2d-ligand-levels-in-tumor-cells
#14
Lijun Xu, Mingjing Shen, Xiaodong Chen, Rongying Zhu, Dong-Rong Yang, Ying Tsai, Peter C Keng, Yuhchyau Chen, Soo Ok Lee
BACKGROUND: Obesity affects prostate cancer (PCa) progression, and the periprostatic adipose tissue adjacent to the prostate is considered a driving force of disease progression. Adipocytes are the main cell population in adipose tissues and their paracrine role contributes to PCa progression, however its implication in modulating immune reactions remains largely unknown. We investigated the adipocyte role in controlling the susceptibility of castration-resistant PCa (CRPC) cells to the cytotoxic action of natural killer (NK) cells...
January 12, 2018: Prostate
https://www.readbyqxmd.com/read/29329580/evidence-for-the-activation-of-pyroptotic-and-apoptotic-pathways-in-rpe-cells-associated-with-nlrp3-inflammasome-in-the-rodent-eye
#15
Jiangyuan Gao, Jing Z Cui, Eleanor To, Sijia Cao, Joanne A Matsubara
BACKGROUND: Age-related macular degeneration (AMD) is a devastating eye disease causing irreversible vision loss in the elderly. Retinal pigment epithelium (RPE), the primary cell type that is afflicted in AMD, undergoes programmed cell death in the late stages of the disease. However, the exact mechanisms for RPE degeneration in AMD are still unresolved. The prevailing theories consider that each cell death pathway works independently and without regulation of each other. Building upon our previous work in which we induced a short burst of inflammasome activity in vivo, we now investigate the effects of prolonged inflammasome activity on RPE cell death mechanisms in rats...
January 12, 2018: Journal of Neuroinflammation
https://www.readbyqxmd.com/read/29328976/pattern-of-programmed-cell-death-ligand-1-expression-and-cd8-positive-t-cell-infiltration-before-and-after-chemoradiotherapy-in-rectal-cancer
#16
Atsushi Ogura, Takashi Akiyoshi, Noriko Yamamoto, Hiroshi Kawachi, Yuichi Ishikawa, Seiichi Mori, Koji Oba, Masato Nagino, Yosuke Fukunaga, Masashi Ueno
BACKGROUND: The synergistic effect of combining immune checkpoint inhibitors with radiotherapy was reported recently, but there are few studies on programmed cell death-ligand 1 (PD-L1) expression in rectal cancer treated by preoperative chemoradiotherapy (CRT). The aim of the present study was to investigate the PD-L1 expression status before and after CRT and its association with clinicopathological characteristics and recurrence in rectal cancer. METHODS: Immunostainings of PD-L1 and CD8 were performed in 287 patients with rectal cancer treated by CRT...
January 9, 2018: European Journal of Cancer
https://www.readbyqxmd.com/read/29327044/association-of-the-lung-immune-prognostic-index-with-immune-checkpoint-inhibitor-outcomes-in-patients-with-advanced-non-small-cell-lung-cancer
#17
Laura Mezquita, Edouard Auclin, Roberto Ferrara, Melinda Charrier, Jordi Remon, David Planchard, Santiago Ponce, Luis Paz Ares, Laura Leroy, Clarisse Audigier-Valette, Enriqueta Felip, Jorge Zerón-Medina, Pilar Garrido, Solenn Brosseau, Gérard Zalcman, Julien Mazieres, Caroline Caramela, Jihene Lahmar, Julien Adam, Nathalie Chaput, Jean Charles Soria, Benjamin Besse
Importance: Derived neutrophils/(leukocytes minus neutrophils) ratio (dNLR) and lactate dehydrogenase (LDH) level have been correlated with immune checkpoint inhibitor (ICI) outcomes in patients with melanoma. Objective: To determine whether pretreatment dNLR and LDH are associated with resistance to ICIs in patients with advanced non-small cell lung cancer (NSCLC). Design, Setting, and Participants: Multicenter retrospective study with a test (n = 161) and a validation set (n = 305) treated with programmed death 1/programmed death ligand 1 (PD-1/PD-L1) inhibitors in 8 European centers, and a control cohort (n = 162) treated with chemotherapy only...
January 11, 2018: JAMA Oncology
https://www.readbyqxmd.com/read/29326986/measles-virus-background-and-oncolytic-virotherapy
#18
REVIEW
Sankhajit Bhattacharjee, Pramod Kumar Yadava
Measles is a highly transmissible disease caused by measles virus and remains a major cause of child mortality in developing countries. Measles virus nucleoprotein (N) encapsidates the RNA genome of the virus for providing protection from host cell endonucleases and for specific recognition of viral RNA as template for transcription and replication. This protein is over-expressed at the time of viral replication. The C-terminal of N protein is intrinsically disordered, which enables this protein to interact with several host cell proteins...
March 2018: Biochemistry and Biophysics Reports
https://www.readbyqxmd.com/read/29326816/immune-checkpoint-inhibition-prospects-for-prevention-and-therapy-of-hepatocellular-carcinoma
#19
REVIEW
Caryn L Elsegood, Janina Ee Tirnitz-Parker, John K Olynyk, George Ct Yeoh
The global prevalence of liver cancer is rapidly rising, mostly as a result of the amplified incidence rates of viral hepatitis, alcohol abuse and obesity in recent decades. Treatment options for liver cancer are remarkably limited with sorafenib being the gold standard for advanced, unresectable hepatocellular carcinoma but offering extremely limited improvement of survival time. The immune system is now recognised as a key regulator of cancer development through its ability to protect against infection and chronic inflammation, which promote cancer development, and eliminate tumour cells when present...
November 2017: Clinical & Translational Immunology
https://www.readbyqxmd.com/read/29325739/anti-programmed-cell-death-1-ligand-1-pd-1-pd-l1-antibodies-for-the-treatment-of-urothelial-carcinoma-state-of-the-art-and-future-development
#20
REVIEW
Thomas Powles, Andrea Necchi, Galit Rosen, Subramanian Hariharan, Andrea B Apolo
Immunotherapy with programmed cell death 1/ligand 1 (PD-1/PD-L1) checkpoint inhibitors has expanded a previously limited pool of effective treatment options for patients with metastatic urothelial carcinoma, particularly those with recurring or refractory disease and those who are ineligible for cisplatin. This review reports key findings from completed and ongoing clinical trials that highlight the potential of PD-1/PD-L1 blockade in urothelial carcinoma. A literature search was performed of PubMed, Embase, ClinicalTrials...
December 6, 2017: Clinical Genitourinary Cancer
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