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Programmed cell death

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https://www.readbyqxmd.com/read/28214657/ipilimumab-alone-or-in-combination-with-nivolumab-after-progression-on-anti-pd-1-therapy-in-advanced-melanoma
#1
Lisa Zimmer, Susmitha Apuri, Zeynep Eroglu, Lisa A Kottschade, Andrea Forschner, Ralf Gutzmer, Max Schlaak, Lucie Heinzerling, Angela M Krackhardt, Carmen Loquai, Svetomir N Markovic, Richard W Joseph, Kelly Markey, Jochen S Utikal, Carsten Weishaupt, Simone M Goldinger, Vernon K Sondak, Jonathan S Zager, Dirk Schadendorf, Nikhil I Khushalani
BACKGROUND: The anti-programmed cell death-1 (PD-1) inhibitors pembrolizumab and nivolumab alone or in combination with ipilimumab have shown improved objective response rates and progression-free survival compared to ipilimumab only in advanced melanoma patients. Anti-PD-1 therapy demonstrated nearly equal clinical efficacy in patients who had progressed after ipilimumab or were treatment-naïve. However, only limited evidence exists regarding the efficacy of ipilimumab alone or in combination with nivolumab after treatment failure to anti-PD-therapy...
February 16, 2017: European Journal of Cancer
https://www.readbyqxmd.com/read/28214654/programmed-cell-death-protein-1-pd-1-inhibitor-therapy-in-patients-with-advanced-melanoma-and-preexisting-autoimmunity-or-ipilimumab-triggered-autoimmunity
#2
Ralf Gutzmer, Anika Koop, Friedegund Meier, Jessica C Hassel, Patrick Terheyden, Lisa Zimmer, Lucie Heinzerling, Selma Ugurel, Claudia Pföhler, Anja Gesierich, Elisabeth Livingstone, Imke Satzger, Katharina C Kähler
AIM: Programmed cell death protein 1 (PD-1) inhibitors are a common treatment strategy for metastatic melanoma and other tumour entities. Clinical trials usually exclude patients with preexisting autoimmune diseases, thus experience with PD-1 inhibitor (PD-1i) in this patient population is limited. PATIENTS AND METHODS: Metastatic melanoma patients with preexisting autoimmune disorders or previous ipilimumab-triggered immune-related adverse events (irAE) undergoing treatment with PD-1i from seven German skin cancer centres were evaluated retrospectively with regard to flare of the preexisting autoimmunity and development of new, not preexisting irAE as well as response to PD-1i therapy...
February 16, 2017: European Journal of Cancer
https://www.readbyqxmd.com/read/28214651/a-review-on-the-evolution-of-pd-1-pd-l1-immunotherapy-for-bladder-cancer-the-future-is-now
#3
REVIEW
Joaquin Bellmunt, Thomas Powles, Nicholas J Vogelzang
The treatment of bladder cancer has evolved over time to encompass not only the traditional modalities of chemotherapy and surgery, but has been particularly impacted by the use of immunotherapy. The first immunotherapy was the live, attenuated bacterial Bacillus Calmette-Guérin vaccine, which has been the standard of care non-muscle-invasive bladder cancer since 1990. Modern immunotherapy has focused on inhibitors of checkpoint proteins, which are molecules that impede immune function, thereby allowing tumor cells to grow and proliferate unregulated...
February 2, 2017: Cancer Treatment Reviews
https://www.readbyqxmd.com/read/28214087/targeting-the-pd-1-pd-l1-axis-in-non-small-cell-lung-cancer
#4
REVIEW
Rajiv Kumar, Dearbhaile Collins, Saoirse Dolly, Fiona McDonald, Mary E R O'Brien, Timothy A Yap
The last decade has witnessed rapid advances in the discovery and development of immune checkpoint inhibitors in cancer medicine, particularly drugs targeting programmed cell death 1 (PD-1) and programmed cell death ligand 1 (PD-L1) in non-small cell lung cancer (NSCLC). The proven antitumor efficacy coupled with low rates of drug-related toxicities observed, albeit idiosyncratic, with these novel immunotherapeutics have led to the registration of multiple PD-1 and PD-L1 inhibitors, such as nivolumab, pembrolizumab, and atezolizumab, in second-line advanced NSCLC, whereas durvalumab and avelumab are in late-phase clinical testing...
December 23, 2016: Current Problems in Cancer
https://www.readbyqxmd.com/read/28213726/pd-1-and-pd-l1-antibodies-in-cancer-current-status-and-future-directions
#5
REVIEW
Arjun Vasant Balar, Jeffrey S Weber
Immunotherapy has moved to the center stage of cancer treatment with the recent success of trials in solid tumors with PD-1/PD-L1 axis blockade. Programmed death-1 or PD-1 is a checkpoint molecule on T cells that plays a vital role in limiting adaptive immune responses and preventing autoimmune and auto-inflammatory reactivity in the normal host. In cancer patients, PD-1 expression is very high on T cells in the tumor microenvironment, and PD-L1, its primary ligand, is variably expressed on tumor cells and antigen-presenting cells within tumors, providing a potent inhibitory influence within the tumor microenvironment...
February 17, 2017: Cancer Immunology, Immunotherapy: CII
https://www.readbyqxmd.com/read/28213434/malaria-during-pregnancy
#6
Michal Fried, Patrick E Duffy
One hundred and twenty-five million women in malaria-endemic areas become pregnant each year (see Dellicour et al. PLoS Med7: e1000221 [2010]) and require protection from infection to avoid disease and death for themselves and their offspring. Chloroquine prophylaxis was once a safe approach to prevention but has been abandoned because of drug-resistant parasites, and intermittent presumptive treatment with sulfadoxine-pyrimethamine, which is currently used to protect pregnant women throughout Africa, is rapidly losing its benefits for the same reason...
February 17, 2017: Cold Spring Harbor Perspectives in Medicine
https://www.readbyqxmd.com/read/28213003/the-expression-of-pd-l1-protein-as-a-prognostic-factor-in-lung-squamous-cell-carcinoma
#7
Kazuki Takada, Tatsuro Okamoto, Gouji Toyokawa, Yuka Kozuma, Taichi Matsubara, Naoki Haratake, Takaki Akamine, Shinkichi Takamori, Masakazu Katsura, Fumihiro Shoji, Yoshinao Oda, Yoshihiko Maehara
BACKGROUND: Programmed cell death-1 (PD-1)/programmed cell death-ligand 1 (PD-L1) pathway-targeted immunotherapy has become the standard option of care in the management of lung cancer. The expression of the PD-L1 protein in lung cancer is expected to be a prognostic factor or to predict the response to PD-1-blocking antibodies. However, the association between PD-L1 positivity and the clinicopathological features and patient outcomes in lung squamous cell carcinoma (SCC) remains unclear because the definitive cut-off value for the expression of PD-L1 protein remains to be established...
February 2017: Lung Cancer: Journal of the International Association for the Study of Lung Cancer
https://www.readbyqxmd.com/read/28212992/nivolumab-induced-interstitial-lung-disease-analysis-of-two-phase-ii-studies-patients-with-recurrent-or-advanced-non-small-cell-lung-cancer
#8
Terufumi Kato, Noriyuki Masuda, Yoichi Nakanishi, Masashi Takahashi, Toyoaki Hida, Hiroshi Sakai, Shinji Atagi, Shiro Fujita, Hiroshi Tanaka, Koji Takeda, Miyako Satouchi, Yoshinobu Namba, Tomohide Tamura
OBJECTIVES: Drug-induced interstitial lung disease (ILD) is often associated with high mortality; however it is difficult to predict and manage. we examined the clinical findings and imaging characteristics of nivolumab induced ILD reported in the two phase II studies patients with recurrent or advanced non-small-cell lung cancer. MATERIALS AND METHODS: We examined the clinical findings and imaging characteristics of all cases of ILD reported in two phase II trials of nivolumab, an anti-programmed death-1 antibody, in Japanese patients with recurrent or advanced non-small-cell lung cancer...
February 2017: Lung Cancer: Journal of the International Association for the Study of Lung Cancer
https://www.readbyqxmd.com/read/28212990/high-plasma-levels-of-soluble-programmed-cell-death-ligand-1-are-prognostic-for-reduced-survival-in-advanced-lung-cancer
#9
Yusuke Okuma, Yukio Hosomi, Yoshiro Nakahara, Kageaki Watanabe, Yukiko Sagawa, Sadamu Homma
OBJECTIVES: Programmed cell death-ligand 1 (PD-L1) expressed in tumor tissues is a key molecule for immune suppression, given its role in immune checkpoints. The significance and implication of soluble PD-L1 (sPD-L1) in the blood of lung cancer patients remain unknown. PATIENTS AND METHODS: Blood samples were prospectively collected from patients with advanced lung cancer, and the plasma sPD-L1 concentrations were measured by enzyme-linked immunosorbent assay. The correlations of the plasma sPD-L1 levels with clinico-pathological status, laboratory data, and survival of the patients were analyzed...
February 2017: Lung Cancer: Journal of the International Association for the Study of Lung Cancer
https://www.readbyqxmd.com/read/28212734/role-of-granule-proteases-in-the-life-and-death-of-neutrophils
#10
REVIEW
Charaf Benarafa, Hans-Uwe Simon
Neutrophils constitute a crucial component of the innate immune defenses against microbes. Produced in the bone marrow and patrolling in blood vessels, neutrophils are recruited to injured tissues and are immediately active to contain pathogen invasion. Neutrophils undergo programmed cell death by multiple, context-specific pathways, which have consequences on immunopathology and disease outcome. Studies in the last decade indicate additional functions for neutrophils - or a subset of neutrophils - in modulating adaptive responses and tumor progression...
January 15, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28212395/delayed-apoptosis-allows-islet-%C3%AE-cells-to-implement-an-autophagic-mechanism-to-promote-cell-survival
#11
Heather L Hayes, Brett S Peterson, Jonathan M Haldeman, Christopher B Newgard, Hans E Hohmeier, Samuel B Stephens
Increased β-cell death coupled with the inability to replicate existing β-cells drives the decline in β-cell mass observed in the progression of both major forms of diabetes. Understanding endogenous mechanisms of islet cell survival could have considerable value for the development of novel strategies to limit β-cell loss and thereby promote β-cell recovery. Insulinoma cells have provided useful insight into β-cell death pathways but observations made in cell lines sometimes fail to translate to primary islets...
2017: PloS One
https://www.readbyqxmd.com/read/28212363/vegf-inhibitors-in-renal-cell-carcinoma
#12
Pankit Vachhani, Saby George
The arrival of targeted therapies-vascular endothelial growth factor (VEGF) pathway inhibitors and mammalian target of rapamycin (mTOR) inhibitors-and programmed death 1 (PD-1) inhibitors has transformed the management of renal cell carcinoma (RCC). Once considered fatal, with a median survival of approximately 1 year, these agents have nearly tripled overall survival and have raised hopes of a possible cure for advanced RCC. This review begins with a brief discussion of the seminal von Hippel-Lindau/hypoxia-inducible factor axis in RCC...
December 2016: Clinical Advances in Hematology & Oncology: H&O
https://www.readbyqxmd.com/read/28212060/pembrolizumab-as-second-line-therapy-for-advanced-urothelial-carcinoma
#13
Joaquim Bellmunt, Ronald de Wit, David J Vaughn, Yves Fradet, Jae-Lyun Lee, Lawrence Fong, Nicholas J Vogelzang, Miguel A Climent, Daniel P Petrylak, Toni K Choueiri, Andrea Necchi, Winald Gerritsen, Howard Gurney, David I Quinn, Stéphane Culine, Cora N Sternberg, Yabing Mai, Christian H Poehlein, Rodolfo F Perini, Dean F Bajorin
Background Patients with advanced urothelial carcinoma that progresses after platinum-based chemotherapy have a poor prognosis and limited treatment options. Methods In this open-label, international, phase 3 trial, we randomly assigned 542 patients with advanced urothelial cancer that recurred or progressed after platinum-based chemotherapy to receive pembrolizumab (a highly selective, humanized monoclonal IgG4κ isotype antibody against programmed death 1 [PD-1]) at a dose of 200 mg every 3 weeks or the investigator's choice of chemotherapy with paclitaxel, docetaxel, or vinflunine...
February 17, 2017: New England Journal of Medicine
https://www.readbyqxmd.com/read/28211869/non-apoptotic-cell-death-in-animal-development
#14
REVIEW
Lena M Kutscher, Shai Shaham
Programmed cell death (PCD) is an important process in the development of multicellular organisms. Apoptosis, a form of PCD characterized morphologically by chromatin condensation, membrane blebbing, and cytoplasm compaction, and molecularly by the activation of caspase proteases, has been extensively investigated. Studies in Caenorhabditis elegans, Drosophila, mice, and the developing chick have revealed, however, that developmental PCD also occurs through other mechanisms, morphologically and molecularly distinct from apoptosis...
February 17, 2017: Cell Death and Differentiation
https://www.readbyqxmd.com/read/28211077/severe-bullous-pemphigoid-associated-with-pembrolizumab-therapy-for-metastatic-melanoma-with-complete-regression
#15
O Rofe, G Bar-Sela, Z Keidar, T Sezin, C D Sadik, R Bergman
Bullous pemphigoid (BP) is considered to be a humorally mediated autoimmune disease, but autoreactive T-cells and T-regulatory cells (Tregs) have also been implicated in this disease. Tregs and the programmed death-1 (PD-1) : programmed death ligand (PD-L) pathway are both critical in terminating immune response, and elimination of either can result in breakdown of tolerance and development of autoimmunity. We report a patient with metastatic malignant melanoma (MM), who underwent pembrolizumab (anti-PD-1) therapy following unsuccessful treatment with ipilimumab [anti-cytotoxic T-lymphocyte-associated protein (CTLA)-4]...
February 16, 2017: Clinical and Experimental Dermatology
https://www.readbyqxmd.com/read/28209995/rna-seq-based-transcriptomic-and-metabolomic-analysis-reveal-stress-responses-and-programmed-cell-death-induced-by-acetic-acid-in-saccharomyces-cerevisiae
#16
Yachen Dong, Jingjin Hu, Linlin Fan, Qihe Chen
As a typical harmful inhibitor in cellulosic hydrolyzates, acetic acid not only hinders bioethanol production, but also induces cell death in Saccharomyces cerevisiae. Herein, we conducted both transcriptomic and metabolomic analyses to investigate the global responses under acetic acid stress at different stages. There were 295 up-regulated and 427 down-regulated genes identified at more than two time points during acetic acid treatment (150 mM, pH 3.0). These differentially expressed genes (DEGs) were mainly involved in intracellular homeostasis, central metabolic pathway, transcription regulation, protein folding and stabilization, ubiquitin-dependent protein catabolic process, vesicle-mediated transport, protein synthesis, MAPK signaling pathways, cell cycle, programmed cell death, etc...
February 17, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28209992/from-basic-apoptosis-discoveries-to-advanced-selective-bcl-2-family-inhibitors
#17
REVIEW
Avi Ashkenazi, Wayne J Fairbrother, Joel D Leverson, Andrew J Souers
Members of the B cell lymphoma 2 (BCL-2) gene family have a central role in regulating programmed cell death by controlling pro-apoptotic and anti-apoptotic intracellular signals. In cancer, apoptosis evasion through dysregulation of specific BCL-2 family genes is a recurring event; accordingly, selective inhibition of specific anti-apoptotic BCL-2 family proteins represents an exciting therapeutic opportunity. A combination of nuclear magnetic resonance (NMR)-based screening and structure-based drug design has yielded the first bona fide BCL-2 homology 3 (BH3) mimetics, including the BCL-2 and BCL-XL dual antagonist navitoclax, which is the first BCL-2 family inhibitor to show efficacy in patients with cancer...
February 17, 2017: Nature Reviews. Drug Discovery
https://www.readbyqxmd.com/read/28207525/plasma-levels-of-soluble-programmed-death-ligand-1-may-be-associated-with-overall-survival-in-nonsmall-cell-lung-cancer-patients-receiving-thoracic-radiotherapy
#18
Jing Zhao, Peng Zhang, Jianhua Wang, Qingsong Xi, Xueqi Zhao, Minghua Ji, Guangyuan Hu
Immune-checkpoint signaling plays an important role in immunosuppression of tumors. We aimed to investigate the association of soluble programmed death-ligand 1 (sPD-L1) level in plasma with overall survival (OS) in locally advanced or inoperable nonsmall-cell lung cancer (NSCLC) patients treated with thoracic radiotherapy (TRT). We used ELISA to evaluate the sPD-L1 levels at diagnosis and during TRT in 126 clinically inoperable NSCLC patients. OS rates were followed up and recorded. SPSS software and GraphPad Prism 5 were used for statistics...
February 2017: Medicine (Baltimore)
https://www.readbyqxmd.com/read/28207501/pd-l1-pd-1-check-point-in-gastric-carcinoma-with-lymphoid-stroma-case-report-with-immunochemical-study
#19
Anna Crescenzi, Chiara Taffon, Michele Donati, Michele Pier Luca Guarino, Sergio Valeri, Roberto Coppola
INTRODUCTION: Gastric carcinoma with lymphoid stroma is an unusual type of gastric tumor associated with a better prognosis than typical gastric carcinomas. The hallmark of this cancer is a prominent lymphoid infiltration of the stroma that represents an intense host lymphocytic response. The programmed death 1-programmed death-ligand 1 (PD-1/PD-L1) axis has recently emerged as a master immune checkpoint that controls antitumor immune responses against many neoplasms. PATIENT'S CONCERNS CASE STUDY AND OUTCOME: We report the case of a male patient with gastric carcinoma with lymphoid stroma with a large mass infiltrating the gastric wall without nodal metastasis...
February 2017: Medicine (Baltimore)
https://www.readbyqxmd.com/read/28205127/apoptosis-induced-by-a-snake-venom-metalloproteinase-from-bothrops-alternatus-venom-in-c2c12-muscle-cells
#20
Soledad Bustillo, Andrea C Van de Velde, Verónica Matzner Perfumo, Claudia C Gay, Laura C Leiva
In this study, the apoptosis inducing effects of baltergin as well as its influence on cell adhesion and migration on muscles cells in vitro were studied. Morphological analysis made by scanning electron and phase contrast microscopy demonstrated typical futures of programmed cell death, apoptosis. This mechanism was confirmed by fluorescence staining, molecular analysis of endonuclease activity and increased mRNA expression level of two representative genes (p53 and bax). On the other hand, baltergin exert an inhibition effect on myoblast cell adhesion and migration in vitro probably through a mechanism that involves the interaction of this enzyme with cell integrins...
February 15, 2017: Apoptosis: An International Journal on Programmed Cell Death
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