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Programmed Cell death AND disease

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https://www.readbyqxmd.com/read/28529902/current-state-of-immunotherapy-for-non-small-cell-lung-cancer
#1
REVIEW
Jyoti Malhotra, Salma K Jabbour, Joseph Aisner
Lung cancer is the leading cause of cancer mortality and non-small cell lung cancer (NSCLC) accounts for more than 85% of all lung cancers. Platinum-based doublet chemotherapy is the standard first-line treatment for metastatic NSCLC when genomic testing reveals no targetable alteration such as epidermal growth factor receptor (EGFR) mutations, anaplastic lymphoma kinase (ALK) or ROS1 translocation/re-arrangements. But, chemotherapy produces response rates ranging only between 15-30%. For patients whose disease progresses on first-line chemotherapy, second-line therapy historically consists of taxane-based salvage chemotherapy with a response rate of less than 25%...
April 2017: Translational Lung Cancer Research
https://www.readbyqxmd.com/read/28529715/inducing-death-in-tumor-cells-roles-of-the-inhibitor-of-apoptosis-proteins
#2
REVIEW
Darren Finlay, Peter Teriete, Mitchell Vamos, Nicholas D P Cosford, Kristiina Vuori
The heterogeneous group of diseases collectively termed cancer results not just from aberrant cellular proliferation but also from a lack of accompanying homeostatic cell death. Indeed, cancer cells regularly acquire resistance to programmed cell death, or apoptosis, which not only supports cancer progression but also leads to resistance to therapeutic agents. Thus, various approaches have been undertaken in order to induce apoptosis in tumor cells for therapeutic purposes. Here, we will focus our discussion on agents that directly affect the apoptotic machinery itself rather than on drugs that induce apoptosis in tumor cells indirectly, such as by DNA damage or kinase dependency inhibition...
2017: F1000Research
https://www.readbyqxmd.com/read/28522460/soluble-pd-l1-as-a-biomarker-in-malignant-melanoma-and-checkpoint-blockade
#3
Jun Zhou, Kathleen M Mahoney, Anita Giobbie-Hurder, Fengmin Zhao, Sandra Lee, Xiaoyun Liao, Scott Rodig, Jingjing Li, Xinqi Wu, Lisa H Butterfield, Matthias Piesche, Michael P Manos, Lauren M Eastman, Glenn Dranoff, Gordon J Freeman, F Stephen Hodi
Blockade of the pathway including Programmed death-ligand 1 (PD-L1) and its receptor Programmed cell death protein 1 (PD-1) has produced clinical benefits in patients with a variety of cancers.  Elevated levels of soluble PD-L1 (sPD-L1) have been associated with worse prognosis in renal cell carcinoma and multiple myeloma.  However, the regulatory roles and function of sPD-L1 particularly in connection with immune checkpoint blockade treatment are not fully understood.  We identified four splice variants of PD-L1 in melanoma cells, and all of them are secreted...
May 18, 2017: Cancer Immunology Research
https://www.readbyqxmd.com/read/28515919/programmed-death-ligand-1-expression-is-associated-with-fibrosarcomatous-transformation-of-dermatofibrosarcoma-protuberans
#4
Kenji Tsuchihashi, Hitoshi Kusaba, Yuichi Yamada, Yuta Okumura, Hozumi Shimokawa, Masato Komoda, Keita Uchino, Tomoyasu Yoshihiro, Nobuhiro Tsuruta, Fumiyasu Hanamura, Kyoko Inadomi, Mamoru Ito, Kosuke Sagara, Michitaka Nakano, Kenta Nio, Shuji Arita, Hiroshi Ariyama, Kenichi Kohashi, Ryuji Tominaga, Yoshinao Oda, Koichi Akashi, Eishi Baba
Dermatofibrosarcoma protuberans (DFSP) is a locally invading tumor, characterized by the presence of the collagen type I α 1 (COL1A1)-platelet-derived growth factor (PDGF) β fusion gene. We herein report the case of a 31-year-old man with a history of resection of an abdominal wall DFSP. The patient presented with chest pain and a computed tomography scan revealed a large mass in the posterior mediastinum and another mass in the right lung. The mediastinal mass was a sarcomatous lesion expressing the COL1A1-PDGFβ fusion gene, suggesting that it represented a metastasis of the DFSP following fibrosarcomatous (FS) transformation...
May 2017: Molecular and Clinical Oncology
https://www.readbyqxmd.com/read/28515726/comparative-analysis-of-immune-checkpoint-molecules-and-their-potential-role-in-the-transmissible-tasmanian-devil-facial-tumor-disease
#5
Andrew S Flies, Nicholas B Blackburn, Alan Bruce Lyons, John D Hayball, Gregory M Woods
Immune checkpoint molecules function as a system of checks and balances that enhance or inhibit immune responses to infectious agents, foreign tissues, and cancerous cells. Immunotherapies that target immune checkpoint molecules, particularly the inhibitory molecules programmed cell death 1 and cytotoxic T-lymphocyte-associated protein 4 (CTLA-4), have revolutionized human oncology in recent years, yet little is known about these key immune signaling molecules in species other than primates and rodents. The Tasmanian devil facial tumor disease is caused by transmissible cancers that have resulted in a massive decline in the wild Tasmanian devil population...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28514834/antitumor-activity-of-brazilian-red-propolis-fractions-against-hep-2-cancer-cell-line
#6
Caroline Olivieri da Silva Frozza, Denis Amilton Santos, Luciane Corbellini Rufatto, Luciane Minetto, Fernando Joel Scariot, Sergio Echeverrigaray, Claus Tröger Pich, Sidnei Moura, Francine Ferreira Padilha, Sibele Borsuk, Lucielli Savegnago, Tiago Collares, Fabiana Kömmling Seixas, Odir Dellagostin, Mariana Roesch-Ely, João Antonio Pêgas Henriques
Continuous increases in the rates of tumor diseases have highlighted the need for identification of novel and inexpensive antitumor agents from natural sources. In this study, we investigated the effects of enriched fraction from hydroalcoholic Brazilian red propolis extract against Hep-2 cancer cell line. Initially 201 fractions were arranged in 12 groups according to their chromatographic characteristics (A-L). After an in vitro cell viability screening, J and L were further selected as promising enriched fractions for this study...
May 13, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28514441/pd-1-expression-by-tumour-associated-macrophages-inhibits-phagocytosis-and-tumour-immunity
#7
Sydney R Gordon, Roy L Maute, Ben W Dulken, Gregor Hutter, Benson M George, Melissa N McCracken, Rohit Gupta, Jonathan M Tsai, Rahul Sinha, Daniel Corey, Aaron M Ring, Andrew J Connolly, Irving L Weissman
Programmed cell death protein 1 (PD-1) is an immune checkpoint receptor that is upregulated on activated T cells for the induction of immune tolerance. Tumour cells frequently overexpress the ligand for PD-1, programmed cell death ligand 1 (PD-L1), facilitating their escape from the immune system. Monoclonal antibodies that block the interaction between PD-1 and PD-L1, by binding to either the ligand or receptor, have shown notable clinical efficacy in patients with a variety of cancers, including melanoma, colorectal cancer, non-small-cell lung cancer and Hodgkin's lymphoma...
May 17, 2017: Nature
https://www.readbyqxmd.com/read/28511367/neurobehavioural-changes-in-a-hemiparkinsonian-rat-model-induced-by-rotenone
#8
REVIEW
Sukala Puthuparambil Maniyath, Narayanan Solaiappan, Muthusamy Rathinasamy
INTRODUCTION: Rotenone, a mitochondrial complex I inhibitor is used as a neurotoxin agent to reproduce the neuropathological, and behavioural feature of Parkinson's Disease (PD) in rat. Due to acute and chronic exposure of rotenone with various doses through different routes of administration, mortality is being reported. Low dose takes a longer duration to produce PD symptoms in animals. This present study was designed to create hemiparkinsonian 'partial' lesion model by rotenone at a single moderate dose in two sites of striatum in albino rats and also to assess its toxicity by behavioural parameters and by microscopic study...
March 2017: Journal of Clinical and Diagnostic Research: JCDR
https://www.readbyqxmd.com/read/28508312/trpc-channels-and-programmed-cell-death
#9
Jian Zhou, Yichang Jia
Neurotrophins, including nerve growth factor (NGF) and brain-derived neurotrophic factor (BDNF), bind to their high-affinity receptors to promote neuronal survival during brain development. One of the key downstream pathways is the phospholipase C (PLC) pathway, which not only plays a central role in calcium release from internal store but also in activation of TRPC channels coupled with neurotrophin receptors. TRPC channels are required for the neurotrophin-mediated neuronal protective effects. In addition, activation of TRPC channels is able to protect neurons in the absence of neurotrophin...
2017: Advances in Experimental Medicine and Biology
https://www.readbyqxmd.com/read/28505981/severe-exacerbation-of-myasthenia-gravis-associated-with-checkpoint-inhibitor-immunotherapy
#10
Dana S Cooper, Matthew N Meriggioli, Philip D Bonomi, Rabia Malik
Monoclonal antibodies that target either PD-1 or PD-L1 have recently been approved for treatment of advanced non-small cell lung cancer. These antibodies are immune checkpoint inhibitors which have been shown to exacerbate Myasthenia Gravis (MG) and other autoimmune diseases. While effective in preventing tumor cells from evading immune attack, immune checkpoint inhibitors such as nivolumab, an antibody directed against the programmed cell death protein-1 (PD-1) receptor located on T-cells, may also cause immune dysregulation and could cause or potentiate pre-existing autoimmune conditions...
May 6, 2017: Journal of Neuromuscular Diseases
https://www.readbyqxmd.com/read/28504837/immunotherapy-for-metastatic-renal-cell-carcinoma
#11
REVIEW
Susanne Unverzagt, Ines Moldenhauer, Monika Nothacker, Dorothea Roßmeißl, Andreas V Hadjinicolaou, Frank Peinemann, Francesco Greco, Barbara Seliger
BACKGROUND: Since the mid-2000s, the field of metastatic renal cell carcinoma (mRCC) has experienced a paradigm shift from non-specific therapy with broad-acting cytokines to specific regimens, which directly target the cancer, the tumour microenvironment, or both.Current guidelines recommend targeted therapies with agents such as sunitinib, pazopanib or temsirolimus (for people with poor prognosis) as the standard of care for first-line treatment of people with mRCC and mention non-specific cytokines as an alternative option for selected patients...
May 15, 2017: Cochrane Database of Systematic Reviews
https://www.readbyqxmd.com/read/28503708/stress-and-the-nonsense-mediated-rna-decay-pathway
#12
REVIEW
Alexandra E Goetz, Miles Wilkinson
Cells respond to internal and external cellular stressors by activating stress-response pathways that re-establish homeostasis. If homeostasis is not achieved in a timely manner, stress pathways trigger programmed cell death (apoptosis) to preserve organism integrity. A highly conserved stress pathway is the unfolded protein response (UPR), which senses excessive amounts of unfolded proteins in the ER. While a physiologically beneficial pathway, the UPR requires tight regulation to provide a beneficial outcome and avoid deleterious consequences...
May 13, 2017: Cellular and Molecular Life Sciences: CMLS
https://www.readbyqxmd.com/read/28502094/programmed-cell-death-ligand-1-pd-l1-overexpression-in-ampulla-of-vater-carcinoma-and-its-pre-invasive-lesions
#13
Deborah Saraggi, Francesca Galuppini, Andrea Remo, Emanuele D L Urso, Deborah Bacchin, Roberta Salmaso, Cristiano Lanza, Riccardo Q Bao, Giuseppe Niccolò Fanelli, Vincenza Guzzardo, Claudio Luchini, Marco Scarpa, Fabio Farinati, Matteo Fassan, Massimo Rugge
AIMS: PD-1/PD-L1 checkpoint immunotherapy has recently been proposed as a promising treatment in relapsed/refractory disease, eventually used in combination with the traditional chemotherapy in different cancer settings. No data are still now available about PD-L1 expression in ampulla of Vater carcinoma and its preinvasive lesions. METHODS AND RESULTS: We assessed the immunohistochemical expression of PD-L1 in a series of 26 ampullary adenocarcinomas, 50 ampullary dysplastic lesions, and 10 normal duodenal mucosa samples...
May 14, 2017: Histopathology
https://www.readbyqxmd.com/read/28501937/expression-of-pd-l1-in-keratoacanthoma-and-different-stages-of-progression-in-cutaneous-squamous-cell-carcinoma
#14
Thilo Gambichler, Martha Gnielka, Ines Rüddel, Eggert Stockfleth, Markus Stücker, Lutz Schmitz
BACKGROUND: Programmed cell death 1 (PD-1) and its ligands (PD-L1) play a major role in the immune responses of a variety of cancers. OBJECTIVES: To investigate the expression of PD-L1 in different progression forms of cutaneous squamous cell carcinoma (cSCC) and keratoacanthoma (KA). METHODS: We performed immunohistochemical staining of 21 KA, 26 actinic keratoses (AK), 20 Bowen´s diseases (BD), and 26 high-risk cSCC. The staining patterns were assessed using the tumour proportion score and staining intensity evaluation...
May 13, 2017: Cancer Immunology, Immunotherapy: CII
https://www.readbyqxmd.com/read/28501913/chronic-myeloid-leukemia-immunobiology-and-novel-immunotherapeutic-approaches
#15
Emilie Cayssials, Francois Guilhot
Imatinib has revolutionized the treatment and prognosis of chronic myeloid leukemia (CML) with survival rates now approaching those of the age-matched healthy population. To be able to discontinue tyrosine kinase inhibitor (TKI) treatment, it is necessary to develop complementary therapies to target minimal residual disease. Recent findings by a number of investigators in both CML mouse models and CML patients offer evidence that many factors in the leukemic microenvironment can collectively contribute to immune escape, including expansion of myeloid-derived suppressor cells, programmed death-1/programmed death-1 ligand interactions resulting in T-cell impairment, expression of soluble suppressive factors such as soluble CD25, and down-regulation of MHC molecules by CML cells...
May 13, 2017: BioDrugs: Clinical Immunotherapeutics, Biopharmaceuticals and Gene Therapy
https://www.readbyqxmd.com/read/28500617/post-chemotherapy-pd-l1-expression-correlates-with-clinical-outcomes-in-japanese-bladder-cancer-patients-treated-with-total-cystectomy
#16
Daisuke Noro, Shingo Hatakeyama, Takahiro Yoneyama, Yasuhiro Hashimoto, Takuya Koie, Toshiaki Kawaguchi, Chikara Ohyama
Programmed cell death ligand-1 (PD-L1) is a key target molecule of immunotherapy that is frequently overexpressed in bladder cancer. In the present study, we examined whether PD-L1 expression is associated with clinical outcomes in bladder cancer patients. We enrolled 102 bladder cancer patients treated with cystectomy at the Aomori Prefectural Hospital between April 2004 and May 2014. We conducted an immunohistochemical examination of PD-L1 expression using the SP142 assay. PD-L1 expression was scored at three diagnostic levels (0/1/2)...
June 2017: Medical Oncology
https://www.readbyqxmd.com/read/28496333/immune-checkpoint-blockade-the-role-of-pd-1-pd-l-axis-in-lymphoid-malignancies
#17
REVIEW
Cristina Ilcus, Cristina Bagacean, Adrian Tempescul, Cristian Popescu, Andrada Parvu, Mihai Cenariu, Corina Bocsan, Mihnea Zdrenghea
The co-inhibitory receptor programmed cell death (PD)-1, expressed by immune effector cells, is credited with a protective role for normal tissue during immune responses, by limiting the extent of effector activation. Its presently known ligands, programmed death ligands (PD-Ls) 1 and 2, are expressed by a variety of cells including cancer cells, suggesting a role for these molecules as an immune evasion mechanism. Blocking of the PD-1-PD-L signaling axis has recently been shown to be effective and was clinically approved in relapsed/refractory tumors such as malignant melanoma and lung cancer, but also classical Hodgkin's lymphoma...
2017: OncoTargets and Therapy
https://www.readbyqxmd.com/read/28495592/mir-21-promotes-fibrogenesis-in-peritoneal-dialysis
#18
Melisa Lopez-Anton, Mark Lambie, Manuel Lopez-Cabrera, Claus P Schmitt, Vicente Ruiz-Carpio, Maria Bartosova, Betti Schaefer, Simon Davies, Timothy Stone, Robert Jenkins, Philip R Taylor, Nicholas Topley, Timothy Bowen, Donald Fraser
Peritoneal dialysis (PD) is a life-saving form of renal replacement therapy for those with end-stage kidney disease. Mesothelial cells (MCs) line the peritoneal cavity and help define peritoneal response to treatment-associated injury, a major reason for treatment failure. miRNAs are important regulators, but their roles in peritoneal fibrosis are largely unknown. In this study, miR-21 was one of the most abundant miRNAs in primary MCs, and was up-regulated by the profibrotic cytokine transforming growth factor-β1 and in PD effluent-derived MCs exhibiting mesenchymal phenotypic change...
May 8, 2017: American Journal of Pathology
https://www.readbyqxmd.com/read/28493410/expression-and-prognostic-significance-of-programmed-death-protein-1-and-programmed-death-ligand-1-and-cytotoxic-t-lymphocyte-associated-molecule-4-in-hepatocellular-carcinoma
#19
Hyeyoon Chang, Wonkyung Jung, Aeree Kim, Han Kyeom Kim, Wan Bae Kim, Ji Hoon Kim, Baek-Hui Kim
Hepatocellular carcinoma (HCC) is one of the most common malignancies and causes of death worldwide. In this study, we assessed the correlation between clinicopathologic factors with programmed cell death protein 1 (PD-1) and programmed cell death ligand-1 (PD-L1), and cytotoxic T lymphocyte-associated molecule-4 (CTLA-4) expressions. Furthermore, we analyzed the prognostic significance of these proteins in a subgroup of patients. We retrospectively evaluated the PD-1, PD-L1, and CTLA-4 expressions in 294 HCC tissue microarray samples using immunohistochemistry...
May 11, 2017: APMIS: Acta Pathologica, Microbiologica, et Immunologica Scandinavica
https://www.readbyqxmd.com/read/28492834/apoptosis-and-vocal-fold-disease-clinically-relevant-implications-of-epithelial-cell-death
#20
Carolyn K Novaleski, Bruce D Carter, M Preeti Sivasankar, Sheila H Ridner, Mary S Dietrich, Bernard Rousseau
Purpose: Vocal fold diseases affecting the epithelium have a detrimental impact on vocal function. This review article provides an overview of apoptosis, the most commonly studied type of programmed cell death. Because apoptosis can damage epithelial cells, this article examines the implications of apoptosis on diseases affecting the vocal fold cover. Method: A review of the extant literature was performed. We summarized the topics of epithelial tissue properties and apoptotic cell death, described what is currently understood about apoptosis in the vocal fold, and proposed several possible explanations for how the role of abnormal apoptosis during wound healing may be involved in vocal pathology...
May 10, 2017: Journal of Speech, Language, and Hearing Research: JSLHR
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