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Programmed Cell death AND disease

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https://www.readbyqxmd.com/read/29149835/forkhead-transcription-factors-formulating-a-foxo-target-for-cognitive-loss
#1
Kenneth Maiese
BACKGROUND: With almost 47 million individuals worldwide suffering from some aspect of dementia, it is clear that cognitive loss impacts a significant proportion of the global population. Unfortunately, definitive treatments to resolve or prevent the onset of cognitive loss are limited. In most cases such care is currently non-existent prompting the need for novel treatment strategies. METHODS: Mammalian forkhead transcription factors of the O class (FoxO) are one such avenue of investigation that offer an exciting potential to bring new treatments forward for disorders that involve cognitive loss...
November 15, 2017: Current Neurovascular Research
https://www.readbyqxmd.com/read/29146617/cure-in-advanced-renal-cell-cancer-is-it-an-achievable-goal
#2
Dhanusha Sabanathan, John J Park, Manuel Marquez, Louise Francisco, Natalie Byrne, Howard Gurney
BACKGROUND: Immunotherapy has historically been of interest in the management of metastatic renal cell cancer (mRCC) because of its relative chemoresistance and the reproducible but low incidence of spontaneous remission in metastatic disease. Recently, targeted immunotherapies in the form of checkpoint inhibitors have shown durable responses in approximately 20%-30% of patients with solid tumors, with a much more acceptable side-effect profile. Anti-programmed death receptor 1 (PD-1)/programmed death receptor ligand 1 antibodies rely on the presence of host T cells in the tumor microenvironment to be stimulated in order to activate an antitumor response...
November 16, 2017: Oncologist
https://www.readbyqxmd.com/read/29146060/clinicopathologic-correlation-of-programmed-death-ligand-1-expression-in-non-small-cell-lung-carcinomas-a-report-from-india
#3
Archana George Vallonthaiel, Prabhat Singh Malik, Varsha Singh, Vinay Kumar, Sunil Kumar, Mehar Chand Sharma, Sandeep Mathur, Sudheer Arava, Randeep Guleria, Deepali Jain
INTRODUCTION: Increased expression of Programmed death ligand-1 (PD-L1) on cancer cells and immune cells predict response to PD-1/PDL1 inhibitors. Data regarding frequency and pattern of PD-L1 expression in NSCLC from India is not available. OBJECTIVES: To analyse PD-L1 expression on tumour cells (TC) and immune cells (IC) and to correlate PD-L1 expression with baseline clinico-pathological characteristics, oncogenic drivers and outcome data. MATERIALS AND METHODS: PD-L1 expression on tumour cells and immune cells was analysed...
December 2017: Annals of Diagnostic Pathology
https://www.readbyqxmd.com/read/29145543/association-of-ipilimumab-with-safety-and-antitumor-activity-in-women-with-metastatic-or-recurrent-human-papillomavirus-related-cervical-carcinoma
#4
Stephanie Lheureux, Marcus O Butler, Blaise Clarke, Mihaela C Cristea, Lainie P Martin, Katia Tonkin, Gini F Fleming, Anna V Tinker, Hal W Hirte, Daliah Tsoref, Helen Mackay, Neesha C Dhani, Prafull Ghatage, Johanne Weberpals, Stephen Welch, Nhu-An Pham, Vinicius Motta, Valentin Sotov, Lisa Wang, Katherine Karakasis, Smitha Udagani, Suzanne Kamel-Reid, Howard Z Streicher, Patricia Shaw, Amit M Oza
Importance: Based on evidence of human papillomavirus (HPV)-induced immune evasion, immunotherapy may be an attractive strategy in cervical cancer. Ipilimumab is a fully humanized monoclonal antibody that blocks cytotoxic T-lymphocyte antigen-4 (CTLA-4), which acts to downregulate the T-cell immune response. Objective: To assess the safety and antitumor activity of ipilimumab in recurrent cervical cancer. Design, Setting, and Participants: A multicenter trial was designed for patients with metastatic cervical cancer (squamous cell carcinoma or adenocarcinoma) with measurable disease and progression after at least 1 line of platinum chemotherapy...
November 16, 2017: JAMA Oncology
https://www.readbyqxmd.com/read/29144460/inflammation-induced-iga-cells-dismantle-anti-liver-cancer-immunity
#5
Shabnam Shalapour, Xue-Jia Lin, Ingmar N Bastian, John Brain, Alastair D Burt, Alexander A Aksenov, Alison F Vrbanac, Weihua Li, Andres Perkins, Takaji Matsutani, Zhenyu Zhong, Debanjan Dhar, Jose A Navas-Molina, Jun Xu, Rohit Loomba, Michael Downes, Ruth T Yu, Ronald M Evans, Pieter C Dorrestein, Rob Knight, Christopher Benner, Quentin M Anstee, Michael Karin
The role of adaptive immunity in early cancer development is controversial. Here we show that chronic inflammation and fibrosis in humans and mice with non-alcoholic fatty liver disease is accompanied by accumulation of liver-resident immunoglobulin-A-producing (IgA(+)) cells. These cells also express programmed death ligand 1 (PD-L1) and interleukin-10, and directly suppress liver cytotoxic CD8(+) T lymphocytes, which prevent emergence of hepatocellular carcinoma and express a limited repertoire of T-cell receptors against tumour-associated antigens...
November 16, 2017: Nature
https://www.readbyqxmd.com/read/29143824/pd-1-is-a-haploinsufficient-suppressor-of-t-cell-lymphomagenesis
#6
Tim Wartewig, Zsuzsanna Kurgyis, Selina Keppler, Konstanze Pechloff, Erik Hameister, Rupert Öllinger, Roman Maresch, Thorsten Buch, Katja Steiger, Christof Winter, Roland Rad, Jürgen Ruland
T cell non-Hodgkin lymphomas are a heterogeneous group of highly aggressive malignancies with poor clinical outcomes. T cell lymphomas originate from peripheral T cells and are frequently characterized by genetic gain-of-function variants in T cell receptor (TCR) signalling molecules. Although these oncogenic alterations are thought to drive TCR pathways to induce chronic proliferation and cell survival programmes, it remains unclear whether T cells contain tumour suppressors that can counteract these events...
November 15, 2017: Nature
https://www.readbyqxmd.com/read/29141886/pd-l1-genetic-overexpression-or-pharmacological-restoration-in-hematopoietic-stem-and-progenitor-cells-reverses-autoimmune-diabetes
#7
Moufida Ben Nasr, Sara Tezza, Francesca D'Addio, Chiara Mameli, Vera Usuelli, Anna Maestroni, Domenico Corradi, Silvana Belletti, Luca Albarello, Gabriella Becchi, Gian Paolo Fadini, Christian Schuetz, James Markmann, Clive Wasserfall, Leonard Zon, Gian Vincenzo Zuccotti, Paolo Fiorina
Immunologically based clinical trials performed thus far have failed to cure type 1 diabetes (T1D), in part because these approaches were nonspecific. Because the disease is driven by autoreactive CD4 T cells, which destroy β cells, transplantation of hematopoietic stem and progenitor cells (HSPCs) has been recently offered as a therapy for T1D. Our transcriptomic profiling of HSPCs revealed that these cells are deficient in programmed death ligand 1 (PD-L1), an important immune checkpoint, in the T1D nonobese diabetic (NOD) mouse model...
November 15, 2017: Science Translational Medicine
https://www.readbyqxmd.com/read/29139554/immune-checkpoint-inhibitors-new-strategies-to-checkmate-cancer
#8
REVIEW
Ruairi A M Wilson, T R Jeffry Evans, Alasdair R Fraser, Robert J B Nibbs
Immune checkpoint inhibitors (ICIs) targeting Cytotoxic T-Lymphocyte-Associated protein 4 (CTLA-4) or Programmed cell Death protein 1 (PD-1) receptors have demonstrated remarkable efficacy in subsets of patients with malignant disease. This emerging treatment modality holds great promise for future cancer treatment and has engaged pharmaceutical research interests in tumour immunology. While ICIs can induce rapid and durable responses in some patients, identifying predictive factors for effective clinical responses has proven challenging...
November 15, 2017: Clinical and Experimental Immunology
https://www.readbyqxmd.com/read/29137141/steroid-and-xenobiotic-receptor-signalling-in-apoptosis-and-autophagy-of-the-nervous-system
#9
REVIEW
Agnieszka Wnuk, Małgorzata Kajta
Apoptosis and autophagy are involved in neural development and in the response of the nervous system to a variety of insults. Apoptosis is responsible for cell elimination, whereas autophagy can eliminate the cells or keep them alive, even in conditions lacking trophic factors. Therefore, both processes may function synergistically or antagonistically. Steroid and xenobiotic receptors are regulators of apoptosis and autophagy; however, their actions in various pathologies are complex. In general, the estrogen (ER), progesterone (PR), and mineralocorticoid (MR) receptors mediate anti-apoptotic signalling, whereas the androgen (AR) and glucocorticoid (GR) receptors participate in pro-apoptotic pathways...
November 11, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29136011/ten-year-experience-with-antiretroviral-treatment-in-cambodia-trends-in-patient-characteristics-and-treatment-outcomes
#10
Phirum Lay, Sokkab An, Sunpiseth Soeung, Pich Sovannary Srey, Sopheak Thai, Lutgarde Lynen, Johan van Griensven
BACKGROUND: Although HIV disease stage at ART initiation critically determines ART outcomes, few reports have longitudinally monitored this within Asia. Using prospectively collected data from a large ART program at Sihanouk Hospital Center of Hope in Cambodia, we report on the change in patient characteristics and outcomes over a ten-year period. METHODS: We conducted a retrospective analysis including all adults (≥ 18 years old) starting ART from March 2003-March 2013 in a non-governmental hospital in Phnom Penh, Cambodia...
2017: PloS One
https://www.readbyqxmd.com/read/29134678/systemic-immune-checkpoint-blockade-with-anti-pd1-antibodies-does-not-alter-cerebral-amyloid-%C3%AE-burden-in-several-amyloid-transgenic-mouse-models
#11
Martine Latta-Mahieu, Bradford Elmer, Alexis Bretteville, Yaming Wang, Mati Lopez-Grancha, Philippe Goniot, Nicolas Moindrot, Paul Ferrari, Véronique Blanc, Nathalie Schussler, Emmanuel Brault, Valérie Roudières, Véronique Blanchard, Zhi-Yong Yang, Pascal Barneoud, Philippe Bertrand, Bart Roucourt, Sofie Carmans, Astrid Bottelbergs, Liesbeth Mertens, Cindy Wintmolders, Peter Larsen, Caroline Hersley, Tyler McGathey, Margaret M Racke, Ling Liu, Jirong Lu, Michael J O'Neill, David R Riddell, Andreas Ebneth, Gary J Nabel, Laurent Pradier
Chronic inflammation represents a central component in the pathogenesis of Alzheimer's disease (AD). Recent work suggests that breaking immune tolerance by Programmed cell Death-1 (PD1) checkpoint inhibition produces an IFN-γ-dependent systemic immune response, with infiltration of the brain by peripheral myeloid cells and neuropathological as well as functional improvements even in mice with advanced amyloid pathology (Baruch et al., (): Nature Medicine, 22:135-137). Immune checkpoint inhibition was therefore suggested as potential treatment for neurodegenerative disorders when activation of the immune system is appropriate...
November 14, 2017: Glia
https://www.readbyqxmd.com/read/29133121/analysis-of-early-death-in-japanese-patients-with-advanced-non-small-cell-lung-cancer-treated-with-nivolumab
#12
Takako Inoue, Motohiro Tamiya, Akihiro Tamiya, Kenji Nakahama, Yoshihiko Taniguchi, Takayuki Shiroyama, Shin-Ichi Isa, Kazumi Nishino, Toru Kumagai, Kei Kunimasa, Madoka Kimura, Hidekazu Suzuki, Tomonori Hirashima, Shinji Atagi, Fumio Imamura
BACKGROUND: The increased risk for early death owing to anti-programmed cell death 1 inhibitors is a major disadvantage that requires special management. We evaluated the frequency, causes, and risk factors of early death during nivolumab treatment for non-small cell lung cancer (NSCLC) in a Japanese clinical setting. PATIENTS AND METHODS: The medical records of patients with NSCLC who started receiving nivolumab between December 17, 2015 and July 31, 2016 in 3 Japanese institutes were collected...
October 13, 2017: Clinical Lung Cancer
https://www.readbyqxmd.com/read/29131527/3d-matrix-embedding-inhibits-cycloheximide-mediated-sensitization-to-tnf-alpha-induced-apoptosis-of-human-endothelial-cells
#13
Michael Saemisch, Markus Nickmann, Lisa Riesinger, Elazer R Edelman, Heiko Methe
The programmed form of cell death (apoptosis) is essential for normal development of multicellular organisms. Dysregulation of apoptosis has been linked with embryonal death and is involved in the pathophysiology of various diseases. Others and we previously demonstrated endothelial biology being intertwined with biochemical and structural composition of the subendothelial basement membrane. We now demonstrate that a three-dimensional growing environment significantly shields endothelial cells from cytokine-induced apoptosis...
November 13, 2017: Journal of Tissue Engineering and Regenerative Medicine
https://www.readbyqxmd.com/read/29129441/health-related-quality-of-life-results-for-pembrolizumab-versus-chemotherapy-in-advanced-pd-l1-positive-nsclc-keynote-024-a-multicentre-international-randomised-open-label-phase-3-trial
#14
Julie R Brahmer, Delvys Rodríguez-Abreu, Andrew G Robinson, Rina Hui, Tibor Csőszi, Andrea Fülöp, Maya Gottfried, Nir Peled, Ali Tafreshi, Sinead Cuffe, Mary O'Brien, Suman Rao, Katsuyuki Hotta, Jin Zhang, Gregory M Lubiniecki, Anne C Deitz, Reshma Rangwala, Martin Reck
BACKGROUND: In the phase 3 KEYNOTE-024 trial, treatment with pembrolizumab conferred longer progression-free survival than did platinum-based therapy in patients with treatment-naive, advanced non-small-cell lung cancer (NSCLC) with a programmed cell death-ligand 1 (PD-L1) tumour proportion score of 50% or greater (PD-L1-positive). Here we report the prespecified exploratory endpoint of pembrolizumab versus chemotherapy on patient-reported outcomes (PROs). METHODS: In this multicentre, international, randomised, open-label, phase 3 trial, we recruited patients with treatment-naive, stage IV NSCLC in 102 sites in 16 countries...
November 9, 2017: Lancet Oncology
https://www.readbyqxmd.com/read/29129093/xxxxx
#15
Tomas G Lyons, Geoffrey Y Ku
The poor prognosis for patients with esophagogastric cancers (EGC) requires the development of newer more effective therapies to further improve the treatment outcomes for this disease. Immunotherapy is a novel treatment strategy that is dramatically changing the treatment landscape for several types of cancers. Cytotoxic T lymphocyte antigen-4 (CTLA-4) and programmed death the programmed death (PD)-1/PD-ligand are essential immune checkpoint inhibitors that suppress T cell activation. Targeting of these immune checkpoints with monoclonal antibodies has shown clinical efficacy in several solid tumors which has led to their approval and use in routine clinical practice...
October 2017: Chinese Clinical Oncology
https://www.readbyqxmd.com/read/29128181/predictive-relevance-of-programmed-cell-death-protein-1-and-tumor-infiltrating-lymphocyte-expression-in-papillary-thyroid-cancer
#16
Marra J Aghajani, Tao Yang, Charles E McCafferty, Susannah Graham, Xiaojuan Wu, Navin Niles
BACKGROUND: Co-signaling molecule programmed cell death 1 ligand 1 has been shown to induce potent inhibition of T cell-mediated antitumoral immunity. Our study aimed to investigate the prognostic value of programmed cell death 1 ligand 1 expression and tumor-infiltrating lymphocyte density as biomarkers in specimens from patients with papillary thyroid cancer. METHODS: We retrospectively analyzed the data and tissue samples of 75 patients with papillary thyroid cancer...
November 8, 2017: Surgery
https://www.readbyqxmd.com/read/29126496/chemotherapy-for-oral-cancer
#17
REVIEW
Lee Hartner
The use of chemotherapy, including immunotherapy, in oral squamous cell carcinoma has expanded considerably in the past several years. Its use mirrors that in the treatment of squamous cell carcinoma affecting other structures in the head and neck. This article summarizes the current evidence that guides use of chemotherapy both in combination with radiation and as monotherapy for patients with advanced disease. It also addresses the expanding role of immunotherapy, particularly use of programmed cell death-ligand 1 inhibitors, in the treatment of advanced disease...
January 2018: Dental Clinics of North America
https://www.readbyqxmd.com/read/29122359/prognostic-impact-of-rita-expression-in-patients-with-anal-squamous-cell-carcinoma-treated-with-chemoradiotherapy
#18
Franz Rödel, Kerstin Steinhäuser, Nina-Naomi Kreis, Alexandra Friemel, Daniel Martin, Ulrike Wieland, Margret Rave-Fränk, Panagiotis Balermpas, Emmanouil Fokas, Frank Louwen, Claus Rödel, Juping Yuan
BACKGROUND: RBP-J interacting and tubulin-associated protein (RITA) has been identified as a negative regulator of the Notch signalling pathway and its deregulation is involved in the pathogenesis of several tumour entities. RITA's impact on the response of anal squamous cell carcinoma (SCC) to anticancer treatment, however, remains elusive. MATERIALS AND METHODS: In our retrospective study immunohistochemical evaluation of RITA was performed on 140 pre-treatment specimens and was correlated with clinical and histopathologic characteristics and clinical endpoints cumulative incidence of local control (LC), distant recurrence (DC), disease-free survival (DFS) and overall survival (OS)...
November 6, 2017: Radiotherapy and Oncology: Journal of the European Society for Therapeutic Radiology and Oncology
https://www.readbyqxmd.com/read/29118026/carbon-monoxide-in-lung-cell-physiology-and-disease
#19
Stefan W Ryter, Kevin C Ma, Augustine M K Choi
Carbon monoxide (CO) is an endogenously produced gas that has gained recognition as a biological signal transduction effector with properties similar, but not identical, to that of nitric oxide (NO). CO, which binds primarily to heme iron, may activate the hemoprotein guanylate cyclase (sGC), although with lower potency than NO. Furthermore, CO can modulate the activities of several cellular signaling molecules such as p38 MAPK, ERK1/2, JNK, AKT, NF-κB, and others. Emerging studies suggest that mitochondria, the energy-generating organelle of cells, represent a key target of CO action in eukaryotes...
November 8, 2017: American Journal of Physiology. Cell Physiology
https://www.readbyqxmd.com/read/29116900/safety-and-antitumor-activity-of-the-anti-programmed-death-1-antibody-pembrolizumab-in-patients-with-advanced-esophageal-carcinoma
#20
Toshihiko Doi, Sarina A Piha-Paul, Shadia I Jalal, Sanatan Saraf, Jared Lunceford, Minori Koshiji, Jaafar Bennouna
Purpose The anti-programmed death-1 antibody pembrolizumab was evaluated in KEYNOTE-028, a multicohort, phase IB study of patients with programmed death ligand-1 (PD-L1)-positive advanced solid tumors. Results from the esophageal carcinoma cohort are reported herein. Patients and Methods Eligible patients with squamous cell carcinoma or adenocarcinoma of the esophagus or gastroesophageal junction in whom standard therapy failed and who had PD-L1-positive tumors received pembrolizumab 10 mg/kg every 2 weeks for up to 2 years or until confirmed disease progression or intolerable toxicity...
November 8, 2017: Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology
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