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https://www.readbyqxmd.com/read/28528510/immunogenomics-using-genomics-to-personalize-cancer-immunotherapy
#1
Rance C Siniard, Shuko Harada
While the use of genomic data has the potential to revolutionize patient care, there is still much work to be done with regard to the transformation of host-tumor interactions into favorable clinical outcomes for our patients. High-throughput technologies, such as next-generation sequencing (NGS), have rapidly advanced our understanding of oncology, and we are learning that most tumors do not simply possess consistently mutated genes that are responsible for tumorigenesis, facilitating the need for personalized cancer therapy...
May 20, 2017: Virchows Archiv: An International Journal of Pathology
https://www.readbyqxmd.com/read/28527857/novel-immunologic-approaches-to-melanoma-treatment
#2
I Escandell, J M Martín, E Jordá
Approaches to treating melanoma have changed radically since the introduction of immunotherapy, and survival figures are now higher than possible with earlier therapies. The immunomodulators currently available mainly block CTLA-4 (cytotoxicT lymphocyte-associated molecule-4) and PD-1 (programed cell death protein 1) translocated to the cell surface, where they inhibit the antitumor immune response. Treatments blocking these molecules are being more widely used. Research now seeks new molecular targets, the best combinations of available drugs, and biomarkers that can identify ideal candidates for each one...
May 17, 2017: Actas Dermo-sifiliográficas
https://www.readbyqxmd.com/read/28527652/uveitis-induced-by-programmed-cell-death-protein-1-inhibitor-therapy-with-nivolumab-in-metastatic-melanoma-patient
#3
Hiroaki Kanno, Kyoko Ishida, Wataru Yamada, Takashi Nishida, Nobumichi Takahashi, Kiyofumi Mochizuki, Yuki Mizuno, Kanako Matsuyama, Tomoko Takahashi, Mariko Seishima
Nivolumab, a new immune checkpoint inhibitor, binds to programmed cell death-protein 1 receptors on T cell, blockades binding of its ligands, and augments the immunologic reaction against tumor cells. Augmented immune response, however, may lead to immune-related adverse events. Herein we describe a rare case of bilateral anterior uveitis induced by nivolumab treatment for metastatic melanoma. A 54-year-old woman presented with mild conjunctival redness and blurred vision two months after initiating nivolumab treatment...
May 17, 2017: Journal of Infection and Chemotherapy: Official Journal of the Japan Society of Chemotherapy
https://www.readbyqxmd.com/read/28527340/induction-of-cell-death-by-tospoviral-protein-nss-and-the-motif-critical-for-cell-death-does-not-control-rna-silencing-suppression-activity
#4
Ajeet Singh, Vipin Permar, R K Jain, Suneha Goswami, Ranjeet Ranjan Kumar, Tomas Canto, Peter Palukaitis, Shelly Praveen
Groundnut bud necrosis virus induces necrotic symptoms in different hosts. Previous studies showed reactive oxygen species-mediated programmed cell death (PCD) resulted in necrotic symptoms. Transgenic expression of viral protein NSs mimics viral symptoms. Here, we showed a role for NSs in influencing oxidative burst in the cell, by analyzing H2O2 accumulation, activities of antioxidant enzymes and expression levels of vacuolar processing enzymes, H2O2-responsive microRNA 319a.2 plus its possible target metacaspase-8...
May 17, 2017: Virology
https://www.readbyqxmd.com/read/28526063/targeting-the-cxcr4-pathway-using-a-novel-anti-cxcr4-igg1-antibody-pf-06747143-in-chronic-lymphocytic-leukemia
#5
Manoj K Kashyap, Carlos I Amaya-Chanaga, Deepak Kumar, Brett Simmons, Nanni Huser, Yin Gu, Max Hallin, Kevin Lindquist, Rolla Yafawi, Michael Y Choi, Ale-Ali Amine, Laura Z Rassenti, Cathy Zhang, Shu-Hui Liu, Tod Smeal, Valeria R Fantin, Thomas J Kipps, Flavia Pernasetti, Januario E Castro
BACKGROUND: The CXCR4-CXCL12 axis plays an important role in the chronic lymphocytic leukemia (CLL)-microenvironment interaction. Overexpression of CXCR4 has been reported in different hematological malignancies including CLL. Binding of the pro-survival chemokine CXCL12 with its cognate receptor CXCR4 induces cell migration. CXCL12/CXCR4 signaling axis promotes cell survival and proliferation and may contribute to the tropism of leukemia cells towards lymphoid tissues and bone marrow...
May 19, 2017: Journal of Hematology & Oncology
https://www.readbyqxmd.com/read/28525842/indole-coumarin-thiadiazole-hybrids-an-appraisal-of-their-mcf-7%C3%A2-cell-growth-inhibition-apoptotic-antimetastatic-and-computational-bcl-2-binding-potential
#6
Pooja R Kamath, Dhanya Sunil, Manu M Joseph, Abdul Ajees Abdul Salam, Sreelekha T T
Cancer therapeutic potential of thiadiazole hybrids incorporating pharmacologically active indole and coumarin moieties have not been explored much. In the current investigation, three new thiadiazole hybrids with spacers of varying lengths linking indole and thiadiazole units were synthesized and their structures were well-established using various spectroscopic techniques. 3-(1-(5-(3-(1H-indol-3-yl)propyl)-1,3,4-thiadiazol-2-ylimino)ethyl)-6-bromo-2H-chromen-2-one (IPTBC) exhibited dose-dependent cytotoxicity in breast adenocarcinoma (MCF-7) cells...
May 11, 2017: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28524855/viral-hijacking-of-host-caspases-an-emerging-category-of-pathogen-host-interactions
#7
REVIEW
Patrick F Connolly, Howard O Fearnhead
Viruses co-evolve with their hosts, and many viruses have developed mechanisms to suppress or modify the host cell apoptotic response for their own benefit. Recently, evidence has emerged for the opposite strategy. Some viruses have developed the ability to co-opt apoptotic caspase activity to facilitate their own proliferation. In these strategies, viral proteins are cleaved by host caspases to create cleavage products with novel activities which facilitate viral replication. This represents a novel and interesting class of viral-host interactions, and also represents a new group of non-apoptotic roles for caspases...
May 19, 2017: Cell Death and Differentiation
https://www.readbyqxmd.com/read/28524659/synthesis-molecular-docking-molecular-dynamics-studies-and-biological-evaluation-of-4h-chromone-1-2-3-4-tetrahydropyrimidine-5-carboxylate-derivatives-as-potential-anti-leukemic-agents
#8
Zahra Dolatkhah, Shahrzad Javanshir, Ahmad Shahir Sadr, Jaber Hosseini, Soroush Sardari
Series of 4H-chromone-1,2,3,4-tetrahydropyrimidine-5-carboxylates derivatives were synthesized via a three component one-pot condensation of chromone-3-carbaldehyde, alkyl acetoacetate and urea or thiourea, using MCM-41-SO3H as an efficient Nano-catalysts, and evaluated for their anti-cancer activity using a combined in silico docking and molecular dynamics protocol to estimate the binding affinity of the title compounds with the Bcr-Abl oncogene. Two programs, AutoDock 4 and AutoDock Vina software were applied to dock the target protein with synthesized compounds and ATP...
May 19, 2017: Journal of Chemical Information and Modeling
https://www.readbyqxmd.com/read/28524096/itraq-mitoproteome-analysis-reveals-mechanisms-of-programmed-cell-death-in-arabidopsis-thaliana-induced-by-ochratoxin-a
#9
Yan Wang, Xiaoli Peng, Zhuojun Yang, Weiwei Zhao, Wentao Xu, Junran Hao, Weihong Wu, Xiao Li Shen, Yunbo Luo, Kunlun Huang
Ochratoxin A (OTA) is one of the most common and dangerous mycotoxins in the world. Previous work indicated that OTA could elicit spontaneous HR-like lesions formation Arabidopsis thaliana, reactive oxygen species (ROS) play an important role in OTA toxicity, and their major endogenous source is mitochondria. However, there has been no evidence as to whether OTA induces directly PCD in plants until now. In this study, the presence of OTA in Arabidopsisthaliana leaves triggered accelerated respiration, increased production of mitochondrial ROS, the opening of ROS-dependent mitochondrial permeability transition pores and a decrease in mitochondrial membrane potential as well as the release of cytochrome c into the cytosol...
May 18, 2017: Toxins
https://www.readbyqxmd.com/read/28524003/targeting-the-programmed-cell-death-1-pathway-in-genitourinary-tumors-current-progress-and-future-perspectives
#10
Rodolfo Montironi, Liang Cheng, Holger Moch, Antonio Lopez-Beltran, Marina Scarpelli, Francesco Massari, Michelangelo Fiorentino, Chiara Ciccarese, Michael Koch, Hristos Z Kaimakliotis, Lisha Wang, Roberto Pili, Steven A Mann
Immune checkpoint inhibitors have revolutionized the treatment many malignancies with over a dozen new United States Food and Drug Administration (FDA) approvals in the past six years. Due to the combination of potent treatment success and potentially deadly adverse effects from immune checkpoint inhibitors, gathering prognostic and predictive information about FDA-indicated tumors is prudent. PD-L1 expression is a poor prognostic factor and predictive of better responses from both PD-1 and PD-L1 inhibitors in a variety of tumor types including RCC and urothelial carcinoma...
May 18, 2017: Current Drug Metabolism
https://www.readbyqxmd.com/read/28522811/pd-l1-expression-in-xp11-2-translocation-renal-cell-carcinoma-indicator-of-tumor-aggressiveness
#11
Kun Chang, Yuanyuan Qu, Bo Dai, Jian-Yuan Zhao, Hualei Gan, Guohai Shi, Yiping Zhu, Yijun Shen, Yao Zhu, Hailiang Zhang, Dingwei Ye
Programmed death ligand-1 (PD-L1), a promising antitumor target, has proven clinical value against many malignancies. However, the PD-L1 content of Xp11.2 translocation renal cell carcinoma (Xp11.2 RCC) and its correlation with clinical outcomes remain unclear. This study aimed to investigate PD-L1 expression in Xp11.2 RCC and to assess its prognostic value. Formalin-fixed paraffin-embedded specimens from 36 adult patients that were histologically confirmed (by fluorescence in situ hybridization) were subjected to immunohistochemical analysis...
May 18, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28522738/imaging-of-programmed-death-ligand-1-pd-l1-impact-of-protein-concentration-on-distribution-of-anti-pd-l1-spect-agent-in-an-immunocompetent-melanoma-murine-model
#12
Jessie R Nedrow, Anders Josefsson, Sunju Park, Sagar Ranka, Sanchita Roy, George Sgouros
Programmed cell Death Ligand 1 (PD-L1) is part of an immune checkpoint system that is essential for preventing autoimmunity and cancer. Recent approaches in immunotherapy targeting immune checkpoints have shown great promise in a variety of cancers, including metastatic melanoma. The use of targeted molecular imaging would help identify patients who will best respond to anti-PD-L1 treatment while potentially providing key information to limit immune-related adverse effects (irAEs). Recently, we developed an antibody based PD-L1-targeted imaging agent to identify PD-L1 positive tumors in vivo...
May 18, 2017: Journal of Nuclear Medicine: Official Publication, Society of Nuclear Medicine
https://www.readbyqxmd.com/read/28522568/peroxisome-proliferator-activated-receptor-gamma-enhances-human-pulmonary-artery-smooth-muscle-cell-apoptosis-through-microrna-21-and-programmed-cell-death-4
#13
David Emerson Green, Tamara C Murphy, Bum-Yong Kang, Brahmchetna Bedi, Zhihong Yuan, Ruxana T Sadikot, C Michael Hart
Pulmonary hypertension (PH) is a progressive disorder whose cellular pathogenesis involves enhanced smooth muscle cell (SMC) proliferation and resistance to apoptosis signals. Existing evidence demonstrates that the tumor suppressor, programmed cell death 4 (PDCD4) affects patterns of cell growth and repair responses in the systemic vasculature following experimental injury. In the current study, the regulation PDCD4 and its functional effects on growth and apoptosis susceptibility in pulmonary artery smooth muscle cells was explored...
May 18, 2017: American Journal of Physiology. Lung Cellular and Molecular Physiology
https://www.readbyqxmd.com/read/28522460/soluble-pd-l1-as-a-biomarker-in-malignant-melanoma-and-checkpoint-blockade
#14
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/28521675/chemotherapy-with-si-rna-and-anti-cancer-drugs
#15
Kamaljeet Kaur, Goutam Rath, Saket Chandra, Ranjit Singh, Amit K Goyal
To treat cancer, chemotherapy is a key therapeutic approach which is associated with several limitations. This chemotherapeutical agents exhibit multi drug resistance coupled with undesirable side effects. This multidrug resistance is exhibited by tumor cell due to actuation of drug out flow mechanism, programmed cell death and protection mechanisms etc. One of the therapeutic approaches to cure cancer is RNA interference (RNAi). Small interfering RNA (si-RNA) is considered as a major therapeutic tool used to control expression of a particular gene...
May 18, 2017: Current Drug Delivery
https://www.readbyqxmd.com/read/28515919/programmed-death-ligand-1-expression-is-associated-with-fibrosarcomatous-transformation-of-dermatofibrosarcoma-protuberans
#16
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
#17
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/28515246/immunotherapies-for-lung-cancer
#18
Matthew A Gubens
In 2017, immunotherapy is the standard of care for patients with non-small cell lung cancer (NSCLC) either in the first or second line depending on programmed death ligand-1 (PD-L1) and mutation status. For first-line therapy, pembrolizumab is currently the standard of care for patients whose tumors express PD-L1 >50%. All patients with NSCLC should undergo PD-L1 testing before initiating treatment on pembrolizumab. For patients not eligible in the first line, immunotherapy is the standard of care for most in the second line...
May 2017: Journal of the National Comprehensive Cancer Network: JNCCN
https://www.readbyqxmd.com/read/28515244/what-when-and-how-of-biomarker-testing-in-non-small-cell-lung-cancer
#19
Gregory L Riely
Biomarker testing is recommended for all patients diagnosed with non-small cell lung cancer. At a minimum, testing should include the mutations/fusions EGFR, ALK, ROS1, and the protein programmed death ligand-1 (PD-L1), because FDA-approved therapies are available for these alterations. Other actionable molecular findings include RET rearrangements, BRAF(V600E) mutations, and MET exon 14 alterations. If adequate testing was not performed at treatment initiation, molecular testing should be performed before administration of subsequent lines of therapy...
May 2017: Journal of the National Comprehensive Cancer Network: JNCCN
https://www.readbyqxmd.com/read/28515000/mitochondrial-and-endoplasmic-reticulum-calcium-homeostasis-and-cell-death
#20
REVIEW
Saverio Marchi, Simone Patergnani, Sonia Missiroli, Giampaolo Morciano, Alessandro Rimessi, Mariusz R Wieckowski, Carlotta Giorgi, Paolo Pinton
The endoplasmic reticulum (ER) and mitochondria cannot be considered as static structures, as they intimately communicate, forming very dynamic platforms termed mitochondria-associated membranes (MAMs). In particular, the ER transmits proper Ca(2+) signals to mitochondria, which decode them into specific inputs to regulate essential functions, including metabolism, energy production and apoptosis. Here, we will describe the different molecular players involved in the transfer of Ca(2+) ions from the ER lumen to the mitochondrial matrix and how modifications in both ER-mitochondria contact sites and Ca(2+) signaling can alter the cell death execution program...
May 5, 2017: Cell Calcium
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