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Programmed cell death

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https://www.readbyqxmd.com/read/29667169/expression-of-scavenger-receptor-marco-defines-a-targetable-tumor-associated-macrophage-subset-in-non-small-cell-lung-cancer
#1
Linnéa La Fleur, Vanessa F Boura, Andrey Alexeyenko, Anders Berglund, Victor Pontén, Johanna Sm Mattsson, Dijana Djureinovic, Johan Persson, Hans Brunnström, Johan Isaksson, Eva Brandén, Hirsh Koyi, Patrick Micke, Mikael Ci Karlsson, Johan Botling
Tumor-associated macrophages (TAMs) are attractive targets for immunotherapy. Recently, studies in animal models showed that treatment with an anti-TAM antibody directed against the scavenger receptor MARCO resulted in suppression of tumor growth and metastatic dissemination. Here we investigated the expression of MARCO in relation to other macrophage markers and immune pathways in a non-small cell lung cancer (NSCLC) cohort (n=352). MARCO, CD68, CD163, MSR1 and programmed death ligand-1 (PD-L1) were analyzed by immunohistochemistry and immunofluorescence, and associations to other immune cells and regulatory pathways were studied in a subset of cases (n=199) with available RNA-seq data...
April 18, 2018: International Journal of Cancer. Journal International du Cancer
https://www.readbyqxmd.com/read/29667000/a-novel-mitochondrial-orf147-causes-cytoplasmic-male-sterility-in-pigeonpea-by-modulating-aberrant-anther-dehiscence
#2
Pooja Bhatnagar-Mathur, Ranadheer Gupta, Palakolanu Sudhakar Reddy, Bommineni Pradeep Reddy, Dumbala Srinivas Reddy, C V Sameerkumar, Rachit Kumar Saxena, Kiran K Sharma
A novel open reading frame (ORF) identified and cloned from the A4 cytoplasm of Cajanus cajanifolius induced partial to complete male sterility when introduced into Arabidopsis and tobacco. Pigeonpea (Cajanus cajan L. Millsp.) is the only legume known to have commercial hybrid seed technology based on cytoplasmic male sterility (CMS). We identified a novel ORF (orf147) from the A4 cytoplasm of C. cajanifolius that was created via rearrangements in the CMS line and co-transcribes with the known and unknown sequences...
April 17, 2018: Plant Molecular Biology
https://www.readbyqxmd.com/read/29666474/the-cisd-gene-family-regulates-physiological-germline-apoptosis-through-ced-13-and-the-canonical-cell-death-pathway-in-caenorhabditis-elegans
#3
Skylar D King, Chipo F Gray, Luhua Song, Rachel Nechushtai, Tina L Gumienny, Ron Mittler, Pamela A Padilla
Programmed cell death, which occurs through a conserved core molecular pathway, is important for fundamental developmental and homeostatic processes. The human iron-sulfur binding protein NAF-1/CISD2 binds to Bcl-2 and its disruption in cells leads to an increase in apoptosis. Other members of the CDGSH iron sulfur domain (CISD) family include mitoNEET/CISD1 and Miner2/CISD3. In humans, mutations in CISD2 result in Wolfram syndrome 2, a disease in which the patients display juvenile diabetes, neuropsychiatric disorders and defective platelet aggregation...
April 17, 2018: Cell Death and Differentiation
https://www.readbyqxmd.com/read/29666298/delayed-autoimmune-toxicity-occurring-several-months-after-cessation-of-anti-pd-1-therapy
#4
Sagun Parakh, Jonathan Cebon, Oliver Klein
Treatment with anti-programmed cell death protein 1 (PD-1) antibodies has demonstrated clinical efficacy in a whole range of malignancies including advanced melanoma, renal cell cancer, bladder cancer, and non-small cell lung cancer. Immune-related adverse events are a unique side effect of checkpoint regulator therapy including anti-PD-1 antibodies. Treatment-related autoimmunity can occur in any organ system, with the median onset usually within 5-15 weeks from the commencement of therapy, depending on the organ system involved...
April 17, 2018: Oncologist
https://www.readbyqxmd.com/read/29666149/genetic-and-phenotypic-difference-in-cd8-t-cell-exhaustion-between-chronic-hepatitis-b-infection-and-hepatocellular-carcinoma
#5
Xiaochen Wang, Qifeng He, Haiyuan Shen, Xiao-Jie Lu, Beicheng Sun
BACKGROUND: Several recent studies published have suggested that T cell exhaustion exists both in chronic infection and cancer. However, to date, few studies have investigated their differences. Here we designed this study to explore the genetic and phenotypic difference in CD8+ T cell exhaustion between chronic hepatitis B (CHB) and hepatocellular carcinoma (HCC). METHODS: In this study, we assayed the phenotypes and functional states of CD8+ T cells separating from human CHB tissues and HCC tissues, and re-analyse the single-cell sequencing data (GSE98638) published previously...
April 17, 2018: Journal of Medical Genetics
https://www.readbyqxmd.com/read/29666026/cervical-cancer-state-of-the-science-from-angiogenesis-blockade-to-checkpoint-inhibition
#6
REVIEW
Lindsey E Minion, Krishnansu S Tewari
Vascular endothelial growth factor (VEGF) has emerged as a therapeutic target in several malignancies, including cervical cancer. Chemotherapy doublets combined with the fully humanized monoclonal antibody, bevacizumab, now constitute first-line therapy for women struggling with recurrent/metastatic cervical carcinoma. Regulatory approval for this indication was based on the phase III randomized trial, GOG 240, which demonstrated a statistically significant and clinically meaningful improvement in overall survival when bevacizumab was added to chemotherapy: 17...
March 2018: Gynecologic Oncology
https://www.readbyqxmd.com/read/29665734/in-vivo-antitumor-effects-of-mk615-led-by-pd-l1-downregulation
#7
Masashi Yanaki, Masayuki Kobayashi, Atsushi Aruga, Minoru Nomura, Makoto Ozaki
BACKGROUND/AIM: MK615 extracted from Prunus mume was reported to have anti-inflammatory effects. In this article, we examined the in vivo antitumor effect of MK615 (an extract from Japanese apricot) using mouse tumor xenografts and focusing on the downregulation of PD-L1 (programmed death-ligand 1), a ligand of programmed cell death-1, a surface protein of activated T cells. MATERIALS AND METHODS: B16/BL6 melanoma cells were injected into C57BL/6 or BALB/c-nu/nu mice to establish lung metastasis...
April 1, 2018: Integrative Cancer Therapies
https://www.readbyqxmd.com/read/29665726/dexmedetomidine-mitigates-microglia-mediated-neuroinflammation-through-up-regulation-of-programmed-cell-death-protein-1-in-a-rat-spinal-cord-injury-model
#8
Hefan He, Yingying Zhou, Yilin Zhou, Jiayuan Zhuang, Xu He, Siyuan Wang, Wenping Lin
Excessive neuroinflammation aggravates neurological damage after spinal cord injury (SCI). Controlling neuroinflammation might favor neuroregeneration and tissue repair. Dexmedetomidine is reported to inhibit post-SCI neuroinflammation in previous research. In the current study, to determine the mechanisms by which dexmedetomidine inhibits neuroinflammation, we tested the effect of dexmedetomidine hydrochloride on microglia in vitro and in a rat SCI model. We found that dexmedetomidine hydrochloride up-regulated programmed cell death protein 1 (PD-1), an immunoregulatory molecule, in activated microglia but not in resting microglia...
April 18, 2018: Journal of Neurotrauma
https://www.readbyqxmd.com/read/29665677/a-nanoscale-metal-organic-framework-overcomes-hypoxia-for-photodynamic-therapy-primed-cancer-immunotherapy
#9
Guangxu Lan, Kaiyuan Ni, Ziwan Xu, Samuel S Veroneau, Yang Song, Wenbin Lin
Immunotherapy has become a promising cancer therapy, but only works for a subset of cancer patients. Immunogenic photodynamic therapy (PDT) can prime cancer immunotherapy to increase the response rates, but its efficacy is severely limited by tumor hypoxia. Here we report a nanoscale metal-organic framework, Fe-TBP, as a novel nanophotosensitizer to overcome tumor hypoxia and sensitize effective PDT, priming non-inflamed tumors for cancer immunotherapy. Fe-TBP was built from iron clusters and porphyrin ligands and sensitized PDT under both normoxic and hypoxic conditions...
April 18, 2018: Journal of the American Chemical Society
https://www.readbyqxmd.com/read/29665555/hesperidin-promotes-programmed-cell-death-by-downregulation-of-nongenomic-estrogen-receptor-signalling-pathway-in-endometrial-cancer-cells
#10
Z B Cincin, B Kiran, Y Baran, B Cakmakoglu
Endometrial carcinoma (EC) is the most common malignant gynecologic tumor in women. EC is thought to be caused by increasing estrogen levels relative to progesterone in the body. Hesperidin (Hsd), a biologically active flavonoid, could be extracted from Citrus species. It has been recently shown that Hsd could exert anticarcinogenic properties in different cancer types. However, the effects of Hsd and its molecular mechanisms on EC remain unclear. In this study, the antiproliferative, apoptotic and genomic effects of Hsd in EC and its underlying mechanisms were identified...
April 14, 2018: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/29664018/increased-vessel-perfusion-predicts-the-efficacy-of-immune-checkpoint-blockade
#11
Xichen Zheng, Zhaoxu Fang, Xiaomei Liu, Shengming Deng, Pei Zhou, Xuexiang Wang, Chenglin Zhang, Rongping Yin, Haitian Hu, Xiaolan Chen, Yijie Han, Yun Zhao, Steven H Lin, Songbing Qin, Xiaohua Wang, Betty Ys Kim, Penghui Zhou, Wen Jiang, Qingyu Wu, Yuhui Huang
Immune checkpoint blockade (ICB) has demonstrated curative potential in several types of cancer, but only for a small number of patients. Thus, the identification of reliable and noninvasive biomarkers for predicting ICB responsiveness is an urgent unmet need. Here, we show that ICB increased tumor vessel perfusion in treatment-sensitive EO771 and MMTV-PyVT breast tumor as well as CT26 and MCA38 colon tumor models, but not in treatment-resistant MCaP0008 and 4T1 breast tumor models. In the sensitive tumor models, the ability of anti-cytotoxic T lymphocyte-associated protein 4 or anti-programmed cell death 1 therapy to increase vessel perfusion strongly correlated with its antitumor efficacy...
April 16, 2018: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/29663889/necroptosis-signaling-pathways-in-stroke-from-mechanisms-to-therapies
#12
Huang Jun-Long, Li Yi, Zhao Bao-Lian, Li Jia-Si, Zhang Ning, Ye Zhou-Heng, Sun Xue-Jun, Liu Wen-Wu
It has been confirmed that apoptosis, autophagy and necrosis are the three major modes of cell death. For a long time, necrosis is regarded as a deranged or accidental cell demise. In recent years, there is evidence showing that necrotic cell death can be a well regulated and orchestrated event, which is also known as programmed cell death or "necroptosis". Necroptosis can be triggered by a variety of external stimuli and regulated by a caspase-independent pathway. It plays a key role in the pathogenesis of some diseases including neurological diseases...
April 16, 2018: Current Neuropharmacology
https://www.readbyqxmd.com/read/29663398/transition-of-the-programmed-death-1-pathway-from-the-primary-colorectal-cancer-to-its-corresponding-pulmonary-metastasis
#13
Ei Miyamoto, Toyofumi F Chen-Yoshikawa, Chiyuki Ueshima, Akihiko Yoshizawa, Masatsugu Hamaji, Takamasa Yamamoto, Kenji Kawada, Hironori Haga, Yoshiharu Sakai, Hiroshi Date
BACKGROUND AND OBJECTIVES: The inhibition of the programmed death 1 (PD-1)/its ligand 1 (PD-L1) pathway may be associated with clinical responses in colorectal cancer (CRC). We aimed to characterize the transition of PD-1/PD-L1 expression through pulmonary metastasis (PM) and its clinical relevance. METHODS: This study retrospectively reviewed 50 patients who had curative resection of primary CRC and its PM. We evaluated the presence of PD-1+ tumor-infiltrating lymphocytes (TILs) and PD-L1+ tumor cells in both the primary tumor and its PM by immunohistochemistry...
April 17, 2018: Journal of Surgical Oncology
https://www.readbyqxmd.com/read/29662549/tumour-necrosis-factor-interferon-gamma-and-interleukins-as-predictive-markers-of-antiprogrammed-cell-death-protein-1-treatment-in-advanced-non-small-cell-lung-cancer-a-pragmatic-approach-in-clinical-practice
#14
Efimia Boutsikou, Kalliopi Domvri, Georgia Hardavella, Dora Tsiouda, Konstantinos Zarogoulidis, Theodoros Kontakiotis
Background: The emergence of novel antiprogrammed cell death protein-1 (PD-1) inhibitors in non-small cell lung cancers (NSCLC) has revolutionized the therapeutic landscape of this disease. Although overall survival (OS) has improved in the first- and second-line therapy settings for advanced NSCLC, the benefit is not universal. In a climate of global scrutiny for healthcare costs and potential for toxicities related to immunotherapy, appropriate patient selection is crucial. The aim of this study was to evaluate potential prognostic and predictive biomarkers interferon-gamma (IFN-γ), tumour necrosis factor-alpha (TNF-α) and a panel of interleukins (ILs) in the peripheral blood, and assess any correlation with response to anti-PD-1 inhibition, progression-free survival and OS in NSCLC patients...
2018: Therapeutic Advances in Medical Oncology
https://www.readbyqxmd.com/read/29662547/pd-l1-expression-testing-in-non-small-cell-lung-cancer
#15
REVIEW
Cristina Teixidó, Noelia Vilariño, Roxana Reyes, Noemí Reguart
In recent years, immunotherapy has revolutionized and changed the standard of care in patients with advanced non-small cell lung cancer (NSCLC). Immune checkpoint inhibitors, fundamentally those that act by blocking the programmed cell death receptor-1 (PD-1) and its ligand the programmed cell death ligand-1 (PD-L1) have emerged as novel treatment strategies in NSCLC, demonstrating undoubted superiority over chemotherapy in terms of efficacy. Several of these immune checkpoint modulators have recently gained regulatory approval for the treatment of advanced NSCLC, such as nivolumab, atezolizumab and pembrolizumab in first-line (only the latter) and second-line settings, and more recently, durvalumab as maintenance after chemoradiotherapy in locally advanced disease...
2018: Therapeutic Advances in Medical Oncology
https://www.readbyqxmd.com/read/29662546/combination-of-immunotherapy-with-chemotherapy-and-radiotherapy-in-lung-cancer-is-this-the-beginning-of-the-end-for-cancer
#16
REVIEW
Chiara Lazzari, Niki Karachaliou, Alessandra Bulotta, Mariagrazia Viganó, Aurora Mirabile, Elena Brioschi, Mariacarmela Santarpia, Luca Gianni, Rafael Rosell, Vanesa Gregorc
Immune checkpoint inhibitors have significantly improved overall survival with an acceptable safety profile in a substantial proportion of non-small cell lung cancer (NSCLC) patients. However, not all patients are sensitive to immune checkpoint blockade and, in some cases, programmed death 1 (PD-1) or programmed death ligand 1 (PD-L1) inhibitors accelerate tumor progression. Several combination strategies are under evaluation, including the concomitant or sequential evaluation of chemotherapy or radiotherapy with immunotherapy...
2018: Therapeutic Advances in Medical Oncology
https://www.readbyqxmd.com/read/29662169/distinct-myeloid-cell-subsets-promote-meningeal-remodeling-and-vascular-repair-after-mild-traumatic-brain-injury
#17
Matthew V Russo, Lawrence L Latour, Dorian B McGavern
Mild traumatic brain injury (mTBI) can cause meningeal vascular injury and cell death that spreads into the brain parenchyma and triggers local inflammation and recruitment of peripheral immune cells. The factors that dictate meningeal recovery after mTBI are unknown at present. Here we demonstrated that most patients who had experienced mTBI resolved meningeal vascular damage within 2-3 weeks, although injury persisted for months in a subset of patients. To understand the recovery process, we studied a mouse model of mTBI and found extensive meningeal remodeling that was temporally reliant on infiltrating myeloid cells with divergent functions...
April 16, 2018: Nature Immunology
https://www.readbyqxmd.com/read/29662161/pan-cancer-analysis-of-somatic-mutations-and-transcriptomes-reveals-common-functional-gene-clusters-shared-by-multiple-cancer-types
#18
Hyeongmin Kim, Yong-Min Kim
To discover functional gene clusters across cancers, we performed a systematic pan-cancer analysis of 33 cancer types. We identified genes that were associated with somatic mutations and were the cores of a co-expression network. We found that multiple cancer types have relatively exclusive hub genes individually; however, the hub genes cooperate with each other based on their functional relationship. When we built a protein-protein interaction network of hub genes and found nine functional gene clusters across cancer types, the gene clusters divided not only the region of the network map, but also the function of the network by their distinct roles related to the development and progression of cancer...
April 16, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29661791/interferon-%C3%AE-and-its-important-roles-in-promoting-and-inhibiting-spontaneous-and-therapeutic-cancer-immunity
#19
Elise Alspach, Danielle M Lussier, Robert D Schreiber
Originally identified in studies of cellular resistance to viral infection, interferon (IFN)-γ is now known to represent a distinct member of the IFN family and plays critical roles not only in orchestrating both innate and adaptive immune responses against viruses, bacteria, and tumors, but also in promoting pathologic inflammatory processes. IFN-γ production is largely restricted to T lymphocytes and natural killer (NK) cells and can ultimately lead to the generation of a polarized immune response composed of T helper (Th)1 CD4+ T cells and CD8+ cytolytic T cells...
April 16, 2018: Cold Spring Harbor Perspectives in Biology
https://www.readbyqxmd.com/read/29661720/pd-l1-immuno-expression-assay-in-thymomas-study-of-84-cases-and-review-of-literature
#20
Prerna Guleria, Nuzhat Husain, Saumya Shukla, Sunil Kumar, Rajinder Parshad, Deepali Jain
BACKGROUND AND AIMS: Programmed death ligand 1 (PD-L1), an immune check point inhibitor, is known to be expressed in several malignancies and is being considered as a prognostic factor and a potential immunotherapeutic target. The aim of this study was to characterize PD-L1 expression in thymomas and to determine correlation with clinicopathological features and previously published studies in the literature. METHODS: Tissue microarrays were prepared from selected blocks of thymomas and immunohistochemistry (IHC) for PD-L1 was performed...
April 4, 2018: Annals of Diagnostic Pathology
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