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https://www.readbyqxmd.com/read/29055014/protein-acyltransferase-dhhc3-regulates-breast-tumor-growth-oxidative-stress-and-senescence
#1
Martin E Hemler, Chandan Sharma, Hong-Xing Wang, Qinglin Li, Konstantin Knoblich, Emily S Reisenbichler, Andrea L Richardson
DHHC-type protein acyltransferases may regulate the localization, stability and/or activity of their substrates. In this study, we show that the protein palmitoyltransferase DHHC3 is upregulated in malignant and metastatic human breast cancer. Elevated expression of DHHC3 correlated with diminished patient survival in breast cancer and six other human cancer types. ZDHHC3 ablation in human MDA-MB-231 mammary tumor cell xenografts reduced the sizes of both the primary tumor and metastatic lung colonies. Gene array data and fluorescence dye assays documented increased oxidative stress and senescence in ZDHHC3-ablated cells...
October 20, 2017: Cancer Research
https://www.readbyqxmd.com/read/29054784/developing-a-xenograft-human-tumor-model-in-immunocompetent-mice
#2
Matthew T Basel, Sanjeev Narayanan, Chanran Ganta, Tej B Shreshta, Alejandro Marquez, Marla Pyle, Jennifer Hill, Stefan H Bossmann, Deryl L Troyer
Animal models are essential to cancer research, but current xenograft models are limited in their utility especially due to the lack of an immune system. Here we demonstrate that a xenograft tumor model can be developed in immunocompetent mice by tolerizing murine fetuses to human tumor cells. A375 human melanoma cells were injected into day E14 fetuses and after birth mice were challenged with A375 cells to determine their ability to develop tumors. Intravenous injections of cells resulted in metastatic-like lung tumors, which were verified to be human in origin by immunohistochemistry and PCR...
October 17, 2017: Cancer Letters
https://www.readbyqxmd.com/read/29053400/programmed-death-ligand-1-immunohistochemistry-testing-a-review-of-analytical-assays-and-clinical-implementation-in-non-small-cell-lung-cancer
#3
Reinhard Büttner, John R Gosney, Birgit Guldhammer Skov, Julien Adam, Noriko Motoi, Kenneth J Bloom, Manfred Dietel, John W Longshore, Fernando López-Ríos, Frédérique Penault-Llorca, Giuseppe Viale, Andrew C Wotherspoon, Keith M Kerr, Ming-Sound Tsao
Purpose Three programmed death-1/programmed death-ligand 1 (PD-L1) inhibitors are currently approved for treatment of non-small-cell lung cancer (NSCLC). Treatment with pembrolizumab in NSCLC requires PD-L1 immunohistochemistry (IHC) testing. Nivolumab and atezolizumab are approved without PD-L1 testing, though US Food and Drug Administration-cleared complementary PD-L1 tests are available for both. PD-L1 IHC assays used to assess PD-L1 expression in patients treated with programmed death-1/PD-L1 inhibitors in clinical trials include PD-L1 IHC 28-8 pharmDx (28-8), PD-L1 IHC 22C3 pharmDx (22C3), Ventana PD-L1 SP142 (SP142), and Ventana PD-L1 SP263 (SP263)...
October 20, 2017: Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology
https://www.readbyqxmd.com/read/29050127/-immune-related-pneumonitis-caused-by-programmed-death-1-inhibitor-pembrolizumab-a-case-report-and-literature-review
#4
Y L Chen, J Zhao, R Jia, H Y Wang, J Zheng, C Q Bai, M Z Wang, J M Xu
Objective: To investigate the risk factors, clinical manifestations, radiological features, diagnosis, treatment and prognosis of immune-related pneumonitis caused by programmed death-1(PD-1)/PD-L1 inhibitors. Methods: The clinical data of immune-related pneumonitis caused by PD-1 inhibitor Pembrolizumab in a patient with advanced esophageal carcinoma admitted to the 307(th) Hospital of Chinese People's Liberation Army was retrospectively analyzed and the related literatures were reviewed. We searched Medline database using the keywords"PD-1 inhibitor","PD-L1 inhibitor","Pembrolizumab","Nivolumab","Atezolizumab"combined with"Pneumonitis"by Mar 31, 2017...
October 12, 2017: Chinese Journal of Tuberculosis and Respiratory Diseases
https://www.readbyqxmd.com/read/29049803/prognostic-significance-of-immune-nutritional-parameters-for-surgically-resected-elderly-lung-cancer-patients-a-multicentre-retrospective-study
#5
Fumihiro Shoji, Naoko Miura, Taichi Matsubara, Takaki Akamine, Yuka Kozuma, Naoki Haratake, Shinkichi Takamori, Masakazu Katsura, Kazuki Takada, Gouji Toyokawa, Tomoyoshi Takenaka, Koji Yamazaki, Tatsuro Okamoto, Sadanori Takeo, Yoshihiko Maehara
OBJECTIVES: The world's population is rapidly ageing, and the age of patients with lung cancer will increase as well. The prognostic nutritional index, controlling nutritional status and the geriatric nutritional risk index (GNRI) are useful parameters for evaluating immune-nutritional status. We aimed to perform a multicentre retrospective study to investigate the correlations of these immune-nutritional parameters with postoperative comorbidities or surgical outcomes of elderly patients with non-small-cell lung cancer (NSCLC)...
October 16, 2017: Interactive Cardiovascular and Thoracic Surgery
https://www.readbyqxmd.com/read/29048660/canonical-and-non-canonical-wnt-signaling-in-cancer-stem-cells-and-their-niches-cellular-heterogeneity-omics-reprogramming-targeted-therapy-and-tumor-plasticity-review
#6
Masaru Katoh
Cancer stem cells (CSCs), which have the potential for self-renewal, differentiation and de-differentiation, undergo epigenetic, epithelial-mesenchymal, immunological and metabolic reprogramming to adapt to the tumor microenvironment and survive host defense or therapeutic insults. Intra-tumor heterogeneity and cancer-cell plasticity give rise to therapeutic resistance and recurrence through clonal replacement and reactivation of dormant CSCs, respectively. WNT signaling cascades cross-talk with the FGF, Notch, Hedgehog and TGFβ/BMP signaling cascades and regulate expression of functional CSC markers, such as CD44, CD133 (PROM1), EPCAM and LGR5 (GPR49)...
September 19, 2017: International Journal of Oncology
https://www.readbyqxmd.com/read/29047229/enhanced-inflammation-and-attenuated-tumor-suppressor-pathways-are-associated-with-oncogene-induced-lung-tumors-in-aged-mice
#7
Neha Parikh, Ryan L Shuck, Mihai Gagea, Lanlan Shen, Lawrence A Donehower
Aging is often accompanied by a dramatic increase in cancer susceptibility. To gain insights into how aging affects tumor susceptibility, we generated a conditional mouse model in which oncogenic Kras(G12D) was activated specifically in lungs of young (3-5 months) and old (19-24 months) mice. Activation of Kras(G12D) in old mice resulted in shorter survival and development of higher-grade lung tumors. Six weeks after Kras(G12D) activation, old lung tissues contained higher numbers of adenomas than their young tissue counterparts...
October 18, 2017: Aging Cell
https://www.readbyqxmd.com/read/29046030/-immunopathology-of-chronic-obstructive-pulmonary-disease
#8
Nora Ernestina Martínez-Aguilar, María Eugenia Vargas-Camaño, Rogelio Ramsés Hernández-Pliego, Genny Margarita Chaia-Semerena, María Rosario Pérez-Chavira
Chronic obstructive pulmonary disease (COPD) is a common, preventable and treatable condition that has a complex pathophysiology and an even more complex immunopathological process. The purpose of this review was to analyze COPD immunopathological aspects, which was addressed by undertaking a literature search for the most relevant documents indexed in the PubMed database over the last 10 years. Different conclusions could be drawn: in COPD immunopathology there are immune and non-immune inflammatory changes with oxidative stress imbalance, there are alterations in the protease/anti-protease ratio caused by direct and indirect genetic and epigenetic-environmental defects; COPD produces irreversible tissue damage and chronic inflammation with tissue repair alteration, which induces chronic obstruction of the airway, bronchitis and systemic damage...
July 2017: Revista Alergia Mexico: Organo Oficial de la Sociedad Mexicana de Alergia e Inmunología, A.C
https://www.readbyqxmd.com/read/29038654/cpg-odn-facilitates-effective-intratracheal-immunization-and-recall-of-memory-against-neoantigen-expressing-alveolar-cells
#9
Mathias Riehn, Marcin Cebula, Hansjörg Hauser, Dagmar Wirth
Intrapulmonary immune reactions are impaired by the tolerogenic environment of the lung. This is manifested by the absence of effective endogenous T cell responses upon neoantigen expression. This tolerance is considered to contribute to lung cancer and inefficient immune therapeutic interventions. To investigate the mechanisms contributing to lung tolerance and to overcome these restrictions, we developed a transgenic mouse model with induction of a neoantigen (OVA) exclusively in alveolar type II epithelial cells...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/29038249/anti-pd-1-antibody-treatment-promotes-clearance-of-persistent-cryptococcal-lung-infection-in-mice
#10
Jonathan A Roussey, Steven P Viglianti, Seagal Teitz-Tennenbaum, Michal A Olszewski, John J Osterholzer
Activation of immunomodulatory pathways in response to invasive fungi can impair clearance and promote persistent infections. The programmed cell death protein-1 (PD-1) signaling pathway inhibits immune effector responses against tumors, and immune checkpoint inhibitors that block this pathway are being increasingly used as cancer therapy. The objective of this study was to investigate whether this pathway contributes to persistent fungal infection and to determine whether anti-PD-1 Ab treatment improves fungal clearance...
October 16, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/29036791/globo-h-expression-is-associated-with-driver-mutations-and-pd-l1-expressions-in-stage-i-non-small-cell-lung-cancer
#11
Ching-Yao Yang, Mong-Wei Lin, Yih-Leong Chang, Chen-Tu Wu
BACKGROUND: Globo H is a tumor-associated carbohydrate antigen exclusively expressed in cancer cells rather than normal tissue. Globo H has been found on many cancers of epithelial origins, and become an attractive target for cancer vaccine. OBJECTIVES: We aimed to study the expression of Globo H in non-small cell lung cancer (NSCLC) patients, and correlated its expression with common driver mutations, clinical outcomes, and status of immune checkpoint, programmed death-ligand 1 (PD-L1)...
September 29, 2017: Cancer Biomarkers: Section A of Disease Markers
https://www.readbyqxmd.com/read/29036261/development-of-halo-nevi-in-a-lung-cancer-patient-a-novel-immune-related-cutaneous-event-from-atezolizumab
#12
Mathew R Birnbaum, Michelle W Ma, Michael A Casey, Bijal D Amin, Mark Jacobson, Haiying Cheng, Beth N McLellan
Immunotherapy-induced vitiligo is an immune-related adverse event (irAE) observed in metastatic melanoma patients treated with immune checkpoint inhibitors that target the cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) and programmed cell death-1 (PD-1) pathways. To date, the development of leukoderma, poliosis, and halo nevi during immunotherapy has largely been reported in metastatic melanoma patients. We report a case of immunotherapy-induced leukoderma presenting as halo nevi in a patient with non-small cell lung cancer (NSCLC) treated with atezolizumab, a programmed cell death ligand (PD-L1) antibody...
October 1, 2017: Journal of Drugs in Dermatology: JDD
https://www.readbyqxmd.com/read/29035945/the-functional-consequences-of-the-microbiome-in-hiv-insights-from-metabolomic-studies
#13
Sergio Serrano-Villar, Santiago Moreno, Manuel Ferrer
PURPOSE OF REVIEW: It is critical to gain insight into the metabolic pathways by which the microbiota might influence HIV immunopathogenesis to exploit host-microbiota interactions. The aim of this review is to sketch a very broad picture of recent advances in our knowledge of how HIV might affect the microbiota, with a focus on specific gene products, particularly, metabolites produced by the microbiota that may affect HIV immunopathogenesis. RECENT FINDINGS: First, we describe the different approaches used to explore imbalances in effector microbial products during HIV infection...
October 14, 2017: Current Opinion in HIV and AIDS
https://www.readbyqxmd.com/read/29033936/coinhibitory-receptor-expression-and-immune-checkpoint-blockade-maintaining-a-balance-in-cd8-t-cell-responses-to-chronic-viral-infections-and-cancer
#14
REVIEW
Isobel S Okoye, Michael Houghton, Lorne Tyrrell, Khaled Barakat, Shokrollah Elahi
In cancer and chronic viral infections, T cells are exposed to persistent antigen stimulation. This results in expression of multiple inhibitory receptors also called "immune checkpoints" by T cells. Although these inhibitory receptors under normal conditions maintain self-tolerance and prevent immunopathology, their sustained expression deteriorates T cell function: a phenomenon called exhaustion. Recent advances in cancer immunotherapy involve blockade of cytotoxic T lymphocyte antigen-4 and programmed cell death 1 in order to reverse T cell exhaustion and reinvigorate immunity, which has translated to dramatic clinical remission in many cases of metastatic melanoma and lung cancer...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/29032709/putative-predictors-of-efficacy-for-immune-checkpoint-inhibitors-in-non-small-cell-lung-cancer-facing-the-complexity-of-the-immune-system
#15
Giulia Grizzi, Mario Caccese, Anastasios Gkountakos, Luisa Carbognin, Giampaolo Tortora, Emilio Bria, Sara Pilotto
In non-small-cell lung cancer (NSCLC) the recent introduction of immunotherapy in daily clinical practice produced a wave of enthusiasm, however, this was rapidly moderated by the evidence that only some patients could experience a relevant clinical benefit. Therefore, a great effort from the scientific community has been dedicated to the identification and validation of reliable biomarkers able to drive the activity of immunotherapeutic agents. Areas covered. This analysis aims to review the main findings about predictive biomarkers for immunotherapy in lung cancer, retracing the history of PD-L1 and focusing on a series of innovative candidates, such as mutational load, immune cells populations and microbiome...
October 14, 2017: Expert Review of Molecular Diagnostics
https://www.readbyqxmd.com/read/29031828/non-progressing-cancer-patients-have-persistent-b-cell-responses-expressing-shared-antibody-paratopes-that-target-public-tumor-antigens
#16
Jeff DeFalco, Michael Harbell, Amy Manning-Bog, Gilson Baia, Alexander Scholz, Beatriz Millare, May Sumi, Danhui Zhang, Felix Chu, Christine Dowd, Patricia Zuno-Mitchell, Dongkyoon Kim, Yvonne Leung, Shuwei Jiang, Xiaobin Tang, Kevin S Williamson, Xiaomu Chen, Sean M Carroll, Gregg Espiritu Santo, Nicole Haaser, Ngan Nguyen, Eldar Giladi, David Minor, Yann Chong Tan, Jeremy B Sokolove, Lawrence Steinman, Tito A Serafini, Guy Cavet, Norman M Greenberg, Jacob Glanville, Wayne Volkmuth, Daniel E Emerling, William H Robinson
There is significant debate regarding whether B cells and their antibodies contribute to effective anti-cancer immune responses. Here we show that patients with metastatic but non-progressing melanoma, lung adenocarcinoma, or renal cell carcinoma exhibited increased levels of blood plasmablasts. We used a cell-barcoding technology to sequence their plasmablast antibody repertoires, revealing clonal families of affinity matured B cells that exhibit progressive class switching and persistence over time. Anti-CTLA4 and other treatments were associated with further increases in somatic hypermutation and clonal family size...
October 11, 2017: Clinical Immunology: the Official Journal of the Clinical Immunology Society
https://www.readbyqxmd.com/read/29031195/ginsenoside-rg3-attenuates-cisplatin-resistance-in-lung-cancer-by-downregulating-pd-l1-and-resuming-immune
#17
Zhansheng Jiang, Yanfang Yang, Yinli Yang, Yu Zhang, Zhensong Yue, Zhanyu Pan, Xiubao Ren
Programmed death ligand 1 (PD-L1) as one the most important immune checkpoint was verified to involve in chemotherapy resistance in non-small cell lung cancer (NSCLC). Ginsenoside Rg3 is isolated from Chinese herb-Panax ginseng which is recognized to boost immune and has anti-cancer activity against a majority of carcinomas including NSCLC. In this study, we aim to identify whether Rg3 could attenuate the PD-L1 expression induced by resistance to cisplatin and draw out the underlying mechanisms of PD-L1 in this process...
October 11, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/29029813/innovative-therapy-monoclonal-antibodies-and-beyond
#18
M Di Nicola, L Apetoh, M Bellone, M P Colombo, G Dotti, S Ferrone, M Muscolini, J Hiscott, A Anichini, S M Pupa, F de Braud, M Del Vecchio
The seventh Edition of "Innovative Therapy, Monoclonal Antibodies and Beyond" Meeting took place in Milan, Italy, on January 27, 2017. The two sessions of the meeting were focused on: 1) Preclinical assays and novel biotargets; and 2) monoclonal antibodies, cell therapies and targeted molecules. Between these two sessions, a lecture entitled "HLA-antigens modulation and response to immune checkpoint inhibitor immunotherapy" was also presented. Despite the impressive successes in cancer immunotherapy in recent years, the response to immune based interventions occurs only in a minority of patients (∼20%)...
October 5, 2017: Cytokine & Growth Factor Reviews
https://www.readbyqxmd.com/read/29029603/the-pathophysiological-role-of-mitochondrial-oxidative-stress-in-lung-diseases
#19
REVIEW
Xiaojing Liu, Zhihong Chen
Mitochondria are critically involved in reactive oxygen species (ROS)-dependent lung diseases, such as lung fibrosis, asbestos, chronic airway diseases and lung cancer. Mitochondrial DNA (mtDNA) encodes mitochondrial proteins and is more sensitive to oxidants than nuclear DNA. Damage to mtDNA causes mitochondrial dysfunction, including electron transport chain impairment and mitochondrial membrane potential loss. Furthermore, damaged mtDNA also acts as a damage-associated molecular pattern (DAMP) that drives inflammatory and immune responses...
October 13, 2017: Journal of Translational Medicine
https://www.readbyqxmd.com/read/29029530/which-treatment-is-preferred-for-advanced-non-small-cell-lung-cancer-with-wild-type-epidermal-growth-factor-receptor-in-second-line-therapy-a-meta-analysis-comparing-immune-checkpoint-inhibitor-tyrosine-kinase-inhibitor-and-chemotherapy
#20
Di Wu, Chongyang Duan, Fenfang Wu, Liyong Chen, Size Chen
BACKGROUND: The recommendations regarding the optimum treatment for advanced non-small-cell lung cancer (NSCLC) patients with wild-type (WT) epidermal growth factor receptor (EGFR) tumors remain unclear. This meta-analysis was conducted to assess the efficacy among programmed death-ligand 1 (PD-L1)/programmed death-1 (PD-1) antibody, EGFR-tyrosine kinase inhibitors (TKI) and chemotherapy in second-and third-line therapy. PATIENTS AND METHODS: Randomized trials investigating two of the three treatments were searched and included...
September 12, 2017: Oncotarget
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