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https://www.readbyqxmd.com/read/29674124/diverse-toxic-effectors-are-harbored-by-vgrg-islands-for-interbacterial-antagonism-in-type-vi-secretion-system
#1
Jiale Ma, Min Sun, Zihao Pan, Chengping Lu, Huochun Yao
The type VI secretion system (T6SS) is considered as one of the key competition strategies by injecting toxic effectors for intestinal pathogens to acquire optimal colonization in host gut, a microenviroment with high-density polymicrobial community where bacteria compete for niches and resources. Enterotoxigenic Escherichia coli (ETEC), a major cause of infectious diarrhea in human and animals, widely encode T6SS clusters in their genomes. In this report, we first identified VT1, a novel amidase effector in ETEC, significantly hydrolyzed D-lactyl-L-Ala crosslinks between N-acetylmuramoyl and L-Ala in peptidoglycan...
April 16, 2018: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/29562194/regulation-and-function-of-the-pd-l1-checkpoint
#2
REVIEW
Chong Sun, Riccardo Mezzadra, Ton N Schumacher
Expression of programmed death-ligand 1 (PD-L1) is frequently observed in human cancers. Binding of PD-L1 to its receptor PD-1 on activated T cells inhibits anti-tumor immunity by counteracting T cell-activating signals. Antibody-based PD-1-PD-L1 inhibitors can induce durable tumor remissions in patients with diverse advanced cancers, and thus expression of PD-L1 on tumor cells and other cells in the tumor microenviroment is of major clinical relevance. Here we review the roles of the PD-1-PD-L1 axis in cancer, focusing on recent findings on the mechanisms that regulate PD-L1 expression at the transcriptional, posttranscriptional, and protein level...
March 20, 2018: Immunity
https://www.readbyqxmd.com/read/29413890/indoleamine-2-3-dioxygenase-and-its-therapeutic-inhibition-in-cancer
#3
George C Prendergast, William J Malachowski, Arpita Mondal, Peggy Scherle, Alexander J Muller
The tryptophan catabolic enzyme indoleamine 2,3-dioxygenase-1 (IDO1) has attracted enormous attention in driving cancer immunosuppression, neovascularization, and metastasis. IDO1 suppresses local CD8+ T effector cells and natural killer cells and induces CD4+ T regulatory cells (iTreg) and myeloid-derived suppressor cells (MDSC). The structurally distinct enzyme tryptophan dioxygenase (TDO) also has been implicated recently in immune escape and metastatic progression. Lastly, emerging evidence suggests that the IDO1-related enzyme IDO2 may support IDO1-mediated iTreg and contribute to B-cell inflammed states in certain cancers...
2018: International Review of Cell and Molecular Biology
https://www.readbyqxmd.com/read/29303414/expression-of-aromatase-in-tumor-related-stroma-is-associated-with-human-bladder-cancer-progression
#4
Shulin Wu, Jianheng Ye, Zongwei Wang, Sharron X Lin, Min Lu, Yingke Liang, Xuejin Zhu, Aria F Olumi, Wei-de Zhong, Chin-Lee Wu
Putative gender differences in bladder cancer (BCa) have been proposed to result from sex hormone influence. Aromatase is the key enzyme catalyzing the conversion of androgens to estrogens which may result in an intratumoral microenviroment with increased estrogen production. In this study, we investigated the expression pattern of aromatase and its association with BCa progression. Tissue samples from 88 BCa patients who underwent cystectomy were obtained. Using immunohistochemistry (IHC), expression of aromatase in tumor epithelium (TE) and tumor related stroma (TS) were evaluated separately, and the association of aromatase expression status with pathologic variables and overall survival (OS) outcome was examined...
March 4, 2018: Cancer Biology & Therapy
https://www.readbyqxmd.com/read/29238041/foxo1-is-a-regulator-of-mhc-ii-expression-and-anti-tumor-effect-of-tumor-associated-macrophages
#5
Jing-Bo Yang, Zhi-Bin Zhao, Qing-Zhi Liu, Tai-Dou Hu, Jie Long, Kai Yan, Zhe-Xiong Lian
Macrophages are a critical component in host immune responses against tumor. In this work we investigated the role of forkhead box O1 (FoxO1) in the transcriptional regulation in macrophages, which affects the anti-tumor functions of tumor-associated macrophages (TAMs). First, we showed that TAMs expressed reduced levels of FoxO1, which was associated with their protumoral M2 polarization state. The suppression of FoxO1 expression in TAM was induced by the hypoxic condition in the tumor microenviroment. Next, we confirmed that FoxO1 positively regulates MHC-II genes by binding to the promoter region of Ciita gene, the master activator of multiple MHC-II genes...
March 2018: Oncogene
https://www.readbyqxmd.com/read/29204829/spinal-cord-stem-cells-in-their-microenvironment-the-ependyma-as-a-stem-cell-niche
#6
Nicolás Marichal, Cecilia Reali, Omar Trujillo-Cenóz, Raúl E Russo
The ependyma of the spinal cord is currently proposed as a latent neural stem cell niche. This chapter discusses recent knowledge on the developmental origin and nature of the heterogeneous population of cells that compose this stem cell microenviroment, their diverse physiological properties and regulation. The chapter also reviews relevant data on the ependymal cells as a source of plasticity for spinal cord repair.
2017: Advances in Experimental Medicine and Biology
https://www.readbyqxmd.com/read/29199217/a-novel-probe-with-a-chlorinated-%C3%AE-cyanoacetophenone-acceptor-moiety-shows-near-infrared-fluorescence-specific-for-tau-fibrils
#7
Kwang-Su Park, Kyungha Yoo, Mi Kyoung Kim, Woong Jung, Yoon Kyung Choi, Youhoon Chong
Development of a novel, tau-selective near-infrared fluorescence (NIRF) probe was attempted by combining the 3,5-dimethoxy-N,N-dimethylaniline-4-yl moiety with an α-cyanoacetophenone via hexatrienyl π-linker. In particular, for structure-activity relationship study of the α-cyanoacetophenones, a chlorine substituent was introduced to the aromatic ring to give a series of compounds (2a-2d). Among those, compound 2c with meta-chloro aryl substituent was identified as a tau-selective NIRF probe: selectivity for tau over amyloid β (Aβ) and bovine serum albumin (BSA) was estimated to be 10...
2017: Chemical & Pharmaceutical Bulletin
https://www.readbyqxmd.com/read/29152107/neoadjuvant-olaparib-targets-hypoxia-to-improve-radioresponse-in-a-homologous-recombination-proficient-breast-cancer-model
#8
Gerben R Borst, Ramya Kumareswaran, Hatice Yücel, Seyda Telli, Trevor Do, Trevor McKee, Gaetano Zafarana, Jos Jonkers, Marcel Verheij, Mark J O'Connor, Sven Rottenberg, Robert G Bristow
Clinical trials are studying the benefits of combining the PARP-1 inhibitor olaparib with chemotherapy and radiotherapy treatment in a variety of cancer increasing the therapeutic ratio for olaparib may come from its ability to modify the tumour microenvironment by targeting homologous recombination-deficient, hypoxic tumour clonogens, and/or increasing tumour-associated vasodilation to improve oxygenation. Herein, we investigated the effect of prolonged neoadjuvant exposure to olaparib on the tumor microenvironment using a genetically-engineered mouse p53-/- syngeneic breast cancer model, which is proficient in homology-directed DNA repair...
October 20, 2017: Oncotarget
https://www.readbyqxmd.com/read/29138761/a-metastasis-biomarker-metasite-breast-%C3%A2-score-is-associated-with-distant-recurrence-in-hormone-receptor-positive-her2-negative-early-stage-breast-cancer
#9
Joseph A Sparano, Robert Gray, Maja H Oktay, David Entenberg, Thomas Rohan, Xiaonan Xue, Michael Donovan, Michael Peterson, Anthony Shuber, Douglas A Hamilton, Timothy D'Alfonso, Lori J Goldstein, Frank Gertler, Nancy E Davidson, John Condeelis, Joan Jones
Metastasis is the primary cause of death in early-stage breast cancer. We evaluated the association between a metastasis biomarker, which we call "Tumor Microenviroment of Metastasis" (TMEM), and risk of recurrence. TMEM are microanatomic structures where invasive tumor cells are in direct contact with endothelial cells and macrophages, and which serve as intravasation sites for tumor cells into the circulation. We evaluated primary tumors from 600 patients with Stage I-III breast cancer treated with adjuvant chemotherapy in trial E2197 (NCT00003519), plus endocrine therapy for hormone receptor (HR)+ disease...
2017: NPJ Breast Cancer
https://www.readbyqxmd.com/read/29055087/metabolism-and-tam-functions-it-takes-two-to-tango
#10
REVIEW
Massimiliano Mazzone, Alessio Menga, Alessandra Castegna
From the evidence on clinical studies and experimental mouse models we now know that tumor-associated macrophages (TAMs) sustain tumor development in many different ways. They play a role in angiogenesis, tumor cell invasion, and metastasis formation. Additionally, TAMs interfere with natural killer and T-cell antitumoral activities, producing an immune-suppressive environment that protects tumor cell growth. This indicates that the tumoricidal activity of macrophages within the tumor microenviroment is lost due to an imbalance of the regulatory mechanisms underpinning these cells' function...
February 2018: FEBS Journal
https://www.readbyqxmd.com/read/29033453/polycystic-kidney-disease-modulation-of-cystogenesis-by-the-microenviroment
#11
Ellen F Carney
No abstract text is available yet for this article.
December 2017: Nature Reviews. Nephrology
https://www.readbyqxmd.com/read/28948499/cd133-positive-u87-glioblastoma-cells-derived-exosomal-micrornas-in-hypoxia-versus-normoxia-microenviroment
#12
Guobin Zhang, Yunsheng Zhang, Sen Cheng, Zhen Wu, Fusheng Liu, Junting Zhang
Hypoxia is a major regulator of glioma development and aggressiveness. However, how CD133 positive U87 glioblastoma cells adapt to hypoxia and communicate with their surrounding microenvironment during tumor development remain important questions. Communication with host cells and stroma via exosomes represents one pathway by which tumors can modify their surroundings to achieve a tumor-permissive environment. MicroRNAs are thought to be essential actors of tumorigenesis as they are able to control the expression of numerous genes...
October 2017: Journal of Neuro-oncology
https://www.readbyqxmd.com/read/28935774/immunotherapy-a-new-and-old-approach-to-treatment-of-soft-tissue-and-bone-sarcomas
#13
REVIEW
Michael J Nathenson, Anthony P Conley, Edward Sausville
Soft tissue and bone sarcomas are a rare and heterogeneous form of cancer. With standard of care treatment options including surgery, radiation, and chemotherapy, the long-term survival is still low for high-risk soft tissue sarcoma patients. New treatment strategies are needed. Immunotherapy offers a new potential treatment paradigm with great promise. Immunotherapy of soft tissue sarcomas dates back to Dr. Coley's first use of toxins in the late 1800s. A variety of strategies of immunotherapy have been tried in soft tissue and bone sarcomas, including various vaccines and cytokines, with limited success...
January 2018: Oncologist
https://www.readbyqxmd.com/read/28923837/mechanoregulation-of-clathrin-mediated-endocytosis
#14
Joshua P Ferguson, Scott D Huber, Nathan M Willy, Esra Aygün, Sevde Goker, Tugba Atabey, Comert Kural
We characterized the tension response of clathrin-mediated endocytosis by using various cell manipulation methodologies. Elevated tension in a cell hinders clathrin-mediated endocytosis through inhibition of de novo coat initiation, elongation of clathrin coat lifetimes and reduction of high-magnitude growth rates. Actin machinery supplies an inward pulling force necessary for internalization of clathrin coats under high tension. These findings suggest that the physical cues cells receive from their microenvironment are major determinants of clathrin-mediated endocytic activity...
November 1, 2017: Journal of Cell Science
https://www.readbyqxmd.com/read/28910901/-clinical-research-on-immune-checkpoint-and-head-and-neck-squamous-cell-carcinoma
#15
D Yu, X M Qi, X Zhao, Y Liu, K Xue, C S Jin, L J Wen
T cell immune checkpoint pathways contribute to tumor immune escape. Many studies have shown that immune checkpoint is demonstrably correlated with tumor grade or prognosis in several types of malignancies and immune checkpoint has become a new biological index for tumor detection and prognosis. Immune checkpoint inhibitors have shown promising tumor outcomes in clinical trials for some advanced solid tumors and it will become a new target for cancer immunotherapy. In this review we will explore the correlation between expressions of immune checkpoint-associated genes and proteins in immune microenviroment and prognosis of head and neck squamous cell carcinoma, and specifically will discuss how this pathway can be manipulated with immune therapeutic drugs...
September 7, 2017: Zhonghua Er Bi Yan Hou Tou Jing Wai Ke za Zhi, Chinese Journal of Otorhinolaryngology Head and Neck Surgery
https://www.readbyqxmd.com/read/28818640/the-influence-of-physical-activity-in-the-anti-tumor-immune-response-in-experimental-breast-tumor
#16
Thiago M Bianco, Douglas R Abdalla, Chamberttan S Desidério, Sofie Thys, Cindy Simoens, John-Paul Bogers, Eddie F C Murta, Márcia A Michelin
This study aimed to investigate the influence of physical activity in innate immunity to conduce to an effective antitumoral immune response analyzing the phenotype and activation status of infiltrating cells. We analysed the intracellular cytokines and the transcription factors of tumor infiltrating lymphocytes (TILS) and spleen leukocytes. The Nos2 gene expression was evaluated in spleen cells and futhermore the ROS production was measured and spleen cells; another cell evaluated was dendritic cells (TIDCs), their cytokines expression and membrane molecules; finally to understood the results obtained, we analysed the dendritic cells obtained from bone marrow...
August 14, 2017: Immunology Letters
https://www.readbyqxmd.com/read/28798901/translational-dysregulation-in-cancer-molecular-insights-and-potential-clinical-applications-in-biomarker-development
#17
REVIEW
Christos Vaklavas, Scott W Blume, William E Grizzle
Although transcript levels have been traditionally used as a surrogate measure of gene expression, it is increasingly recognized that the latter is extensively and dynamically modulated at the level of translation (messenger RNA to protein). Over the recent years, significant progress has been made in dissecting the complex posttranscriptional mechanisms that regulate gene expression. This advancement in knowledge came hand in hand with the progress made in the methodologies to study translation both at gene-specific as well as global genomic level...
2017: Frontiers in Oncology
https://www.readbyqxmd.com/read/28683469/lurbinectedin-reduces-tumour-associated-macrophages-and-the-inflammatory-tumour-microenvironment-in-preclinical-models
#18
Cristina Belgiovine, Ezia Bello, Manuela Liguori, Ilaria Craparotta, Laura Mannarino, Lara Paracchini, Luca Beltrame, Sergio Marchini, Carlos M Galmarini, Alberto Mantovani, Roberta Frapolli, Paola Allavena, Maurizio D'Incalci
BACKGROUND: Lurbinectedin is a novel anticancer agent currently undergoing late-stage (Phase II /III) clinical evaluation in platinum-resistant ovarian, BRCA1/2-mutated breast and small-cell lung cancer. Lurbinectedin is structurally related to trabectedin and it inhibits active transcription and the DNA repair machinery in tumour cells. METHODS: In this study we investigated whether lurbinectedin has the ability to modulate the inflammatory microenvironment and the viability of myeloid cells in tumour-bearing mice...
August 22, 2017: British Journal of Cancer
https://www.readbyqxmd.com/read/28620146/mitochondrial-asncmtrna-1-and-asncmtrna-2-as-potent-targets-to-inhibit-tumor-growth-and-metastasis-in-the-renca-murine-renal-adenocarcinoma-model
#19
Vincenzo Borgna, Jaime Villegas, Verónica A Burzio, Sebastián Belmar, Mariela Araya, Emanuel Jeldes, Lorena Lobos-González, Verónica Silva, Claudio Villota, Luciana Oliveira-Cruz, Constanza Lopez, Teresa Socias, Octavio Castillo, Luis O Burzio
Knockdown of antisense noncoding mitochondrial RNAs (ASncmtRNAs) induces apoptosis in several human and mouse tumor cell lines, but not normal cells, suggesting this approach for a selective therapy against different types of cancer. Here we show that in vitro knockdown of murine ASncmtRNAs induces apoptotic death of mouse renal adenocarcinoma RenCa cells, but not normal murine kidney epithelial cells. In a syngeneic subcutaneous RenCa model, treatment delayed and even reversed tumor growth. Since the subcutaneous model does not reflect the natural microenviroment of renal cancer, we used an orthotopic model of RenCa cells inoculated under the renal capsule...
July 4, 2017: Oncotarget
https://www.readbyqxmd.com/read/28588447/the-effects-of-epidermal-neural-crest-stem-cells-on-local-inflammation-microenvironment-in-the-defected-sciatic-nerve-of-rats
#20
Yue Li, Dongdong Yao, Jieyuan Zhang, Bin Liu, Lu Zhang, Hua Feng, Bingcang Li
Cell-based therapy is a promising strategy for the repair of peripheral nerve injuries (PNIs). epidermal neural crest stems cells (EPI-NCSCs) are thought to be important donor cells for repairing PNI in different animal models. Following PNI, inflammatory response is important to regulate the repair process. However, the effects of EPI-NCSCs on regulation of local inflammation microenviroment have not been investigated extensively. In the present study, these effects were studied by using 10 mm defected sciatic nerve, which was bridged with 15 mm artificial nerve composed of EPI-NCSCs, extracellular matrix (ECM) and poly (lactide-co-glycolide) (PLGA)...
2017: Frontiers in Molecular Neuroscience
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