Cell Stress最新文献

{"title":"Endoplasmic reticulum and Golgi stress in microcephaly.","authors":"Sandrine Passemard,&nbsp;Franck Perez,&nbsp;Pierre Gressens,&nbsp;Vincent El Ghouzzi","doi":"10.15698/cst2019.12.206","DOIUrl":"https://doi.org/10.15698/cst2019.12.206","url":null,"abstract":"<p><p>Microcephaly is a neurodevelopmental condition characterized by a small brain size associated with intellectual deficiency in most cases and is one of the most frequent clinical sign encountered in neurodevelopmental disorders. It can result from a wide range of environmental insults occurring during pregnancy or postnatally, as well as from various genetic causes and represents a highly heterogeneous condition. However, several lines of evidence highlight a compromised mode of division of the cortical precursor cells during neurogenesis, affecting neural commitment or survival as one of the common mechanisms leading to a limited production of neurons and associated with the most severe forms of congenital microcephaly. In this context, the emergence of the endoplasmic reticulum (ER) and the Golgi apparatus as key guardians of cellular homeostasis, especially through the regulation of proteostasis, has raised the hypothesis that pathological ER and/or Golgi stress could contribute significantly to cortical impairments eliciting microcephaly. In this review, we discuss recent findings implicating ER and Golgi stress responses in early brain development and provide an overview of microcephaly-associated genes involved in these pathways.</p>","PeriodicalId":36371,"journal":{"name":"Cell Stress","volume":"3 12","pages":"369-384"},"PeriodicalIF":6.4,"publicationDate":"2019-10-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6883743/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"37453676","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"LTX-315 sequentially promotes lymphocyte-independent and lymphocyte-dependent antitumor effects.","authors":"Hsin-Wei Liao, Christopher Garris, Christina Pfirschke, Steffen Rickelt, Sean Arlauckas, Marie Siwicki, Rainer H Kohler, Ralph Weissleder, Vibeke Sundvold-Gjerstad, Baldur Sveinbjørnsson, Øystein Rekdal, Mikael J Pittet","doi":"10.15698/cst2019.11.204","DOIUrl":"10.15698/cst2019.11.204","url":null,"abstract":"<p><p>LTX-315 is an oncolytic peptide that has antitumor efficacy in mice grafted with various tumor cell lines and is currently being tested in phase II clinical trials. Here we aimed to further evaluate LTX-315 in conditional genetic mouse models of cancer that typically resist current treatment options and to better understand the drug's mode of action <i>in vivo</i>. We report LTX-315 mediates profound antitumor effects against <i>Braf-</i> and <i>Pten</i>-driven melanoma and delays the progression of <i>Kras-</i> and <i>P53-</i>driven soft tissue sarcoma in mice. Additionally, we show in melanoma that LTX-315 triggers two sequential phases of antitumor response. The first phase of response, which begins within minutes of drug delivery into tumors, is defined by disrupted tumor vasculature and decreased tumor burden and occurs independently of lymphocytes. The second phase of response, which continues over weeks, is defined by long-term alteration of the tumor microenvironment; the changes induced by LTX-315 are most notably characterized by CD8+ T cell infiltration. We further show that these CD8+ T cells are involved in suppressing melanoma outgrowth in mice and report similar CD8+ T cell infiltration following LTX-315 treatment in melanoma and sarcoma patients. Taken together, these findings reveal LTX-315's multiple antitumor effects, including disrupting the tumor vasculature and promoting the conversion of poorly immunogenic tumors into ones that display antitumor T cell immunity.</p>","PeriodicalId":36371,"journal":{"name":"Cell Stress","volume":"3 1","pages":"348-360"},"PeriodicalIF":6.4,"publicationDate":"2019-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6859426/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"46533893","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Anti-regulatory T cells are natural regulatory effector T cells.","authors":"Niels Ødum","doi":"10.15698/cst2019.10.199","DOIUrl":"https://doi.org/10.15698/cst2019.10.199","url":null,"abstract":"It is well established that the immune system uses regulatory immune-suppressive cells to inhibit and terminate immune reactions and maintain immune balance. In the last decade, Andersen and colleagues have discovered that regulatory cells also can have effector capabilities that counteract the many immune-suppressive feedback mechanisms that regulatory cells mediate. These authors have described pro-inflammatory antigen-specific T cells that react towards immune-suppressive cells [1,2]. Indeed, because of their reactive ability against regulatory immune cells, these effector T cells have been designated as antiregulatory T cells or anti-Tregs [3]. Anti-Tregs recognize proteins that regulatory cells express, including PD-L1 [47]. Spontaneous CD8+ and CD4+ T-cell reactivity against PD-L1 has been described in patients with cancer and in healthy individuals. Naturally occurring PD-L1–specific T cells can recognize PD-L1–expressing immune cells and malignant cells [8]. Activation of PD-L1–specific T cells has been described as modulating adaptive immune reactions directly and indirectly. The addition of PD-L1–specific T cells to cultured peripheral blood mononuclear cells (PBMCs) one week after viral antigen stimulation results in an immense increase in virus-specific T cells. Likewise, the co-stimulation of PD-L1 epitopes with viral epitopes results in expansion of virus-specific T cells. Thus, activation of PDL1–specific T cells enhances the effector phase of an ongoing immune response. In the current issue of Cell Stress, Andersen and colleagues further characterize the natural function of PD-L1– specific T cells, showing a direct link between inflammation and expansion of this cell population [9]. PD-L1 is expressed even in very potent antigen-presenting cells early during the inflammatory process. This expression occurs because of induction by both type I and II interferons (IFNs), which are present at the inflammation site. PD-L1 thus plays a central role in the counter-regulation of immune responses. Andersen and colleagues also show that circulating PDL1–specific T cells expand in response to pro-inflammatory mediators, such as IFN- and interleukin-2, in the absence of antigen-specific stimulation. PD-L1–specific T cells therefore expand as a first response to inflammation and can function as helper cells at the inflammation site, where they also can aid in the response to infected cells. Further evidence for these roles is the increased susceptibility of target cells to PD-L1–specific T-cell recognition in the presence of IFN- [4]. In their current work in Cell Stress, Andersen et al. provide further support for the natural regulatory role of PD-L1–specific anti-Tregs, showing that addition of inflammation-induced PD-L1–specific T cells to unstimulated PBMC cultures indeed influences Treg numbers [9]. PD-L1 is not the only target that regulatory immune cells express and that anti-Tregs can recognize. The metabolic enzymes indoleamine-pyrr","PeriodicalId":36371,"journal":{"name":"Cell Stress","volume":"3 10","pages":"310-311"},"PeriodicalIF":6.4,"publicationDate":"2019-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6789433/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41214971","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The impact of endothelial cell death in the brain and its role after stroke: A systematic review","authors":"M. Zille, Maulana Ikhsan, Yun Jiang, J. Lampe, Jan Wenzel, M. Schwaninger","doi":"10.15698/cst2019.11.203","DOIUrl":"https://doi.org/10.15698/cst2019.11.203","url":null,"abstract":"The supply of oxygen and nutrients to the brain is vital for its function and requires a complex vascular network that, when disturbed, results in profound neurological dysfunction. As part of the pathology in stroke, endothelial cells die. As endothelial cell death affects the surrounding cellular environment and is a potential target for the treatment and prevention of neurological disorders, we have systematically reviewed important aspects of endothelial cell death with a particular focus on stroke. After screening 2876 publications published between January 1, 2010 and August 7, 2019, we identified 154 records to be included. We found that endothelial cell death occurs rapidly as well as later after the onset of stroke conditions. Among the different cell death mechanisms, apoptosis was the most widely investigated (92 records), followed by autophagy (20 records), while other, more recently defined mechanisms received less attention, such as lysosome-dependent cell death (2 records) and necroptosis (2 records). We also discuss the differential vulnerability of brain cells to injury after stroke and the role of endothelial cell death in the no-reflow phenomenon with a special focus on the microvasculature. Further investigation of the different cell death mechanisms using novel tools and biomarkers will greatly enhance our understanding of endothelial cell death. For this task, at least two markers/criteria are desirable to determine cell death subroutines according to the recommendations of the Nomenclature Committee on Cell Death.","PeriodicalId":36371,"journal":{"name":"Cell Stress","volume":"3 1","pages":"330 - 347"},"PeriodicalIF":6.4,"publicationDate":"2019-09-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"46544959","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Acyl-CoA-binding protein (ACBP): the elusive 'hunger factor' linking autophagy to food intake.","authors":"José Manuel Bravo-San Pedro, Valentina Sica, Frank Madeo, Guido Kroemer","doi":"10.15698/cst2019.10.200","DOIUrl":"10.15698/cst2019.10.200","url":null,"abstract":"<p><p>The best-known appetite-regulating factors identified in rodents are leptin, an appetite inhibitor, and ghrelin, an appetite stimulator. Rare cases of loss-of-functions mutations affecting leptin and its receptor, as well as polymorphisms concerning ghrelin and its receptor, have been documented in human obesity, apparently validating the relevance of leptin and ghrelin for human physiology. Paradoxically, however, the overwhelming majority of obese individuals manifest high leptin and low ghrelin plasma levels, suggesting that both factors are not directly disease-relevant. We recently discovered that acyl-CoA-binding protein (ACBP), also known as diazepam-binding inhibitor (DBI), acts as an efficient lipogenic and appetite stimulator in mice. Indeed, in response to starvation, ACBP/DBI is released from tissues in an autophagy-dependent fashion and increases in the plasma. Intravenous injection of ACBP/DBI stimulates feeding behavior through a reduction of circulating glucose levels, and consequent activation of orexigenic neurons in the hypothalamus. In contrast, neutralization of ACBP/DBI abolishes the hyperphagia observed after starvation of mice. Of note, ACBP/DBI is increased in the plasma of obese persons and mice, pointing to a convergence (rather than divergence) between its role in appetite stimulation and human obesity. Based on our results, we postulate a novel 'hunger reflex' in which starvation induces a surge in extracellular ACBP/DBI, which in turn stimulates feeding behavior. Thus, ACBP/DBI might be the elusive 'hunger factor' that explains increased food uptake in obesity.</p>","PeriodicalId":36371,"journal":{"name":"Cell Stress","volume":"3 1","pages":"312-318"},"PeriodicalIF":4.1,"publicationDate":"2019-09-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6789435/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"42019532","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Inflammation induced PD-L1-specific T cells","authors":"Shamaila Munir, M. Lundsager, M. Jørgensen, M. Hansen, Trine H Petersen, C. Bonefeld, C. Friese, Ö. Met, P. Straten, M. Andersen","doi":"10.15698/cst2019.10.201","DOIUrl":"https://doi.org/10.15698/cst2019.10.201","url":null,"abstract":"PD-L1-specific T cells are a natural part of the T-cell repertoire in humans. Hence, we have previously described spontaneous CD8+ and CD4+ T-cell reactivity against PD-L1 in the peripheral blood of patients with various cancers as well as in healthy donors. It is well described that the expression of the PD-L1 protein is introduced in cells by pro-inflammatory cytokines, e.g. IFN-γ. In the current study, we were able to directly link inflammation with PD-L1-specific T cells by showing that inflammatory mediators such as IFN-γ generate measurable numbers of PD-L1-specific T cells in human PBMCs as well as in in vivo models. These PD-L1-specific T cells can vigorously modulate the cell compartments of the local environment. PD-L1-specific T cells may be important for immune homeostasis by sustaining the ongoing inflammatory response by the suppression of regulatory cell function both directly and indirectly.","PeriodicalId":36371,"journal":{"name":"Cell Stress","volume":"3 1","pages":"319 - 327"},"PeriodicalIF":6.4,"publicationDate":"2019-09-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"43266601","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Gold Nanoparticles sensitize pancreatic cancer cells to gemcitabine.","authors":"Yanyan Huai, Yushan Zhang, Xunhao Xiong, Shamik Das, Resham Bhattacharya, Priyabrata Mukherjee","doi":"10.15698/cst2019.08.195","DOIUrl":"10.15698/cst2019.08.195","url":null,"abstract":"<p><p>Pancreatic ductal adenocarcinoma (PDAC) is one of the deadliest solid cancers with dismal prognosis. Several mechanisms that are mainly responsible for aggressiveness and therapy resistance of PDAC cells include epithelial to mesenchymal transition (EMT), stemness and Mitogen Activated Protein Kinase (MAPK) signaling. Strategies that inhibit these mechanisms are critically important to improve therapeutic outcome in PDAC. In the current study, we wanted to investigate whether gold nanoparticles (AuNPs) could sensitize pancreatic cancer cells to the chemotherapeutic agent gemcitabine. We demonstrated that treatment with AuNPs of 20 nm diameter inhibited migration and colony forming ability of pancreatic cancer cells. Pre-treatment with AuNPs sensitized pancreatic cancer cells to gemcitabine in both viability and colony forming assays. Mechanistically, pre-treatment of pancreatic cancer cells with AuNPs decreased gemcitabine induced EMT, stemness and MAPK activation. Taken together, these findings suggest that AuNPs could be considered as a potential agent to sensitize pancreatic cancer cells to gemcitabine.</p>","PeriodicalId":36371,"journal":{"name":"Cell Stress","volume":"3 8","pages":"267-279"},"PeriodicalIF":6.4,"publicationDate":"2019-07-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6702449/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41180164","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Unraveling the molecular principles by which ceramides commit cells to death","authors":"Shashank Dadsena, Dina G. Hassan, J. Holthuis","doi":"10.15698/cst2019.08.196","DOIUrl":"https://doi.org/10.15698/cst2019.08.196","url":null,"abstract":"Ceramides are central intermediates of sphingolipid metabolism that can activate a variety of tumor suppressive cellular programs, including cell cycle arrest, senescence and apoptosis. Indeed, perturbations in ceramide generation and turnover are frequently linked to cancer cell survival and resistance to chemotherapy. Consequently, the potential of ceramide-based therapeutics in the treatment of cancer has become a major focus of interest. A growing body of evidence indicates that ceramides can act directly on mitochondria to trigger apoptotic cell death. However, molecular details of the underlying mechanism are scarce. In our recent study (Dadsena S et al., 2019, Nat Commun 10:1832), we used a photoactivatable ceramide probe combined with computer simulations and functional studies to identify the voltage-dependent anion channel VDAC2 as a critical effector of ceramide-induced mitochondrial apoptosis. Collectively, our findings provide a novel molecular framework for how ceramides execute their widely acclaimed anti-neoplastic activities.","PeriodicalId":36371,"journal":{"name":"Cell Stress","volume":"3 1","pages":"280 - 283"},"PeriodicalIF":6.4,"publicationDate":"2019-07-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"45197543","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Immunosurveillance of cancer cell stress.","authors":"Seila Lorenzo-Herrero, Christian Sordo-Bahamonde, Segundo González, Alejandro López-Soto","doi":"10.15698/cst2019.09.198","DOIUrl":"10.15698/cst2019.09.198","url":null,"abstract":"<p><p>Cancer development is tightly controlled by effector immune responses that recognize and eliminate malignantly transformed cells. Nonetheless, certain immune subsets, such as tumor-associated macrophages, have been described to promote tumor growth, unraveling a double-edge role of the immune system in cancer. Cell stress can modulate the crosstalk between immune cells and tumor cells, reshaping tumor immunogenicity and/or immune function and phenotype. Infiltrating immune cells are exposed to the challenging conditions typically present in the tumor microenvironment. In return, the myriad of signaling pathways activated in response to stress conditions may tip the balance toward stimulation of antitumor responses or immune-mediated tumor progression. Here, we explore how distinct situations of cellular stress influence innate and adaptive immunity and the consequent impact on cancer establishment and progression.</p>","PeriodicalId":36371,"journal":{"name":"Cell Stress","volume":"3 1","pages":"295-309"},"PeriodicalIF":4.1,"publicationDate":"2019-07-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6732214/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"43622671","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Myelopoiesis, metabolism and therapy: a crucial crossroads in cancer progression","authors":"A. Sica, V. Guarneri, A. Gennari","doi":"10.15698/cst2019.09.197","DOIUrl":"https://doi.org/10.15698/cst2019.09.197","url":null,"abstract":"Cancers promote immunological stresses that induce alterations of the myelopoietic output, defined as emergency myelopoiesis, which lead to the generation of different myeloid populations endowed with tumor-promoting activities. New evidence indicates that acquisition of this tumor-promoting phenotype by myeloid cells is the result of a multistep process, encompassing initial events originating into the bone marrow and later steps operating in the tumor microenvironment. The careful characterization of these sequential mechanisms is likely to offer new potential therapeutic opportunities. Here, we describe relevant mechanisms of myeloid cells reprogramming that instate immune dysfunctions and limit effective responses to anticancer therapy and discuss the influence that metabolic events, as well as chemotherapy, elicit on such events.","PeriodicalId":36371,"journal":{"name":"Cell Stress","volume":"3 1","pages":"284 - 294"},"PeriodicalIF":6.4,"publicationDate":"2019-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"46556299","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}