Cell Stress最新文献_第7页

Targeting immune-checkpoint inhibitor resistance mechanisms by MEK inhibitor and agonist anti-CD40 antibody combination therapy. 靶向免疫检查点抑制剂MEK抑制剂与激动剂抗cd40抗体联合治疗的耐药机制。

IF 6.4

Cell Stress Pub Date : 2020-08-06 DOI: 10.15698/cst2020.10.233

Daniel Baumann, Rienk Offringa

{"title":"Targeting immune-checkpoint inhibitor resistance mechanisms by MEK inhibitor and agonist anti-CD40 antibody combination therapy.","authors":"Daniel Baumann, Rienk Offringa","doi":"10.15698/cst2020.10.233","DOIUrl":"https://doi.org/10.15698/cst2020.10.233","url":null,"abstract":"The widespread application of immune-checkpoint blockade (ICB) has resulted in unprecedented response rates in patients with immunogenic cancers, such as melanoma and lung cancer. However, sub-groups of patients with these indications do not respond to ICB, and the same applies to patients with other cancer types. Mechanisms of resistance to ICB include low tumor immunogenicity associated with low T cell infiltration ('cold' tumors), suppression of anti-tumor immunity by immunosuppressive cells in the tumor microenvironment (TME), lack of antigen-presentation and immune escape (e.g. by downregulation of MHC-I on tumor cells) as well as oncologic pathways that suppress immune responses. Combination strategies, involving cytostatic drugs, harbor the potential to overcome refractoriness to immunotherapy. However, suppression of immune cell function by cytostatic drugs may limit the efficacy. In our study, we show that combination treatment of targeted inhibition of mitogen-activated protein kinase (MAPK) kinase (MEK) and agonist immunostimulatory anti-CD40 antibody (Ab) is particularly suitable in counteracting aforementioned ICB resistance mechanisms (Fig. 1).","PeriodicalId":36371,"journal":{"name":"Cell Stress","volume":null,"pages":null},"PeriodicalIF":6.4,"publicationDate":"2020-08-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7520667/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38462552","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}

引用次数: 3

Hyaluronan goes to great length. 透明质酸的作用很长。

IF 6.4

Cell Stress Pub Date : 2020-07-17 DOI: 10.15698/cst2020.09.231

Vera Gorbunova, Masaki Takasugi, Andrei Seluanov

{"title":"Hyaluronan goes to great length.","authors":"Vera Gorbunova, Masaki Takasugi, Andrei Seluanov","doi":"10.15698/cst2020.09.231","DOIUrl":"https://doi.org/10.15698/cst2020.09.231","url":null,"abstract":"Hyaluronan is a major non-protein component of extracellular matrix that affects biomechanical properties of tissues and interacts with cell receptors. Hyaluronan is a linear glycosaminoglycan composed of repeating disaccharides of (β, 1-4)-glucuronic acid (GlcUA) and (β, 1-3)-N-acetyl glucosamine (GlcNAc). The length of hyaluronan can range from an oligomer to an extremely long form up to millions of daltons. The concept that emerged in the field is that high (HMW-HA) and low (LMW-HA) molecular weight hyaluronans have different biological properties and trigger different signaling cascades within the cells. LMW-HA is associated with inflammation, tissue injury and metastasis, while HMW-HA improves tissue homeostasis and has anti-inflammatory and antimetastatic properties. HMW-HA is used in the clinic to treat arthritis, and as a filler in surgery and in the form of rinses to treat local inflammation. However, HMW-HA products used in the clinic come in a range of sizes between 0.5-6 mDa that are used interchangeably. Remarkably, the tissues of a long-lived and cancer-resistant rodent, the naked mole rat, contain abundant HA of very high molecular weight. While human fibroblasts secrete HA up to 2 MDa, naked mole rat fibroblasts produce HA of 6-12 MDa. Does this very high HMW-HA (vHMW-HA) differ functionally from HMW-HA? We found that vHMW-HA has superior cytoprotective properties compared to HMW-HA, and interacts differently with the CD44 receptor leading to distinct transcriptional changes (Takasugi et al. (2020), Nat Commun). These results indicate that vHMW-HA has greater therapeutic benefits than the standard HMW-HA.","PeriodicalId":36371,"journal":{"name":"Cell Stress","volume":null,"pages":null},"PeriodicalIF":6.4,"publicationDate":"2020-07-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7453635/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38459336","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}

引用次数: 6

PRMT5 function and targeting in cancer. PRMT5在癌症中的功能和靶向性。

IF 6.4

Cell Stress Pub Date : 2020-07-13 DOI: 10.15698/cst2020.08.228

Hyungsoo Kim, Ze'ev A Ronai

引用次数: 85

Regulation of immune checkpoint blockade efficacy in breast cancer by FIP200: A canonical-autophagy-independent function. FIP200对乳腺癌免疫检查点阻断疗效的调节:一种典型的自噬独立功能。

IF 6.4

Cell Stress Pub Date : 2020-07-02 DOI: 10.15698/cst2020.08.229

Syn Kok Yeo, Jun-Lin Guan

{"title":"Regulation of immune checkpoint blockade efficacy in breast cancer by FIP200: A canonical-autophagy-independent function.","authors":"Syn Kok Yeo, Jun-Lin Guan","doi":"10.15698/cst2020.08.229","DOIUrl":"https://doi.org/10.15698/cst2020.08.229","url":null,"abstract":"Immune checkpoint blockade (ICB) has emerged as a promising therapeutic strategy because of its potential to induce durable therapeutic responses in cancer patients. However, in the case of breast cancer, its application and efficacy has been limited. As such, combinatorial therapeutic strategies that can unlock the potential of ICB in breast cancer are of urgent need. In view of that, autophagy-related proteins that play a role in the autophagic cell recycling process have been implicated in the regulation of inflammatory and anti-tumor immune responses. Accordingly, autophagy-related proteins represent a group of prospective therapeutic targets in conjunction with ICB. In our recent study (Okamoto T et al. (2020), Cancer Res), we developed immune-competent mouse models of breast cancer which were deficient for the autophagic function of FIP200 or had FIP200 completely ablated to test the efficacy of ICB. We showed that although FIP200's autophagy function was required for progression of PyMT-driven mammary tumors, FIP200's canonical-autophagy-independent function was responsible for increased T-cell infiltration, IFN-signaling and ICB efficacy. These findings provide genetic proof of principle for a combinatorial therapeutic strategy that involves ablation of FIP200 to improve ICB efficacy in non-responsive breast cancers.","PeriodicalId":36371,"journal":{"name":"Cell Stress","volume":null,"pages":null},"PeriodicalIF":6.4,"publicationDate":"2020-07-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7380453/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38228743","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}

引用次数: 1

Exploiting the circuit breaker cancer evolution model in human clear cell renal cell carcinoma. 人透明细胞肾细胞癌断路器癌进化模型的建立。

IF 6.4

Cell Stress Pub Date : 2020-06-25 DOI: 10.15698/cst2020.08.227

James J Hsieh, Emily H Cheng

{"title":"Exploiting the circuit breaker cancer evolution model in human clear cell renal cell carcinoma.","authors":"James J Hsieh, Emily H Cheng","doi":"10.15698/cst2020.08.227","DOIUrl":"10.15698/cst2020.08.227","url":null,"abstract":"The incessant interactions between susceptible humans and their respective macro/microenvironments registered throughout their lifetime result in the ultimate manifestation of individual cancers. With the average lifespan exceeding 50 years of age in humans since the beginning of 20th century, aging - the \"time\" factor - has played an ever-increasing role alongside host and environmental factors in cancer incidences. Cancer is a genetic/epigenetic disease due to gain-of-function mutations in cancer-causing genes (oncogene; OG) and/or loss-of-function mutations in tumor-suppressing genes (tumor suppressor genes; TSG). In addition to their integral relationship with cancer, a timely deployment of specific OG and/or TSG is in fact needed for higher organisms like human to cope with respective physiological and pathological conditions. Over the past decade, extensive human kidney cancer genomics have been performed and novel mouse models recapitulating human kidney cancer pathobiology have been generated. With new genomic, genetic, mechanistic, clinical and therapeutic insights accumulated from studying clear cell renal cell carcinoma (ccRCC)-the most common type of kidney cancer, we conceived a cancer evolution model built upon the OG-TSG signaling pair analogous to the electrical circuit breaker (CB) that permits necessary signaling output and at the same time prevent detrimental signaling overdrive. Hence, this viewpoint aims at providing a step-by-step mechanistic explanation/illustration concerning how inherent OG-TSG CBs intricately operate in concert for the organism's wellbeing; and how somatic mutations, the essential component for genetic adaptability, inadvertently triggers a sequential outage of specific sets of CBs that normally function to maintain and protect and individual tissue homeostasis.","PeriodicalId":36371,"journal":{"name":"Cell Stress","volume":null,"pages":null},"PeriodicalIF":6.4,"publicationDate":"2020-06-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7380452/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38228742","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}

引用次数: 2

High mitochondrial calcium levels precede neuronal death in vivo in Alzheimer's disease. 阿尔茨海默病患者体内高线粒体钙水平先于神经元死亡。

IF 6.4

Cell Stress Pub Date : 2020-06-18 DOI: 10.15698/cst2020.07.226

Maria Calvo-Rodriguez, Brian J Bacskai

{"title":"High mitochondrial calcium levels precede neuronal death in vivo in Alzheimer's disease.","authors":"Maria Calvo-Rodriguez, Brian J Bacskai","doi":"10.15698/cst2020.07.226","DOIUrl":"https://doi.org/10.15698/cst2020.07.226","url":null,"abstract":"Alzheimer's disease (AD), the most common cause of dementia, affects millions of people worldwide. Suggested mechanisms of neurotoxicity in AD include impaired calcium (Ca2+) homeostasis and mitochondrial dysfunction, both contributing to neuronal damage. Little was known about the exact mitochondrial Ca2+ homeostasis in the living brain, particularly in AD. Only now, with the development of intravital imaging techniques and transgenic mouse models of the disease, we are able to directly observe Ca2+ levels in specific regions or particular subcellular compartments of cells, such as mitochondria. Using multiphoton microscopy, a Ca2+ reporter targeted to mitochondria and a mouse model of cerebral β amyloidosis (APP/PS1), our recent study (Nat Comms 2020, 11:2146) found elevated mitochondrial Ca2+ concentration in the transgenic mouse after plaque deposition, and after topical application of natural soluble amyloid beta (Aβ) oligomers to the healthy mouse brain at concentrations similar to those found in the human brain. Elevated Ca2+ in mitochondria preceded neuronal death and could be targeted for neuroprotective therapies in AD. Here, we describe our main findings and pose new questions for future studies aimed at better understanding mitochondrial Ca2+ dyshomeostasis in AD.","PeriodicalId":36371,"journal":{"name":"Cell Stress","volume":null,"pages":null},"PeriodicalIF":6.4,"publicationDate":"2020-06-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7328672/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38144967","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}

引用次数: 11

The role of lipids in autophagy and its implication in neurodegeneration. 脂质在自噬中的作用及其在神经变性中的意义。

IF 6.4

Cell Stress Pub Date : 2020-05-19 DOI: 10.15698/cst2020.07.225

Sergio Hernandez-Diaz, Sandra-Fausia Soukup

{"title":"The role of lipids in autophagy and its implication in neurodegeneration.","authors":"Sergio Hernandez-Diaz, Sandra-Fausia Soukup","doi":"10.15698/cst2020.07.225","DOIUrl":"https://doi.org/10.15698/cst2020.07.225","url":null,"abstract":"Neurodegenerative diseases are, at present, major socio-economic burdens without effective treatments and their increasing prevalence means that these diseases will be a challenge for future generations. Neurodegenerative diseases may differ in etiology and pathology but are often caused by the accumulation of dysfunctional and aggregation-prone proteins. Autophagy, a conserved cellular mechanism, deals with cellular stress and waste product build-up and has been shown to reduce the accumulation of dysfunctional proteins in animal models of neurodegenerative diseases. Historically, progress in understanding the precise function of lipids has traditionally been far behind other biological molecules (like proteins) but emerging works demonstrate the importance of lipids in the autophagy pathway and how the disturbance of lipid metabolism is connected to neurodegeneration. Here we review how altered autophagy and the disturbance of lipid metabolism, particularly of phosphoinositols and sphingolipids, feature in neurodegenerative diseases and address work from the field that suggests that these potentially offer an opportunity of therapeutic intervention.","PeriodicalId":36371,"journal":{"name":"Cell Stress","volume":null,"pages":null},"PeriodicalIF":6.4,"publicationDate":"2020-05-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7328674/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38144969","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}

引用次数: 16

Immune system activation by natural products and complex fractions: a network pharmacology approach in cancer treatment. 天然产物和复杂组分激活免疫系统:癌症治疗中的网络药理学方法。

IF 6.4

Cell Stress Pub Date : 2020-05-18 DOI: 10.15698/cst2020.07.224

Alejandra Gomez-Cadena, Alfonso Barreto, Susana Fioretino, Camilla Jandus

引用次数: 10

Mitochondria, mitophagy, and metabolic disease: towards assembling the puzzle. 线粒体、线粒体自噬和代谢性疾病:走向拼图。

IF 6.4

Cell Stress Pub Date : 2020-05-14 DOI: 10.15698/cst2020.06.222

Zhiyong Chen, Marine Berquez, Alessandro Luciani

{"title":"Mitochondria, mitophagy, and metabolic disease: towards assembling the puzzle.","authors":"Zhiyong Chen, Marine Berquez, Alessandro Luciani","doi":"10.15698/cst2020.06.222","DOIUrl":"https://doi.org/10.15698/cst2020.06.222","url":null,"abstract":"Dysregulation of the mitochondrial network in terminally differentiated cells contributes to a broad spectrum of disorders. Methylmalonic acidemia (MMA) is an autosomal recessive inborn error of intermediary metabolism caused by the deficiency of methylmalonyl-CoA mutase (MMUT) - a mitochondrial enzyme that mediates the degradation of certain amino acids and lipids. The loss of MMUT activity triggers an accumulation of toxic endogenous metabolites causing severe organ dysfunctions and life-threatening complications. How MMUT deficiency instigates mitochondrial distress and tissue damage remains poorly understood. Using cell and animal-based models, we recently discovered that MMUT deficiency disables the PINK1-induced translocation of PRKN/Parkin to MMA-damaged mitochondria, impeding their delivery and subsequent dismantling by macroautophagy/autophagy-lysosome degradation systems (Luciani et al. Nat Commun. 11(1):970). This promotes an accumulation of damaged and/or dysfunctional mitochondria that spark epithelial distress and tissue damage. Using a systems biology approach based on drug-disease network perturbation modeling, we predicted targetable pathways, whose modulation repairs mitochondrial dysfunctions in patient-derived kidney cells and ameliorates disease-relevant phenotypes in mmut-deficient zebrafish. These results unveil a link between primary MMUT deficiency, defective mitophagy, and cell distress, offering promising therapeutic avenues for MMA and other mitochondria-related diseases.","PeriodicalId":36371,"journal":{"name":"Cell Stress","volume":null,"pages":null},"PeriodicalIF":6.4,"publicationDate":"2020-05-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7278521/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38055233","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}

引用次数: 9

HIF1α or mitophagy: which drives cardiomyocyte differentiation? HIF1α和有丝分裂：哪个驱动心肌细胞分化？

IF 6.4

Cell Stress Pub Date : 2020-05-11 DOI: 10.15698/cst2020.05.219

Beatriz Villarejo-Zori, Juan Ignacio Jiménez-Loygorri, Patricia Boya

引用次数: 0