Pharmacological research最新文献

{"title":"Melatonin increases Olaparib sensitivity and suppresses cancer-associated fibroblast infiltration via suppressing the LAMB3-CXCL2 axis in TNBC","authors":"Yi-Wen Lai ,&nbsp;Zei-Wei Liu ,&nbsp;Mei-Hsiang Lin ,&nbsp;Ching-Chieh Yang ,&nbsp;Cheng-Ying Chu ,&nbsp;Chu-Hung Chung ,&nbsp;Cheng-Wei Lin","doi":"10.1016/j.phrs.2024.107429","DOIUrl":"10.1016/j.phrs.2024.107429","url":null,"abstract":"<div><div>Triple-negative breast cancer (TNBC) is the most malignant breast cancer subtype, characterized with high aggressiveness and a high recurrence rate. Olaparib is the first US Food and Drug Administration-approved poly(ADP ribose) polymerase (PARP) inhibitor (PARPi) to treat breast cancer patients with a germline BRCA1 or BRCA2 mutation. However, resistance to Olaparib treatment restricts the therapeutic effects, and thus novel therapeutics are urgently required. In the present study, we identified that the combination of melatonin and Olaparib synergistically enhanced the sensitivity of TNBC cells. Moreover, melatonin exerted promising antitumor activities in Olaparib-resistant cells, implying the potential for its clinical application. An RNA-sequencing analysis revealed that melatonin treatment downregulated laminin subunit beta 3 (LAMB3) expression. Genetic ablation of LAMB3 significantly increased Olaparib sensitivity, and subsequently suppressed proliferation, epithelial-to-mesenchymal transition (EMT)-related gene expressions, and aggressiveness of breast cancer cells. Accordingly, LAMB3 expression was positively correlated with C-X-C motif chemokine ligand 2 (CXCL2), and they collaboratively promoted cancer-associated fibroblast (CAF) infiltration. An <em>in vivo</em> study demonstrated that combined treatment with melatonin and Olaparib showed enhanced inhibitory efficacy against tumor growth, LAMB3 expression, CXCL2 levels, and CAF infiltration compared to single treatment groups, and combined treatment with melatonin and Olaparib significantly ameliorated the immunosuppressive tumor microenvironment. These findings illustrate a promising therapeutic strategy using melatonin to overcome Olaparib resistance and activate antitumor immunity via attenuating the LAMB3-CXCL2 axis in breast cancer patients.</div></div>","PeriodicalId":19918,"journal":{"name":"Pharmacological research","volume":"209 ","pages":"Article 107429"},"PeriodicalIF":9.1,"publicationDate":"2024-09-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142293012","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Human F-ATP synthase as a drug target","authors":"Christoph Gerle ,&nbsp;Chimari Jiko ,&nbsp;Atsuki Nakano ,&nbsp;Ken Yokoyama ,&nbsp;Chai C. Gopalasingam ,&nbsp;Hideki Shigematsu ,&nbsp;Kazuhiro Abe","doi":"10.1016/j.phrs.2024.107423","DOIUrl":"10.1016/j.phrs.2024.107423","url":null,"abstract":"<div><div>Practical and conceptual barriers have kept human F-ATP synthase out of reach as a target for the treatment of human diseases. Although this situation has persisted for decades, it may change in the near future. In this review the principal functionalities of human F-ATP synthase--proton motive force / ATP interconversion, membrane bending and mitochondrial permeability transition--are surveyed in the context of their respective potential for pharmaceutical intervention. Further, the technical requirements necessary to allow drug designs that are effective at the multiple levels of functionality and modality of human F-ATP synthase are discussed. The structure-based development of gastric proton pump inhibitors is used to exemplify what might be feasible for human F-ATP synthase. And finally, four structural regions of the human F-ATP synthase are examined as potential sites for the development of structure based drug development.</div></div>","PeriodicalId":19918,"journal":{"name":"Pharmacological research","volume":"209 ","pages":"Article 107423"},"PeriodicalIF":9.1,"publicationDate":"2024-09-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1043661824003682/pdfft?md5=0e47dcd3b2e458dd98aae8915ea9ad9f&pid=1-s2.0-S1043661824003682-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142293010","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Mitochondria-targeted hydrogen sulfide donor reduces fatty liver and obesity in mice fed a high fat diet by inhibiting de novo lipogenesis and inflammation via mTOR/SREBP-1 and NF-κB signaling pathways","authors":"Aneta Stachowicz ,&nbsp;Klaudia Czepiel ,&nbsp;Anna Wiśniewska ,&nbsp;Kamila Stachyra ,&nbsp;Magdalena Ulatowska-Białas ,&nbsp;Beata Kuśnierz-Cabala ,&nbsp;Marcin Surmiak ,&nbsp;Grzegorz Majka ,&nbsp;Katarzyna Kuś ,&nbsp;Mark E. Wood ,&nbsp;Roberta Torregrossa ,&nbsp;Matthew Whiteman ,&nbsp;Rafał Olszanecki","doi":"10.1016/j.phrs.2024.107428","DOIUrl":"10.1016/j.phrs.2024.107428","url":null,"abstract":"<div><p>Metabolic diseases that include obesity and metabolic-associated fatty liver disease (MAFLD) are a rapidly growing worldwide public health problem. The pathogenesis of MAFLD includes abnormally increased lipogenesis, chronic inflammation, and mitochondrial dysfunction. Mounting evidence suggests that hydrogen sulfide (H₂S) is an important player in the liver, regulating lipid metabolism and mitochondrial function. However, direct delivery of H₂S to mitochondria has not been investigated as a therapeutic strategy in obesity-related metabolic disorders. Therefore, our aim was to comprehensively evaluate the influence of prolonged treatment with a mitochondria sulfide delivery molecule (AP39) on the development of fatty liver and obesity in a high fat diet (HFD) fed mice. Our results demonstrated that AP39 reduced hepatic steatosis in HFD-fed mice, which was corresponded with decreased triglyceride content. Furthermore, treatment with AP39 downregulated pathways related to biosynthesis of unsaturated fatty acids, lipoprotein assembly and PPAR signaling. It also led to a decrease in hepatic <em>de novo</em> lipogenesis by downregulating mTOR/SREBP-1/SCD1 pathway. Moreover, AP39 administration alleviated obesity in HFD-fed mice, which was reflected by reduced weight of mice and adipose tissue, decreased leptin levels in the plasma and upregulated expression of adipose triglyceride lipase in epididymal white adipose tissue (eWAT). Finally, AP39 reduced inflammation in the liver and eWAT measured as the expression of proinflammatory markers (<em>Il1b, Il6, Tnf</em>, <em>Mcp1</em>), which was due to downregulated mTOR/NF-κB pathway. Taken together, mitochondria-targeted sulfide delivery molecules could potentially provide a novel therapeutic approach to the treatment/prevention of obesity-related metabolic disorders.</p></div>","PeriodicalId":19918,"journal":{"name":"Pharmacological research","volume":"209 ","pages":"Article 107428"},"PeriodicalIF":9.1,"publicationDate":"2024-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1043661824003736/pdfft?md5=e56c7e6ddc9bd5790b953902f032656d&pid=1-s2.0-S1043661824003736-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142267607","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Molecular mechanisms underlying hepatoprotective activity of lutein in the context of intestinal failure-associated liver disease","authors":"Izabela Żółnowska ,&nbsp;Aleksandra Gostyńska-Stawna ,&nbsp;Maciej Stawny","doi":"10.1016/j.phrs.2024.107421","DOIUrl":"10.1016/j.phrs.2024.107421","url":null,"abstract":"<div><p>Intestinal failure-associated liver disease (IFALD) is a spectrum of liver diseases occurring in patients not exposed to liver-damaging factors other than those linked to intestinal dysfunction. The pathogenesis of this disease is multifactorial. It is estimated that up to 90 % of people taking long-term parenteral nutrition may develop IFALD, with particular risk for premature neonates and infants due to their immature antioxidant protection and bile acid metabolism. The lack of effective prevention and treatment methods for IFALD encourages scientists to search for new therapeutic solutions. The use of lutein as a substance with antioxidant and anti-inflammatory effects seems to be of great potential in such indication, especially since patients on parenteral nutrition are at risk of deficits in various plant-based nutrients, including lutein. In this review, we explain the pathogenesis of IFALD and summarize knowledge of the hepatoprotective properties of lutein, underscoring its potential as a treatment option. The hepatoprotective effects of lutein and their proposed mechanisms of action are supported by studies on cells and animals exposed to various liver-damaging factors, such as lipopolysaccharide, high-fat diet, alcohol, and more. Finally, we provide perspectives on the future application of lutein in therapy.</p></div>","PeriodicalId":19918,"journal":{"name":"Pharmacological research","volume":"209 ","pages":"Article 107421"},"PeriodicalIF":9.1,"publicationDate":"2024-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1043661824003669/pdfft?md5=92dde2611e7fee5d8ed114874628986c&pid=1-s2.0-S1043661824003669-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142238765","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Alternative splicing of Mff regulates AMPK-mediated phosphorylation, mitochondrial fission and antiviral response","authors":"Yuki Hanada ,&nbsp;Risa Maeda ,&nbsp;Takaya Ishihara ,&nbsp;Masaki Nakahashi ,&nbsp;Yuichi Matsushima ,&nbsp;Emi Ogasawara ,&nbsp;Toshihiko Oka ,&nbsp;Naotada Ishihara","doi":"10.1016/j.phrs.2024.107414","DOIUrl":"10.1016/j.phrs.2024.107414","url":null,"abstract":"<div><p>Mitochondrial morphology and function change dynamically in response to intracellular signaling and the surrounding environment. The mitochondrial fission factor Mff, which localizes to the outer mitochondrial membrane, mediates not only mitochondrial fission by recruiting the dynamin-related GTPase Drp1 to mitochondrial fission sites but also the double-stranded RNA-induced antiviral response on mitochondria through mitochondrial antiviral signaling (MAVS). Mff is reported to be regulated by AMP-activated protein kinase (AMPK)-mediated protein phosphorylation and alternative pre-mRNA splicing; however, the relationships among RNA splicing, phosphorylation, and multiple functions of Mff have not been fully understood. Here, we showed that mouse Mff has a tissue-specific splicing pattern, and at least eight Mff splice isoforms were expressed in mouse embryonic fibroblasts (MEFs). We introduced single Mff isoforms into Mff knockout MEFs and found that insertion of exon 6 just after the phosphorylation site, by the alternative splicing, reduced its phosphorylation by AMPK and its functions in mitochondrial fission and the antiviral response. In addition, the underlying mechanism repressing these functions was independent of phosphorylation. These results indicate that multiple functions of Mff on mitochondria are regulated by AMPK-mediated phosphorylation and alternative splicing, under the control of energy metabolism and cellular differentiation.</p></div>","PeriodicalId":19918,"journal":{"name":"Pharmacological research","volume":"209 ","pages":"Article 107414"},"PeriodicalIF":9.1,"publicationDate":"2024-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1043661824003591/pdfft?md5=3733cacbdfdeed08e6c84579793571fd&pid=1-s2.0-S1043661824003591-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142267608","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Palmatine protects against atherosclerosis by gut microbiota and phenylalanine metabolism","authors":"Anlu Wang ,&nbsp;Baoyi Guan ,&nbsp;Linghua Yu ,&nbsp;Qiyu Liu ,&nbsp;Yuanlong Hou ,&nbsp;Ziguang Li ,&nbsp;Daming Sun ,&nbsp;Hao Xu","doi":"10.1016/j.phrs.2024.107413","DOIUrl":"10.1016/j.phrs.2024.107413","url":null,"abstract":"<div><p>Accumulating evidence illuminated that gut microbiota directly modulates the development of atherosclerosis (AS) through interactions with metaflammation. The natural bioactive isoquinoline alkaloid palmatine (PAL), which is extracted from one of the herbs (Coptis chinensis) of the anti-AS formular, is of particular interest due to its pharmacological properties. ApoE-/- mice were administered PAL or vehicle; plaque areas, and stability were assessed by histopathological and immunohistochemistry analysis, serum glycolysis and lipid levels, and inflammation levels were also evaluated. 16S rRNA sequencing and metabolomics analysis were employed to evaluate microbial composition and serum metabolites. Microbial culture experiments were designed to reveal the target microbiota and associated metabolites. Cell culture and transcriptome were performed to elucidate the function of microbial metabolites on THP-1. PAL reduced the area of plaque and necrotic core, improving inflammatory infiltration within plaques, improving glycolipid metabolism, and reducing the levels of serum inflammatory cytokines in a dose-dependent manner. PAL treatment reshaped the composition of the gut microbiota, especially, reducing the relative abundance of <em>Desulfovibrio piger (D. piger)</em> in a dose-dependent manner and serum level of hippuric acid (HA). <em>D. piger</em> was able to convert phenylalanine into 3-phenylpropionic acid (precursor of HA). Finally, we verified HA accelerated the progression of AS and increased the secretions of inflammatory cytokines in vivo and in vitro. In conclusion, PAL exhibited anti-AS effects by regulating the gut microbiota-phenylalanine metabolism axis.</p></div>","PeriodicalId":19918,"journal":{"name":"Pharmacological research","volume":"209 ","pages":"Article 107413"},"PeriodicalIF":9.1,"publicationDate":"2024-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S104366182400358X/pdfft?md5=b3edef6ca3133b0be22e8afaa5af4e1c&pid=1-s2.0-S104366182400358X-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142267609","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Developing patient-derived organoids to demonstrate JX24120 inhibits SAMe synthesis in endometrial cancer by targeting MAT2B","authors":"Chunxue Zhang ,&nbsp;Xiaojing Lu ,&nbsp;Ting Ni ,&nbsp;Qi Wang ,&nbsp;Xiaoyan Gao ,&nbsp;Xiao Sun ,&nbsp;Jian Li ,&nbsp;Fei Mao ,&nbsp;Jin Hou ,&nbsp;Yudong Wang","doi":"10.1016/j.phrs.2024.107420","DOIUrl":"10.1016/j.phrs.2024.107420","url":null,"abstract":"<div><p>Endometrial cancer (EC) is one of the most common gynecologic malignancies, which lacking effective drugs for intractable conditions or patients unsuitable for surgeries. Recently, the patient-derived organoids (PDOs) are found feasible for cancer research and drug discoveries. Here, we have successfully established a panel of PDOs from EC and conducted drug repurposing screening and mechanism analysis for cancer treatment. We confirmed that the regulatory β subunit of methionine adenosyltransferase (MAT2B) is highly correlated with malignant progression in endometrial cancer. Through drug screening on PDOs, we identify JX24120, chlorpromazine derivative, as a specific inhibitor for MAT2B, which directly binds to MAT2B (<em>K</em>_<em>d</em> = 4.724 μM) and inhibits the viability of EC PDOs and canonical cell lines. Correspondingly, gene editing assessment demonstrates that JX24120 suppresses tumor growth depending on the presence of MAT2B <em>in vivo</em> and <em>in vitro</em>. Mechanistically, JX24120 induces inhibition of S-adenosylmethionine (SAMe) synthesis, leading to suppressed mTORC1 signaling, abnormal energy metabolism and protein synthesis, and eventually apoptosis. Taken together, our study offers a novel approach for drug discovery and efficacy assessment by using the PDOs models. These findings suggest that JX24120 may be a potent MAT2B inhibitor and will hopefully serve as a prospective compound for endometrial cancer therapy.</p></div>","PeriodicalId":19918,"journal":{"name":"Pharmacological research","volume":"209 ","pages":"Article 107420"},"PeriodicalIF":9.1,"publicationDate":"2024-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1043661824003657/pdfft?md5=d55775db0bd3d9768b8f65349d5f4d09&pid=1-s2.0-S1043661824003657-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142267606","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Orosomucoid 2 is an endogenous regulator of neuronal mitochondrial biogenesis and promotes functional recovery post-stroke","authors":"Kai Jing ,&nbsp;Ruinan Gu ,&nbsp;Feng Chen ,&nbsp;Jingjing Wan ,&nbsp;Yang Sun ,&nbsp;Pengyue Guo ,&nbsp;Fei Chen ,&nbsp;Jiayi Feng ,&nbsp;Jinmin Guo ,&nbsp;Xia Liu","doi":"10.1016/j.phrs.2024.107422","DOIUrl":"10.1016/j.phrs.2024.107422","url":null,"abstract":"<div><p>Development of functional recovery therapies is critical to reduce the global impact of stroke as the leading cause of long-term disability. Our previous studies found that acute-phase protein orosomucoid (ORM) could provide an up to 6 h therapeutic time window to reduce infarct volume in acute ischemic stroke by improving endothelial function. However, its role in neurons and functional recovery post-stroke remains largely unknown. Here, we showed that exogenous ORM administration with initial injection at 0.5 h (early) or 12 h (delayed) post-MCAO daily for consecutive 7 days significantly decreased infarct area, improved motor and cognitive functional recovery, and promoted mitochondrial biogenesis after MCAO. While neuron-specific knockout of ORM2, a dominant subtype of ORM in the brain, produced opposite effects which could be rescued by exogenous ORM. <em>In vitro</em>, exogenous ORM protected SH-SY5Y cells from OGD-induced damage and promoted mitochondrial biogenesis, while endogenous ORM2 deficiency worsened these processes. Mechanistically, inactivation of CCR5 or AMPK eliminated the protective effects of ORM on neuronal damage and mitochondrial biogenesis. Taken together, our findings demonstrate that ORM, mainly ORM2, is an endogenous regulator of neuronal mitochondrial biogenesis by activating CCR5/AMPK signaling pathway, and might act as a potential therapeutic target for the functional recovery post-stroke.</p></div>","PeriodicalId":19918,"journal":{"name":"Pharmacological research","volume":"209 ","pages":"Article 107422"},"PeriodicalIF":9.1,"publicationDate":"2024-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1043661824003670/pdfft?md5=74c745ae0dab55a9bd23540ed1197938&pid=1-s2.0-S1043661824003670-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142238767","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A new perspective on liver diseases: Focusing on the mitochondria-associated endoplasmic reticulum membranes","authors":"Mengyu Guo ,&nbsp;Runping Liu ,&nbsp;Fukun Zhang ,&nbsp;Jiaorong Qu ,&nbsp;Yun Yang ,&nbsp;Xiaojiaoyang Li","doi":"10.1016/j.phrs.2024.107409","DOIUrl":"10.1016/j.phrs.2024.107409","url":null,"abstract":"<div><p>The pathogenesis of liver diseases is multifaceted and intricate, posing a persistent global public health challenge with limited therapeutic options. Therefore, further research into liver diseases is imperative for better comprehension and advancement in treatment strategies. Numerous studies have confirmed the endoplasmic reticulum (ER) and mitochondria as key organelles driving liver diseases. Notably, the mitochondrial-associated ER membranes (MAMs) establish a physical and functional connection between the ER and mitochondria, highlighting the importance of inter-organelle communication in maintaining their functional homeostasis. This review delves into the intricate architecture and regulative mechanism of the integrated MAM that facilitate the physiological transfer of signals and substances between organelles. Additionally, we also provide a detailed overview regarding the varied pathogenic roles of malfunctioning MAM in liver diseases, focusing on its involvement in the progression of ER stress and mitochondrial dysfunction, the regulation of mitochondrial dynamics and Ca²⁺ transfer, as well as the disruption of lipid and glucose homeostasis. Furthermore, the current challenges and prospects associated with MAM in liver disease research are thoroughly discussed. In conclusion, elucidating the specific structure and function of MAM in different liver diseases may pave the way for novel therapeutic strategies.</p></div>","PeriodicalId":19918,"journal":{"name":"Pharmacological research","volume":"208 ","pages":"Article 107409"},"PeriodicalIF":9.1,"publicationDate":"2024-09-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1043661824003542/pdfft?md5=e93fe6672e6ddcc206ed93403a7a510d&pid=1-s2.0-S1043661824003542-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142244198","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Extracellular vesicles in the HCC microenvironment: Implications for therapy and biomarkers","authors":"Le Cheng ,&nbsp;Limin Zhang ,&nbsp;Xiaoxiao Wang ,&nbsp;Yufei Wang ,&nbsp;Jiahui Yu ,&nbsp;Mengnan Li ,&nbsp;Zhaowu Ma ,&nbsp;Paul Chi-Lui Ho ,&nbsp;Xiaoguang Chen ,&nbsp;Lingzhi Wang ,&nbsp;Gautam Sethi ,&nbsp;Boon-Cher Goh","doi":"10.1016/j.phrs.2024.107419","DOIUrl":"10.1016/j.phrs.2024.107419","url":null,"abstract":"<div><p>Hepatocellular carcinoma (HCC) stands as the sixth most prevalent cancer and the third leading cause of cancer mortality globally. Despite surgical resection being the preferred approach for early-stage HCC, most patients are diagnosed at intermediate to advanced stages, limiting treatment options to chemotherapy and immunotherapy, which often yield poor outcomes. Extracellular vesicles (EVs), minute lipid-bilayered particles released by diverse cells under various physiological and pathological conditions, are crucial for mediating communication between cells. Mounting evidence indicates that EVs sourced from different cells can profoundly influence the HCC tumor microenvironment (TME), thereby affecting the progression of HCC. Given their immunogenicity and liver-targeting properties, these EVs not only hold promise for HCC treatment but also provide avenues for advancing early diagnostic methods and assessing prognosis. This review not only describes the function of EVs within the HCC tumor microenvironment but also analyzes their therapeutic advantages and explores their significance in various therapeutic approaches for HCC, including chemotherapy, immunotherapy, combination therapy, and their role as innovative drug delivery carriers. Furthermore, it highlights the potential of EVs as biomarkers for the diagnosis and prognosis of HCC.</p></div>","PeriodicalId":19918,"journal":{"name":"Pharmacological research","volume":"209 ","pages":"Article 107419"},"PeriodicalIF":9.1,"publicationDate":"2024-09-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1043661824003645/pdfft?md5=0ab7e64bb420f6c9229a873230fa8944&pid=1-s2.0-S1043661824003645-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142238066","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}