Pharmaceuticals (Basel, Switzerland)最新文献

{"title":"Gut Microbiota-Assisted Synthesis, Cellular Interactions and Synergistic Perspectives of Equol as a Potent Anticancer Isoflavone.","authors":"Hardeep Singh Tuli,&nbsp;Ajay Kumar,&nbsp;Katrin Sak,&nbsp;Diwakar Aggarwal,&nbsp;Dhruv Sanjay Gupta,&nbsp;Ginpreet Kaur,&nbsp;Kanupriya Vashishth,&nbsp;Kuldeep Dhama,&nbsp;Jagjit Kaur,&nbsp;Adesh K Saini,&nbsp;Mehmet Varol,&nbsp;Esra Capanoglu,&nbsp;Shafiul Haque","doi":"10.3390/ph15111418","DOIUrl":"https://doi.org/10.3390/ph15111418","url":null,"abstract":"<p><p>It is well known that, historically, plants have been an important resource of anticancer agents, providing several clinically approved drugs. Numerous preclinical studies have shown a strong anticancer potential of structurally different phytochemicals, including polyphenolic constituents of plants, flavonoids. In this review article, suppressing effects of equol in different carcinogenesis models are unraveled, highlighting the mechanisms involved in these anticancer activities. Among flavonoids, daidzein is a well-known isoflavone occurring in soybeans and soy products. In a certain part of population, this soy isoflavone is decomposed to equol under the action of gut microflora. Somewhat surprisingly, this degradation product has been shown to be more bioactive than its precursor daidzein, revealing a strong and multifaceted anticancer potential. In this way, it is important to bear in mind that the metabolic conversion of plant flavonoids might lead to products that are even more efficient than the parent compounds themselves, definitely deserving further studies.</p>","PeriodicalId":520747,"journal":{"name":"Pharmaceuticals (Basel, Switzerland)","volume":" ","pages":""},"PeriodicalIF":4.6,"publicationDate":"2022-11-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9697248/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40485190","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":"IL-17/Notch1/STAT3 Pathway Contributes to 5-Fluorouracil-Induced Intestinal Mucositis in Rats: Amelioration by Thymol Treatment.","authors":"Amira M Badr,&nbsp;Layla A Alkharashi,&nbsp;Iman O Sherif,&nbsp;Alaa A Alanteet,&nbsp;Hind N Alotaibi,&nbsp;Yasmen F Mahran","doi":"10.3390/ph15111412","DOIUrl":"https://doi.org/10.3390/ph15111412","url":null,"abstract":"<p><p>5-Fluorouracil (5-FU) is an anticancer drug with intestinal mucositis (IM) as a deleterious side effect. Thymol is a monoterpene phenol which has been reported to possess an antioxidant and anti-inflammatory activity versus 5-FU-induced IM. The Notch pathway affects multiple cellular activities, such as cellular proliferation, in addition to inflammatory responses modulation. Accordingly, this work was carried out in order to elucidate the role of the Notch pathway in 5-FU-induced IM and to further elucidate the immunomodulatory protective mechanisms of thymol. Experimental rats were divided randomly into four groups: Control, 5-FU, 5-FU+thymol (60 mg/kg/day), and 5-FU+thymol (120 mg/kg/day). 5-FU was injected intraperitoneally at a dose of 150 mg/kg on days 6 and 7, while thymol was orally administered daily for 11 days. By the end of the study, intestinal tissues were collected for the determination of IL-17, CD4, CD8, Notch1, Hes-1, pSTAT3, and STAT-3 protein expressions. The effect of thymol on 5-FU cytotoxicity was also examined using WST1 assay. 5-FU induced a marked increase in IL-17 levels, along with a marked downregulation of CD4 and the upregulation of CD8, Notch1, Hes-1 protein expressions, and activation of STAT3 in the intestinal tissue when compared with the control group. Thymol ameliorated the changes that occurred in these parameters. Additionally, cytotoxicity testing revealed that thymol augmented the antiproliferative action of 5-FU against breast and colorectal human cancer cell lines. This study was the first to show that the IL-17/Notch1/STAT3 pathway is involved in the molecular mechanism of 5-FU-induced IM, as well as the immunomodulatory activity of thymol.</p>","PeriodicalId":520747,"journal":{"name":"Pharmaceuticals (Basel, Switzerland)","volume":" ","pages":""},"PeriodicalIF":4.6,"publicationDate":"2022-11-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9693479/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40485185","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":"A Review of Pickering Emulsions: Perspectives and Applications.","authors":"Fernanda Brito de Carvalho-Guimarães,&nbsp;Kamila Leal Correa,&nbsp;Tatiane Pereira de Souza,&nbsp;Jesus Rafael Rodríguez Amado,&nbsp;Roseane Maria Ribeiro-Costa,&nbsp;José Otávio Carréra Silva-Júnior","doi":"10.3390/ph15111413","DOIUrl":"https://doi.org/10.3390/ph15111413","url":null,"abstract":"<p><p>Pickering emulsions are systems composed of two immiscible fluids stabilized by organic or inorganic solid particles. These solid particles of certain dimensions (micro- or nano-particles), and desired wettability, have been shown to be an alternative to conventional emulsifiers. The use of biodegradable and biocompatible stabilizers of natural origin, such as clay minerals, presents a promising future for the development of Pickering emulsions and, with this, they deliver some advantages, especially in the area of biomedicine. In this review, the effects and characteristics of microparticles in the preparation and properties of Pickering emulsions are presented. The objective of this review is to provide a theoretical basis for a broader type of emulsion, in addition to reviewing the main aspects related to the mechanisms and applications to promote its stability. Through this review, we highlight the use of this type of emulsion and its excellent properties as permeability promoters of solid particles, providing ideal results for local drug delivery and use in Pickering emulsions.</p>","PeriodicalId":520747,"journal":{"name":"Pharmaceuticals (Basel, Switzerland)","volume":" ","pages":""},"PeriodicalIF":4.6,"publicationDate":"2022-11-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9698490/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40485186","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":"Copaiba Oil Resin Exerts an Additive Effect to Babassu Oil on Behavioral Changes in Human Endometriotic Cell Cultures.","authors":"Julianna Henriques da Silva,&nbsp;Leticia Coli Louvisse de Abreu,&nbsp;Renato Ferrari,&nbsp;Celia Yelimar Palmero Quintana,&nbsp;Eliane Gouvêa de Oliveira Barros,&nbsp;Natália de Moraes Cordeiro,&nbsp;Bruno Pontes,&nbsp;Valeria Pereira de Sousa,&nbsp;Lucio Mendes Cabral,&nbsp;Patricia Dias Fernandes,&nbsp;Luiz Eurico Nasciutti","doi":"10.3390/ph15111414","DOIUrl":"https://doi.org/10.3390/ph15111414","url":null,"abstract":"<p><strong>Background: </strong>Current drugs for the treatment of endometriosis are not able to completely cure the condition, and significant side effects hinder the continuation of treatment. Therefore, it is necessary to search for new drug candidates. In the present paper, the use of plant extracts is highlighted. Babassu oil and Copaiba oil resin have several therapeutic properties. We investigated the in vitro effects of two nanoemulsions containing oil extracted from Babassu (<i>Orbignya speciosa</i>) nuts (called SNEDDS-18) and/or oil resin extracted from Copaiba trunk (<i>Copaifera langsdorffii</i>) (called SNEDDS-18/COPA) on cultured human eutopic endometrium stromal cells from endometrial biopsies of patients without (CESC) and with (EuESC) endometriosis as well as human stromal cells from biopsies of endometriotic lesions (EctESC).</p><p><strong>Methods: </strong>CESC, EuESC, and EctESC were taken and treated with SNEDDS-18 and SNEDDS-18/COPA to evaluate their effects on cytotoxicity, cell morphology, proliferation, and signaling pathways.</p><p><strong>Results: </strong>After 48 h of incubation with SNEDDS-18 and SNEDDS-18/COPA, cell viability and proliferation were inhibited, especially in EctESC. The lowest concentration of both nanoemulsions reduced cell viability and proliferation and broke down the cytoskeleton in EctESCs. After 24 h of treatment a decrease in IL-1, TNF-α, and MCP-1 was observed, as well as an increase in IL-10 production.</p><p><strong>Conclusions: </strong>Both nanoemulsions can affect endometriotic stromal cell behaviors, thus revealing two potential candidates for new phytotherapeutic agents for the management of endometriosis.</p>","PeriodicalId":520747,"journal":{"name":"Pharmaceuticals (Basel, Switzerland)","volume":" ","pages":""},"PeriodicalIF":4.6,"publicationDate":"2022-11-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9695379/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40485187","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":"Research Progress on Therapeutic Targeting of Cancer-Associated Fibroblasts to Tackle Treatment-Resistant NSCLC.","authors":"Chenxin Li,&nbsp;Yusong Qiu,&nbsp;Yong Zhang","doi":"10.3390/ph15111411","DOIUrl":"https://doi.org/10.3390/ph15111411","url":null,"abstract":"<p><p>Non-small cell lung cancer (NSCLC) accounts for most lung cancer cases and is the leading cause of cancer-related deaths worldwide. Treatment options for lung cancer are no longer limited to surgery, radiotherapy, and chemotherapy, as targeted therapy and immunotherapy offer a new hope for patients. However, drug resistance in chemotherapy and targeted therapy, and the low response rates to immunotherapy remain important challenges. Similar to tumor development, drug resistance occurs because of significant effects exerted by the tumor microenvironment (TME) along with cancer cell mutations. Cancer-associated fibroblasts (CAFs) are a key component of the TME and possess multiple functions, including cross-talking with cancer cells, remodeling of the extracellular matrix (ECM), secretion of various cytokines, and promotion of epithelial-mesenchymal transition, which in turn provide support for the growth, invasion, metastasis, and drug resistance of cancer cells. Therefore, CAFs represent valuable therapeutic targets for lung cancer. Herein, we review the latest progress in the use of CAFs as potential targets and mediators of drug resistance for NSCLC treatment. We explored the role of CAFs on the regulation of the TME and surrounding ECM, with particular emphasis on treatment strategies involving combined CAF targeting within the current framework of cancer treatment.</p>","PeriodicalId":520747,"journal":{"name":"Pharmaceuticals (Basel, Switzerland)","volume":" ","pages":""},"PeriodicalIF":4.6,"publicationDate":"2022-11-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9696940/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40485184","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":"Nitro-Containing Self-Immolative Systems for Biological Applications.","authors":"Cédric Spitz,&nbsp;Nicolas Primas,&nbsp;Thierry Terme,&nbsp;Patrice Vanelle","doi":"10.3390/ph15111404","DOIUrl":"https://doi.org/10.3390/ph15111404","url":null,"abstract":"<p><p>Since its introduction in 1981, the chemistry of self-immolative systems has received increasing attention in different application areas, such as analytical chemistry, medicinal chemistry, and materials science. This strategy is based on a stimulation that triggers a cascade of disassembling reactions leading to the release of smaller molecules. The particular reactivity of the nitro group, due to its powerful electron-withdrawing nature, has been exploited in the field of self-immolative chemistry. In this context, the present review describes the major role of the nitro group in self-immolative processes depending on its position.</p>","PeriodicalId":520747,"journal":{"name":"Pharmaceuticals (Basel, Switzerland)","volume":" ","pages":""},"PeriodicalIF":4.6,"publicationDate":"2022-11-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9695724/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40483290","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":"In Vitro and In Vivo Evaluation of Hydroxypropyl-β-cyclodextrin-grafted-poly(acrylic acid)/poly(vinyl pyrrolidone) Semi-Interpenetrating Matrices of Dexamethasone Sodium Phosphate.","authors":"Nyla Ajaz,&nbsp;Anum Abbas,&nbsp;Rabia Afshan,&nbsp;Muhammad Irfan,&nbsp;Syed Haroon Khalid,&nbsp;Sajid Asghar,&nbsp;Muhammad Usman Munir,&nbsp;Waleed Y Rizg,&nbsp;Kamlah Ali Majrashi,&nbsp;Sameer Alshehri,&nbsp;Mohammed Alissa,&nbsp;Mohammed Majrashi,&nbsp;Deena M Bukhary,&nbsp;Ghulam Hussain,&nbsp;Fauzia Rehman,&nbsp;Ikram Ullah Khan","doi":"10.3390/ph15111399","DOIUrl":"https://doi.org/10.3390/ph15111399","url":null,"abstract":"<p><p>In this paper, we fabricated semi-interpenetrating polymeric network (semi-IPN) of hydroxypropyl-β-cyclodextrin-<i>grafted</i>-poly(acrylic acid)/poly(vinyl pyrrolidone) (HP-β-CD-g-poly(AA)/PVP) by the free radical polymerization technique, intended for colon specific release of dexamethasone sodium phosphate (DSP). Different proportions of polyvinyl pyrrolidone (PVP), acrylic acid (AA), and hydroxypropyl-beta-cyclodextrin (HP-β-CD) were reacted along with ammonium persulphate (APS) as initiator and methylene-bis-acrylamide (MBA) as crosslinker to develop a hydrogel system with optimum swelling at distal intestinal pH. Initially, all formulations were screened for swelling behavior and AP-8 was chosen as optimum formulation. This formulation was capable of releasing a small amount of drug at acidic pH (1.2), while a maximum amount of drug was released at colonic pH (7.4) by the non-Fickian diffusion mechanism. Fourier transformed infrared spectroscopy (FTIR) revealed successful grafting of components and development of semi-IPN structure without any interaction with DSP. Thermogravimetric analysis (TGA) confirmed the thermal stability of developed semi-IPN. X-ray diffraction (XRD) revealed reduction in crystallinity of DSP upon loading in the hydrogel. The scanning electron microscopic (SEM) images revealed a rough and porous hydrogel surface. The toxicological evaluation of semi-IPN hydrogels confirmed their bio-safety and hemocompatibility. Therefore, the prepared hydrogels were pH sensitive, biocompatible, showed good swelling, mechanical properties, and were efficient in releasing the drug in the colonic environment. Therefore, AP-8 can be deemed as a potential carrier for targeted delivery of DSP to treat inflammatory bowel diseases.</p>","PeriodicalId":520747,"journal":{"name":"Pharmaceuticals (Basel, Switzerland)","volume":" ","pages":""},"PeriodicalIF":4.6,"publicationDate":"2022-11-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9692809/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40493547","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":"Constructing an Intelligent Model Based on Support Vector Regression to Simulate the Solubility of Drugs in Polymeric Media.","authors":"Sait Senceroglu,&nbsp;Mohamed Arselene Ayari,&nbsp;Tahereh Rezaei,&nbsp;Fardad Faress,&nbsp;Amith Khandakar,&nbsp;Muhammad E H Chowdhury,&nbsp;Zanko Hassan Jawhar","doi":"10.3390/ph15111405","DOIUrl":"https://doi.org/10.3390/ph15111405","url":null,"abstract":"<p><p>This study constructs a machine learning method to simultaneously analyze the thermodynamic behavior of many polymer-drug systems. The solubility temperature of Acetaminophen, Celecoxib, Chloramphenicol, D-Mannitol, Felodipine, Ibuprofen, Ibuprofen Sodium, Indomethacin, Itraconazole, Naproxen, Nifedipine, Paracetamol, Sulfadiazine, Sulfadimidine, Sulfamerazine, and Sulfathiazole in 1,3-bis[2-pyrrolidone-1-yl] butane, Polyvinyl Acetate, Polyvinylpyrrolidone (PVP), PVP K12, PVP K15, PVP K17, PVP K25, PVP/VA, PVP/VA 335, PVP/VA 535, PVP/VA 635, PVP/VA 735, Soluplus analyzes from a modeling perspective. The least-squares support vector regression (LS-SVR) designs to approximate the solubility temperature of drugs in polymers from polymer and drug types and drug loading in polymers. The structure of this machine learning model is well-tuned by conducting trial and error on the kernel type (i.e., Gaussian, polynomial, and linear) and methods used for adjusting the LS-SVR coefficients (i.e., leave-one-out and 10-fold cross-validation scenarios). Results of the sensitivity analysis showed that the Gaussian kernel and 10-fold cross-validation is the best candidate for developing an LS-SVR for the given task. The built model yielded results consistent with 278 experimental samples reported in the literature. Indeed, the mean absolute relative deviation percent of 8.35 and 7.25 is achieved in the training and testing stages, respectively. The performance on the largest available dataset confirms its applicability. Such a reliable tool is essential for monitoring polymer-drug systems' stability and deliverability, especially for poorly soluble drugs in polymers, which can be further validated by adopting it to an actual implementation in the future.</p>","PeriodicalId":520747,"journal":{"name":"Pharmaceuticals (Basel, Switzerland)","volume":" ","pages":""},"PeriodicalIF":4.6,"publicationDate":"2022-11-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9696511/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40483291","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":"Pembrolizumab and Chemotherapy Combination Prolonged Progression-Free Survival in Patients with NSCLC with High PD-L1 Expression and Low Neutrophil-to-Lymphocyte Ratio.","authors":"Jeng-Shiuan Tsai,&nbsp;Sheng-Huan Wei,&nbsp;Chian-Wei Chen,&nbsp;Szu-Chun Yang,&nbsp;Yau-Lin Tseng,&nbsp;Po-Lan Su,&nbsp;Chien-Chung Lin,&nbsp;Wu-Chou Su","doi":"10.3390/ph15111407","DOIUrl":"https://doi.org/10.3390/ph15111407","url":null,"abstract":"<p><p>The use of immune checkpoint inhibitors (ICIs) has provided overall survival (OS) benefits in patients with treatment-naïve advanced non-small cell lung cancer (NSCLC) without targetable driver mutations. However, studies comparing ICIs monotherapy with combination therapy either with chemotherapy or radiotherapy in programmed death-ligand 1 high expressors remain limited. This study aimed to retrospectively compare the treatment efficacy of the therapies by studying 47 patients with treatment-naïve advanced NSCLC who received ICI monotherapy (<i>n</i> = 28) or combination therapy either with chemotherapy or radiotherapy (<i>n</i> = 19). Progression-free survival (PFS) and OS were estimated using the Kaplan-Meier method and compared using log-rank tests. It was observed that patients who received combination therapy had a better PFS than monotherapy, but no such significant benefit was observed in OS. The difference in PFS was higher in the subgroup of patients with low neutrophil-to-lymphocyte ratio (NLR) than in the high-NLR patient subgroup. This study suggests that pembrolizumab in combination with chemotherapy or radiotherapy could provide a significant benefit in PFS, especially in patients with treatment-naïve advanced NSCLC with low NLR. Furthermore, our study also demonstrates the potential use of NLR as a biomarker for prediction of treatment outcomes in patients with advanced NSCLC receiving combination therapy.</p>","PeriodicalId":520747,"journal":{"name":"Pharmaceuticals (Basel, Switzerland)","volume":" ","pages":""},"PeriodicalIF":4.6,"publicationDate":"2022-11-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9694359/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40483293","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":"A SERPINE1-Based Immune Gene Signature Predicts Prognosis and Immunotherapy Response in Gastric Cancer.","authors":"Xiang Xu,&nbsp;Lipeng Zhang,&nbsp;Yan Qian,&nbsp;Qian Fang,&nbsp;Yongbiao Xiao,&nbsp;Guizeng Chen,&nbsp;Guojing Cai,&nbsp;Alimujiang Abula,&nbsp;Zhao Wang,&nbsp;Ertao Zhai,&nbsp;Jianhui Chen,&nbsp;Shirong Cai,&nbsp;Hui Wu","doi":"10.3390/ph15111401","DOIUrl":"https://doi.org/10.3390/ph15111401","url":null,"abstract":"<p><p>Immune checkpoint inhibitors (ICIs) therapy has been successfully utilized in the treatment of multiple tumors, but only a fraction of patients with gastric cancer (GC) could greatly benefit from it. A recent study has shown that the tumor microenvironment (TME) can greatly affect the effect of immunotherapy in GC. In this study, we established a novel immune risk signature (IRS) for prognosis and predicting response to ICIs in GC based on the TCGA-STAD dataset. Characterization of the TME was explored and further validated to reveal the underlying survival mechanisms and the potential therapeutic targets of GC. The GC patients were stratified into high- and low-risk groups based on the IRS. Patients in the high-risk group, associated with poorer outcomes, were characterized by significantly higher immune function. Further analysis showed higher T cell immune dysfunction and probability of potential immune escape. In vivo, we detected the expressions of <i>SERPINE1</i> by the quantitative real-time polymerase chain reaction (qPCR)in tumor tissues and adjacent normal tissues. In vitro, knockdown of <i>SERPINE1</i> significantly attenuated malignant biological behaviors of tumor cells in GC. Our signature can effectively predict the prognosis and response to immunotherapy in patients with GC.</p>","PeriodicalId":520747,"journal":{"name":"Pharmaceuticals (Basel, Switzerland)","volume":" ","pages":""},"PeriodicalIF":4.6,"publicationDate":"2022-11-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9692477/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40493549","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}