Experimental and molecular pathology最新文献

{"title":"MicroRNA-575 acts as a novel oncogene via targeting multiple signaling pathways in glioblastoma","authors":"Ashley Gray ,&nbsp;Tiantian Cui ,&nbsp;Erica Hlavin Bell ,&nbsp;Joseph McElroy ,&nbsp;Ebin Sebastian ,&nbsp;Fuhai Li ,&nbsp;Marjolein Geurts ,&nbsp;Kevin Liu ,&nbsp;Pierre Robe ,&nbsp;S. Jaharul Haque ,&nbsp;Arnab Chakravarti","doi":"10.1016/j.yexmp.2022.104813","DOIUrl":"10.1016/j.yexmp.2022.104813","url":null,"abstract":"<div><h3>Purpose</h3><p>Glioblastoma<span> (GBM) patients currently face poor survival outcomes with an average survival period of &lt;15 months, while only 3–5% of patients survive longer than 36 months. Although the mechanisms of tumorigenesis are still being elucidated, miRNAs are promising candidates to explore as novel and prognostic biomarkers in GBM. In this study, we identified the association between miR-575 expression and overall survival (OS) of primary GBM patients and undertook functional studies to discern the contribution of miR-575 to GBM tumorigenesis.</span></p></div><div><h3>Methods</h3><p><span><span>Total RNAs were isolated from 254 FFPE GBM tumor samples and miR expression was assayed (simultaneously) using NanoString Technologies. To determine the association between miR-575 and patients' prognosis, Kaplan-Meier, univariable and multivariable </span>Cox regression<span> analyses were performed. Cell proliferation, colony formation, migration assays were conducted to investigate the function of miR-575 </span></span><em>in vitro</em> and <em>in vivo</em>. <span><em>In silico</em></span><span><span> target gene network analysis was performed to identify the putative targets of miR-575 in GBM, which were further verified by luciferase reporter assay, as well as qPCR and </span>immunoblotting.</span></p></div><div><h3>Results</h3><p>Our clinical data (<em>n</em> = 254) show that miR-575 is associated with worse GBM OS by univariable analysis (UVA, HR = 1.27, <em>p</em>-value&lt;0.001) and multivariable (MVA, HR = 1.23, <em>p</em> = 0.007) analysis incorporating critical clinical variables. Functional studies indicated that overexpression of miR-575 significantly increased cell proliferation and migration of GBM cells <em>in vitro</em>, as well as tumor growth <em>in vivo</em>. Subsequent <em>in silico</em> target gene network and mechanistic studies identified CDKN1B/p27 and PTEN, as potential targets of miR-575 in GBM. MicroRNA-575 can also regulate the activity of AKT and ERK pathways in GBM.</p></div><div><h3>Conclusion</h3><p>miR-575 has prognostic value in GBM, with higher expression associating with worse OS of patients, and contributes to GBM tumorigenesis by regulating multiple signaling pathways in GBM.</p></div>","PeriodicalId":12176,"journal":{"name":"Experimental and molecular pathology","volume":"128 ","pages":"Article 104813"},"PeriodicalIF":3.6,"publicationDate":"2022-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10702393","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Targeted molecular profiling of epithelial ovarian cancer from Italian BRCA wild-type patients with a BRCA and PARP pathways gene panel","authors":"Annamaria Salvati ,&nbsp;Ileana Carnevali ,&nbsp;Elena Alexandrova ,&nbsp;Sofia Facchi ,&nbsp;Susanna Ronchi ,&nbsp;Laura Libera ,&nbsp;Nora Sahnane ,&nbsp;Domenico Memoli ,&nbsp;Jessica Lamberti ,&nbsp;Sonia Amabile ,&nbsp;Stefano Pepe ,&nbsp;Roberta Tarallo ,&nbsp;Fausto Sessa ,&nbsp;Alessandro Weisz ,&nbsp;Maria Grazia Tibiletti ,&nbsp;Francesca Rizzo","doi":"10.1016/j.yexmp.2022.104833","DOIUrl":"10.1016/j.yexmp.2022.104833","url":null,"abstract":"<div><p><span>Ovarian cancer (OC) is the fifth most common type of cancer in women and the fourth most common cause of cancer death in women. Identification of pathogenic variants in OC tissues has an important clinical significance for therapeutic and prevention purposes. This study aims to evaluate the mutational profile of a patient cohort, negative for </span><em>BRCA1/2</em><span><span> germinal variants and Mismatch Repair<span> defects, using next-generation sequencing (NGS) approach on DNA<span> from formalin-fixed paraffin-embedded samples. We used a custom NGS panel, targeting 34 cancer-related genes, mainly of the BRCA and PARP pathways, and analyzed NGS data to identify somatic and </span></span></span>germline<span> variants in Italian patients affected by primary epithelial ovarian cancer. We analyzed 75 epithelial ovarian cancer tissues and identified 54 pathogenic variants and 56 variants of unknown significance. </span></span><em>TP53</em><span> was characterized by the highest mutational rate<span>, occurring in 55% of tested epithelial ovarian cancers (EOCs). Interestingly, a subset of 8 EOCs showed pathogenic variants of homologous recombination pathway, which could be sensitive to PARP-inhibitor therapies. Germline analysis of actionable genes revealed 4 patients carrier of pathogenic germline variants respectively of </span></span><span><em>RAD51C</em></span> (2 patients), <em>RAD51D</em>, and <span><em>PALB2</em></span><span><span>. Molecular profiling<span> of EOCs using our custom NGS panel has enabled the detection of both somatic and germline variants, allowing the selection of patients suitable for targeted therapies, and the identification of high-risk OC families that can benefit from </span></span>genetic counseling and testing.</span></p></div>","PeriodicalId":12176,"journal":{"name":"Experimental and molecular pathology","volume":"128 ","pages":"Article 104833"},"PeriodicalIF":3.6,"publicationDate":"2022-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10703384","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The impact of MCP1-2518A/G and CCR2-V64I genetic polymorphisms in Egyptian sickle cell disease patients","authors":"Nihal Salah Ibrahim ,&nbsp;Manal Mohamed Makhlouf ,&nbsp;Gehan Hamed Shahin ,&nbsp;Mona Kamal Elghamrawy ,&nbsp;Nehad Mohammed Hussein","doi":"10.1016/j.yexmp.2022.104834","DOIUrl":"10.1016/j.yexmp.2022.104834","url":null,"abstract":"<div><h3>Background</h3><p>Sickle cell disease<span><span> (SCD) is an inherited genetic disorders of hemoglobin that causes multisystem morbidity. The pathophysiology<span> of SCD is complex and includes HbS polymerization/sickling, hemolysis, endothelial dysfunction and inflammation. </span></span>Chemokines are proteins playing an important role in the inflammation process and could be involved the context of pro-inflammatory SCD. Some chemokine polymorphism were found to be associated with clinical complication in SCD.</span></p></div><div><h3>Aim of the study</h3><p>Was to explore the frequency and the possible effect of Monocyte<span> Chemo-attractant Protein 1–2518A/G (MCP1–2518A/G) and Chemokine Receptor<span> 2-V64I (CCR2-V64I) genetic polymorphisms on clinical and laboratory disease-related variables in Egyptian Sickle cell disease patients.</span></span></p></div><div><h3>Patients and methods</h3><p>Genotyping of the two genes were performed by PCR-RFLP technique for 80 SCD patients as well as 50 healthy control group.</p></div><div><h3>Results</h3><p>The study revealed that the MCP1–2518 polymorphic genotypes (AG &amp; GG) showed no statistically significant difference in the distribution of the polymorphic genotypes between SCD patients and the controls (<em>p</em> = 0.164). While a significantly higher frequency of the mutant variants CCR2-V64I GA/AA among SCD patients than the control subjects were found (<em>p</em><span><span> = 0.032). Regarding the clinic-pathological features, the frequency of recurrent infections, vaso-occlusive crisis, severe vaso-occlusive crisis and number of hospitalization/year were higher </span>in patients<span> harbouring the MCP1–2518A/G and CCR2-V64I polymorphic genotypes than the wild genotype, and gall bladder<span> complications were higher in MCP1–2518 G allele patients, whereas surgical splenectomy were higher in CCR2-V64I A allele patients (</span></span></span><em>p</em> &lt; 0.05).</p></div><div><h3>In conclusion</h3><p>MCP1–2518A/G and CCR2-V64I genetic polymorphisms may influence the clinical severity of sickle cell disease.</p></div>","PeriodicalId":12176,"journal":{"name":"Experimental and molecular pathology","volume":"128 ","pages":"Article 104834"},"PeriodicalIF":3.6,"publicationDate":"2022-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10335147","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The importance of regulatory pathway mediated by Circ0001955 in colorectal cancer","authors":"Sepideh Kadkhoda ,&nbsp;Soudeh Ghafouri-Fard ,&nbsp;Farshid Noorbakhsh ,&nbsp;Sima Ravaei ,&nbsp;Farzaneh Darbeheshti ,&nbsp;Mahsa M. Amoli ,&nbsp;Reza Taslimi ,&nbsp;Abbas Shakoori","doi":"10.1016/j.yexmp.2022.104819","DOIUrl":"10.1016/j.yexmp.2022.104819","url":null,"abstract":"<div><h3>Introduction</h3><p>Colorectal cancer (CRC) has become one of the most common cancers in recent years. Given the importance that non-coding RNAs have recently acquired in various diseases including cancers, we decided to design this study to evaluate the expression levels of circ0001955/miR-145-5p/ONECUT2 axis in CRC.</p></div><div><h3>Methods</h3><p>After bioinformatics analysis of GEO datasets related to CRC, a putative circ0001955/ miR-145-5p/ ONECUT2 pathway was assumed. Then, the expression levels of these genes were measured in 50 CRC samples and adjacent tissues by qRT- PCR. Also, correlation coefficients, receiver operating characteristic (ROC) curves, and correlation between circ0001955 levels with clinicopathological parameters of patients were analyzed.</p></div><div><h3>Results</h3><p>Circ0001955 and ONECUT2 were considerably up-regulated, while the expression level of miR-145-5p was decreased in CRC samples compared with adjacent tissues (<em>p</em> &lt; 0.05). Moreover, statistically significant correlations were observed between expression levels of circ0001955, miR-145-5p, and ONECUT2. We did not find any significant correlation between circ0001955 expression and clinicopathological parameters.</p></div><div><h3>Conclusion</h3><p>Our study showed that circ0001955 is dysregulated in CRC. This finding can open a new window for researchers for a better understanding of the potential pathways involved in CRC pathogenesis and, consequently, to find new treatment pathways.</p></div>","PeriodicalId":12176,"journal":{"name":"Experimental and molecular pathology","volume":"128 ","pages":"Article 104819"},"PeriodicalIF":3.6,"publicationDate":"2022-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10335816","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Single nucleotide polymorphism patterns associated with a cancer resistant phenotype","authors":"June K. Dunnick ,&nbsp;Arun R. Pandiri ,&nbsp;Keith R. Shockley ,&nbsp;Ronald Herbert ,&nbsp;Deepak Mav ,&nbsp;Dhiral Phadke ,&nbsp;Ruchir R. Shah ,&nbsp;B. Alex Merrick","doi":"10.1016/j.yexmp.2022.104812","DOIUrl":"10.1016/j.yexmp.2022.104812","url":null,"abstract":"<div><h3>Background and aims</h3><p>In this study ten mouse strains representing ~90% of genetic diversity in laboratory mice (B6C3F1/J, C57BL/6J, C3H/HeJ, A/J, NOD.B1oSnH2/J, NZO/HILtJ, 129S1/SvImJ, WSB/EiJ, PWK/PhJ, CAST/EiJ) were examined to identify the mouse strain with the lowest incidence of cancer. The unique single polymorphisms (SNPs) associated with this low cancer incidence are reported.</p></div><div><h3>Methods</h3><p>Evaluations of cancer incidence in the 10 mouse strains were based on gross and microscopic diagnosis of tumors. Single nucleotide polymorphisms (SNPs) in the coding regions of the genome were derived from the respective mouse strains located in the Sanger mouse sequencing database and the B6C3F1/N genome from the National Toxicology Program (NTP).</p></div><div><h3>Results</h3><p>The WSB strain had an overall lower incidence of both benign and malignant tumors compared to the other mouse strains. At 2 years, the incidence of total malignant tumors (Poly-3 incidence rate) ranged from 2% (WSB) to 92% (C3H) in males, and 14% (WSB) to 93% (NZO) in females, and the total incidence of benign and malignant tumor incidence ranged from 13% (WSB) to 99% (C3H) in males and 25% (WSB) to 96% (NOD) in females. Single nucleotide polymorphism (SNP) patterns were examined in the following strains: B6C3F1/N, C57BL/6J, C3H/HeJ, 129S1/SvImJ, A/J, NZO/HILtJ, CAST/EiJ, PWK/PhJ, and WSB/EiJ. We identified 7519 SNPs (involving 5751 Ensembl transcripts of 3453 Ensembl Genes) that resulted in a unique amino acid change in the coding region of the WSB strain.</p></div><div><h3>Conclusions</h3><p>The inherited genetic patterns in the WSB cancer-resistant mouse strain occurred in genes involved in multiple cell functions including mitochondria, metabolic, immune, and membrane-related cell functions. The unique SNP patterns in a cancer resistant mouse strain provides insights for understanding and developing strategies for cancer prevention.</p></div>","PeriodicalId":12176,"journal":{"name":"Experimental and molecular pathology","volume":"128 ","pages":"Article 104812"},"PeriodicalIF":3.6,"publicationDate":"2022-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10114545","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Increased synovial expression of calcitonin gene-related peptide and its potential roles in Charcot Neuroarthropathy","authors":"Yi Guo ,&nbsp;Lew Schon ,&nbsp;Sharada Paudel ,&nbsp;Tyler Feltham ,&nbsp;Lumanti Manandhar ,&nbsp;Zijun Zhang","doi":"10.1016/j.yexmp.2022.104835","DOIUrl":"10.1016/j.yexmp.2022.104835","url":null,"abstract":"<div><h3>Objective</h3><p>Joint destruction in Charcot neuroarthropathy (CNA) is accompanied with abundant hyperplastic synovium<span>. This study aimed to characterize the expression patterns of a group of neuropeptides in the CNA synovium.</span></p></div><div><h3>Methods</h3><p>Synovial specimens were collected during surgery from the CNA (<em>n</em> = 6) and non-CNA joints (<em>n</em><span><span><span> = 14). Tissue samples were processed for protein extraction and western blot<span> for vasoactive intestinal peptide (VIP), </span></span>galanin<span>, and calcitonin gene-related peptide (CGRP). Immunohistochemistry<span> was performed to localize CGRP in the CNA synovium. Additionally, CGRP was applied to fibroblast-like synoviocytes<span> (FLS) isolated from CNA synovium for its effects on cell proliferation and </span></span></span></span>collagenolysis </span><em>in vitro</em>.</p></div><div><h3>Results</h3><p>Western blot detected light bands of VIP in the CNA samples but abundant galanin in both CNA and non-CNA samples. Most of the CNA samples (5/6) increased expression of CGRP, with an average band density about 2 times that in the non-CNA group (<em>p &lt; .05</em>). Immunohistochemistry of CGRP demonstrated intense staining in the intimal layer of the CNA synovium. In tissue culture, adding CGRP (10 nM) in the medium promoted FLS proliferation. In combination with TNF-α, CGRP enhanced FLS-mediated collagenolysis <em>in vitro</em>.</p></div><div><h3>Conclusion</h3><p>This study revealed an increased expression of CGRP in the CNA synovium and demonstrated that CGRP regulates FLS proliferation and collagenolytic activity, suggesting CGRP may contribute to the bone and cartilage destruction in CNA.</p></div>","PeriodicalId":12176,"journal":{"name":"Experimental and molecular pathology","volume":"128 ","pages":"Article 104835"},"PeriodicalIF":3.6,"publicationDate":"2022-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10341494","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Human primary chronic wound derived fibroblasts demonstrate differential pattern in expression of fibroblast specific markers, cell cycle arrest and reduced proliferation","authors":"P. Monika ,&nbsp;M.N. Chandraprabha ,&nbsp;K.N. Chidambara Murthy ,&nbsp;Annapoorni Rangarajan ,&nbsp;P. Veena Waiker ,&nbsp;M. Sathish","doi":"10.1016/j.yexmp.2022.104803","DOIUrl":"https://doi.org/10.1016/j.yexmp.2022.104803","url":null,"abstract":"<div><h3>Introduction</h3><p><span>Although wound refers to simple cut in the skin, most wounds don't heal because of the various local and systemic factors that lead to its complexity and chronicity. Thus, prior understanding of the status of the wound is necessary and methods that can differentiate between the healing and non-healing wounds at a much earlier stage is crucial for a successful </span>treatment.</p></div><div><h3>Methods</h3><p>The current study aims at differentiating Acute Wound Fibroblasts (AWFs) and Chronic Wound Fibroblasts (CWFs) based on differential expression of fibroblast specific markers such as Vimentin<span> and Alpha Smooth Muscle Actin (α-SMA) and compare its cell cycle and proliferation.</span></p></div><div><h3>Results</h3><p>Immunostaining<span><span> and western blotting<span> analysis showed that, AWFs and CWFs differentially expressed vimentin and α-SMA, with AWFs and CWFs showing higher expression of vimentin and α-SMA respectively. AWFs showed higher distributions in G0/G1 (67.43% vs. 62.16%), S phase (22.61% vs. 8.51%) compared to CWFs. However, AWFs showed decreased distributions compared to CWFs in G2 + M phase (8.14% vs. 10.6%). Thus, it was observed that CWFs showed </span></span>cell cycle arrest<span> in the G1/G0 phase and inhibited DNA synthesis<span>, which was further confirmed by reduced proliferation of CWFs. We suggest that, differential expression of the cell specific markers can be attributed to its pathophysiological status and chronicity of the wound and reduced proliferation rate of CWFs is due to lesser expression of vimentin, which is a key protein for in vitro cell proliferation.</span></span></span></p></div><div><h3>Conclusions</h3><p>Outcome of the study serve as an immunological tool to guide the chronicity of the wound, which helps to understand the wound towards design of personalized care. The findings also represent a promising opportunity to gain insight into how cell cycle arrest can impact on wound healing and clinical outcomes.</p></div>","PeriodicalId":12176,"journal":{"name":"Experimental and molecular pathology","volume":"127 ","pages":"Article 104803"},"PeriodicalIF":3.6,"publicationDate":"2022-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"71787910","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Retraction notice to “ Endothelial PECAM-1 and its function in vascular physiology and atherogenic pathology” [Experimental and Molecular Pathology 100 (2016) 409–415]","authors":"Dimitry A. Chistiakov ,&nbsp;Alexander N. Orekhov ,&nbsp;Yuri V. Bobryshev","doi":"10.1016/j.yexmp.2022.104801","DOIUrl":"10.1016/j.yexmp.2022.104801","url":null,"abstract":"","PeriodicalId":12176,"journal":{"name":"Experimental and molecular pathology","volume":"127 ","pages":"Article 104801"},"PeriodicalIF":3.6,"publicationDate":"2022-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0014480022000648/pdfft?md5=948c2d8187f62e1d5ced20eda1e8fb47&pid=1-s2.0-S0014480022000648-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40397910","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Retraction notice to “Silence of lncRNA CHRF protects H9c2 cells against lipopolysaccharide-induced injury via up-regulating microRNA-221” [Experimental and Molecular Pathology 107 (2019) 43–50]","authors":"Lijuan Zhang ,&nbsp;Li Wang ,&nbsp;Enyu Guo ,&nbsp;Yuefeng Qi","doi":"10.1016/j.yexmp.2022.104789","DOIUrl":"10.1016/j.yexmp.2022.104789","url":null,"abstract":"","PeriodicalId":12176,"journal":{"name":"Experimental and molecular pathology","volume":"127 ","pages":"Article 104789"},"PeriodicalIF":3.6,"publicationDate":"2022-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0014480022000521/pdfft?md5=753e29166d65b2e798c77bb06e964d66&pid=1-s2.0-S0014480022000521-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40396331","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"NK1 receptor antagonistic effect of 17-trifluoromethyl phenyl trinor prostaglandin F2α on the growth of human breast cancer cell line","authors":"Mutukuru Mayuri ,&nbsp;Praveen T. Krishnamurthy ,&nbsp;Thangavel Mahalingam Vijayakumar","doi":"10.1016/j.yexmp.2022.104817","DOIUrl":"10.1016/j.yexmp.2022.104817","url":null,"abstract":"<div><h3>Background</h3><p><span>A growing number of genetic<span> and cancer biology<span> investigations have found that the tachykinin NK1 Receptor plays an important role in </span></span></span>cancer cell<span> proliferation and survival. In this study. The present study was designed to evaluate the inhibition of cell growth by 17-trifluoromethyl phenyl trinor prostaglandin<span> F2α with NK1 receptor in breast cancer cell lines.</span></span></p></div><div><h3>Materials and methods</h3><p><span><span>MDB-MB-468 and MCF-7 breast cancer cell lines were used in the experiment were blocked with PGF2a. Cell proliferation and </span>apoptosis<span> were analyzed to evaluate the cytotoxic effect. Cell cycle distribution, Caspase-3 enzyme activity<span>, Bad and Bax protein expression through flow cytometry and </span></span></span>molecular docking were carried out to analyze the NK1 receptor activity.</p></div><div><h3>Results</h3><p><span>We found that PGF2a has a high binding affinity<span><span> towards NK1 Receptor from molecular docking studies. It exerted cytotoxic and antiproliferative effects against MDB-MB-468 and MCF-7 breast cancer cell lines. Our data found that </span>treatment of cells with 17-TPGF2 resulted in cell death and showed that increased expression of Caspase-3, Bad, and Bax protein and further induces </span></span>G2 cell cycle arrest.</p></div><div><h3>Conclusion</h3><p>Overall this study investigates the NK1 receptor antagonistic effect of PGF2 against breast cancer cell lines. However, further studies are needed to better characterize the application of NK1 receptor inhibition in clinical cancer treatment and cytotoxicity effect.</p></div>","PeriodicalId":12176,"journal":{"name":"Experimental and molecular pathology","volume":"127 ","pages":"Article 104817"},"PeriodicalIF":3.6,"publicationDate":"2022-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40553648","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}