Pub Date : 2024-10-28DOI: 10.1016/j.prp.2024.155683
Faezeh Tolue Ghasaban, Meysam Moghbeli
Tumor cell invasion is considered as one of the main therapeutic challenges in cancer patients, which leads to distant metastasis and reduced prognosis. Therefore, investigation of the factors involved in tumor cell invasion improves the therapeutic methods to reduce tumor metastasis. Epithelial-mesenchymal transition (EMT) process has a pivotal role in tumor cell invasion and metastasis, during which tumor cells gain the invasive ability by losing epithelial characteristics and acquiring mesenchymal characteristics. WNT/β-catenin signaling pathway has a key role in tumor cell invasion by regulation of EMT process. Long non-coding RNAs (lncRNAs) have also an important role in EMT process through the regulation of WNT/β-catenin pathway. Deregulation of lncRNAs is associated with tumor metastasis in different tumor types. Therefore, in the present review, we investigated the role of lncRNAs in EMT process and tumor cell invasion through the regulation of WNT/β-catenin pathway. It has been reported that lncRNAs mainly induced the EMT process and tumor cell invasion through the activation of WNT/β-catenin pathway. LncRNAs that regulate the WNT/β-catenin mediated EMT process can be introduced as the prognostic markers as well as suitable therapeutic targets to reduce the tumor metastasis in cancer patients.
{"title":"Long non-coding RNAs as the pivotal regulators of epithelial mesenchymal transition through WNT/β-catenin signaling pathway in tumor cells","authors":"Faezeh Tolue Ghasaban, Meysam Moghbeli","doi":"10.1016/j.prp.2024.155683","DOIUrl":"10.1016/j.prp.2024.155683","url":null,"abstract":"<div><div>Tumor cell invasion is considered as one of the main therapeutic challenges in cancer patients, which leads to distant metastasis and reduced prognosis. Therefore, investigation of the factors involved in tumor cell invasion improves the therapeutic methods to reduce tumor metastasis. Epithelial-mesenchymal transition (EMT) process has a pivotal role in tumor cell invasion and metastasis, during which tumor cells gain the invasive ability by losing epithelial characteristics and acquiring mesenchymal characteristics. WNT/β-catenin signaling pathway has a key role in tumor cell invasion by regulation of EMT process. Long non-coding RNAs (lncRNAs) have also an important role in EMT process through the regulation of WNT/β-catenin pathway. Deregulation of lncRNAs is associated with tumor metastasis in different tumor types. Therefore, in the present review, we investigated the role of lncRNAs in EMT process and tumor cell invasion through the regulation of WNT/β-catenin pathway. It has been reported that lncRNAs mainly induced the EMT process and tumor cell invasion through the activation of WNT/β-catenin pathway. LncRNAs that regulate the WNT/β-catenin mediated EMT process can be introduced as the prognostic markers as well as suitable therapeutic targets to reduce the tumor metastasis in cancer patients.</div></div>","PeriodicalId":19916,"journal":{"name":"Pathology, research and practice","volume":"263 ","pages":"Article 155683"},"PeriodicalIF":2.9,"publicationDate":"2024-10-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142538778","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}
Exosomes are vesicles produced by the human body for carrying certain information from one cell to another. The carriers are nanosized vesicles carrying a wide variety of cargo like RNA, DNA, and proteins. Exosomes are also being used in the early diagnosis of various diseases and disorders. Current research focuses on exosomes tailoring for achieving therapeutic potential in various diseases and disorders. Besides this, their biocompatibility, stability, adjustable efficacy, and targeting properties make them attractive vehicles for formulation developers. Various preclinical studies suggested that the exosome culture cells are also modified with certain genes to achieve the desirable properties of resultant exosomes. The human body also produces some other vesicles like Ectosomes and Exomeres produced along with exosomes. Additionally, vesicles like Migrasomes are produced by migrating cells and apoptotic bodies, and Oncosomes are produced by cancer cells which can also be useful for the diagnosis of various diseases and disorders. For the separation of desired exosomes from other vesicles some latest techniques that can be useful viz differential centrifugation, density gradient centrifugation, and immunoaffinity purification have been discussed. Briefly, this review summarized various techniques of isolation of purified exosomes along with an overview of the application of exosomes in various neurodegenerative disorders and cancer along with various latest aspects of exosomes in disease progression and management which might be beneficial for the researchers.
{"title":"A complete sojourn on exosomes: Potential diagnostic and therapeutic agents","authors":"Sonakshi Garg , Gurisha Garg , Preeti Patel , Manish Kumar , Shubham Thakur , Nitin Sharma , Balak Das Kurmi","doi":"10.1016/j.prp.2024.155674","DOIUrl":"10.1016/j.prp.2024.155674","url":null,"abstract":"<div><div>Exosomes are vesicles produced by the human body for carrying certain information from one cell to another. The carriers are nanosized vesicles carrying a wide variety of cargo like RNA, DNA, and proteins. Exosomes are also being used in the early diagnosis of various diseases and disorders. Current research focuses on exosomes tailoring for achieving therapeutic potential in various diseases and disorders. Besides this, their biocompatibility, stability, adjustable efficacy, and targeting properties make them attractive vehicles for formulation developers. Various preclinical studies suggested that the exosome culture cells are also modified with certain genes to achieve the desirable properties of resultant exosomes. The human body also produces some other vesicles like Ectosomes and Exomeres produced along with exosomes. Additionally, vesicles like Migrasomes are produced by migrating cells and apoptotic bodies, and Oncosomes are produced by cancer cells which can also be useful for the diagnosis of various diseases and disorders. For the separation of desired exosomes from other vesicles some latest techniques that can be useful viz differential centrifugation, density gradient centrifugation, and immunoaffinity purification have been discussed. Briefly, this review summarized various techniques of isolation of purified exosomes along with an overview of the application of exosomes in various neurodegenerative disorders and cancer along with various latest aspects of exosomes in disease progression and management which might be beneficial for the researchers.</div></div>","PeriodicalId":19916,"journal":{"name":"Pathology, research and practice","volume":"264 ","pages":"Article 155674"},"PeriodicalIF":2.9,"publicationDate":"2024-10-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142553856","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}
Pub Date : 2024-10-26DOI: 10.1016/j.prp.2024.155686
Ana Paula Abreu , Jhessica Gomes , Jucileide Mota , Ana Paula Almeida , Rita Carvalhal , Flávia Vidal , Rui Medeiros , Hugo Sousa , Melaine Lawall , Rui M. Gil da Costa , Haissa O. Brito , Luciane M.O. Brito
Deletions of the GSTT1 and GSTM1 are associated with chemical carcinogenesis and genitourinary malignancies like bladder cancer, where they correlate with increased tumor aggressiveness. In uterine cervical lesions, GSTT1 and GSTM1 deletions have also been suggested to facilitate the persistence of human papillomavirus (HPV) infection and HPV-induced carcinogenesis. This work addresses the hypothesis that GSTT1/GSTM1 deletions are associated with presence of HPV DNA and aggressiveness in penile cancer, a rare malignancy with HPV+ and HPV- subtypes. Tumor DNA samples and medical records from HPV+ and HPV- penile cancer patients were analyzed. Each sample was screened for GSTT1 and GSTM1 deletions and for the presence of HPV DNA using PCR-based techniques. 74.5 % of samples contained HPV DNA. 61.8 % of cases showed T2 and T3 staging. There were no differences in the frequencies of GSTT1/GSTM1 genotypes between HPV+ and HPV- cases (p>0.05). GSTT1wt/GSTMnull patients were more likely to have higher TNM stages compared with other genotypes (p=0.012), but no differences were observed concerning perineural invasion nor lymphovascular invasion. These findings indicate that GSTT1 and GSTM1 deletions are common in HPV+ and HPV- penile cancers. GSTM1 deletions in the presence of wild-type GSTT1 seems to be associated with tumor progression, and additional studies are warranted to confirm its potential as a prognostic marker in penile cancer.
{"title":"GSTM1 and GSTT1 deletions in penile cancer are associated with TNM stage but not with HPV DNA status","authors":"Ana Paula Abreu , Jhessica Gomes , Jucileide Mota , Ana Paula Almeida , Rita Carvalhal , Flávia Vidal , Rui Medeiros , Hugo Sousa , Melaine Lawall , Rui M. Gil da Costa , Haissa O. Brito , Luciane M.O. Brito","doi":"10.1016/j.prp.2024.155686","DOIUrl":"10.1016/j.prp.2024.155686","url":null,"abstract":"<div><div>Deletions of the <em>GSTT1</em> and <em>GSTM1</em> are associated with chemical carcinogenesis and genitourinary malignancies like bladder cancer, where they correlate with increased tumor aggressiveness. In uterine cervical lesions, <em>GSTT1</em> and <em>GSTM1</em> deletions have also been suggested to facilitate the persistence of human papillomavirus (HPV) infection and HPV-induced carcinogenesis. This work addresses the hypothesis that <em>GSTT1</em>/<em>GSTM1</em> deletions are associated with presence of HPV DNA and aggressiveness in penile cancer, a rare malignancy with HPV+ and HPV- subtypes. Tumor DNA samples and medical records from HPV+ and HPV- penile cancer patients were analyzed. Each sample was screened for <em>GSTT1</em> and <em>GSTM1</em> deletions and for the presence of HPV DNA using PCR-based techniques. 74.5 % of samples contained HPV DNA. 61.8 % of cases showed T2 and T3 staging. There were no differences in the frequencies of <em>GSTT1/GSTM1</em> genotypes between HPV+ and HPV- cases (<em>p</em>>0.05). <em>GSTT1</em><sup>wt</sup>/<em>GSTM</em><sup><em>null</em></sup> patients were more likely to have higher TNM stages compared with other genotypes (<em>p</em>=0.012), but no differences were observed concerning perineural invasion nor lymphovascular invasion. These findings indicate that <em>GSTT1</em> and <em>GSTM1</em> deletions are common in HPV+ and HPV- penile cancers. <em>GSTM1</em> deletions in the presence of wild-type <em>GSTT1</em> seems to be associated with tumor progression, and additional studies are warranted to confirm its potential as a prognostic marker in penile cancer.</div></div>","PeriodicalId":19916,"journal":{"name":"Pathology, research and practice","volume":"264 ","pages":"Article 155686"},"PeriodicalIF":2.9,"publicationDate":"2024-10-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142553857","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}
Pub Date : 2024-10-26DOI: 10.1016/j.prp.2024.155681
Sun Shin , Hyun Ho Kim , Jae Woong Kim , Doeun Rim , Changhyeok An , Yeun-Jun Chung , Sug Hyung Lee
Neoadjuvant chemotherapy combined with bevacizumab is used to treat colorectal cancer (CRC) patients by targeting tumor and vascular cells. However, it is known that other cells in the tumor microenvironment (TME) also change in response to this treatment. To investigate the changes in TME subpopulations in response to neoadjuvant FOLFOX6 plus bevacizumab, we studied pre- and post-treatment CRC tissues in four patients using single-cell RNA sequencing (scRNA-seq). This analysis classified nine cell types, including epithelial, vascular, immune cells, and fibroblasts. The cellular responses were widespread across the cell types, but there were specific subpopulations that altered, especially in vascular, immune, and fibroblast cells. In vascular subpopulations, CDH13-endothelial, arteriole, and CA4 capillary cells were selectively reduced. In immune cells, CD4+, CD8+ T cells, conventional dendritic cell type 1 (cDC1), and CCL19-expressing migrating DC (migDC-1) increased, while Th17, Th22, and tumor-associated macrophage (TAM) cells decreased, indicating that the treatment might be immunostimulatory. In fibroblasts, two major cancer-associated fibroblasts (matrix CAF (mCAF) and inflammatory CAF (iCAF)) increased, while conventional fibroblasts decreased, suggesting that the treatment remodeled the reparative/inflammatory processes, which might lead to reduced aggressiveness from the cancer-associated fibroblasts. In summary, our study reveals that neoadjuvant FOLFOX6 plus bevacizumab leads to alterations in particular subpopulations of vascular, immune, and reparative/inflammatory cells in the TME of CRCs. These alterations include vascular reduction, immunologic stimulation, and reduction of cancer-associated fibroblasts, which may underlie the responsiveness to the therapy in CRC. Our results may provide insights into the mechanisms of responsiveness/resistance to neoadjuvant FOLFOX6 plus bevacizumab therapy in CRCs.
{"title":"Cellular responses to neoadjuvant FOLFOX6-bevacizumab treatment in colorectal cancers analyzed by single-cell transcriptome analysis","authors":"Sun Shin , Hyun Ho Kim , Jae Woong Kim , Doeun Rim , Changhyeok An , Yeun-Jun Chung , Sug Hyung Lee","doi":"10.1016/j.prp.2024.155681","DOIUrl":"10.1016/j.prp.2024.155681","url":null,"abstract":"<div><div>Neoadjuvant chemotherapy combined with bevacizumab is used to treat colorectal cancer (CRC) patients by targeting tumor and vascular cells. However, it is known that other cells in the tumor microenvironment (TME) also change in response to this treatment. To investigate the changes in TME subpopulations in response to neoadjuvant FOLFOX6 plus bevacizumab, we studied pre- and post-treatment CRC tissues in four patients using single-cell RNA sequencing (scRNA-seq). This analysis classified nine cell types, including epithelial, vascular, immune cells, and fibroblasts. The cellular responses were widespread across the cell types, but there were specific subpopulations that altered, especially in vascular, immune, and fibroblast cells. In vascular subpopulations, CDH13-endothelial, arteriole, and CA4 capillary cells were selectively reduced. In immune cells, CD4+, CD8+ T cells, conventional dendritic cell type 1 (cDC1), and <em>CCL19</em>-expressing migrating DC (migDC-1) increased, while Th17, Th22, and tumor-associated macrophage (TAM) cells decreased, indicating that the treatment might be immunostimulatory. In fibroblasts, two major cancer-associated fibroblasts (matrix CAF (mCAF) and inflammatory CAF (iCAF)) increased, while conventional fibroblasts decreased, suggesting that the treatment remodeled the reparative/inflammatory processes, which might lead to reduced aggressiveness from the cancer-associated fibroblasts. In summary, our study reveals that neoadjuvant FOLFOX6 plus bevacizumab leads to alterations in particular subpopulations of vascular, immune, and reparative/inflammatory cells in the TME of CRCs. These alterations include vascular reduction, immunologic stimulation, and reduction of cancer-associated fibroblasts, which may underlie the responsiveness to the therapy in CRC. Our results may provide insights into the mechanisms of responsiveness/resistance to neoadjuvant FOLFOX6 plus bevacizumab therapy in CRCs.</div></div>","PeriodicalId":19916,"journal":{"name":"Pathology, research and practice","volume":"263 ","pages":"Article 155681"},"PeriodicalIF":2.9,"publicationDate":"2024-10-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142538696","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}
Pub Date : 2024-10-26DOI: 10.1016/j.prp.2024.155680
Julia Ayumi Ikeda Kawasaki , Lais Capelasso Lucas Pinheiro , Isabely Mayara da Silva , Carlos Alberto Miqueloto , Karen Brajão de Oliveira , Diego Luís Ribeiro , Alda Fiorina Maria Losi Guembarovski , Fernando Terziotti , Wilner Martinez-López , Juliana Mara Serpeloni , Roberta Losi Guembarovski
Urothelial bladder carcinoma (UBC) is a malignant neoplasm of the urinary tract that is highly prevalent worldwide and has a high rate of tumor recurrence. It is known that the BCL2 apoptosis regulator (BCL-2) gene encodes a mitochondrial protein that regulates programmed death cells by apoptosis. In contrast, the H2A.X histone variant (H2AX) gene encodes a histone responsible for regulating and signaling genomic instability processes. The present study aimed to analyze the immunostaining profiles of BCL-2 and γ-H2AX proteins in tissue samples (n=80) from UBC patients (muscle-invasive MI; and non-muscle invasive NMI) using indirect immunohistochemistry and to correlate the results with prognostic and clinical parameters. BCL-2 protein expression was cytoplasmic and absent in half of the samples, including the MI and NMI groups. Strong nuclear expression was observed for γ-H2AX, predominant in the MI samples. The immunostaining profile of both proteins was not associated with tumor recurrence or invasion, and no significant associations were found in relation to prognosis (tumor grade, pathological staging). No significant correlation was found between protein profiles in malignant tissue. All in all, BCL-2 and γ-H2AX did not prove to be candidate markers for UBC clinical management in the present sample, despite their expression in malignant bladder tissue.
尿路上皮性膀胱癌（UBC）是一种泌尿系统恶性肿瘤，在全球范围内发病率很高，而且肿瘤复发率也很高。众所周知，BCL2 细胞凋亡调节因子（BCL-2）基因编码一种线粒体蛋白，通过细胞凋亡调节程序性死亡细胞。相比之下，H2A.X组蛋白变体（H2AX）基因编码的组蛋白负责调节基因组不稳定过程并发出信号。本研究旨在使用间接免疫组化方法分析 UBC 患者（肌肉浸润性 MI 和非肌肉浸润性 NMI）组织样本（n=80）中 BCL-2 和 γ-H2AX 蛋白的免疫染色谱，并将结果与预后和临床参数相关联。半数样本（包括 MI 和 NMI 组）的 BCL-2 蛋白呈细胞质表达且缺失。γ-H2AX的核表达较强，主要出现在MI样本中。这两种蛋白的免疫染色与肿瘤复发或侵袭无关，与预后（肿瘤分级、病理分期）也无明显关联。恶性肿瘤组织中的蛋白图谱之间也没有发现明显的相关性。总而言之，尽管BCL-2和γ-H2AX在恶性膀胱组织中也有表达，但在本样本中并未证明它们是UBC临床管理的候选标志物。
{"title":"BCL-2 and γ-H2AX immunostaining profile in urothelial bladder cancer prognosis","authors":"Julia Ayumi Ikeda Kawasaki , Lais Capelasso Lucas Pinheiro , Isabely Mayara da Silva , Carlos Alberto Miqueloto , Karen Brajão de Oliveira , Diego Luís Ribeiro , Alda Fiorina Maria Losi Guembarovski , Fernando Terziotti , Wilner Martinez-López , Juliana Mara Serpeloni , Roberta Losi Guembarovski","doi":"10.1016/j.prp.2024.155680","DOIUrl":"10.1016/j.prp.2024.155680","url":null,"abstract":"<div><div>Urothelial bladder carcinoma (UBC) is a malignant neoplasm of the urinary tract that is highly prevalent worldwide and has a high rate of tumor recurrence. It is known that the <em>BCL2 apoptosis regulator (BCL-2)</em> gene encodes a mitochondrial protein that regulates programmed death cells by apoptosis. In contrast, the <em>H2A.X histone variant</em> (<em>H2AX)</em> gene encodes a histone responsible for regulating and signaling genomic instability processes. The present study aimed to analyze the immunostaining profiles of BCL-2 and γ-H2AX proteins in tissue samples (n=80) from UBC patients (muscle-invasive MI; and non-muscle invasive NMI) using indirect immunohistochemistry and to correlate the results with prognostic and clinical parameters. BCL-2 protein expression was cytoplasmic and absent in half of the samples, including the MI and NMI groups. Strong nuclear expression was observed for γ-H2AX, predominant in the MI samples. The immunostaining profile of both proteins was not associated with tumor recurrence or invasion, and no significant associations were found in relation to prognosis (tumor grade, pathological staging). No significant correlation was found between protein profiles in malignant tissue. All in all, BCL-2 and γ-H2AX did not prove to be candidate markers for UBC clinical management in the present sample, despite their expression in malignant bladder tissue.</div></div>","PeriodicalId":19916,"journal":{"name":"Pathology, research and practice","volume":"264 ","pages":"Article 155680"},"PeriodicalIF":2.9,"publicationDate":"2024-10-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142569203","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}
Pub Date : 2024-10-24DOI: 10.1016/j.prp.2024.155666
Mohamed J. Saadh , Amirmohammad Khalifehsoltani , Abbas Hameed Abdul Hussein , Omer Qutaiba B. Allela , Hayder Naji Sameer , Jasur Rizaev , Huda Ghassan Hameed , Ameer Hassan Idan , Fahad Alsaikhan
Malignant tumors are complicated structures of cancer cells that are constantly in communication with their local and distant environment. Exosomes are released by tumor cells and can facilitate the cell-cell interaction within the local microenvironment and the primary tumor. In fact, exosomes are secreted by both tumor and non-tumor cells, to provide a mutual communication network between cells and their micro- and/or macro-environments. Exososmes can contain a variety of biological cargos mostly based on their originated cells. Uptake of these exosomes by their recipient cells results in the alterations that their cargo can exert. MicroRNAs are identified as one of the most critical exosomal components, considering their pivotal regulatory roles in distinct biological process, including metastasis. Release and absorbance of exosomal microRNAs is possible by various cells within the host, and can have distinct biological consequences. Therefore, in this review we will discuss the role of exosomal microRNAs derived from tumor cells and untransformed cells within their micro- and macroenvironment in cancer progression and metastasis.
{"title":"Exosomal microRNAs in cancer metastasis: A bridge between tumor micro and macroenvironment","authors":"Mohamed J. Saadh , Amirmohammad Khalifehsoltani , Abbas Hameed Abdul Hussein , Omer Qutaiba B. Allela , Hayder Naji Sameer , Jasur Rizaev , Huda Ghassan Hameed , Ameer Hassan Idan , Fahad Alsaikhan","doi":"10.1016/j.prp.2024.155666","DOIUrl":"10.1016/j.prp.2024.155666","url":null,"abstract":"<div><div>Malignant tumors are complicated structures of cancer cells that are constantly in communication with their local and distant environment. Exosomes are released by tumor cells and can facilitate the cell-cell interaction within the local microenvironment and the primary tumor. In fact, exosomes are secreted by both tumor and non-tumor cells, to provide a mutual communication network between cells and their micro- and/or macro-environments. Exososmes can contain a variety of biological cargos mostly based on their originated cells. Uptake of these exosomes by their recipient cells results in the alterations that their cargo can exert. MicroRNAs are identified as one of the most critical exosomal components, considering their pivotal regulatory roles in distinct biological process, including metastasis. Release and absorbance of exosomal microRNAs is possible by various cells within the host, and can have distinct biological consequences. Therefore, in this review we will discuss the role of exosomal microRNAs derived from tumor cells and untransformed cells within their micro- and macroenvironment in cancer progression and metastasis.</div></div>","PeriodicalId":19916,"journal":{"name":"Pathology, research and practice","volume":"263 ","pages":"Article 155666"},"PeriodicalIF":2.9,"publicationDate":"2024-10-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142538779","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}
The dysregulation of circular RNAs (circRNAs) is closely associated with the pathogenesis of colorectal cancer (CRC). The present study aimed to elucidate the biological function and mechanism of circ_0060927 in CRC.
Methods
5-ethynyl-2’-deoxyuridine, Cell Counting Kit-8 (CCK-8), flow cytometry and transwell assays, as well as Xenograft tumor models were adopted for in vitro and in vivo analyses. The interaction between microRNA-331–3p (miR-331–3p) and circ_0060927 or T-box transcription factor 2 (TBX2) was verified by the dual-luciferase reporter and RNA pull-down assays.
Results
Circ_0060927 deficiency inhibited cell proliferation, autophagy, migration, and invasion and increased cell apoptosis and necrosis in CRC cells, as well as inhibited tumor growth in vivo. Circ_0060927 could bind to miR-331–3p, and circ_0060927 regulated CRC cell behaviors via sponging miR-331–3p. TBX2 was targeted by miR-331–3p, and miR-331–3p targeted TBX2 to exert the anti-cancer role in CRC cells. Mechanically, circ_0060927 regulated TBX2 expression by sequestering miR-331–3p in CRC cells.
Conclusion
Circ_0060927 downregulation inhibited CRC progression by regulating the miR-331–3p/TBX2 axis, which might offer a potential treatment target for CRC.
{"title":"Circ_0060927 promotes colorectal cancer development by sponging miR-331-3p and upregulating TBX2","authors":"Dian Yin, XiaoLu Zhai, Xiu Feng, Mei Hua, Jing Liu, Ying Chen","doi":"10.1016/j.prp.2024.155673","DOIUrl":"10.1016/j.prp.2024.155673","url":null,"abstract":"<div><h3>Background</h3><div>The dysregulation of circular RNAs (circRNAs) is closely associated with the pathogenesis of colorectal cancer (CRC). The present study aimed to elucidate the biological function and mechanism of circ_0060927 in CRC.</div></div><div><h3>Methods</h3><div>5-ethynyl-2’-deoxyuridine, Cell Counting Kit-8 (CCK-8), flow cytometry and transwell assays, as well as Xenograft tumor models were adopted for in vitro and in vivo analyses. The interaction between microRNA-331–3p (miR-331–3p) and circ_0060927 or T-box transcription factor 2 (TBX2) was verified by the dual-luciferase reporter and RNA pull-down assays.</div></div><div><h3>Results</h3><div>Circ_0060927 deficiency inhibited cell proliferation, autophagy, migration, and invasion and increased cell apoptosis and necrosis in CRC cells, as well as inhibited tumor growth <em>in vivo</em>. Circ_0060927 could bind to miR-331–3p, and circ_0060927 regulated CRC cell behaviors via sponging miR-331–3p. TBX2 was targeted by miR-331–3p, and miR-331–3p targeted TBX2 to exert the anti-cancer role in CRC cells. Mechanically, circ_0060927 regulated TBX2 expression by sequestering miR-331–3p in CRC cells.</div></div><div><h3>Conclusion</h3><div>Circ_0060927 downregulation inhibited CRC progression by regulating the miR-331–3p/TBX2 axis, which might offer a potential treatment target for CRC.</div></div>","PeriodicalId":19916,"journal":{"name":"Pathology, research and practice","volume":"264 ","pages":"Article 155673"},"PeriodicalIF":2.9,"publicationDate":"2024-10-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142560968","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}
Pub Date : 2024-10-23DOI: 10.1016/j.prp.2024.155671
Giuseppe Broggi , Manuel Mazzucchelli , Serena Salzano , Giuseppe Maria Vincenzo Barbagallo , Francesco Certo , Magda Zanelli , Andrea Palicelli , Maurizio Zizzo , Nektarios Koufopoulos , Gaetano Magro , Rosario Caltabiano
The field of neuropathology, a subspecialty of pathology which studies the diseases affecting the nervous system, is experiencing significant changes due to advancements in artificial intelligence (AI). Traditionally reliant on histological methods and clinical correlations, neuropathology is now experiencing a revolution due to the development of AI technologies like machine learning (ML) and deep learning (DL). These technologies enhance diagnostic accuracy, optimize workflows, and enable personalized treatment strategies. AI algorithms excel at analyzing histopathological images, often revealing subtle morphological changes missed by conventional methods. For example, deep learning models applied to digital pathology can effectively differentiate tumor grades and detect rare pathologies, leading to earlier and more precise diagnoses. Progress in neuroimaging is another helpful tool of AI, as enhanced analysis of MRI and CT scans supports early detection of neurodegenerative diseases. By identifying biomarkers and progression patterns, AI aids in timely therapeutic interventions, potentially slowing disease progression. In molecular pathology, AI’s ability to analyze complex genomic data helps uncover the genetic and molecular basis of neuropathological conditions, facilitating personalized treatment plans. AI-driven automation streamlines routine diagnostic tasks, allowing pathologists to focus on complex cases, especially in settings with limited resources. This review explores AI's integration into neuropathology, highlighting its current applications, benefits, challenges, and future directions.
{"title":"The emerging role of artificial intelligence in neuropathology: Where are we and where do we want to go?","authors":"Giuseppe Broggi , Manuel Mazzucchelli , Serena Salzano , Giuseppe Maria Vincenzo Barbagallo , Francesco Certo , Magda Zanelli , Andrea Palicelli , Maurizio Zizzo , Nektarios Koufopoulos , Gaetano Magro , Rosario Caltabiano","doi":"10.1016/j.prp.2024.155671","DOIUrl":"10.1016/j.prp.2024.155671","url":null,"abstract":"<div><div>The field of neuropathology, a subspecialty of pathology which studies the diseases affecting the nervous system, is experiencing significant changes due to advancements in artificial intelligence (AI). Traditionally reliant on histological methods and clinical correlations, neuropathology is now experiencing a revolution due to the development of AI technologies like machine learning (ML) and deep learning (DL). These technologies enhance diagnostic accuracy, optimize workflows, and enable personalized treatment strategies. AI algorithms excel at analyzing histopathological images, often revealing subtle morphological changes missed by conventional methods. For example, deep learning models applied to digital pathology can effectively differentiate tumor grades and detect rare pathologies, leading to earlier and more precise diagnoses. Progress in neuroimaging is another helpful tool of AI, as enhanced analysis of MRI and CT scans supports early detection of neurodegenerative diseases. By identifying biomarkers and progression patterns, AI aids in timely therapeutic interventions, potentially slowing disease progression. In molecular pathology, AI’s ability to analyze complex genomic data helps uncover the genetic and molecular basis of neuropathological conditions, facilitating personalized treatment plans. AI-driven automation streamlines routine diagnostic tasks, allowing pathologists to focus on complex cases, especially in settings with limited resources. This review explores AI's integration into neuropathology, highlighting its current applications, benefits, challenges, and future directions.</div></div>","PeriodicalId":19916,"journal":{"name":"Pathology, research and practice","volume":"263 ","pages":"Article 155671"},"PeriodicalIF":2.9,"publicationDate":"2024-10-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142528222","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}
Ovarian cancer is one of the most common malignancy in women with significant mortality rate due to the resistance to chemotherapy drugs. Doxorubicin (DOX) is a chemotropic agent in ovarian cancer treatment. Overexpression of multidrug resistance (MDR) genes, such as ABCB1, in cancer cells after chemotherapy is one of main problems in clinical applications. Here we have compared the efficiency of doxorubicin-loaded (NIPAAM-DMAEMA) Fe3O4 nanocomposite (DOX-NANO) against DOX on ABCB1(MDR1) gene expression in the ovarian cancer cell line.
Materials and methods
The cell viability of SKOV-3 cells were evaluated by MTT assay. Real Time PCR was used to measure the expression level of MDR1. MTT data were normalized in 10 different attribute weighting models, also to reveal the interaction between DOX, ABCB1, and ovarian cancer genes, Pathway Studio Database (Elsevier) was used.
Results
Cell viability of SKOV-3cells was significantly decreased after 24, 48 and 72 hours (P < 0.0001) of either DOX with IC50 22.38, 0.61 and 0.072 µg/ml or DOX-NANO treatment with IC50 11.54, 1.01, 0.0126 µg/ ml respectively. treatment. Notable decrease in the expression of MDR gene, ABCB1, was observed 48 hours after treatment with DOX-NANO (P < 0.0001) with 26 % in the assessed with control group. Meta-analysis showed the concentration of 10 μg/ml variables was the second most significant feature, whereas the concentration of 0.01 μg/ml recognized the lowest weights. Also, LGALS3 is an extra cellular receptor with upregulation in ovarian cancer that interacts with ABCB1.
Conclusion
Our findings highlight the beneficial effects of DOX delivery in ovarian cancer cells by nanocomposite as efficient drug delivery method. DOX-NANO is a promising therapeutic reagent to overcome chemotherapy resistance in ovarian cancer.
{"title":"Delivery of doxorubicin by Fe3O4 nanoparticles, reduces multidrug resistance gene expression in ovarian cancer cells","authors":"Roghiyeh Pashaei-Asl , Soheila Motaali , Esmaeil Ebrahimie , Manijeh Mohammadi-Dehcheshmeh , Mansour Ebrahimi , Maryam Pashaiasl","doi":"10.1016/j.prp.2024.155667","DOIUrl":"10.1016/j.prp.2024.155667","url":null,"abstract":"<div><h3>Background</h3><div>Ovarian cancer is one of the most common malignancy in women with significant mortality rate due to the resistance to chemotherapy drugs. Doxorubicin (DOX) is a chemotropic agent in ovarian cancer treatment. Overexpression of multidrug resistance (MDR) genes, such as <em>ABCB1</em>, in cancer cells after chemotherapy is one of main problems in clinical applications. Here we have compared the efficiency of doxorubicin-loaded (NIPAAM-DMAEMA) Fe<sub>3</sub>O<sub>4</sub> nanocomposite (DOX-NANO) against DOX on <em>ABCB1(</em>MDR1) gene expression in the ovarian cancer cell line.</div></div><div><h3>Materials and methods</h3><div>The cell viability of SKOV-3 cells were evaluated by MTT assay. Real Time PCR was used to measure the expression level of MDR1. MTT data were normalized in 10 different attribute weighting models, also to reveal the interaction between DOX, <em>ABCB1</em>, and ovarian cancer genes, Pathway Studio Database (Elsevier) was used.</div></div><div><h3>Results</h3><div>Cell viability of SKOV-3cells was significantly decreased after 24, 48 and 72 hours (P < 0.0001) of either DOX with IC50 22.38, 0.61 and 0.072 µg/ml or DOX-NANO treatment with IC50 11.54, 1.01, 0.0126 µg/ ml respectively. treatment. Notable decrease in the expression of MDR gene, <em>ABCB1</em>, was observed 48 hours after treatment with DOX-NANO (P < 0.0001) with 26 % in the assessed with control group. Meta-analysis showed the concentration of 10 μg/ml variables was the second most significant feature, whereas the concentration of 0.01 μg/ml recognized the lowest weights. Also, <em>LGALS3</em> is an extra cellular receptor with upregulation in ovarian cancer that interacts with <em>ABCB1</em>.</div></div><div><h3>Conclusion</h3><div>Our findings highlight the beneficial effects of DOX delivery in ovarian cancer cells by nanocomposite as efficient drug delivery method. DOX-NANO is a promising therapeutic reagent to overcome chemotherapy resistance in ovarian cancer.</div></div>","PeriodicalId":19916,"journal":{"name":"Pathology, research and practice","volume":"263 ","pages":"Article 155667"},"PeriodicalIF":2.9,"publicationDate":"2024-10-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142538744","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}
Pub Date : 2024-10-21DOI: 10.1016/j.prp.2024.155669
Reham Hammad , Eman Z. Kandeel , Claude Lambert , Ulrich Sack , Sandy Kujumdshiev , Arwa Kamhawy , Omaima I. Abo-Elkheir , Fatma EL-Zahraa Abd El Hakam , Alya Mashaal , Mohammed Ramadan , Abdel-Aziz A. Zidan , Nadia M. Hamdy
Background
Chronic lymphocytic leukemia (CLL) is characterized by a wide range of tumor-induced immune alterations. Regulatory T cells (Treg) play a central role in these immune responses. CD200 and Leukocyte-associated immunoglobulin-like receptor-1 (LAIR-1, CD305) are inhibitory markers said to be involved in Treg immune response. We aimed to analyze the expression of CD200 and LAIR-1 on leukemic cells and assess their interactions with the Treg frequency to elucidate their role in the CLL course.
Subjects and methods
This study was conducted on 70 participants: 50 newly diagnosed CLL cases classified according to Rai staging system into group 1 (n = 25) patients with stages 0, I, and II, and group 2 (n = 25) of advanced patients with stages III and IV. In addition to control group (n = 20) of healthy adults. Flow cytometry was used to investigate Treg frequency in bone marrow (BM) proportional to CD4+ T cell and to assess leukemic cell expression of CD200 and LAIR-1. Also, in-silico database analysis was performed to identify study markers interactions for future personalized target therapy.
Results
Comparison between CLL groups 1 and 2 revealed increased leukemic cell percentage expressing LAIR-1 (p = 0.021) in group 1. Group 2 showed significant increase in frequency of Treg in BM and leukemic cells expressing CD200. There was a strong positive correlation between frequency of Treg and leukemic cells expressing CD200 (r = 0.669, p = 0.000). On the other hand, there was a negative correlation between frequency of Treg and leukemic cell expressing LAIR-1 (r = −0.342, p = 0.015). ROC curve analysis revealed that increased frequency of leukemic cells expressing CD200 yielded sensitivity (SN) and specificity (SP) of 96 % and 84 %, respectively in detecting CLL progression, with an AUC of 0.965. Leukemic cell percentages expressing LAIR-1 yielded a lower SN (75 %), SP (72 %), with an AUC of 0.688.
Conclusion
Treg frequency in BM was significantly increased in CLL advanced stages according to Rai classification. Leukemic cells CD200 and LAIR-1 expression were differently associated with Treg frequency. Increased CD200 expressions on leukemic cells can be considered a sensitive and specific biomarker in detecting CLL progression. As demonstrated by the in-silico research, CD200 blockade targeting may offer therapeutic benefits for CLL treatment through Treg suppression.
{"title":"Leukemic B cells expression of CD200 and Leukocyte-associated immunoglobulin-like receptor-1 (LAIR-1, CD305) in Chronic Lymphocytic Leukemia patients in relation to Treg frequency","authors":"Reham Hammad , Eman Z. Kandeel , Claude Lambert , Ulrich Sack , Sandy Kujumdshiev , Arwa Kamhawy , Omaima I. Abo-Elkheir , Fatma EL-Zahraa Abd El Hakam , Alya Mashaal , Mohammed Ramadan , Abdel-Aziz A. Zidan , Nadia M. Hamdy","doi":"10.1016/j.prp.2024.155669","DOIUrl":"10.1016/j.prp.2024.155669","url":null,"abstract":"<div><h3>Background</h3><div>Chronic lymphocytic leukemia (CLL) is characterized by a wide range of tumor-induced immune alterations. Regulatory T cells (Treg) play a central role in these immune responses. CD200 and Leukocyte-associated immunoglobulin-like receptor-1 (LAIR-1, CD305) are inhibitory markers said to be involved in Treg immune response. We aimed to analyze the expression of CD200 and LAIR-1 on leukemic cells and assess their interactions with the Treg frequency to elucidate their role in the CLL course.</div></div><div><h3>Subjects and methods</h3><div>This study was conducted on 70 participants: 50 newly diagnosed CLL cases classified according to Rai staging system into group 1 (n = 25) patients with stages 0, I, and II, and group 2 (n = 25) of advanced patients with stages III and IV. In addition to control group (n = 20) of healthy adults. Flow cytometry was used to investigate Treg frequency in bone marrow (BM) proportional to CD4+ T cell and to assess leukemic cell expression of CD200 and LAIR-1. Also, <em>in-silico</em> database analysis was performed to identify study markers interactions for future personalized target therapy.</div></div><div><h3>Results</h3><div>Comparison between CLL groups 1 and 2 revealed increased leukemic cell percentage expressing LAIR-1 (<em>p</em> = 0.021) in group 1. Group 2 showed significant increase in frequency of Treg in BM and leukemic cells expressing CD200. There was a strong positive correlation between frequency of Treg and leukemic cells expressing CD200 (r = 0.669, <em>p</em> = 0.000). On the other hand, there was a negative correlation between frequency of Treg and leukemic cell expressing LAIR-1 (r = −0.342, <em>p</em> = 0.015). ROC curve analysis revealed that increased frequency of leukemic cells expressing CD200 yielded sensitivity (SN) and specificity (SP) of 96 % and 84 %, respectively in detecting CLL progression, with an AUC of 0.965. Leukemic cell percentages expressing LAIR-1 yielded a lower SN (75 %), SP (72 %), with an AUC of 0.688.</div></div><div><h3>Conclusion</h3><div>Treg frequency in BM was significantly increased in CLL advanced stages according to Rai classification. Leukemic cells CD200 and LAIR-1 expression were differently associated with Treg frequency. Increased CD200 expressions on leukemic cells can be considered a sensitive and specific biomarker in detecting CLL progression. As demonstrated by the <em>in-silico</em> research, CD200 blockade targeting may offer therapeutic benefits for CLL treatment through Treg suppression.</div></div>","PeriodicalId":19916,"journal":{"name":"Pathology, research and practice","volume":"263 ","pages":"Article 155669"},"PeriodicalIF":2.9,"publicationDate":"2024-10-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142538743","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}
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