Pub Date : 2024-11-08DOI: 10.1016/j.prp.2024.155704
Carlos A. Rubio , Michael Vieth , Corinna Lang-Schwarz
Tubular adenomas (TA) are the most frequent of all colorectal adenomas. Current definitions of TA do not include the phenotype of the dysplastic crypts. We report a novel crypt phenotype characterized by dysplastic crypts with lateral buddings (DCLB). Out of the 309 TA, 25.9 % (n=80) exhibited DCLBs: 12.5 % (n=10) had one DCLB focus/TA, 15.0 % (n=12) had two DCLB foci/TA, 27.5 % (n=22) three had three DCLB foci/TA, 30.0 % (n=24) had four DCLB foci/TA, 12.5 % (n=10) had five DCLB foci/TA, and in the remaining 2.5 %n (n=2) most fields of view at x4 showed DCLB foci. DCLB in TA were generated independently of TA size or degree of dysplasia. The presence of DCLB was not influenced by age, gender or localization. In conclusion, a novel histologic phenotype of TA is showcased. DCLBs are integral components in some of the TA. Recently, another novel dysplastic crypt phenotype in TA characterized by dysplastic crypts in tandem was reported. The awareness that different dysplastic crypt phenotypes thrive in TA might open a new vista on research aimed to learn more about why the most prevalent of all colorectal adenomas thrive with a low capacity to invade the host.
{"title":"Dysplastic crypts with lateral buddings in tubular adenomas","authors":"Carlos A. Rubio , Michael Vieth , Corinna Lang-Schwarz","doi":"10.1016/j.prp.2024.155704","DOIUrl":"10.1016/j.prp.2024.155704","url":null,"abstract":"<div><div>Tubular adenomas (TA) are the most frequent of all colorectal adenomas. Current definitions of TA do not include the phenotype of the dysplastic crypts. We report a novel crypt phenotype characterized by dysplastic crypts with lateral buddings (DCLB). Out of the 309 TA, 25.9 % (n=80) exhibited DCLBs: 12.5 % (n=10) had one DCLB focus/TA, 15.0 % (n=12) had two DCLB foci/TA, 27.5 % (n=22) three had three DCLB foci/TA, 30.0 % (n=24) had four DCLB foci/TA, 12.5 % (n=10) had five DCLB foci/TA, and in the remaining 2.5 %n (n=2) most fields of view at x4 showed DCLB foci. DCLB in TA were generated independently of TA size or degree of dysplasia. The presence of DCLB was not influenced by age, gender or localization. In conclusion, a novel histologic phenotype of TA is showcased. DCLBs are integral components in some of the TA. Recently, another novel dysplastic crypt phenotype in TA characterized by dysplastic crypts in tandem was reported. The awareness that different dysplastic crypt phenotypes thrive in TA might open a new vista on research aimed to learn more about why the most prevalent of all colorectal adenomas thrive with a low capacity to invade the host.</div></div>","PeriodicalId":19916,"journal":{"name":"Pathology, research and practice","volume":"264 ","pages":"Article 155704"},"PeriodicalIF":2.9,"publicationDate":"2024-11-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142625776","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 : 2024-11-08DOI: 10.1016/j.prp.2024.155719
Yaming Hao , Zhixiong Long , Xiufeng Gu
Background
Epithelial-mesenchymal transition (EMT) is an essential process for the metastasis of multiple malignancies, including hepatocellular carcinoma (HCC). Farrerol is a plant-derived flavonoid and has significant pharmacological effects. However, the anticancer activities of farrerol have not been fully elucidated. Here, we investigated the effects of farrerol on HCC progression.
Methods
The potential of farrerol to prevent HCC cell migration and invasiveness was evaluated by wound healing and transwll matrix assays. Immunoblotting, immunofluorescence, and qPCR were used to detect the levels of EMT-related proteins. Transforming growth factor beta (TGF-β) (10 ng/ml) was used to stimulate HCC cells, followed by measurement of cell migration, invasiveness, and the EMT. TGF-β1/Smads signaling was examined by immunoblotting. A xenograft mouse model was used to assess the anticancer efficacy of farrerol in vivo. The expression levels of EMT- and angiogenesis-related proteins in xenograft tumors were evaluated by immunoblotting or immunohistochemistry.
Results
We found that farrerol blocked HCC cell migration and invasiveness. Farrerol upregulated E-cadherin levels and reduced N-cadherin and vimentin levels. Farrerol also downreuglated the expression levels of EMT-related transcription factors including slug, snail, twist, and zeb1. Furthermore, farrerol suppressed TGF-β-stimulated migration, invasiveness, and the EMT in HCC cells. The phosphorylation of Smad 2/3 induced by TGF-β was inhibited by farrerol. Importantly, farrerol suppressed HCC growth and the EMT in vivo. Farrerol also inhibited tumor angiogenesis by inhibiting hypoxia-inducible factor-1 alpha (HIF-1α) and vascular endothelial growth factor (VEGF) in vivo.
Conclusion
Overall, farrerol suppresss HCC by inhibiting migration, invasiveness, the EMT, and angiogenesis, implying that farrerol could be a promising antimetastasis agent for HCC.
{"title":"Farrerol suppresses epithelial-mesenchymal transition in hepatocellular carcinoma via suppression of TGF-β1/Smad2/3 signaling","authors":"Yaming Hao , Zhixiong Long , Xiufeng Gu","doi":"10.1016/j.prp.2024.155719","DOIUrl":"10.1016/j.prp.2024.155719","url":null,"abstract":"<div><h3>Background</h3><div>Epithelial-mesenchymal transition (EMT) is an essential process for the metastasis of multiple malignancies, including hepatocellular carcinoma (HCC). Farrerol is a plant-derived flavonoid and has significant pharmacological effects. However, the anticancer activities of farrerol have not been fully elucidated. Here, we investigated the effects of farrerol on HCC progression.</div></div><div><h3>Methods</h3><div>The potential of farrerol to prevent HCC cell migration and invasiveness was evaluated by wound healing and transwll matrix assays. Immunoblotting, immunofluorescence, and qPCR were used to detect the levels of EMT-related proteins. Transforming growth factor beta (TGF-β) (10 ng/ml) was used to stimulate HCC cells, followed by measurement of cell migration, invasiveness, and the EMT. TGF-β1/Smads signaling was examined by immunoblotting. A xenograft mouse model was used to assess the anticancer efficacy of farrerol <em>in vivo</em>. The expression levels of EMT- and angiogenesis-related proteins in xenograft tumors were evaluated by immunoblotting or immunohistochemistry.</div></div><div><h3>Results</h3><div>We found that farrerol blocked HCC cell migration and invasiveness. Farrerol upregulated E-cadherin levels and reduced N-cadherin and vimentin levels. Farrerol also downreuglated the expression levels of EMT-related transcription factors including slug, snail, twist, and zeb1. Furthermore, farrerol suppressed TGF-β-stimulated migration, invasiveness, and the EMT in HCC cells. The phosphorylation of Smad 2/3 induced by TGF-β was inhibited by farrerol. Importantly, farrerol suppressed HCC growth and the EMT <em>in vivo</em>. Farrerol also inhibited tumor angiogenesis by inhibiting hypoxia-inducible factor-1 alpha (HIF-1α) and vascular endothelial growth factor (VEGF) <em>in vivo</em>.</div></div><div><h3>Conclusion</h3><div>Overall, farrerol suppresss HCC by inhibiting migration, invasiveness, the EMT, and angiogenesis, implying that farrerol could be a promising antimetastasis agent for HCC.</div></div>","PeriodicalId":19916,"journal":{"name":"Pathology, research and practice","volume":"264 ","pages":"Article 155719"},"PeriodicalIF":2.9,"publicationDate":"2024-11-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142625788","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 : 2024-11-08DOI: 10.1016/j.prp.2024.155713
Francisco Revert-Ros , Ignacio Ventura , Jesús A. Prieto-Ruiz , Eduardo Giner-Moreno , Ángela Pérez-Cervera , Judith Pérez-Rojas , Fernando Revert , José Miguel Hernández-Andreu
Liver cancer, particularly hepatocellular carcinoma (HCC), is a major global health challenge, largely associated with cirrhosis caused by various factors. Prognosis is often guided by molecular and histological classifications. In this study, expression of Polyribonucleotide Phosphorylase (PNPT1) in HCC was investigated to better understand its role in tumor behavior and patient outcomes. The expression of the corresponding protein PNPase was assessed in HCC tissue samples using immunohistochemistry, while RNA-seq data from The Cancer Genome Atlas (TCGA) were analyzed via OncoDB. Additionally, PNPT1 silencing in HepG2 cells was followed by gene and protein expression analysis. The results revealed that PNPT1 is overexpressed in HCC tumors, particularly in those expressing E-cadherin. Notably, silencing PNPT1 in HepG2 cells triggered a shift towards a mesenchymal phenotype. In HCC tissues, PNPT1 expression was linked to markers of epithelial phenotype, oxidative stress, and poor prognosis, especially in non-viral HCC cases. These findings suggest that PNPase may play a crucial role in the progression of well-differentiated HCC tumors, serving as a poor prognostic biomarker.
{"title":"Polyribonucleotide phosphorylase is overexpressed in hepatocellular cancer, promoting epithelial phenotype maintenance and tumor progression","authors":"Francisco Revert-Ros , Ignacio Ventura , Jesús A. Prieto-Ruiz , Eduardo Giner-Moreno , Ángela Pérez-Cervera , Judith Pérez-Rojas , Fernando Revert , José Miguel Hernández-Andreu","doi":"10.1016/j.prp.2024.155713","DOIUrl":"10.1016/j.prp.2024.155713","url":null,"abstract":"<div><div>Liver cancer, particularly hepatocellular carcinoma (HCC), is a major global health challenge, largely associated with cirrhosis caused by various factors. Prognosis is often guided by molecular and histological classifications. In this study, expression of Polyribonucleotide Phosphorylase (PNPT1) in HCC was investigated to better understand its role in tumor behavior and patient outcomes. The expression of the corresponding protein PNPase was assessed in HCC tissue samples using immunohistochemistry, while RNA-seq data from The Cancer Genome Atlas (TCGA) were analyzed via OncoDB. Additionally, PNPT1 silencing in HepG2 cells was followed by gene and protein expression analysis. The results revealed that PNPT1 is overexpressed in HCC tumors, particularly in those expressing E-cadherin. Notably, silencing PNPT1 in HepG2 cells triggered a shift towards a mesenchymal phenotype. In HCC tissues, PNPT1 expression was linked to markers of epithelial phenotype, oxidative stress, and poor prognosis, especially in non-viral HCC cases. These findings suggest that PNPase may play a crucial role in the progression of well-differentiated HCC tumors, serving as a poor prognostic biomarker.</div></div>","PeriodicalId":19916,"journal":{"name":"Pathology, research and practice","volume":"264 ","pages":"Article 155713"},"PeriodicalIF":2.9,"publicationDate":"2024-11-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142625810","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}
Glioma is a highly lethal brain cancer in humans. Despite advancements in treatment, the prognosis for patients remains unfavorable. Epigenetic factors, along with their interactions and non-coding RNAs (ncRNAs), are crucial in glioma cells' development and aggressive characteristics. MicroRNAs (miRNAs) are a class of small non-coding RNAs (ncRNAs) that modulate the expression of various genes by binding to target mRNA molecules. They play a critical role in regulating essential biological mechanisms such as cell proliferation and differentiation, cell cycle, and apoptosis. MiR-146a/miR-146b is a significant and prevalent miRNA whose expression alterations are linked to various pathological changes in cancer cells, as well as the modulation of several cellular signaling pathways, including NF-κB, TGF-β, PI3K/Akt, and Notch-1. Scientists may identify novel targets in clinical settings by studying the complicated link between Mir-146a/mir-146b, drug resistance, molecular pathways, and pharmacological intervention in gliomas. Additionally, its interactions with other ncRNAs, such as circular RNA and long non-coding RNA, contribute to the pathogenesis of glioma. As well as miR-146 holds potential as both a diagnostic and therapeutic biomarker for patients with this condition. In the current review, we investigate the significance of miRNAs in the context of glioma, with a particular focus on the critical role of Mir-146a/mir-146b in glioma tumors. Additionally, we examined the clinical relevance of this miRNA, highlighting its potential implications for diagnosis and treatment.
{"title":"MicroRNA-146 family: Molecular insights into their role in regulation of signaling pathways in glioma progression","authors":"Sepideh Mirzaei , Fatemeh Ahangari , Fatemeh Faramarzi , Seyedeh Mahdieh Khoshnazar , Fateme Zare Khormizi , Mahboobeh Aghagolzadeh , Mohammadreza Rostami , Vahid Asghariazar , Mina Alimohammadi , Payman Rahimzadeh , Najma Farahani","doi":"10.1016/j.prp.2024.155707","DOIUrl":"10.1016/j.prp.2024.155707","url":null,"abstract":"<div><div>Glioma is a highly lethal brain cancer in humans. Despite advancements in treatment, the prognosis for patients remains unfavorable. Epigenetic factors, along with their interactions and non-coding RNAs (ncRNAs), are crucial in glioma cells' development and aggressive characteristics. MicroRNAs (miRNAs) are a class of small non-coding RNAs (ncRNAs) that modulate the expression of various genes by binding to target mRNA molecules. They play a critical role in regulating essential biological mechanisms such as cell proliferation and differentiation, cell cycle, and apoptosis. MiR-146a/miR-146b is a significant and prevalent miRNA whose expression alterations are linked to various pathological changes in cancer cells, as well as the modulation of several cellular signaling pathways, including NF-κB, TGF-β, PI3K/Akt, and Notch-1. Scientists may identify novel targets in clinical settings by studying the complicated link between Mir-146a/mir-146b, drug resistance, molecular pathways, and pharmacological intervention in gliomas. Additionally, its interactions with other ncRNAs, such as circular RNA and long non-coding RNA, contribute to the pathogenesis of glioma. As well as miR-146 holds potential as both a diagnostic and therapeutic biomarker for patients with this condition. In the current review, we investigate the significance of miRNAs in the context of glioma, with a particular focus on the critical role of Mir-146a/mir-146b in glioma tumors. Additionally, we examined the clinical relevance of this miRNA, highlighting its potential implications for diagnosis and treatment.</div></div>","PeriodicalId":19916,"journal":{"name":"Pathology, research and practice","volume":"264 ","pages":"Article 155707"},"PeriodicalIF":2.9,"publicationDate":"2024-11-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142625799","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}
Diabetic foot ulcers (DFUs) are a microvascular complication that affects almost 21 % of the diabetic population. DFUs are characterized by lower limb abnormalities, chronic inflammation, and a heightened hypoxic environment. The challenge of healing these chronic wounds arises from impaired blood flow, neuropathy, and dysregulated cell death processes. The pathogenesis of DFUs involves intricate mechanisms of programmed cell death (PCD) in different cell types, which include keratinocytes, fibroblasts, and endothelial cells. The modes of cell death comprise apoptosis, autophagy, ferroptosis, pyroptosis, and NETosis, each defined by distinct biochemical hallmarks. These diverse mechanisms contribute to tissue injury by inducing neutrophil extracellular traps and generating cellular stressors like endoplasmic reticulum stress, oxidative stress, and inflammation. Through a comprehensive review of experimental studies identified from literature databases, this review synthesizes current knowledge on the critical signaling cascades implicated in programmed cell death within the context of diabetic foot ulcer pathology.
{"title":"Pathological insights into cell death pathways in diabetic wound healing","authors":"Kannan Harithpriya, Srinivasan Kaussikaa, Srikanth Kavyashree, AVS Geetha, Kunka Mohanram Ramkumar","doi":"10.1016/j.prp.2024.155715","DOIUrl":"10.1016/j.prp.2024.155715","url":null,"abstract":"<div><div>Diabetic foot ulcers (DFUs) are a microvascular complication that affects almost 21 % of the diabetic population. DFUs are characterized by lower limb abnormalities, chronic inflammation, and a heightened hypoxic environment. The challenge of healing these chronic wounds arises from impaired blood flow, neuropathy, and dysregulated cell death processes. The pathogenesis of DFUs involves intricate mechanisms of programmed cell death (PCD) in different cell types, which include keratinocytes, fibroblasts, and endothelial cells. The modes of cell death comprise apoptosis, autophagy, ferroptosis, pyroptosis, and NETosis, each defined by distinct biochemical hallmarks. These diverse mechanisms contribute to tissue injury by inducing neutrophil extracellular traps and generating cellular stressors like endoplasmic reticulum stress, oxidative stress, and inflammation. Through a comprehensive review of experimental studies identified from literature databases, this review synthesizes current knowledge on the critical signaling cascades implicated in programmed cell death within the context of diabetic foot ulcer pathology.</div></div>","PeriodicalId":19916,"journal":{"name":"Pathology, research and practice","volume":"264 ","pages":"Article 155715"},"PeriodicalIF":2.9,"publicationDate":"2024-11-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142648729","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 : 2024-11-07DOI: 10.1016/j.prp.2024.155716
Shirin Azizidoost , Mohadeseh Sheykhi-Sabzehpoush , Mahrokh Abouali Gale Dari , Małgorzata Józkowiak , Julia Niebora , Dominika Domagała , Krzysztof Data , Piotr Dzięgiel , Paul Mozdziak , Maryam Farzaneh , Bartosz Kempisty
Breast cancer is a prevalent and aggressive disease characterized by high metastasis, recurrence, and mortality rates. While cisplatin is an effective chemotherapy drug, its use is limited by its toxic effects on the body. Despite advancements in therapeutic strategies, the therapeutic response is often unsatisfactory due to drug resistance, leading to poor prognosis. Recent studies have shown that cisplatin interacts with long non-coding RNAs (lncRNAs) and accelerates the development of resistance in tumor cells to therapy. This interaction highlights the complex mechanisms involved in the response of cancer cells to chemotherapy. Several lncRNAs have been identified as key players in mediating cisplatin resistance in breast cancer. These lncRNAs include SNHG15, HULC, HCP5, MT1JP, LncMat2B, DLX6-ASL, Linc00665, CARMN, and Lnc-EinRP44–3:6. These lncRNAs have been shown to target microRNAs and mRNAs and modulate the expression of genes involved in cisplatin resistance, which is important in treating breast cancer.
{"title":"LncRNA-mediated regulation of cisplatin response in breast cancer","authors":"Shirin Azizidoost , Mohadeseh Sheykhi-Sabzehpoush , Mahrokh Abouali Gale Dari , Małgorzata Józkowiak , Julia Niebora , Dominika Domagała , Krzysztof Data , Piotr Dzięgiel , Paul Mozdziak , Maryam Farzaneh , Bartosz Kempisty","doi":"10.1016/j.prp.2024.155716","DOIUrl":"10.1016/j.prp.2024.155716","url":null,"abstract":"<div><div>Breast cancer is a prevalent and aggressive disease characterized by high metastasis, recurrence, and mortality rates. While cisplatin is an effective chemotherapy drug, its use is limited by its toxic effects on the body. Despite advancements in therapeutic strategies, the therapeutic response is often unsatisfactory due to drug resistance, leading to poor prognosis. Recent studies have shown that cisplatin interacts with long non-coding RNAs (lncRNAs) and accelerates the development of resistance in tumor cells to therapy. This interaction highlights the complex mechanisms involved in the response of cancer cells to chemotherapy. Several lncRNAs have been identified as key players in mediating cisplatin resistance in breast cancer. These lncRNAs include SNHG15, HULC, HCP5, MT1JP, LncMat2B, DLX6-ASL, Linc00665, CARMN, and Lnc-EinRP44–3:6. These lncRNAs have been shown to target microRNAs and mRNAs and modulate the expression of genes involved in cisplatin resistance, which is important in treating breast cancer.</div></div>","PeriodicalId":19916,"journal":{"name":"Pathology, research and practice","volume":"264 ","pages":"Article 155716"},"PeriodicalIF":2.9,"publicationDate":"2024-11-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142625795","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 : 2024-11-06DOI: 10.1016/j.prp.2024.155712
Mattia Dominoni , Frediano Socrate Inzani , Andrea Gritti , Marianna Francesca Pasquali , Matteo Mauri , Asaf Eldar , Barbara Gardella
Background and aims
Cervical intraepithelial neoplasia(CIN)and persistent high-risk human papillomavirus (HR-HPV)infection are associated with impaired local cellular immunity; however, the molecular mechanisms underlying these processes are not well understood. The involvement of the programmed death 1/programmed death 1 ligand (PD-1/PD-L1) pathway in the downregulation of T cell function has been demonstrated recently and it is believed to have a role in the onset and persistence of HPV infection and cervical cancer. Our aim is to analyze the role of PD-L1 in the CIN to identify a possible biomarker of HSIL (CIN2+) progression and persistence.
Methods
We performed a systematic review, considering papers published from January 2000 to May 2024, according to PRISMA guideline, in order to obtain a Comprehensive analysis of the literature regarding the role of PD-L1 expression in CIN. The most important medical databases, such as PubMed, Cochrane Database of narrative Reviews, EMBASE, and Web of Science, were consulted. Articles documenting the characteristics and clinical implications of PDL-1 expression in cervical dysplasia were given special consideration.
Results
HR-HPV lesions show a positive expression of PD-L1, which level increase from LSIL (CIN1) to cervical cancer. The expression of PD-L1 in both mononuclear and cervical epithelial cells also exhibit an elevation with the progression of the lesions followed by a overexpression of pro-inflammatory cytokines IFN-γ and IL-12 and downregulation of anti-inflammatory cytokine IL-10 indicating a role of PD-1/PD-L1 pathway in cervical immunity.
Conclusions
PD-1 and PD-L1 may serve as diagnostic and prognostic biomarkers as well as valuable tools in immunotherapy for treating cancer and CIN.
{"title":"The role of programmed death-ligand 1 (PDL-1) in high-grade cervical intraepithelial neoplasia (CIN2+) development and recurrence: A systematic review of literature about HPV-CIN2+-PDL-1 axis","authors":"Mattia Dominoni , Frediano Socrate Inzani , Andrea Gritti , Marianna Francesca Pasquali , Matteo Mauri , Asaf Eldar , Barbara Gardella","doi":"10.1016/j.prp.2024.155712","DOIUrl":"10.1016/j.prp.2024.155712","url":null,"abstract":"<div><h3>Background and aims</h3><div>Cervical intraepithelial neoplasia(CIN)and persistent high-risk human papillomavirus (HR-HPV)infection are associated with impaired local cellular immunity; however, the molecular mechanisms underlying these processes are not well understood. The involvement of the programmed death 1/programmed death 1 ligand (PD-1/PD-L1) pathway in the downregulation of T cell function has been demonstrated recently and it is believed to have a role in the onset and persistence of HPV infection and cervical cancer. Our aim is to analyze the role of PD-L1 in the CIN to identify a possible biomarker of HSIL (CIN2+) progression and persistence.</div></div><div><h3>Methods</h3><div>We performed a systematic review, considering papers published from January 2000 to May 2024, according to PRISMA guideline, in order to obtain a Comprehensive analysis of the literature regarding the role of PD-L1 expression in CIN. The most important medical databases, such as PubMed, Cochrane Database of narrative Reviews, EMBASE, and Web of Science, were consulted. Articles documenting the characteristics and clinical implications of PDL-1 expression in cervical dysplasia were given special consideration.</div></div><div><h3>Results</h3><div>HR-HPV lesions show a positive expression of PD-L1, which level increase from LSIL (CIN1) to cervical cancer. The expression of PD-L1 in both mononuclear and cervical epithelial cells also exhibit an elevation with the progression of the lesions followed by a overexpression of pro-inflammatory cytokines IFN-γ and IL-12 and downregulation of anti-inflammatory cytokine IL-10 indicating a role of PD-1/PD-L1 pathway in cervical immunity.</div></div><div><h3>Conclusions</h3><div>PD-1 and PD-L1 may serve as diagnostic and prognostic biomarkers as well as valuable tools in immunotherapy for treating cancer and CIN.</div></div>","PeriodicalId":19916,"journal":{"name":"Pathology, research and practice","volume":"264 ","pages":"Article 155712"},"PeriodicalIF":2.9,"publicationDate":"2024-11-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142625817","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}
This research aimed to analyze alterations in microRNA expression in the diseases POF (Premature Ovarian Failure), PCOS (Polycystic Ovarian Syndrome), and ovarian cancer in order to understand the molecular changes associated with these conditions. The findings could potentially be utilized for diagnostic, therapeutic, predictive, and preventive purposes. Furthermore, the impact and role of microRNAs in each ailment, along with their functional pathways, were elucidated and examined.
Methods
In this study, the genes involved in the disease were studied, and then the miRNAs that targeted these genes were evaluated, and finally the signaling and functional pathways of each of the miRNAs were assessed. In this process, genetic databases and previous studies were carefully assessed.
Results
miRNAs are short nucleotide sequences that belong to the category of non-coding RNAs. They play a crucial role in various physiological activities, including cell division, growth, differentiation, and cell death (necrosis and apoptosis), miRNAs are involved in various physiological processes Such alterations are common in various diseases, including cancer. miRNAs are involved in various physiological processes, such as folliculogenesis and steroidogenesis, as well as in pathological conditions such as POF, PCOS, and ovarian cancer. They have powerful regulatory effects and controlling the most activities of normal and pathological cells. While microRNAs (miRNAs) play a significant role in normal ovarian functions, there are reports of their expression changes in PCOS, ovarian cancer, and POF.
Conclusions
miRNAs have been found to exert significant influence on both physiological and pathological cellular processes. Understanding the dynamic patterns of miRNA alterations can provide valuable insights for researchers and therapists, enabling them to utilize these biomarkers effectively in diagnostic, therapeutic, and preventive applications.
{"title":"miRNAs in ovarian disorders: Small but strong cast","authors":"Parsa Tafazoli , Hanieh Motahari Rad , Mehri Mashayekhi , Seyedeh Fatemeh Siadat , Rouhollah Fathi","doi":"10.1016/j.prp.2024.155709","DOIUrl":"10.1016/j.prp.2024.155709","url":null,"abstract":"<div><h3>Purpose</h3><div>This research aimed to analyze alterations in microRNA expression in the diseases POF (Premature Ovarian Failure), PCOS (Polycystic Ovarian Syndrome), and ovarian cancer in order to understand the molecular changes associated with these conditions. The findings could potentially be utilized for diagnostic, therapeutic, predictive, and preventive purposes. Furthermore, the impact and role of microRNAs in each ailment, along with their functional pathways, were elucidated and examined.</div></div><div><h3>Methods</h3><div>In this study, the genes involved in the disease were studied, and then the miRNAs that targeted these genes were evaluated, and finally the signaling and functional pathways of each of the miRNAs were assessed. In this process, genetic databases and previous studies were carefully assessed.</div></div><div><h3>Results</h3><div>miRNAs are short nucleotide sequences that belong to the category of non-coding RNAs. They play a crucial role in various physiological activities, including cell division, growth, differentiation, and cell death (necrosis and apoptosis), miRNAs are involved in various physiological processes Such alterations are common in various diseases, including cancer. miRNAs are involved in various physiological processes, such as folliculogenesis and steroidogenesis, as well as in pathological conditions such as POF, PCOS, and ovarian cancer. They have powerful regulatory effects and controlling the most activities of normal and pathological cells. While microRNAs (miRNAs) play a significant role in normal ovarian functions, there are reports of their expression changes in PCOS, ovarian cancer, and POF.</div></div><div><h3>Conclusions</h3><div>miRNAs have been found to exert significant influence on both physiological and pathological cellular processes. Understanding the dynamic patterns of miRNA alterations can provide valuable insights for researchers and therapists, enabling them to utilize these biomarkers effectively in diagnostic, therapeutic, and preventive applications.</div></div>","PeriodicalId":19916,"journal":{"name":"Pathology, research and practice","volume":"264 ","pages":"Article 155709"},"PeriodicalIF":2.9,"publicationDate":"2024-11-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142625801","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}
Oligodendrogliomas (ODGs) are neuroepithelial tumors that need personalized treatment plans because of their unique molecular and histological features. Non-coding RNAs form an epigenetic class of molecules that act as the first steps in gene regulation. They consist of microRNAs, long non-coding RNAs, and circular RNAs. These molecules significantly participate in ODG pathogenesis by regulating ODG initiation, progression, and treatment response. This review is designated to analyze the literature and describe the genomic profile of ODGs, the complex actions of ncRNAs in ODGs pathogenesis and treatment, and their roles as appropriate biomarkers and as one of the precision mechanisms action targets, such as antisense oligonucleotides, small interfering RNAs, gene therapy vectors, peptide nucleic acids, and small molecule inhibitors. Overall, ncRNAs considerably alter the pathological spectrum of ODGs by influencing fundamental processes in tumor biology. Applying ncRNAs in a clinical context exhibits promise for enhanced diagnosis and individualized therapeutic interventions. Nevertheless, the delivery efficacy and potential adverse “off-target” sequels retain the main obstacles undermining clinical potential. Continuous research and technological advancements in ncRNAs offer new insights and promising prospects for revolutionizing oligodendroglioma care, leading to better, personalized treatment outcomes.
{"title":"Non-coding RNAs (ncRNAs) as therapeutic targets and biomarkers in oligodendroglioma","authors":"Mohd. Imran , Abdulmalik Saleh Alfawaz Altamimi , M.Arockia Babu , Kavita Goyal , Irwanjot Kaur , Sachin Kumar , Naveen Sharma , M.Ravi Kumar , Fadiyah Jadid Alanazi , Abeer Nuwayfi Alruwaili , Nouf Afit Aldhafeeri , Haider Ali","doi":"10.1016/j.prp.2024.155708","DOIUrl":"10.1016/j.prp.2024.155708","url":null,"abstract":"<div><div>Oligodendrogliomas (ODGs) are neuroepithelial tumors that need personalized treatment plans because of their unique molecular and histological features. Non-coding RNAs form an epigenetic class of molecules that act as the first steps in gene regulation. They consist of microRNAs, long non-coding RNAs, and circular RNAs. These molecules significantly participate in ODG pathogenesis by regulating ODG initiation, progression, and treatment response. This review is designated to analyze the literature and describe the genomic profile of ODGs, the complex actions of ncRNAs in ODGs pathogenesis and treatment, and their roles as appropriate biomarkers and as one of the precision mechanisms action targets, such as antisense oligonucleotides, small interfering RNAs, gene therapy vectors, peptide nucleic acids, and small molecule inhibitors. Overall, ncRNAs considerably alter the pathological spectrum of ODGs by influencing fundamental processes in tumor biology. Applying ncRNAs in a clinical context exhibits promise for enhanced diagnosis and individualized therapeutic interventions. Nevertheless, the delivery efficacy and potential adverse “off-target” sequels retain the main obstacles undermining clinical potential. Continuous research and technological advancements in ncRNAs offer new insights and promising prospects for revolutionizing oligodendroglioma care, leading to better, personalized treatment outcomes.</div></div>","PeriodicalId":19916,"journal":{"name":"Pathology, research and practice","volume":"264 ","pages":"Article 155708"},"PeriodicalIF":2.9,"publicationDate":"2024-11-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142625803","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 leading cause of cancer-related death among female patients is breast cancer. Among all the types of breast cancer, triple-negative breast cancer (TNBC) is the most dangerous molecular subtype of breast cancer characterized by the absence of estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER-2) expression. Since there is no particular therapeutic strategy for TNBC that has been shown to worsen the disease prognosis, 3D models are superior to 2D models as a predictive tool for drug discovery because they more accurately reflect the in vivo biological components of humans. Importantly, all 3D models struggle to gather many high-quality tumour cells from clinical tumours. Physicians may not get huge tumour tissues from patients, and clinical tumours may have necrosis, fat, and blood vessel components. Therefore, there is an immediate need to find an efficient method to consistently and quickly produce a large number of homogeneous tumour models for individual treatment without cell wastage. Microfluidic technologies, which are specifically engineered to manipulate small quantities of fluids, have been utilised to produce particles for drug delivery applications. This development is indicative of a recent trend, as it provides the ability to regulate particle size and material composition. This review focuses on the topic of tumor-on-a-chip, microfluidic chip manufacturing, and drug screening for triple-negative breast cancer. Particular emphasis is placed on cancer biomarker diagnostics, 3D preclinical model development, and treatment strategies for triple-negative breast cancer.
{"title":"Recent advances in microfluidic chip technologies for applications as preclinical testing devices for the diagnosis and treatment of triple-negative breast cancers","authors":"Thirunavukkarasu Palaniyandi , Maddaly Ravi , Asha Sivaji , Gomathy Baskar , Sandhiya Viswanathan , Mugip Rahaman Abdul Wahab , Hemapreethi Surendran , Sandhya Nedunchezhian , Irfan Ahmad , Vajid Nettoor Veettil","doi":"10.1016/j.prp.2024.155711","DOIUrl":"10.1016/j.prp.2024.155711","url":null,"abstract":"<div><div>The leading cause of cancer-related death among female patients is breast cancer. Among all the types of breast cancer, triple-negative breast cancer (TNBC) is the most dangerous molecular subtype of breast cancer characterized by the absence of estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER-2) expression. Since there is no particular therapeutic strategy for TNBC that has been shown to worsen the disease prognosis, 3D models are superior to 2D models as a predictive tool for drug discovery because they more accurately reflect the <em>in vivo</em> biological components of humans. Importantly, all 3D models struggle to gather many high-quality tumour cells from clinical tumours. Physicians may not get huge tumour tissues from patients, and clinical tumours may have necrosis, fat, and blood vessel components. Therefore, there is an immediate need to find an efficient method to consistently and quickly produce a large number of homogeneous tumour models for individual treatment without cell wastage. Microfluidic technologies, which are specifically engineered to manipulate small quantities of fluids, have been utilised to produce particles for drug delivery applications. This development is indicative of a recent trend, as it provides the ability to regulate particle size and material composition. This review focuses on the topic of tumor-on-a-chip, microfluidic chip manufacturing, and drug screening for triple-negative breast cancer. Particular emphasis is placed on cancer biomarker diagnostics, 3D preclinical model development, and treatment strategies for triple-negative breast cancer.</div></div>","PeriodicalId":19916,"journal":{"name":"Pathology, research and practice","volume":"264 ","pages":"Article 155711"},"PeriodicalIF":2.9,"publicationDate":"2024-11-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142625815","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}
扫码关注我们
求助内容：
应助结果提醒方式：
京公网安备 11010802042870号