Pub Date : 2024-12-30DOI: 10.1016/j.prp.2024.155807
Meihua Lin, Xi Wu, Shuang Zhang
Inflammation is one of the most significant pathological changes in ischemia-reperfusion injury (IRI). Sufentanil has protective effects on IRI by reducing inflammatory responses. This study aimed to investigate the protective effects and possible mechanisms of sufentanil on renal IRI (RIRI). In this study, sufentanil inhibited hypoxia/reoxygenation (H/R)-treated HK-2 proliferation and apoptosis, decreased cleaved caspase3 and increased B-cell Lymphoma 2 (Bcl-2) protein expression, inhibited reactive oxygen species (ROS) generation, and reduced inflammatory factor secretion. Moreover, sufentanil inhibited KCNQ1 overlapping transcript 1 (KCNQ1OT1) expression in H/R-treated HK-2 cells, and pcDNA-KCNQ1OT1 reversed the cell protective effects of sufentanil, whereas miR-211-5p inhibitor here reversed the effects of pcDNA-KCNQ1OT1. Furthermore, miR-211-5p targets the 3'UTR of high mobility group box1 (HMGB1), and HMGB1 reversed the inhibitory effects of miR-211-5p mimic or sufentanil on cell proliferation, apoptosis, oxidative stress, and inflammation. Mechanistic studies revealed that sufentanil alleviated H/R-treated HK-2 cell injury was mediated by inhibiting the toll like receptor 4 (TLR4)/ myeloid differentiation factor 88 (MyD88)/ nuclear factor kappa B (NF-κB) pathway. In renal ischemia-reperfusion (I/R) rats, sufentanil inhibited KCNQ1OT1, HMGB1 and cleaved caspase3 expression, promoted miR-211-5p expression and alleviated inflammatory infiltration in renal tissues.
{"title":"Sufentanil attenuates renal ischemia-reperfusion injury via the lncRNA KCNQ1OT1/miR-211-5p/HMGB1 axis.","authors":"Meihua Lin, Xi Wu, Shuang Zhang","doi":"10.1016/j.prp.2024.155807","DOIUrl":"https://doi.org/10.1016/j.prp.2024.155807","url":null,"abstract":"<p><p>Inflammation is one of the most significant pathological changes in ischemia-reperfusion injury (IRI). Sufentanil has protective effects on IRI by reducing inflammatory responses. This study aimed to investigate the protective effects and possible mechanisms of sufentanil on renal IRI (RIRI). In this study, sufentanil inhibited hypoxia/reoxygenation (H/R)-treated HK-2 proliferation and apoptosis, decreased cleaved caspase3 and increased B-cell Lymphoma 2 (Bcl-2) protein expression, inhibited reactive oxygen species (ROS) generation, and reduced inflammatory factor secretion. Moreover, sufentanil inhibited KCNQ1 overlapping transcript 1 (KCNQ1OT1) expression in H/R-treated HK-2 cells, and pcDNA-KCNQ1OT1 reversed the cell protective effects of sufentanil, whereas miR-211-5p inhibitor here reversed the effects of pcDNA-KCNQ1OT1. Furthermore, miR-211-5p targets the 3'UTR of high mobility group box1 (HMGB1), and HMGB1 reversed the inhibitory effects of miR-211-5p mimic or sufentanil on cell proliferation, apoptosis, oxidative stress, and inflammation. Mechanistic studies revealed that sufentanil alleviated H/R-treated HK-2 cell injury was mediated by inhibiting the toll like receptor 4 (TLR4)/ myeloid differentiation factor 88 (MyD88)/ nuclear factor kappa B (NF-κB) pathway. In renal ischemia-reperfusion (I/R) rats, sufentanil inhibited KCNQ1OT1, HMGB1 and cleaved caspase3 expression, promoted miR-211-5p expression and alleviated inflammatory infiltration in renal tissues.</p>","PeriodicalId":19916,"journal":{"name":"Pathology, research and practice","volume":"266 ","pages":"155807"},"PeriodicalIF":2.9,"publicationDate":"2024-12-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142971866","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}
One of the known histological patterns of endometrioid carcinoma (EC) in uterine corpus cancer is MELF (microcystic, elongated, and fragmented). MELF is associated with lymphovascular invasion and lymph node metastasis. Besides MELF, it is also known that squamous differentiation (SD) often occurs in EC. SD is known to be no significant difference in the frequency of lymph node metastasis in EC. However, there have been no previous reports on the association between MELF and SD. In this research, we investigated the presence of SD in MELF using an antibody to CK5. We examined 28 cases of EC with MELF pattern, in which 15 cases showed SD. Moreover, the relation of lymph node metastasis to SD was examined. Lymph node dissection was performed in 27 out of 28 cases. Among them, 12 cases showed lymph node metastasis. The ratio of lymph node metastasis was significantly higher in EC with SD (64.3 %, 9 in 14 cases) than EC without SD (23.1 %, 3 in 13 cases). In this study, we first showed the association between SD and MELF and that MELF with SD is associated with a high ratio of lymph node metastasis. It is clinically relevant to recognize that MELF with SD is aggressive with a high ratio of lymph node metastasis.
{"title":"Relation of squamous differentiation in endometrioid carcinoma with MELF pattern to a high ratio of lymph node metastasis.","authors":"Shinichiro Tahara, Kazuaki Sato, Kansuke Kido, Eiichi Morii","doi":"10.1016/j.prp.2024.155804","DOIUrl":"https://doi.org/10.1016/j.prp.2024.155804","url":null,"abstract":"<p><p>One of the known histological patterns of endometrioid carcinoma (EC) in uterine corpus cancer is MELF (microcystic, elongated, and fragmented). MELF is associated with lymphovascular invasion and lymph node metastasis. Besides MELF, it is also known that squamous differentiation (SD) often occurs in EC. SD is known to be no significant difference in the frequency of lymph node metastasis in EC. However, there have been no previous reports on the association between MELF and SD. In this research, we investigated the presence of SD in MELF using an antibody to CK5. We examined 28 cases of EC with MELF pattern, in which 15 cases showed SD. Moreover, the relation of lymph node metastasis to SD was examined. Lymph node dissection was performed in 27 out of 28 cases. Among them, 12 cases showed lymph node metastasis. The ratio of lymph node metastasis was significantly higher in EC with SD (64.3 %, 9 in 14 cases) than EC without SD (23.1 %, 3 in 13 cases). In this study, we first showed the association between SD and MELF and that MELF with SD is associated with a high ratio of lymph node metastasis. It is clinically relevant to recognize that MELF with SD is aggressive with a high ratio of lymph node metastasis.</p>","PeriodicalId":19916,"journal":{"name":"Pathology, research and practice","volume":"266 ","pages":"155804"},"PeriodicalIF":2.9,"publicationDate":"2024-12-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142927718","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 : 2024-12-28DOI: 10.1016/j.prp.2024.155793
Marta Joanna Monist, Iwona Paśnik, Marek Semczuk, Andrzej Semczuk
Although mature ovarian teratoma (MOT) is one of the most commonly detected benign tumours worldwide, its malignant transformation is rare. This article presents a case of a 47-year-old woman, operated on for emergency reasons due to a giant painful ovarian tumour, showing preoperatively no signs of malignancy. Surprisingly, a pathological report showed MOT coexisting with an early-stage ovarian adenocarcinoma developing as an endophytic papilloma. Interestingly, a previously unclassified mutation variant in exon 18 of BRCA2 (NM_000059.3):c. 8167 G>A (p.Asp2723Asn) was detected in ovarian adenocarcinoma. A brief literature review has been presented discussing the clinicopathological features of MOT being associated with malignant transformation into an early-stage ovarian adenocarcinoma.
{"title":"Malignant transformation of the mature ovarian teratoma into early-stage ovarian adenocarcinoma: A case report with literature review.","authors":"Marta Joanna Monist, Iwona Paśnik, Marek Semczuk, Andrzej Semczuk","doi":"10.1016/j.prp.2024.155793","DOIUrl":"https://doi.org/10.1016/j.prp.2024.155793","url":null,"abstract":"<p><p>Although mature ovarian teratoma (MOT) is one of the most commonly detected benign tumours worldwide, its malignant transformation is rare. This article presents a case of a 47-year-old woman, operated on for emergency reasons due to a giant painful ovarian tumour, showing preoperatively no signs of malignancy. Surprisingly, a pathological report showed MOT coexisting with an early-stage ovarian adenocarcinoma developing as an endophytic papilloma. Interestingly, a previously unclassified mutation variant in exon 18 of BRCA2 (NM_000059.3):c. 8167 G>A (p.Asp2723Asn) was detected in ovarian adenocarcinoma. A brief literature review has been presented discussing the clinicopathological features of MOT being associated with malignant transformation into an early-stage ovarian adenocarcinoma.</p>","PeriodicalId":19916,"journal":{"name":"Pathology, research and practice","volume":"266 ","pages":"155793"},"PeriodicalIF":2.9,"publicationDate":"2024-12-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142927716","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 : 2024-12-27DOI: 10.1016/j.prp.2024.155799
Nina Bondarenko, Alina Bilokha, Oleksii Bielosludtsev, Petro Hrytsenko, Ihor Shponka
Introduction: Solid pseudopapillary neoplasm (SPN) is a rare pancreatic tumor typically occurring in young females. This case presents an instance of SPN in a 54-year-old Caucasian female, highlighting atypical age of onset and providing new insights into the tumor's clinical and histopathological diversity.
Case report: A 54-year-old female with no significant past medical history presented with upper abdominal discomfort and weakness. Initial diagnostic imaging suggested a pancreatic tumor. The patient underwent laparotomic resection with pancreatic-gastric anastomosis. Histopathological analysis revealed a 2 cm tumor with mixed growth patterns - solid, trabecular, microcystic, and pseudopapillary - with varying cell types including vacuolated, eosinophilic, and clear cells. Despite showing malignant features such as local invasion in the adjacent pancreatic parenchyma, lymphovascular and perineural invasion, areas of haemorrhage, and focal nuclear atypia, no metastasis was observed. Immunohistochemistry confirmed the diagnosis of SPN with aberrant β-catenin expression. The tumor was resected successfully, and the patient had an uneventful recovery with no additional therapy required. A 60-month follow-up showed no recurrence.
Conclusion: This case underscores the rarity of SPN in older patients and the variability in its histopathological presentation. Different growth patterns and microscopic malignant features of SPNs should be taken into account during histological evaluation and pathological reporting, as they may be important for determination of tumor prognostic potential and treatment strategies. Further research is needed to standardize pathologic evaluations and improve understanding of SPN recurrence and management.
{"title":"Solid pseudopapillary neoplasm of the pancreas in a 54-year-old woman: A case report and the literature analysis.","authors":"Nina Bondarenko, Alina Bilokha, Oleksii Bielosludtsev, Petro Hrytsenko, Ihor Shponka","doi":"10.1016/j.prp.2024.155799","DOIUrl":"https://doi.org/10.1016/j.prp.2024.155799","url":null,"abstract":"<p><strong>Introduction: </strong>Solid pseudopapillary neoplasm (SPN) is a rare pancreatic tumor typically occurring in young females. This case presents an instance of SPN in a 54-year-old Caucasian female, highlighting atypical age of onset and providing new insights into the tumor's clinical and histopathological diversity.</p><p><strong>Case report: </strong>A 54-year-old female with no significant past medical history presented with upper abdominal discomfort and weakness. Initial diagnostic imaging suggested a pancreatic tumor. The patient underwent laparotomic resection with pancreatic-gastric anastomosis. Histopathological analysis revealed a 2 cm tumor with mixed growth patterns - solid, trabecular, microcystic, and pseudopapillary - with varying cell types including vacuolated, eosinophilic, and clear cells. Despite showing malignant features such as local invasion in the adjacent pancreatic parenchyma, lymphovascular and perineural invasion, areas of haemorrhage, and focal nuclear atypia, no metastasis was observed. Immunohistochemistry confirmed the diagnosis of SPN with aberrant β-catenin expression. The tumor was resected successfully, and the patient had an uneventful recovery with no additional therapy required. A 60-month follow-up showed no recurrence.</p><p><strong>Conclusion: </strong>This case underscores the rarity of SPN in older patients and the variability in its histopathological presentation. Different growth patterns and microscopic malignant features of SPNs should be taken into account during histological evaluation and pathological reporting, as they may be important for determination of tumor prognostic potential and treatment strategies. Further research is needed to standardize pathologic evaluations and improve understanding of SPN recurrence and management.</p>","PeriodicalId":19916,"journal":{"name":"Pathology, research and practice","volume":"266 ","pages":"155799"},"PeriodicalIF":2.9,"publicationDate":"2024-12-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142927736","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 : 2024-12-26DOI: 10.1016/j.prp.2024.155802
Albino Eccher, Stefano Marletta, Fabio Pagni, Vincenzo L'Imperio, Federico Piacentini, Massimo Dominici, Alberto Cavazza, Carmine Pinto, Matteo Brunelli, Michelangelo Fiorentino, Umberto Malapelle, Marco Maria Baron, Guido Martignoni, Angelo Paolo Dei Tos
Pathology laboratories are currently facing remarkable issues in the management of their archives due to the ongoing increase in the production of formalin-fixed paraffin-embedded (FFPE) blocks, which is often coupled with inadequate spatial and environmental storing conditions. The manual process of storage and retrieving further increases the likelihood of human-based mistakes, wastes professionals' working time, and, ultimately, widens reports signing turn-around times. In the present work, we outline the strategies underlying the development of an automated archive at the pathology services of the University of Modena. The proposed project relies on the controlled interaction of a mechanic robotic arm with racks and shelves in a fully traced manner, driven by the integration with the local laboratory information system (LIS). This automated archive aims to significantly improve the time-saving of laboratory professionals and standardize the storage of FFPE samples both before and after the pathology diagnosis is rendered. The system's modularity suits the needs and spaces of the different institutions, opening novel strategies in archiving thanks to its connection with the LIS and integration with artificial intelligence algorithms.
{"title":"Automate the process of formalin-fixed paraffin-embedded blocks storage in the pathology laboratory: A proof of concept study.","authors":"Albino Eccher, Stefano Marletta, Fabio Pagni, Vincenzo L'Imperio, Federico Piacentini, Massimo Dominici, Alberto Cavazza, Carmine Pinto, Matteo Brunelli, Michelangelo Fiorentino, Umberto Malapelle, Marco Maria Baron, Guido Martignoni, Angelo Paolo Dei Tos","doi":"10.1016/j.prp.2024.155802","DOIUrl":"https://doi.org/10.1016/j.prp.2024.155802","url":null,"abstract":"<p><p>Pathology laboratories are currently facing remarkable issues in the management of their archives due to the ongoing increase in the production of formalin-fixed paraffin-embedded (FFPE) blocks, which is often coupled with inadequate spatial and environmental storing conditions. The manual process of storage and retrieving further increases the likelihood of human-based mistakes, wastes professionals' working time, and, ultimately, widens reports signing turn-around times. In the present work, we outline the strategies underlying the development of an automated archive at the pathology services of the University of Modena. The proposed project relies on the controlled interaction of a mechanic robotic arm with racks and shelves in a fully traced manner, driven by the integration with the local laboratory information system (LIS). This automated archive aims to significantly improve the time-saving of laboratory professionals and standardize the storage of FFPE samples both before and after the pathology diagnosis is rendered. The system's modularity suits the needs and spaces of the different institutions, opening novel strategies in archiving thanks to its connection with the LIS and integration with artificial intelligence algorithms.</p>","PeriodicalId":19916,"journal":{"name":"Pathology, research and practice","volume":"266 ","pages":"155802"},"PeriodicalIF":2.9,"publicationDate":"2024-12-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142927713","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 : 2024-12-26DOI: 10.1016/j.prp.2024.155800
Deeptha T C, Nabeela N K, Charumathi Pushparaj, Arul Narayanasamy, Paulpandi Manickam, Saranya Thiruvenkataswamy, Ramya Sennimalai
Breast cancer remains the leading cause of mortality among women with cancer. This article delves into the intricate relationship between breast cancer and cancer stem cells (CSCs), emphasizing advanced methods for their identification and isolation. The key isolation techniques, such as the mammosphere formation assay, surface marker identification, Side Population assay, and Aldehyde Dehydrogenase assay, are critically examined. Furthermore, the review analyzes CSC-specific molecular signaling pathways, focusing on actionable targets like CD44/CD24, Nanog, and Oct4. The potential of targeted therapies and small molecules that disrupt these pathways is explored. Additionally, the review highlights immunotherapy strategies against CSCs, focusing on resistance mechanisms and the critical role of precision medicine. The study investigates how precision medicine enhances therapeutic outcomes by targeting specific CSC biomarkers. This comprehensive analysis offers insights into recent advancements and emerging strategies in breast cancer treatment, pointing toward future therapeutic innovations.
{"title":"Novel therapeutic approaches targeting cancer stem cells: Unveiling new frontiers in breast cancer treatment.","authors":"Deeptha T C, Nabeela N K, Charumathi Pushparaj, Arul Narayanasamy, Paulpandi Manickam, Saranya Thiruvenkataswamy, Ramya Sennimalai","doi":"10.1016/j.prp.2024.155800","DOIUrl":"https://doi.org/10.1016/j.prp.2024.155800","url":null,"abstract":"<p><p>Breast cancer remains the leading cause of mortality among women with cancer. This article delves into the intricate relationship between breast cancer and cancer stem cells (CSCs), emphasizing advanced methods for their identification and isolation. The key isolation techniques, such as the mammosphere formation assay, surface marker identification, Side Population assay, and Aldehyde Dehydrogenase assay, are critically examined. Furthermore, the review analyzes CSC-specific molecular signaling pathways, focusing on actionable targets like CD44/CD24, Nanog, and Oct4. The potential of targeted therapies and small molecules that disrupt these pathways is explored. Additionally, the review highlights immunotherapy strategies against CSCs, focusing on resistance mechanisms and the critical role of precision medicine. The study investigates how precision medicine enhances therapeutic outcomes by targeting specific CSC biomarkers. This comprehensive analysis offers insights into recent advancements and emerging strategies in breast cancer treatment, pointing toward future therapeutic innovations.</p>","PeriodicalId":19916,"journal":{"name":"Pathology, research and practice","volume":"266 ","pages":"155800"},"PeriodicalIF":2.9,"publicationDate":"2024-12-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142984372","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 : 2024-12-26DOI: 10.1016/j.prp.2024.155801
Domenico Ribatti
Mast cells exert multiple roles beyond their classical role in IgE-mediated allergic reactions. These cells secrete pro-inflammatory and anti-inflammatory agents and change from protective immune cells to pro-inflammatory cells, capable of influencing the progression of different pathological conditions, including tumors, in which they exert anti-tumorigenic and pro-tumorigenic roles. In this context, this article analyzes the potential role played by mast cell-derived proteases in tumor progression and more specifically in driving metastatic process and the potential therapeutic approaches that inhibiting the activation of these cells could help faith cancer spreading.
{"title":"Mast cell proteases and metastasis.","authors":"Domenico Ribatti","doi":"10.1016/j.prp.2024.155801","DOIUrl":"https://doi.org/10.1016/j.prp.2024.155801","url":null,"abstract":"<p><p>Mast cells exert multiple roles beyond their classical role in IgE-mediated allergic reactions. These cells secrete pro-inflammatory and anti-inflammatory agents and change from protective immune cells to pro-inflammatory cells, capable of influencing the progression of different pathological conditions, including tumors, in which they exert anti-tumorigenic and pro-tumorigenic roles. In this context, this article analyzes the potential role played by mast cell-derived proteases in tumor progression and more specifically in driving metastatic process and the potential therapeutic approaches that inhibiting the activation of these cells could help faith cancer spreading.</p>","PeriodicalId":19916,"journal":{"name":"Pathology, research and practice","volume":"266 ","pages":"155801"},"PeriodicalIF":2.9,"publicationDate":"2024-12-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142927717","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 : 2024-12-25DOI: 10.1016/j.prp.2024.155792
Chun Li, Ying Zhao, Chengyuan He, Xingxiang Wang, Qiaotong Ren, Xiaodong Gai, Hefei Wang
Objective: Interleukin-17 E (IL-17E) is a pro-inflammatory cytokine that participates in the inflammatory response and tumorigenesis. However, the function of IL-17E in non-small cell lung cancer (NSCLC) remains largely unknown.
Methods: The clinical value of IL-17E was determined by immunohistochemistry (IHC) in 75 cases of NSCLC tissues. Furthermore, A549 cells were added with recombinant human IL-17E (rhIL-17E) or transfected with IL-17E siRNAs to evaluate the impact on cell proliferation, apoptosis, and epithelial-mesenchymal transition (EMT), as well as explore the link between IL-17E and the NF-κB pathway. Experimental techniques include CCK-8, EdU, colony formation, RT-qPCR, western blotting, flow cytometry, wound-healing, transwell and immunofluorescence assay.
Results: IL-17E levels was elevated in NSCLC tissues and cells, which was related to higher TNM staging, positive lymph node metastasis and decreased tumor differentiation degree. Exogenous recombinant human IL-17E (rhIL-17E) treatment promoted cell proliferation, reduced cell apoptosis, and increased the level of Bcl-2/BAX. Moreover, it enhanced cell migration, invasion, EMT and phosphorylation levels of NF-κB p65. Inversely, knocking down endogenous IL-17E in A549 cells had the opposite effect. Blocking the NF-κB pathway with BAY-117082 reduced IL-17E expression and reversed the malignant effects induced by IL-17E on A549 cells.
Conclusion: IL-17E facilitates NSCLC progression by promoting cell proliferation and EMT via the NF-κB pathway. IL-17E could serve as a potential strategy for NSCLC treatment.
目的:白细胞介素-17 E (IL-17E)是一种参与炎症反应和肿瘤发生的促炎细胞因子。然而,IL-17E在非小细胞肺癌(NSCLC)中的功能在很大程度上仍然未知。方法:采用免疫组化(IHC)方法检测75例非小细胞肺癌组织中IL-17E的临床价值。此外,我们在A549细胞中添加重组人IL-17E (rhIL-17E)或转染IL-17E sirna,以评估IL-17E对细胞增殖、凋亡和上皮-间质转化(EMT)的影响,并探讨IL-17E与NF-κB通路之间的联系。实验技术包括CCK-8、EdU、菌落形成、RT-qPCR、western blotting、流式细胞术、创面愈合、transwell和免疫荧光试验。结果:IL-17E水平在NSCLC组织和细胞中升高,与TNM分期升高、淋巴结转移阳性、肿瘤分化程度降低有关。外源性重组人IL-17E (rhIL-17E)处理促进细胞增殖,减少细胞凋亡,提高Bcl-2/BAX水平。此外,它还能增强细胞迁移、侵袭、EMT和NF-κB p65的磷酸化水平。相反,在A549细胞中敲低内源性IL-17E具有相反的效果。用BAY-117082阻断NF-κB通路可降低IL-17E的表达,逆转IL-17E对A549细胞的恶性作用。结论:IL-17E通过NF-κB通路促进细胞增殖和EMT,从而促进NSCLC的进展。IL-17E可作为非小细胞肺癌治疗的潜在策略。
{"title":"IL-17E facilitates cell proliferation and epithelial-mesenchymal transition in A549 NSCLC cells by regulating the NF-κB pathway.","authors":"Chun Li, Ying Zhao, Chengyuan He, Xingxiang Wang, Qiaotong Ren, Xiaodong Gai, Hefei Wang","doi":"10.1016/j.prp.2024.155792","DOIUrl":"https://doi.org/10.1016/j.prp.2024.155792","url":null,"abstract":"<p><strong>Objective: </strong>Interleukin-17 E (IL-17E) is a pro-inflammatory cytokine that participates in the inflammatory response and tumorigenesis. However, the function of IL-17E in non-small cell lung cancer (NSCLC) remains largely unknown.</p><p><strong>Methods: </strong>The clinical value of IL-17E was determined by immunohistochemistry (IHC) in 75 cases of NSCLC tissues. Furthermore, A549 cells were added with recombinant human IL-17E (rhIL-17E) or transfected with IL-17E siRNAs to evaluate the impact on cell proliferation, apoptosis, and epithelial-mesenchymal transition (EMT), as well as explore the link between IL-17E and the NF-κB pathway. Experimental techniques include CCK-8, EdU, colony formation, RT-qPCR, western blotting, flow cytometry, wound-healing, transwell and immunofluorescence assay.</p><p><strong>Results: </strong>IL-17E levels was elevated in NSCLC tissues and cells, which was related to higher TNM staging, positive lymph node metastasis and decreased tumor differentiation degree. Exogenous recombinant human IL-17E (rhIL-17E) treatment promoted cell proliferation, reduced cell apoptosis, and increased the level of Bcl-2/BAX. Moreover, it enhanced cell migration, invasion, EMT and phosphorylation levels of NF-κB p65. Inversely, knocking down endogenous IL-17E in A549 cells had the opposite effect. Blocking the NF-κB pathway with BAY-117082 reduced IL-17E expression and reversed the malignant effects induced by IL-17E on A549 cells.</p><p><strong>Conclusion: </strong>IL-17E facilitates NSCLC progression by promoting cell proliferation and EMT via the NF-κB pathway. IL-17E could serve as a potential strategy for NSCLC treatment.</p>","PeriodicalId":19916,"journal":{"name":"Pathology, research and practice","volume":"266 ","pages":"155792"},"PeriodicalIF":2.9,"publicationDate":"2024-12-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142927715","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 : 2024-12-25DOI: 10.1016/j.prp.2024.155762
Fang Liu, Hui Fang, Weigang Zhang, Yuan Yuan, Zhe Yang, Lei Wang, Gang Wang
Pemphigoid nodularis and prurigo nodularis have similar clinicopathological features and are difficult to distinguish. Enzyme-linked immunosorbent assays (ELISA) and direct/indirect immunofluorescence can support the diagnosis of pemphigoid nodularis, but sometimes show contradictory results or are unavailable. We aimed to develop a practical method for differentiating between pemphigoid nodularis and prurigo nodularis. We analyzed the results of ELISA, direct immunofluorescence (DIF), and C3d and C4d immunohistochemistry (IHC) in 15 and 25 cases of pemphigoid nodularis and prurigo nodularis, respectively. C3d and C4d IHC results were positive in 8/15 (53.3 %) and 13/15 (86.7 %) patients with pemphigoid nodularis, respectively, and negative in all 25 patients with prurigo nodularis. The highest sensitivity (86.7 %) and negative predictive values (92.6 %) were observed in both C4d IHC and anti-BP180 ELISA, whereas C3d IHC exhibited the lowest sensitivity (53.3 %) and negative predictive values (78.1 %). Therefore, anti-BP180 ELISA and C4d IHC were the most sensitive markers to diagnose pemphigoid nodularis. The combination of DIF, ELISA, and C4d IHC is a relatively accurate panel of investigations for distinguishing pemphigoid nodularis from prurigo nodularis.
{"title":"C4d immunostaining facilitates differentiation of pemphigoid nodularis from prurigo nodularis.","authors":"Fang Liu, Hui Fang, Weigang Zhang, Yuan Yuan, Zhe Yang, Lei Wang, Gang Wang","doi":"10.1016/j.prp.2024.155762","DOIUrl":"https://doi.org/10.1016/j.prp.2024.155762","url":null,"abstract":"<p><p>Pemphigoid nodularis and prurigo nodularis have similar clinicopathological features and are difficult to distinguish. Enzyme-linked immunosorbent assays (ELISA) and direct/indirect immunofluorescence can support the diagnosis of pemphigoid nodularis, but sometimes show contradictory results or are unavailable. We aimed to develop a practical method for differentiating between pemphigoid nodularis and prurigo nodularis. We analyzed the results of ELISA, direct immunofluorescence (DIF), and C3d and C4d immunohistochemistry (IHC) in 15 and 25 cases of pemphigoid nodularis and prurigo nodularis, respectively. C3d and C4d IHC results were positive in 8/15 (53.3 %) and 13/15 (86.7 %) patients with pemphigoid nodularis, respectively, and negative in all 25 patients with prurigo nodularis. The highest sensitivity (86.7 %) and negative predictive values (92.6 %) were observed in both C4d IHC and anti-BP180 ELISA, whereas C3d IHC exhibited the lowest sensitivity (53.3 %) and negative predictive values (78.1 %). Therefore, anti-BP180 ELISA and C4d IHC were the most sensitive markers to diagnose pemphigoid nodularis. The combination of DIF, ELISA, and C4d IHC is a relatively accurate panel of investigations for distinguishing pemphigoid nodularis from prurigo nodularis.</p>","PeriodicalId":19916,"journal":{"name":"Pathology, research and practice","volume":"266 ","pages":"155762"},"PeriodicalIF":2.9,"publicationDate":"2024-12-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142927714","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 : 2024-12-24DOI: 10.1016/j.prp.2024.155798
Jesús Delgado-de la Mora, Majd Al Assaad, Selda Karaaslan, Kevin Hadi, Ahmed Halima, Aditya Deshpande, Jyothi Manohar, Michael Sigouros, Juan S Medina-Martínez, Michael D Lieberman, Andrea Sboner, Elizabeta C Popa, José Jessurun, Olivier Elemento, Allyson J Ocean, Erika Hissong, Juan Miguel Mosquera
Pancreatic acinar cell carcinoma (PACC) is a rare pancreatic tumor with a heterogeneous clinical course and, except for radical surgery, limited treatment options. We present a comprehensive study encompassing whole-genome and RNA sequencing of 7 tumor samples from 3 metastatic PACC patients to further delineate its genomic landscape and potential therapeutic implications. Our findings reveal distinct signatures of homologous recombination deficiency (HRD) in patients harboring pathogenic germline BRCA1/2 and FANCL mutations, demonstrating favorable responses to poly (ADP-ribose) polymerase 1 (PARP) inhibitors with prolonged disease-free intervals. Additionally, we first describe structural variants in PACC, including BRCA1::TRIM47 fusion and another variant impacting FANCC, both events related to HRD, and we also identify alterations in the mitogen-activated protein kinase (MAPK) pathway, including RAF1 duplication as well as novel BRAF::SORBS2 and MAP7D2::SND1 gene fusions, offering potential targets for therapy. Our study underscores the importance of genome and transcriptome-wide profiling of PACC, to help guide personalized treatment strategies to improve patient outcomes.
{"title":"Whole genome and transcriptome analysis of pancreatic acinar cell carcinoma elucidates mechanisms of homologous recombination deficiency and unravels novel relevant fusion events.","authors":"Jesús Delgado-de la Mora, Majd Al Assaad, Selda Karaaslan, Kevin Hadi, Ahmed Halima, Aditya Deshpande, Jyothi Manohar, Michael Sigouros, Juan S Medina-Martínez, Michael D Lieberman, Andrea Sboner, Elizabeta C Popa, José Jessurun, Olivier Elemento, Allyson J Ocean, Erika Hissong, Juan Miguel Mosquera","doi":"10.1016/j.prp.2024.155798","DOIUrl":"10.1016/j.prp.2024.155798","url":null,"abstract":"<p><p>Pancreatic acinar cell carcinoma (PACC) is a rare pancreatic tumor with a heterogeneous clinical course and, except for radical surgery, limited treatment options. We present a comprehensive study encompassing whole-genome and RNA sequencing of 7 tumor samples from 3 metastatic PACC patients to further delineate its genomic landscape and potential therapeutic implications. Our findings reveal distinct signatures of homologous recombination deficiency (HRD) in patients harboring pathogenic germline BRCA1/2 and FANCL mutations, demonstrating favorable responses to poly (ADP-ribose) polymerase 1 (PARP) inhibitors with prolonged disease-free intervals. Additionally, we first describe structural variants in PACC, including BRCA1::TRIM47 fusion and another variant impacting FANCC, both events related to HRD, and we also identify alterations in the mitogen-activated protein kinase (MAPK) pathway, including RAF1 duplication as well as novel BRAF::SORBS2 and MAP7D2::SND1 gene fusions, offering potential targets for therapy. Our study underscores the importance of genome and transcriptome-wide profiling of PACC, to help guide personalized treatment strategies to improve patient outcomes.</p>","PeriodicalId":19916,"journal":{"name":"Pathology, research and practice","volume":"266 ","pages":"155798"},"PeriodicalIF":2.9,"publicationDate":"2024-12-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142896672","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}