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Sufentanil attenuates renal ischemia-reperfusion injury via the lncRNA KCNQ1OT1/miR-211-5p/HMGB1 axis. 舒芬太尼通过lncRNA kcnq10t1 /miR-211-5p/HMGB1轴减轻肾缺血再灌注损伤。
IF 2.9 4区 医学 Q2 PATHOLOGY Pub Date : 2024-12-30 DOI: 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.

炎症反应是缺血再灌注损伤(ischemia-reperfusion injury, IRI)最重要的病理变化之一。舒芬太尼通过减少炎症反应对IRI具有保护作用。本研究旨在探讨舒芬太尼对肾IRI (RIRI)的保护作用及其可能机制。在本研究中,舒芬太尼抑制缺氧/再氧化(H/R)处理的HK-2增殖和凋亡,降低cleaved caspase3,增加b细胞淋巴瘤2 (Bcl-2)蛋白表达,抑制活性氧(ROS)的产生,减少炎症因子的分泌。此外,舒芬太尼在H/ r处理的HK-2细胞中抑制KCNQ1重叠转录本1 (kcnq10ot1)的表达,pcdna - kcnq10ot1逆转了舒芬太尼的细胞保护作用,而miR-211-5p抑制剂逆转了pcdna - kcnq10ot1的作用。此外,miR-211-5p靶向高迁移率组1 (HMGB1)的3'UTR, HMGB1逆转了miR-211-5p模拟物或舒芬太尼对细胞增殖、凋亡、氧化应激和炎症的抑制作用。机制研究表明,舒芬太尼减轻H/ r处理的HK-2细胞损伤是通过抑制toll样受体4 (TLR4)/髓样分化因子88 (MyD88)/核因子κB (NF-κB)通路介导的。在肾缺血再灌注(I/R)大鼠中,舒芬太尼抑制kcnq10t1、HMGB1和cleaved caspase3表达,促进miR-211-5p表达,减轻肾组织炎症浸润。
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引用次数: 0
Relation of squamous differentiation in endometrioid carcinoma with MELF pattern to a high ratio of lymph node metastasis. MELF型子宫内膜样癌鳞状分化与淋巴结转移率高的关系。
IF 2.9 4区 医学 Q2 PATHOLOGY Pub Date : 2024-12-30 DOI: 10.1016/j.prp.2024.155804
Shinichiro Tahara, Kazuaki Sato, Kansuke Kido, Eiichi Morii

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.

子宫内膜样癌(EC)在子宫体癌中已知的组织学模式之一是MELF(微囊、细长和碎片化)。MELF与淋巴血管侵袭和淋巴结转移有关。除了MELF外,我们还知道EC中经常发生鳞状分化(SD)。已知SD对EC的淋巴结转移频率无显著差异。然而,先前没有关于MELF与SD之间关系的报道。在这项研究中,我们使用一种针对CK5的抗体来研究SD在MELF中的存在。我们检查了28例伴有MELF模式的EC,其中15例出现SD。并观察淋巴结转移与SD的关系。28例患者中27例行淋巴结清扫术。其中12例出现淋巴结转移。伴有SD的EC的淋巴结转移率(64.3 %,14例中9例)明显高于无SD的EC(23.1 %,13例中3例)。在这项研究中,我们首次发现了SD与MELF之间的关联,并且MELF合并SD与高淋巴结转移率相关。认识到MELF合并SD具有侵袭性,淋巴结转移率高,具有临床意义。
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引用次数: 0
Malignant transformation of the mature ovarian teratoma into early-stage ovarian adenocarcinoma: A case report with literature review. 成熟卵巢畸胎瘤向早期卵巢腺癌恶性转化1例并文献复习。
IF 2.9 4区 医学 Q2 PATHOLOGY Pub Date : 2024-12-28 DOI: 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.

虽然成熟卵巢畸胎瘤(MOT)是世界上最常见的良性肿瘤之一,但其恶性转化是罕见的。这篇文章提出了一个47岁的妇女,手术的紧急原因,由于一个巨大的卵巢肿瘤疼痛,显示术前没有恶性肿瘤的迹象。令人惊讶的是,病理报告显示MOT与发展为内生乳头状瘤的早期卵巢腺癌共存。有趣的是,BRCA2外显子18 (NM_000059.3)的一个先前未分类的突变变体:c。8167 G>A (p.Asp2723Asn)在卵巢腺癌中检测到。我们对MOT与早期卵巢腺癌恶性转化相关的临床病理特征进行了简要的文献回顾。
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引用次数: 0
Solid pseudopapillary neoplasm of the pancreas in a 54-year-old woman: A case report and the literature analysis. 54岁女性胰腺实性假乳头状肿瘤1例报告及文献分析。
IF 2.9 4区 医学 Q2 PATHOLOGY Pub Date : 2024-12-27 DOI: 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.

实性假乳头状肿瘤是一种罕见的胰腺肿瘤,多见于年轻女性。本病例为54岁白人女性SPN病例,突出了非典型发病年龄,并为肿瘤的临床和组织病理学多样性提供了新的见解。病例报告:54岁女性,既往无明显病史,以上腹部不适和虚弱表现。初步诊断影像学提示胰腺肿瘤。患者行开腹切除胰胃吻合术。组织病理学分析显示一个2 cm的肿瘤,具有混合生长模式-实体,小梁,微囊性和假乳头状-不同的细胞类型,包括空泡细胞,嗜酸性细胞和透明细胞。尽管表现出恶性特征,如邻近胰腺实质局部浸润,淋巴血管和神经周围浸润,出血区域和局灶性核异型,但未观察到转移。免疫组化证实SPN伴β-catenin异常表达。肿瘤被成功切除,患者顺利恢复,不需要额外的治疗。60个月随访未见复发。结论:该病例强调了老年患者中SPN的罕见性及其组织病理表现的可变性。SPNs的不同生长模式和显微恶性特征在组织学评估和病理报告中应予以考虑,因为它们可能对确定肿瘤预后潜力和治疗策略很重要。需要进一步的研究来规范病理评估,提高对SPN复发和治疗的认识。
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引用次数: 0
Automate the process of formalin-fixed paraffin-embedded blocks storage in the pathology laboratory: A proof of concept study. 自动化过程福尔马林固定石蜡包埋块存储在病理实验室:概念研究的证明。
IF 2.9 4区 医学 Q2 PATHOLOGY Pub Date : 2024-12-26 DOI: 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.

由于福尔马林固定石蜡包埋(FFPE)块的生产不断增加,加上空间和环境存储条件不足,病理学实验室目前在档案管理方面面临着显著的问题。手动存储和检索过程进一步增加了人为错误的可能性,浪费了专业人员的工作时间,并最终延长了报告签署的周转时间。在目前的工作中,我们概述了在摩德纳大学病理服务自动化档案发展的基本策略。拟议的项目依赖于机械机械臂与机架和货架以完全跟踪的方式进行控制交互,并由与当地实验室信息系统(LIS)的集成驱动。这种自动化存档旨在显著提高实验室专业人员的时间节省,并在病理诊断之前和之后标准化FFPE样本的存储。该系统的模块化适合不同机构的需求和空间,由于与LIS的连接和与人工智能算法的集成,在存档方面开辟了新的策略。
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引用次数: 0
Novel therapeutic approaches targeting cancer stem cells: Unveiling new frontiers in breast cancer treatment. 针对癌症干细胞的新治疗方法:揭示乳腺癌治疗的新领域。
IF 2.9 4区 医学 Q2 PATHOLOGY Pub Date : 2024-12-26 DOI: 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.

乳腺癌仍然是癌症妇女死亡的主要原因。本文深入探讨了乳腺癌与癌症干细胞(CSCs)之间的复杂关系,重点介绍了其鉴定和分离的先进方法。关键的分离技术,如乳腺球形成试验,表面标记鉴定,侧群体试验,醛脱氢酶试验,严格检查。此外,本文还分析了csc特异性分子信号通路,重点关注CD44/CD24、Nanog和Oct4等可操作靶点。靶向治疗和小分子破坏这些途径的潜力被探索。此外,本文还重点介绍了针对CSCs的免疫治疗策略,重点介绍了耐药机制和精准医学的关键作用。该研究探讨了精准医学如何通过靶向特定的CSC生物标志物来提高治疗效果。这项综合分析为乳腺癌治疗的最新进展和新兴策略提供了见解,并指出了未来的治疗创新。
{"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}
引用次数: 0
Mast cell proteases and metastasis. 肥大细胞蛋白酶和转移。
IF 2.9 4区 医学 Q2 PATHOLOGY Pub Date : 2024-12-26 DOI: 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.

肥大细胞在ige介导的过敏反应中发挥着多种作用。这些细胞分泌促炎和抗炎剂,从保护性免疫细胞转变为促炎细胞,能够影响包括肿瘤在内的不同病理状况的进展,在其中它们发挥抗肿瘤和促肿瘤的作用。在此背景下,本文分析了肥大细胞来源的蛋白酶在肿瘤进展中发挥的潜在作用,更具体地说,在驱动转移过程中,以及抑制这些细胞的激活可能有助于抑制癌症扩散的潜在治疗方法。
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引用次数: 0
IL-17E facilitates cell proliferation and epithelial-mesenchymal transition in A549 NSCLC cells by regulating the NF-κB pathway. IL-17E通过调节NF-κB通路促进A549 NSCLC细胞增殖和上皮-间质转化。
IF 2.9 4区 医学 Q2 PATHOLOGY Pub Date : 2024-12-25 DOI: 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}
引用次数: 0
C4d immunostaining facilitates differentiation of pemphigoid nodularis from prurigo nodularis. C4d免疫染色有助于类天疱疮结节与结节性痒疹的鉴别。
IF 2.9 4区 医学 Q2 PATHOLOGY Pub Date : 2024-12-25 DOI: 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.

类天疱疮结节和结节性痒疹具有相似的临床病理特征,难以区分。酶联免疫吸附试验(ELISA)和直接/间接免疫荧光可以支持类天疱疮结节的诊断,但有时显示相互矛盾的结果或不可用。我们的目的是建立一个实用的方法来鉴别类天疱疮结节和结节性痒疹。对15例类天疱疮结节和25例结节性痒疹分别进行ELISA、直接免疫荧光(DIF)和C3d、C4d免疫组化(IHC)检测。类天疱疮结节性患者中C3d和C4d IHC结果分别为8/15(53.3 %)和13/15(86.7 %)阳性,25例结节性痒疹患者中C3d和C4d结果均为阴性。C4d IHC和抗bp180 ELISA的灵敏度最高(86.7 %),阴性预测值为92.6 %,而C3d IHC的灵敏度最低(53.3% %),阴性预测值为78.1 %。因此,抗bp180 ELISA和C4d免疫组化是诊断类天疱疮结节最敏感的标志物。联合DIF, ELISA和C4d免疫组化是鉴别类天疱疮结节和结节性痒疹的一个相对准确的调查小组。
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引用次数: 0
Whole genome and transcriptome analysis of pancreatic acinar cell carcinoma elucidates mechanisms of homologous recombination deficiency and unravels novel relevant fusion events. 胰腺腺泡细胞癌的全基因组和转录组分析阐明了同源重组缺陷的机制,揭示了新的相关融合事件。
IF 2.9 4区 医学 Q2 PATHOLOGY Pub Date : 2024-12-24 DOI: 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.

胰腺腺泡细胞癌(PACC)是一种罕见的胰腺肿瘤,具有异质性的临床病程,除根治性手术外,治疗方案有限。我们提出了一项全面的研究,包括来自3名转移性PACC患者的7个肿瘤样本的全基因组和RNA测序,以进一步描绘其基因组景观和潜在的治疗意义。我们的研究结果揭示了同源重组缺陷(HRD)在携带致病性种系BRCA1/2和FANCL突变的患者中的明显特征,表明对多(adp -核糖)聚合酶1 (PARP)抑制剂的有利反应与延长的无病间隔。此外,我们首先描述了PACC的结构变异,包括BRCA1::TRIM47融合和另一种影响FANCC的变异,这两种事件都与HRD相关,我们还发现了丝裂原活化蛋白激酶(MAPK)途径的改变,包括RAF1重复以及新的BRAF::SORBS2和MAP7D2::SND1基因融合,为治疗提供了潜在的靶点。我们的研究强调了PACC基因组和转录组谱分析的重要性,有助于指导个性化治疗策略以改善患者预后。
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