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Farrerol suppresses epithelial-mesenchymal transition in hepatocellular carcinoma via suppression of TGF-β1/Smad2/3 signaling 法瑞罗通过抑制 TGF-β1/Smad2/3 信号传导抑制肝细胞癌的上皮-间质转化
IF 2.9 4区 医学 Q2 PATHOLOGY Pub Date : 2024-11-08 DOI: 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.
背景:上皮细胞-间质转化(EMT)是包括肝细胞癌(HCC)在内的多种恶性肿瘤转移的重要过程。远志酚是一种植物黄酮类化合物,具有显著的药理作用。然而,远志酚的抗癌活性尚未完全阐明。在此,我们研究了远志酚对 HCC 进展的影响:方法:通过伤口愈合和转基质试验评估了远志酚防止 HCC 细胞迁移和侵袭的潜力。免疫印迹、免疫荧光和 qPCR 被用来检测 EMT 相关蛋白的水平。用转化生长因子β(TGF-β)(10 ng/ml)刺激 HCC 细胞,然后测量细胞迁移、侵袭性和 EMT。免疫印迹法检测了 TGF-β1/Smads 信号传导。采用异种移植小鼠模型评估法罗洛尔在体内的抗癌效果。免疫印迹法或免疫组化法评估了异种移植瘤中EMT和血管生成相关蛋白的表达水平:结果:我们发现法乐洛尔能阻止 HCC 细胞的迁移和侵袭。结果:我们发现法雷罗能阻断 HCC 细胞的迁移和侵袭性。法雷罗能上调 E-cadherin 水平,降低 N-cadherin 和波形蛋白水平。法罗洛尔还能降低 EMT 相关转录因子(包括 slug、snail、twist 和 zeb1)的表达水平。此外,法罗洛尔还能抑制 TGF-β 刺激的 HCC 细胞迁移、侵袭性和 EMT。法罗洛尔抑制了 TGF-β 诱导的 Smad 2/3 磷酸化。重要的是,法勒洛尔能抑制 HCC 在体内的生长和 EMT。法罗洛尔还通过抑制体内缺氧诱导因子-1α(HIF-1α)和血管内皮生长因子(VEGF)来抑制肿瘤血管生成:总之,远志酚通过抑制迁移、侵袭性、EMT和血管生成来抑制HCC,这意味着远志酚可能是一种很有前途的HCC抗转移剂。
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引用次数: 0
Polyribonucleotide phosphorylase is overexpressed in hepatocellular cancer, promoting epithelial phenotype maintenance and tumor progression 多核苷酸磷酸酶在肝细胞癌中过度表达,促进上皮表型的维持和肿瘤的进展。
IF 2.9 4区 医学 Q2 PATHOLOGY Pub Date : 2024-11-08 DOI: 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.
肝癌,尤其是肝细胞癌(HCC),是全球健康面临的一大挑战,主要与各种因素导致的肝硬化有关。预后通常以分子和组织学分类为指导。本研究调查了多核苷酸磷酸酶(PNPT1)在 HCC 中的表达,以更好地了解其在肿瘤行为和患者预后中的作用。研究采用免疫组化方法评估了 HCC 组织样本中相应蛋白 PNPase 的表达,并通过 OncoDB 分析了癌症基因组图谱(TCGA)中的 RNA-seq 数据。此外,还通过基因和蛋白质表达分析对 HepG2 细胞中的 PNPT1 进行了沉默。结果显示,PNPT1 在 HCC 肿瘤中表达过高,尤其是在表达 E-cadherin 的肿瘤中。值得注意的是,在 HepG2 细胞中沉默 PNPT1 会引发向间充质表型的转变。在 HCC 组织中,PNPT1 的表达与上皮表型、氧化应激和预后不良的标志物有关,尤其是在非病毒性 HCC 病例中。这些研究结果表明,PNPase 在分化良好的 HCC 肿瘤的进展过程中可能起着关键作用,是预后不良的生物标志物。
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引用次数: 0
MicroRNA-146 family: Molecular insights into their role in regulation of signaling pathways in glioma progression MicroRNA-146 家族:从分子角度揭示它们在胶质瘤进展过程中调控信号通路的作用。
IF 2.9 4区 医学 Q2 PATHOLOGY Pub Date : 2024-11-07 DOI: 10.1016/j.prp.2024.155707
Sepideh Mirzaei , Fatemeh Ahangari , Fatemeh Faramarzi , Seyedeh Mahdieh Khoshnazar , Fateme Zare Khormizi , Mahboobeh Aghagolzadeh , Mohammadreza Rostami , Vahid Asghariazar , Mina Alimohammadi , Payman Rahimzadeh , Najma Farahani
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.
胶质瘤是一种致死率极高的人类脑癌。尽管在治疗方面取得了进展,但患者的预后仍然不容乐观。表观遗传因子及其与非编码 RNA(ncRNA)的相互作用对胶质瘤细胞的发展和侵袭特性至关重要。微小RNA(miRNA)是一类小型非编码RNA(ncRNA),通过与目标mRNA分子结合来调节各种基因的表达。它们在调节细胞增殖和分化、细胞周期和细胞凋亡等重要生物机制方面发挥着关键作用。MiR-146a/miR-146b 是一种重要而普遍的 miRNA,其表达改变与癌细胞的各种病理变化以及 NF-κB、TGF-β、PI3K/Akt 和 Notch-1 等多种细胞信号通路的调节有关。科学家们可以通过研究 Mir-146a/mir-146b、胶质瘤的耐药性、分子通路和药物干预之间的复杂联系,确定新的临床靶点。此外,它与其他 ncRNA(如环状 RNA 和长非编码 RNA)之间的相互作用也有助于胶质瘤的发病机制。此外,miR-146 还有可能成为胶质瘤患者的诊断和治疗生物标志物。在本综述中,我们研究了 miRNA 在胶质瘤中的意义,尤其关注 Mir-146a/mir-146b 在胶质瘤肿瘤中的关键作用。此外,我们还研究了这种 miRNA 的临床意义,强调了它对诊断和治疗的潜在影响。
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引用次数: 0
Pathological insights into cell death pathways in diabetic wound healing 糖尿病伤口愈合过程中细胞死亡途径的病理学研究。
IF 2.9 4区 医学 Q2 PATHOLOGY Pub Date : 2024-11-07 DOI: 10.1016/j.prp.2024.155715
Kannan Harithpriya, Srinivasan Kaussikaa, Srikanth Kavyashree, AVS Geetha, Kunka Mohanram Ramkumar
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.
糖尿病足溃疡(DFU)是一种微血管并发症,影响着近 21% 的糖尿病患者。糖尿病足溃疡的特点是下肢异常、慢性炎症和高缺氧环境。血流受阻、神经病变和细胞死亡过程失调是愈合这些慢性伤口的难题。DFUs的发病机制涉及不同细胞类型(包括角质形成细胞、成纤维细胞和内皮细胞)中程序性细胞死亡(PCD)的复杂机制。细胞死亡的模式包括细胞凋亡、自噬、铁跃变、热跃变和NETosis,每种模式都有不同的生化特征。这些不同的机制通过诱导中性粒细胞胞外陷阱和产生细胞应激源(如内质网应激、氧化应激和炎症)造成组织损伤。通过对文献数据库中的实验研究进行全面回顾,本综述综合了目前有关糖尿病足溃疡病理学中程序性细胞死亡所涉及的关键信号级联的知识。
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引用次数: 0
LncRNA-mediated regulation of cisplatin response in breast cancer LncRNA 介导的乳腺癌顺铂反应调控。
IF 2.9 4区 医学 Q2 PATHOLOGY Pub Date : 2024-11-07 DOI: 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.
乳腺癌是一种常见的侵袭性疾病,具有高转移率、高复发率和高死亡率的特点。顺铂是一种有效的化疗药物,但其对人体的毒性作用限制了它的使用。尽管治疗策略不断进步,但由于耐药性的存在,治疗效果往往不尽人意,导致预后不良。最近的研究表明,顺铂与长非编码 RNA(lncRNA)相互作用,加速了肿瘤细胞耐药性的产生。这种相互作用凸显了癌细胞对化疗反应的复杂机制。有几种 lncRNA 已被确定为介导乳腺癌顺铂耐药性的关键因素。这些lncRNA包括SNHG15、HULC、HCP5、MT1JP、LncMat2B、DLX6-ASL、Linc00665、CARMN和Lnc-EinRP44-3:6。这些lncRNAs已被证明以microRNAs和mRNAs为靶标,并调节涉及顺铂耐药性的基因的表达,这对治疗乳腺癌非常重要。
{"title":"LncRNA-mediated regulation of cisplatin response in breast cancer","authors":"Shirin Azizidoost ,&nbsp;Mohadeseh Sheykhi-Sabzehpoush ,&nbsp;Mahrokh Abouali Gale Dari ,&nbsp;Małgorzata Józkowiak ,&nbsp;Julia Niebora ,&nbsp;Dominika Domagała ,&nbsp;Krzysztof Data ,&nbsp;Piotr Dzięgiel ,&nbsp;Paul Mozdziak ,&nbsp;Maryam Farzaneh ,&nbsp;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}
引用次数: 0
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 程序性死亡配体 1 (PDL-1) 在高级别宫颈上皮内瘤变(CIN2+)发展和复发中的作用:关于HPV-CIN2+-PDL-1轴的文献系统综述。
IF 2.9 4区 医学 Q2 PATHOLOGY Pub Date : 2024-11-06 DOI: 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.
背景与目的:宫颈上皮内瘤变(CIN)和高危人乳头瘤病毒(HR-HPV)持续感染与局部细胞免疫功能受损有关;然而,这些过程的分子机制尚不十分清楚。程序性死亡 1/程序性死亡 1 配体(PD-1/PD-L1)通路参与下调 T 细胞功能的作用最近已得到证实,并且被认为在 HPV 感染和宫颈癌的发病和持续存在中发挥作用。我们的目的是分析 PD-L1 在 CIN 中的作用,以确定 HSIL(CIN2+)进展和持续的可能生物标志物:我们根据 PRISMA 指南,对 2000 年 1 月至 2024 年 5 月期间发表的论文进行了系统性综述,以全面分析有关 PD-L1 表达在 CIN 中作用的文献。研究人员查阅了最重要的医学数据库,如 PubMed、Cochrane 叙事性综述数据库、EMBASE 和 Web of Science。特别考虑了记录宫颈发育不良中 PDL-1 表达的特征和临床意义的文章:结果:HR-HPV 病变显示出 PD-L1 的阳性表达,其水平从 LSIL(CIN1)上升到宫颈癌。PD-L1在单核细胞和宫颈上皮细胞中的表达也随着病变的进展而升高,随后促炎细胞因子IFN-γ和IL-12过度表达,抗炎细胞因子IL-10下调,这表明PD-1/PD-L1通路在宫颈免疫中发挥作用:结论:PD-1 和 PD-L1 可作为诊断和预后的生物标志物,也是治疗癌症和 CIN 的免疫疗法的重要工具。
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引用次数: 0
miRNAs in ovarian disorders: Small but strong cast 卵巢疾病中的 miRNAs:小而强
IF 2.9 4区 医学 Q2 PATHOLOGY Pub Date : 2024-11-06 DOI: 10.1016/j.prp.2024.155709
Parsa Tafazoli , Hanieh Motahari Rad , Mehri Mashayekhi , Seyedeh Fatemeh Siadat , Rouhollah Fathi

Purpose

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.
目的:本研究旨在分析微RNA在卵巢早衰(POF)、多囊卵巢综合征(PCOS)和卵巢癌等疾病中的表达变化,以了解与这些疾病相关的分子变化。研究结果可用于诊断、治疗、预测和预防。此外,还阐明并研究了 microRNA 在每种疾病中的影响和作用及其功能通路:在这项研究中,首先研究了与疾病有关的基因,然后评估了针对这些基因的 miRNA,最后评估了每种 miRNA 的信号传导和功能通路。结果:miRNA 是一种短核苷酸序列,属于非编码 RNA。它们在细胞分裂、生长、分化和细胞死亡(坏死和凋亡)等各种生理活动中发挥着至关重要的作用,miRNAs 参与了各种生理过程。 miRNAs 参与了卵泡生成和类固醇生成等各种生理过程,也参与了 POF、PCOS 和卵巢癌等病理情况。它们具有强大的调节作用,控制着正常细胞和病理细胞的大部分活动。结论:研究发现,miRNAs 对细胞的生理和病理过程都有重要影响。了解 miRNA 改变的动态模式可为研究人员和治疗师提供有价值的见解,使他们能有效地利用这些生物标记物进行诊断、治疗和预防。
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引用次数: 0
Non-coding RNAs (ncRNAs) as therapeutic targets and biomarkers in oligodendroglioma 作为少突胶质细胞瘤治疗靶点和生物标志物的非编码 RNA(ncRNA)。
IF 2.9 4区 医学 Q2 PATHOLOGY Pub Date : 2024-11-06 DOI: 10.1016/j.prp.2024.155708
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
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.
少突胶质瘤(ODGs)是一种神经上皮性肿瘤,由于其独特的分子和组织学特征,需要个性化的治疗方案。非编码 RNA 是一类表观遗传分子,是基因调控的第一步。它们由 microRNA、长非编码 RNA 和环状 RNA 组成。这些分子通过调控 ODG 的发生、发展和治疗反应,在很大程度上参与了 ODG 的发病机制。本综述旨在分析文献,描述 ODGs 的基因组概况、ncRNAs 在 ODGs 发病和治疗过程中的复杂作用,以及它们作为适当生物标志物和精准机制作用靶点(如反义寡核苷酸、小干扰 RNAs、基因治疗载体、肽核酸和小分子抑制剂)的作用。总之,ncRNA 通过影响肿瘤生物学的基本过程,大大改变了 ODGs 的病理范围。将 ncRNA 应用于临床有望加强诊断和个体化治疗干预。然而,传递效果和潜在的 "脱靶 "不良后果仍然是影响临床应用潜力的主要障碍。ncRNAs的持续研究和技术进步为少突胶质细胞瘤治疗的革命性变革提供了新的见解和广阔前景,从而带来更好的个性化治疗效果。
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引用次数: 0
Recent advances in microfluidic chip technologies for applications as preclinical testing devices for the diagnosis and treatment of triple-negative breast cancers 微流控芯片技术作为临床前检测设备用于诊断和治疗三阴性乳腺癌的最新进展。
IF 2.9 4区 医学 Q2 PATHOLOGY Pub Date : 2024-11-06 DOI: 10.1016/j.prp.2024.155711
Thirunavukkarasu Palaniyandi , Maddaly Ravi , Asha Sivaji , Gomathy Baskar , Sandhiya Viswanathan , Mugip Rahaman Abdul Wahab , Hemapreethi Surendran , Sandhya Nedunchezhian , Irfan Ahmad , Vajid Nettoor Veettil
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.
乳腺癌是女性患者因癌症死亡的首要原因。在所有类型的乳腺癌中,三阴性乳腺癌(TNBC)是最危险的乳腺癌分子亚型,其特点是没有雌激素受体(ER)、孕激素受体(PR)和人表皮生长因子受体 2(HER-2)表达。由于目前还没有针对 TNBC 的特定治疗策略能使疾病预后恶化,三维模型比二维模型更能准确反映人体体内的生物成分,因此更适合作为药物发现的预测工具。重要的是,所有三维模型都难以从临床肿瘤中收集到大量高质量的肿瘤细胞。医生可能无法从患者身上获得巨大的肿瘤组织,而且临床肿瘤可能有坏死、脂肪和血管成分。因此,当务之急是找到一种有效的方法,在不造成细胞浪费的情况下,持续、快速地制作大量同质肿瘤模型,用于个体治疗。微流体技术专门设计用于操作少量流体,已被用于生产给药颗粒。这一发展表明了最近的趋势,因为它提供了调节颗粒大小和材料成分的能力。本综述的重点是芯片肿瘤、微流控芯片制造和三阴性乳腺癌药物筛选。其中特别强调了癌症生物标记诊断、三维临床前模型开发以及三阴性乳腺癌的治疗策略。
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引用次数: 0
Micropapillary pattern in serous borderline ovarian tumor and the risk of extraovarian localization of low-grade serous carcinoma (‘invasive implants’): A systematic review and meta-analysis 浆液性边界卵巢肿瘤的微乳头状形态与低级别浆液性癌("浸润性种植")的卵巢外定位风险:系统综述与荟萃分析。
IF 2.9 4区 医学 Q2 PATHOLOGY Pub Date : 2024-11-06 DOI: 10.1016/j.prp.2024.155714
Giulia Scaglione , Antonio Travaglino , Antonio Raffone , Angela Santoro , Damiano Arciuolo , Caterina Fulgione , Nicoletta D’Alessandris , Giuseppe Pannone , Belen Padial Urtueta , Nadine Narducci , Francesca Addante , Jvan Casarin , Susanna Ronchi , Eleonora Di Lauro , Stefano La Rosa , Livia Maccio , Frediano Inzani , Gian Franco Zannoni
In serous borderline ovarian tumor (SBOT), a micropapillary (MP) pattern has been considered analogous to intraepithelial low-grade serous carcinoma (LGSC). On this account, it is reasonable to hypothesize that MP-SBOT is more likely to be associated with extraovarian LGSC localizations (also referred to as 'invasive implants') compared to conventional SBOT. The aim of this study was to investigate the potential association between a MP pattern and invasive implants in SBOT. Three electronic databases were searched from 2000 (year of publication of histological criteria for MP-SBOT) to 2023 for all studies assessing the presence of invasive implants in conventional SBOT vs MP-SBOT. Exclusion criteria were sample size <20, overlapping patient data, reviews. The association between MP pattern and invasive implants was assessed by using odds ratio (OR), with a significant p-value<0.05. Seven studies with 1766 SBOT were included, out of which 205 (11.5 %) were MP-SBOT, 462 (26 %) had implants and 62 (3.5 %) had invasive implants. A MP pattern was significantly associated with the presence of invasive implants (OR=7.33, 95 % CI 3.61–14.86) (p<0.001), with low heterogeneity among studies (I2=28 %). In conclusion, a MP pattern in SBOT is significantly associated with extraovarian LGSC localization, supporting that it represents intraepithelial LGSC.
在浆液性边界卵巢肿瘤(SBOT)中,微乳头状(MP)模式被认为类似于上皮内低级别浆液性癌(LGSC)。因此,我们有理由假设,与传统的 SBOT 相比,MP-SBOT 更有可能与卵巢外 LGSC 定位(也称为 "浸润性种植")有关。本研究旨在调查 MP 模式与 SBOT 侵袭性种植之间的潜在关联。研究人员检索了从 2000 年(MP-SBOT 组织学标准公布的年份)到 2023 年的三个电子数据库中所有评估传统 SBOT 与 MP-SBOT 中是否存在浸润性植入物的研究。排除标准为样本量为 2=28 %)。总之,SBOT 中的 MP 模式与卵巢外 LGSC 定位显著相关,支持 MP 模式代表上皮内 LGSC。
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Pathology, research and practice
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