首页 > 最新文献

Pathology, research and practice最新文献

英文 中文
Expression of histone methyltransferase WHSC1 in invasive breast cancer and its correlation with clinical and pathological data 组蛋白甲基转移酶 WHSC1 在浸润性乳腺癌中的表达及其与临床和病理数据的相关性
IF 2.9 4区 医学 Q2 PATHOLOGY Pub Date : 2024-10-06 DOI: 10.1016/j.prp.2024.155647
Wei Lin , Xian Wu , Sunwang Xu , Dexing Wang , Jinshu Chen , Linying Chen , Xiangjin Chen

Background

The WHSC1 protein facilitates specific dimethylation of histone H3 at the K36 position, enhancing gene transcription and expression. Studies have confirmed its high expression in diverse malignant tumors. We aimed to identify novel molecular markers to assess the biological behavior of breast cancer cells.

Methods

We conducted a comprehensive analysis of mRNA expression in breast cancer and adjacent tissues based on TCGA data. We enrolled 141 breast cancer patients treated at the First Affiliated Hospital of Fujian Medical University between 2012 and 2016. Patient clinical information and pathological specimens were obtained. We utilized tissue microarray (TMA) technology. We employed the chi-square test for between-group comparisons, with p < 0.05 indicating statistical significance. Furthermore, we analyzed the associations between WHSC1 expression and clinical or pathological data.

Results

WHSC1 mRNA expression was significantly higher in breast cancer tissues than in adjacent tissues (p < 0.001). Moreover, high WHSC1 protein expression in breast cancer was associated with several important clinical parameters, such as pathological type (p = 0.007), high Ki67 expression(Ki67>20 %) (p < 0.001), lymph node metastasis (p < 0.001), T stage (p = 0.011), N stage (p < 0.001), postoperative pathological stage (p < 0.001), premenopausal status (p = 0.004), and positive HER2 status (p < 0.001). Multivariate regression analysis showed that high WHSC1 expression, elevated Ki67 levels, and positive HER2 status were independent risk factors for axillary lymph node metastasis in breast cancer patients.

Conclusion

WHSC1 protein expression is upregulated in breast cancer patients and represents an independent risk factor influencing axillary lymph node metastasis, highlighting its potential significance as a strong candidate biomarker.
背景WHSC1蛋白可促进组蛋白H3在K36位置的特异性二甲基化,从而增强基因转录和表达。研究证实它在各种恶性肿瘤中的高表达。我们的目的是找出新的分子标记物来评估乳腺癌细胞的生物学行为。方法我们根据 TCGA 数据对乳腺癌和邻近组织的 mRNA 表达进行了全面分析。我们纳入了 2012 年至 2016 年期间在福建医科大学附属第一医院接受治疗的 141 例乳腺癌患者。我们获得了患者的临床信息和病理标本。我们采用了组织芯片(TMA)技术。我们采用卡方检验进行组间比较,以 p < 0.05 表示统计学意义。此外,我们还分析了WHSC1表达与临床或病理数据之间的关联。结果WHSC1 mRNA在乳腺癌组织中的表达明显高于邻近组织(p < 0.001)。此外,乳腺癌中 WHSC1 蛋白的高表达与几个重要的临床参数有关,如病理类型(p = 0.007)、高 Ki67 表达(Ki67>20 %)(p < 0.001)、淋巴结转移(p <0.001)、T期(p = 0.011)、N期(p <0.001)、术后病理分期(p <0.001)、绝经前状态(p = 0.004)和HER2阳性状态(p <0.001)。多变量回归分析表明,WHSC1高表达、Ki67水平升高和HER2阳性是乳腺癌患者发生腋窝淋巴结转移的独立危险因素。
{"title":"Expression of histone methyltransferase WHSC1 in invasive breast cancer and its correlation with clinical and pathological data","authors":"Wei Lin ,&nbsp;Xian Wu ,&nbsp;Sunwang Xu ,&nbsp;Dexing Wang ,&nbsp;Jinshu Chen ,&nbsp;Linying Chen ,&nbsp;Xiangjin Chen","doi":"10.1016/j.prp.2024.155647","DOIUrl":"10.1016/j.prp.2024.155647","url":null,"abstract":"<div><h3>Background</h3><div>The WHSC1 protein facilitates specific dimethylation of histone H3 at the K36 position, enhancing gene transcription and expression. Studies have confirmed its high expression in diverse malignant tumors. We aimed to identify novel molecular markers to assess the biological behavior of breast cancer cells.</div></div><div><h3>Methods</h3><div>We conducted a comprehensive analysis of mRNA expression in breast cancer and adjacent tissues based on TCGA data. We enrolled 141 breast cancer patients treated at the First Affiliated Hospital of Fujian Medical University between 2012 and 2016. Patient clinical information and pathological specimens were obtained. We utilized tissue microarray (TMA) technology. We employed the chi-square test for between-group comparisons, with p &lt; 0.05 indicating statistical significance. Furthermore, we analyzed the associations between WHSC1 expression and clinical or pathological data.</div></div><div><h3>Results</h3><div>WHSC1 mRNA expression was significantly higher in breast cancer tissues than in adjacent tissues (p &lt; 0.001). Moreover, high WHSC1 protein expression in breast cancer was associated with several important clinical parameters, such as pathological type (p = 0.007), high Ki67 expression(Ki67>20 %) (p &lt; 0.001), lymph node metastasis (p &lt; 0.001), T stage (p = 0.011), N stage (p &lt; 0.001), postoperative pathological stage (p &lt; 0.001), premenopausal status (p = 0.004), and positive HER2 status (p &lt; 0.001). Multivariate regression analysis showed that high WHSC1 expression, elevated Ki67 levels, and positive HER2 status were independent risk factors for axillary lymph node metastasis in breast cancer patients.</div></div><div><h3>Conclusion</h3><div>WHSC1 protein expression is upregulated in breast cancer patients and represents an independent risk factor influencing axillary lymph node metastasis, highlighting its potential significance as a strong candidate biomarker.</div></div>","PeriodicalId":19916,"journal":{"name":"Pathology, research and practice","volume":"263 ","pages":"Article 155647"},"PeriodicalIF":2.9,"publicationDate":"2024-10-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142419552","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}
引用次数: 0
Expression of CD68 and CD163 in malignant epithelial cells of oral squamous cell carcinoma: Phenotypic shift or mere cell fusion 口腔鳞状细胞癌恶性上皮细胞中 CD68 和 CD163 的表达:表型转变还是单纯的细胞融合?
IF 2.9 4区 医学 Q2 PATHOLOGY Pub Date : 2024-10-06 DOI: 10.1016/j.prp.2024.155639
Ahmed Abdelaziz Mohamed Essa , Mohammed Abdulaziz Mohammed Korayem , Mohammed A. Alghamdi , Rajab A. Alzahrani , Nuha Mohammed Malibari , Hebatalla Elmetwally Kandil

Background / purpose

The progression of epithelial to mesenchymal tissue (EMT) is a highly intricate process that facilitates the transformation of cancer cells, allowing them to changeover their characteristic epithelial properties to mesenchymal attributes. This notable change empowers the cells with enhanced mobility and the ability to migrate to distant locations. Furthermore, it is imperative to adopt the idea of macrophage tumor cell fusion to achieve comprehensive considerate of this phenomenon. Our primary objective was to conduct a thorough investigation of macrophage-restricted antigens expression, specifically CD68 and CD163, in malignant epithelial cells of oral cavity squamous cell carcinoma (OSCC) to elucidate aforementioned perceptions.

Materials and methods

CD68 and CD163 immunohistochemical expression were assessed in oral squamous cell carcinoma (OSCC), encompassing both the neoplastic cells and the tumor-associated macrophages (TAMs).

Results

Both CD68 and CD163 antigens were revealed in OSCC malignant epithelial cells in a granular cell pattern, localized in membrane and cytoplasm of tumor cells respectively as well as in the infiltrating TAMs.

Conclusion

The macrophage antigens were not limited to the infiltrating tumor-associated macrophages (TAMs), but were also observed in a substantial proportion of OSCC malignant epithelial cells within the tumor parenchyma. This particular expression pattern may represent a subset of tumor cells that have undergone an epithelial to a mesenchymal phenotypic transition. In addition, fusion of macrophages with tumor cells cannot be excluded; both might be associated with increased metastatic activity of OSCC.
背景/目的:上皮组织向间充质组织(EMT)的转变是一个非常复杂的过程,它促进了癌细胞的转化,使癌细胞从其特有的上皮特性转变为间充质特性。这一显著变化增强了细胞的流动性和向远处迁移的能力。此外,必须采用巨噬细胞与肿瘤细胞融合的观点来全面考虑这一现象。我们的主要目的是对口腔鳞状细胞癌(OSCC)恶性上皮细胞中巨噬细胞限制性抗原(尤其是 CD68 和 CD163)的表达进行深入研究,以阐明上述观点:评估口腔鳞状细胞癌(OSCC)中 CD68 和 CD163 的免疫组化表达,包括肿瘤细胞和肿瘤相关巨噬细胞(TAMs):结果:CD68和CD163抗原在OSCC恶性上皮细胞中均以颗粒状细胞形态出现,分别定位于肿瘤细胞膜和细胞质以及浸润的TAMs中:结论:巨噬细胞抗原并不局限于浸润的肿瘤相关巨噬细胞(TAMs),在肿瘤实质内的相当一部分 OSCC 恶性上皮细胞中也能观察到巨噬细胞抗原。这种特殊的表达模式可能代表了从上皮细胞向间充质表型转变的肿瘤细胞亚群。此外,还不能排除巨噬细胞与肿瘤细胞融合的可能性;两者都可能与 OSCC 转移活动的增加有关。
{"title":"Expression of CD68 and CD163 in malignant epithelial cells of oral squamous cell carcinoma: Phenotypic shift or mere cell fusion","authors":"Ahmed Abdelaziz Mohamed Essa ,&nbsp;Mohammed Abdulaziz Mohammed Korayem ,&nbsp;Mohammed A. Alghamdi ,&nbsp;Rajab A. Alzahrani ,&nbsp;Nuha Mohammed Malibari ,&nbsp;Hebatalla Elmetwally Kandil","doi":"10.1016/j.prp.2024.155639","DOIUrl":"10.1016/j.prp.2024.155639","url":null,"abstract":"<div><h3>Background / purpose</h3><div>The progression of epithelial to mesenchymal tissue (EMT) is a highly intricate process that facilitates the transformation of cancer cells, allowing them to changeover their characteristic epithelial properties to mesenchymal attributes. This notable change empowers the cells with enhanced mobility and the ability to migrate to distant locations. Furthermore, it is imperative to adopt the idea of macrophage tumor cell fusion to achieve comprehensive considerate of this phenomenon. Our primary objective was to conduct a thorough investigation of macrophage-restricted antigens expression, specifically CD68 and CD163, in malignant epithelial cells of oral cavity squamous cell carcinoma (OSCC) to elucidate aforementioned perceptions.</div></div><div><h3>Materials and methods</h3><div>CD68 and CD163 immunohistochemical expression were assessed in oral squamous cell carcinoma (OSCC), encompassing both the neoplastic cells and the tumor-associated macrophages (TAMs).</div></div><div><h3>Results</h3><div>Both CD68 and CD163 antigens were revealed in OSCC malignant epithelial cells in a granular cell pattern, localized in membrane and cytoplasm of tumor cells respectively as well as in the infiltrating TAMs.</div></div><div><h3>Conclusion</h3><div>The macrophage antigens were not limited to the infiltrating tumor-associated macrophages (TAMs), but were also observed in a substantial proportion of OSCC malignant epithelial cells within the tumor parenchyma. This particular expression pattern may represent a subset of tumor cells that have undergone an epithelial to a mesenchymal phenotypic transition. In addition, fusion of macrophages with tumor cells cannot be excluded; both might be associated with increased metastatic activity of OSCC.</div></div>","PeriodicalId":19916,"journal":{"name":"Pathology, research and practice","volume":"263 ","pages":"Article 155639"},"PeriodicalIF":2.9,"publicationDate":"2024-10-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142392387","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
Unraveling the genetic and singaling landscapes of pediatric cancer 揭示小儿癌症的遗传和基因景观。
IF 2.9 4区 医学 Q2 PATHOLOGY Pub Date : 2024-10-05 DOI: 10.1016/j.prp.2024.155635
Gowrang Kasaba Manjunath , Krishna Veni Ankam , Tikam Chand Dakal , MV Srihari Sharma , Disha Nashier , Tamoghna Mitra , Abhishek Kumar
Pediatric cancer (PAEC) arises from gene mutations and their disrupted pathways, often driven by genetic instability affecting cell signaling. These pathways can help identify cancer triggers. Genomic studies have examined PAEC gene etiologies and disorders, but further analysis is needed to understand tumor progression mechanisms. We systematically analyzed PAEC datasets from cBioPortal, encompassing thirteen studies with 6568 samples. We identified 827 PAEC genes with mutation frequencies over fifteen across four tiers (I-IV). Tier I (mutation frequency ≥1 %) includes 40 genes, while Tier II(0.90–0.70 %), Tier III(0.60–0.50 %), and Tier IV(0.40–0.10 %) comprise 126, 336, and 325 genes, respectively. Key Tier I genes include TP53(5 %), NRAS(2.2 %), KRAS(1.8 %), CTNNB1(1.4 %), ATM(1.3 %), CREBBP(1.2 %), JAK2 (1.1 %), PIK3CA(1 %), PTEN(1 %), BRAF(0.9 %), EGFR(0.9 %), PIK3R1(0.8 %), and PTPN11(0.8 %). These genes participate in various signaling pathways (PI3K/AKT/mTOR, RAS/RAF/MAPK, JAK/STAT, and WNT/β-catenin), which are interconnected. We compared several PAEC panels with Tier I genes, and we found that the most shared across PAEC panels were TP53 (8), PTEN (7), and ATM (4). We further examined roles of TP53 in normal cells versus PEAC tumors using digital cellular and pathological imaging data supported by Human Protein Atlas. TP53 is expressed in cytosol, nucleosol, and vesicles and during cell-cycle TP53 protein in key regulator and it is present during all major cell-cycle events. Balancing of TP53WT and TP53MUT is the hallmark of the TP53 pathophysiology with severe functional implications. Notably, genes linked to insulin metabolism disorders may be PAEC risk factors, suggesting metabolic pathways as key research targets. This study highlights the therapeutic, prognostic, and diagnostic significance of these genes and pathways, emphasizing the need for ongoing PAEC research.
小儿癌症(PAEC)源于基因突变及其紊乱的通路,通常由影响细胞信号传导的遗传不稳定性驱动。这些通路有助于确定癌症诱因。基因组研究对 PAEC 基因病因和疾病进行了研究,但要了解肿瘤进展机制还需要进一步的分析。我们系统分析了来自 cBioPortal 的 PAEC 数据集,包括 13 项研究和 6568 个样本。我们发现了 827 个突变频率超过 15 的 PAEC 基因,它们分布在四个层级(I-IV)。一级(突变频率≥1%)包括 40 个基因,二级(0.90-0.70%)、三级(0.60-0.50%)和四级(0.40-0.10%)分别包括 126、336 和 325 个基因。关键的一级基因包括 TP53(5 %)、NRAS(2.2 %)、KRAS(1.8 %)、CTNNB1(1.4 %)、ATM(1.3 %)、CREBBP(1.2 %)、JAK2(1.1 %)、PIK3CA(1 %)、PTEN(1 %)、BRAF(0.9 %)、EGFR(0.9 %)、PIK3R1(0.8 %)和 PTPN11(0.8 %)。这些基因参与了各种信号通路(PI3K/AKT/mTOR、RAS/RAF/MAPK、JAK/STAT 和 WNT/β-catenin),而这些通路是相互关联的。我们比较了几个 PAEC 面板与一级基因,发现 PAEC 面板中共享最多的基因是 TP53(8 个)、PTEN(7 个)和 ATM(4 个)。我们利用人类蛋白质图谱(Human Protein Atlas)支持的数字细胞和病理成像数据,进一步研究了 TP53 在正常细胞与 PEAC 肿瘤中的作用。TP53 在细胞膜、核膜和囊泡中表达,在细胞周期中,TP53 蛋白是关键的调节因子,它存在于所有主要的细胞周期事件中。TP53WT 和 TP53MUT 的平衡是 TP53 病理生理学的标志,具有严重的功能影响。值得注意的是,与胰岛素代谢紊乱有关的基因可能是 PAEC 的风险因素,这表明代谢途径是关键的研究目标。本研究强调了这些基因和通路在治疗、预后和诊断方面的意义,强调了对 PAEC 进行持续研究的必要性。
{"title":"Unraveling the genetic and singaling landscapes of pediatric cancer","authors":"Gowrang Kasaba Manjunath ,&nbsp;Krishna Veni Ankam ,&nbsp;Tikam Chand Dakal ,&nbsp;MV Srihari Sharma ,&nbsp;Disha Nashier ,&nbsp;Tamoghna Mitra ,&nbsp;Abhishek Kumar","doi":"10.1016/j.prp.2024.155635","DOIUrl":"10.1016/j.prp.2024.155635","url":null,"abstract":"<div><div>Pediatric cancer (PAEC) arises from gene mutations and their disrupted pathways, often driven by genetic instability affecting cell signaling. These pathways can help identify cancer triggers. Genomic studies have examined PAEC gene etiologies and disorders, but further analysis is needed to understand tumor progression mechanisms. We systematically analyzed PAEC datasets from cBioPortal, encompassing thirteen studies with 6568 samples. We identified 827 PAEC genes with mutation frequencies over fifteen across four tiers (I-IV). Tier I (mutation frequency ≥1 %) includes 40 genes, while Tier II(0.90–0.70 %), Tier III(0.60–0.50 %), and Tier IV(0.40–0.10 %) comprise 126, 336, and 325 genes, respectively. Key Tier I genes include TP53(5 %), NRAS(2.2 %), KRAS(1.8 %), CTNNB1(1.4 %), ATM(1.3 %), CREBBP(1.2 %), JAK2 (1.1 %), PIK3CA(1 %), PTEN(1 %), BRAF(0.9 %), EGFR(0.9 %), PIK3R1(0.8 %), and PTPN11(0.8 %). These genes participate in various signaling pathways (PI3K/AKT/mTOR, RAS/RAF/MAPK, JAK/STAT, and WNT/β-catenin), which are interconnected. We compared several PAEC panels with Tier I genes, and we found that the most shared across PAEC panels were TP53 (8), PTEN (7), and ATM (4). We further examined roles of TP53 in normal cells versus PEAC tumors using digital cellular and pathological imaging data supported by Human Protein Atlas. TP53 is expressed in cytosol, nucleosol, and vesicles and during cell-cycle TP53 protein in key regulator and it is present during all major cell-cycle events. Balancing of TP53<sup>WT</sup> and TP53<sup>MUT</sup> is the hallmark of the TP53 pathophysiology with severe functional implications. Notably, genes linked to insulin metabolism disorders may be PAEC risk factors, suggesting metabolic pathways as key research targets. This study highlights the therapeutic, prognostic, and diagnostic significance of these genes and pathways, emphasizing the need for ongoing PAEC research.</div></div>","PeriodicalId":19916,"journal":{"name":"Pathology, research and practice","volume":"263 ","pages":"Article 155635"},"PeriodicalIF":2.9,"publicationDate":"2024-10-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142406691","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
Exploring hypoxia-induced ncRNAs as biomarkers and therapeutic targets in lung cancer 探索缺氧诱导的 ncRNAs 作为肺癌的生物标记物和治疗靶点。
IF 2.9 4区 医学 Q2 PATHOLOGY Pub Date : 2024-10-05 DOI: 10.1016/j.prp.2024.155613
Lakshmi Thangavelu , Mohd Imran , Shaker Huwaylan Alsharari , Akrm M. Abdulaziz , Abdulaziz Mohsin Alawlaqi , Mehnaz Kamal , M.M. Rekha , Mandeep Kaur , Pradeep Soothwal , Isha Arora , M.Ravi Kumar , Ashish Singh Chauhan
Lung cancer is a deadly disease, causing nearly 20 % of all cancer deaths globally. A key factor in lung cancer's development and resistance to treatment is hypoxia, a condition where tumor cells experience low oxygen levels. In this low-oxygen environment, special molecules called non-coding RNAs (ncRNAs) become critical players. NcRNAs, including lncRNAs, miRNAs, circRNAs, and siRNAs, control how genes function and how cells behave. Some ncRNAs, like HIF1A-AS2 and HOTAIR, are linked to the aggressive spread of lung cancer, making them potential targets for therapy. Others, like certain miRNAs, show promise as early detection tools due to their influence on tumor blood vessel formation and metabolism. This complex interplay between hypoxia and ncRNAs is crucial for understanding lung cancer. For example, circRNAs can control the activity of miRNAs, impacting how tumors respond to low oxygen. Additionally, siRNAs offer a potential strategy to overcome treatment resistance caused by hypoxia. By studying the intricate relationship between hypoxia and ncRNAs, scientists hope to uncover new biomarkers for lung cancer. This knowledge will pave the way for developing more effective and targeted treatments for this devastating disease.
肺癌是一种致命的疾病,造成的死亡人数占全球癌症死亡总人数的近 20%。肺癌发病和抗药性的一个关键因素是缺氧,即肿瘤细胞处于低氧状态。在这种低氧环境中,被称为非编码 RNA(ncRNA)的特殊分子成为关键角色。NcRNA 包括 lncRNA、miRNA、circRNA 和 siRNA,它们控制着基因的功能和细胞的行为。一些 ncRNA,如 HIF1A-AS2 和 HOTAIR,与肺癌的侵袭性扩散有关,因此是潜在的治疗靶点。其他一些 ncRNA,如某些 miRNA,由于影响肿瘤血管的形成和新陈代谢,有望成为早期检测工具。缺氧与 ncRNA 之间复杂的相互作用对于了解肺癌至关重要。例如,circRNAs 可以控制 miRNAs 的活性,从而影响肿瘤对低氧的反应。此外,siRNAs 还为克服低氧引起的治疗耐药性提供了一种潜在的策略。通过研究低氧与 ncRNA 之间错综复杂的关系,科学家们希望能发现肺癌的新生物标记物。这些知识将为开发更有效、更有针对性的治疗方法铺平道路。
{"title":"Exploring hypoxia-induced ncRNAs as biomarkers and therapeutic targets in lung cancer","authors":"Lakshmi Thangavelu ,&nbsp;Mohd Imran ,&nbsp;Shaker Huwaylan Alsharari ,&nbsp;Akrm M. Abdulaziz ,&nbsp;Abdulaziz Mohsin Alawlaqi ,&nbsp;Mehnaz Kamal ,&nbsp;M.M. Rekha ,&nbsp;Mandeep Kaur ,&nbsp;Pradeep Soothwal ,&nbsp;Isha Arora ,&nbsp;M.Ravi Kumar ,&nbsp;Ashish Singh Chauhan","doi":"10.1016/j.prp.2024.155613","DOIUrl":"10.1016/j.prp.2024.155613","url":null,"abstract":"<div><div>Lung cancer is a deadly disease, causing nearly 20 % of all cancer deaths globally. A key factor in lung cancer's development and resistance to treatment is hypoxia, a condition where tumor cells experience low oxygen levels. In this low-oxygen environment, special molecules called non-coding RNAs (ncRNAs) become critical players. NcRNAs, including lncRNAs, miRNAs, circRNAs, and siRNAs, control how genes function and how cells behave. Some ncRNAs, like HIF1A-AS2 and HOTAIR, are linked to the aggressive spread of lung cancer, making them potential targets for therapy. Others, like certain miRNAs, show promise as early detection tools due to their influence on tumor blood vessel formation and metabolism. This complex interplay between hypoxia and ncRNAs is crucial for understanding lung cancer. For example, circRNAs can control the activity of miRNAs, impacting how tumors respond to low oxygen. Additionally, siRNAs offer a potential strategy to overcome treatment resistance caused by hypoxia. By studying the intricate relationship between hypoxia and ncRNAs, scientists hope to uncover new biomarkers for lung cancer. This knowledge will pave the way for developing more effective and targeted treatments for this devastating disease.</div></div>","PeriodicalId":19916,"journal":{"name":"Pathology, research and practice","volume":"263 ","pages":"Article 155613"},"PeriodicalIF":2.9,"publicationDate":"2024-10-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142392386","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
Cultures derived from pancreatic cancer xenografts with long-term gemcitabine treatment produce chemoresistant secondary xenografts: Establishment of isogenic gemcitabine-sensitive and -resistant models 从长期吉西他滨治疗的胰腺癌异种移植物中提取的培养物会产生化疗耐药的继发性异种移植物:建立对吉西他滨敏感和耐药的同种异基因模型。
IF 2.9 4区 医学 Q2 PATHOLOGY Pub Date : 2024-10-05 DOI: 10.1016/j.prp.2024.155632
Yasuyo Kobayashi-Ooka , Tsuyoshi Akagi , Taiko Sukezane , Emmy Yanagita , Tomoo Itoh , Ken Sasai
In attempts to establish sophisticated models to reproduce the process of acquired drug resistance, we transformed normal human pancreatic ductal epithelial cells by introducing genes for multiple cellular factors. We also created isogenic gemcitabine-sensitive and -resistant models by short- and long-term gemcitabine treatment, respectively. These models demonstrated differences in drug resistance in vivo, but not in vitro. Gemcitabine treatment also induced squamous transdifferentiation in xenografts in mice. The transcription factor p63 was identified as a possible resistance-determining factor but was unlikely to be solely responsible for the resistance to gemcitabine. This system would prove useful to discover novel molecular targets to overcome chemotherapy resistance, by allowing the evaluation of molecules of interest in xenograft models after in vitro genetic ablation.
为了建立复杂的模型来重现获得性耐药性的过程,我们通过引入多种细胞因子的基因来改造正常人的胰腺导管上皮细胞。我们还通过短期和长期吉西他滨治疗,分别建立了对吉西他滨敏感和耐药的同源模型。这些模型在体内表现出耐药性差异,但在体外没有。吉西他滨治疗还能诱导小鼠异种移植物发生鳞状分化。转录因子 p63 被确定为可能的耐药性决定因素,但不可能是导致吉西他滨耐药性的唯一原因。该系统可在体外基因消融后对异种移植模型中的相关分子进行评估,从而有助于发现克服化疗耐药性的新型分子靶点。
{"title":"Cultures derived from pancreatic cancer xenografts with long-term gemcitabine treatment produce chemoresistant secondary xenografts: Establishment of isogenic gemcitabine-sensitive and -resistant models","authors":"Yasuyo Kobayashi-Ooka ,&nbsp;Tsuyoshi Akagi ,&nbsp;Taiko Sukezane ,&nbsp;Emmy Yanagita ,&nbsp;Tomoo Itoh ,&nbsp;Ken Sasai","doi":"10.1016/j.prp.2024.155632","DOIUrl":"10.1016/j.prp.2024.155632","url":null,"abstract":"<div><div>In attempts to establish sophisticated models to reproduce the process of acquired drug resistance, we transformed normal human pancreatic ductal epithelial cells by introducing genes for multiple cellular factors. We also created isogenic gemcitabine-sensitive and -resistant models by short- and long-term gemcitabine treatment, respectively. These models demonstrated differences in drug resistance <em>in vivo</em>, but not <em>in vitro</em>. Gemcitabine treatment also induced squamous transdifferentiation in xenografts in mice. The transcription factor p63 was identified as a possible resistance-determining factor but was unlikely to be solely responsible for the resistance to gemcitabine. This system would prove useful to discover novel molecular targets to overcome chemotherapy resistance, by allowing the evaluation of molecules of interest in xenograft models after <em>in vitro</em> genetic ablation.</div></div>","PeriodicalId":19916,"journal":{"name":"Pathology, research and practice","volume":"263 ","pages":"Article 155632"},"PeriodicalIF":2.9,"publicationDate":"2024-10-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142406688","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
Ensemble approach of deep learning models for binary and multiclass classification of histopathological images for breast cancer 用于乳腺癌组织病理学图像二元和多类分类的深度学习模型集合方法
IF 2.9 4区 医学 Q2 PATHOLOGY Pub Date : 2024-10-05 DOI: 10.1016/j.prp.2024.155644
Madhumita Pal , Ganapati Panda , Ranjan K. Mohapatra , Adyasha Rath , Sujata Dash , Mohd Asif Shah , Saurav Mallik
Breast cancer (BC) is the most frequently occurring cancer disease observed in women after lung cancer. Out of different stages, invasive ductal BC causes maximum deaths in women. In this work, three deep learning (DL) models such as Vision Transformer (ViT), Convmixer, and Visual Geometry Group-19 (VGG-19) are implemented for the detection and classification of different breast cancer tumors with the help of Breast cancer histopathological (Break His) image database. The performance of each model is evaluated using an 80:20 training scheme and measured in terms of accuracy, precision, recall, loss, F1-score, and area under the curve (AUC). From the simulation result, ViT showed the best performance for binary classification of breast cancer tumors with accuracy, precision, recall, and F1-score of 99.89 %, 98.29 %, 98.29 %, and 98.29 %, respectively. Also, ViT showed the best performance in terms of accuracy (98.21 %), average Precision (89.84 %), recall (89.97 %), and F1-score (88.75) for eight class classifications. Moreover, we have also ensemble the ViT-Convmixer model and observed that the performance of the ensemble model is reduced as compared to the ViT model. We have also compared the performance of the proposed best model with other existing models reported by several research groups. The study will help find suitable models that will increase accuracy in early diagnoses of BC. We hope the study will also help to minimize human errors in the early diagnosis of this fatal disease and administer appropriate treatment. The proposed model may also be implemented for the detection of other diseases with improved accuracy.
乳腺癌(BC)是继肺癌之后女性最常见的癌症疾病。在不同阶段的乳腺癌中,浸润性乳腺导管癌导致的女性死亡人数最多。在这项工作中,在乳腺癌组织病理学(Break His)图像数据库的帮助下,实现了三种深度学习(DL)模型,如视觉变换器(ViT)、Convmixer 和视觉几何组-19(VGG-19),用于不同乳腺癌肿瘤的检测和分类。采用 80:20 的训练方案对每个模型的性能进行了评估,并从准确度、精确度、召回率、损失、F1 分数和曲线下面积(AUC)等方面进行了测量。从模拟结果来看,ViT 在乳腺癌肿瘤的二元分类中表现最佳,准确率、精确率、召回率和 F1 分数分别为 99.89 %、98.29 %、98.29 % 和 98.29 %。此外,ViT 在八个分类的准确率(98.21 %)、平均精度(89.84 %)、召回率(89.97 %)和 F1 分数(88.75)方面表现最佳。此外,我们还对 ViT-Convmixer 模型进行了集合,观察到集合模型的性能比 ViT 模型有所下降。我们还将提议的最佳模型的性能与几个研究小组报告的其他现有模型进行了比较。这项研究将有助于找到合适的模型,从而提高 BC 早期诊断的准确性。我们希望这项研究还有助于在早期诊断这种致命疾病时尽量减少人为错误,并进行适当的治疗。建议的模型也可用于其他疾病的检测,以提高准确性。
{"title":"Ensemble approach of deep learning models for binary and multiclass classification of histopathological images for breast cancer","authors":"Madhumita Pal ,&nbsp;Ganapati Panda ,&nbsp;Ranjan K. Mohapatra ,&nbsp;Adyasha Rath ,&nbsp;Sujata Dash ,&nbsp;Mohd Asif Shah ,&nbsp;Saurav Mallik","doi":"10.1016/j.prp.2024.155644","DOIUrl":"10.1016/j.prp.2024.155644","url":null,"abstract":"<div><div>Breast cancer (BC) is the most frequently occurring cancer disease observed in women after lung cancer. Out of different stages, invasive ductal BC causes maximum deaths in women. In this work, three deep learning (DL) models such as Vision Transformer (ViT), Convmixer, and Visual Geometry Group-19 (VGG-19) are implemented for the detection and classification of different breast cancer tumors with the help of Breast cancer histopathological (Break His) image database. The performance of each model is evaluated using an 80:20 training scheme and measured in terms of accuracy, precision, recall, loss, F1-score, and area under the curve (AUC). From the simulation result, ViT showed the best performance for binary classification of breast cancer tumors with accuracy, precision, recall, and F1-score of 99.89 %, 98.29 %, 98.29 %, and 98.29 %, respectively. Also, ViT showed the best performance in terms of accuracy (98.21 %), average Precision (89.84 %), recall (89.97 %), and F1-score (88.75) for eight class classifications. Moreover, we have also ensemble the ViT-Convmixer model and observed that the performance of the ensemble model is reduced as compared to the ViT model. We have also compared the performance of the proposed best model with other existing models reported by several research groups. The study will help find suitable models that will increase accuracy in early diagnoses of BC. We hope the study will also help to minimize human errors in the early diagnosis of this fatal disease and administer appropriate treatment. The proposed model may also be implemented for the detection of other diseases with improved accuracy.</div></div>","PeriodicalId":19916,"journal":{"name":"Pathology, research and practice","volume":"263 ","pages":"Article 155644"},"PeriodicalIF":2.9,"publicationDate":"2024-10-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142419553","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
miR-17–5p/STAT3/H19: A novel regulatory axis tuning ULBP2 expression in young breast cancer patients miR-17-5p/STAT3/H19:调节年轻乳腺癌患者 ULBP2 表达的新型调控轴。
IF 2.9 4区 医学 Q2 PATHOLOGY Pub Date : 2024-10-05 DOI: 10.1016/j.prp.2024.155638
A.M. Abdelhamid , Y. Zeinelabdeen , T. Manie , E. Khallaf , R.A. Assal , R.A. Youness

Background and aim

UL-16 binding protein 2 (ULBP2) is a highly altered ligand for the activating receptor, NKG2D in breast cancer (BC). However, the mechanism behind its de-regulation in BC patients remains to be explored. The sophisticated crosstalk between miR-17–5p, the lncRNA H19, and STAT3 as a possible upstream regulatory loop for ULBP2 in young BC patients and cell lines remains as an unexplored area. Therefore, this study aimed at unravelling the ncRNA circuit regulating ULBP2 in young BC patients and cell lines.

Patients and methods

A total of 30 BC patients were recruited for this study. The expression levels of miR-17–5p, lncRNA H19, and STAT3 were examined in 30 BC tissues compared to their normal counterparts. In addition, the expression signatures of those transcripts were compared in young (<40 years) and old BC (≥40 years) patients. miR-17–5p oligonucleotides, STAT3 and H19 siRNAs were transfected in MDA-MB-231 cells using HiPerfect® Transfection Reagent. miR-17–5p and the transcripts of the target genes quantified using RT-qPCR. Their relative expression was calculated using the 2–ΔΔCT method.

Results

Through acting as a ceRNA circuit that antagonizes the function of miR-17–5p, H19 prevented the miR-17–5p-induced downregulation of STAT3; this mechanism further contributes to the pathogenesis of BC. Ectopic expression of miR-17–5p in MDA-MB-231 cells displayed its prominent role as an indirect potential activator of NK cells by significantly repressing the expression levels of the oncogenic mediator STAT3 and the oncogenic lncRNA H19 and inducing ULBP2 expression level by 3 folds in TNBC cell lines compared to mock cells. Furthermore, knocking down of STAT3 repressed the lncRNA H19 and increased ULBP2 expression levels, whereas siRNAs against H19 increased the expression levels of ULBP2.

Conclusion

This study highlighted the crosstalk between the novel regulatory network composed of miR-17–5p, H19 and STAT3, and their impact on ULBP2 in BC. Moreover, this study underscored the potential role of miR-17–5p in counteracting the immune evasion tactics, particularly the shedding of ULBP2 in young BC patients, through the modulation of the STAT3/H19/ULBP2 regulatory axis. Thus, targeting this novel regulatory network could potentially enhance our understanding and advance the future application of the innate system-mediated immunotherapy in BC.
背景和目的:UL-16 结合蛋白 2(ULBP2)是乳腺癌(BC)活化受体 NKG2D 的一种高度改变的配体。然而,其在 BC 患者中的去调控机制仍有待探索。在年轻的 BC 患者和细胞系中,miR-17-5p、lncRNA H19 和 STAT3 之间的复杂串扰可能是 ULBP2 的上游调控环路,这仍是一个尚未探索的领域。因此,本研究旨在揭示年轻的BC患者和细胞系中调控ULBP2的ncRNA回路:本研究共招募了 30 名 BC 患者。与正常人相比,研究人员检测了 30 例 BC 组织中 miR-17-5p、lncRNA H19 和 STAT3 的表达水平。此外,还比较了这些转录本在年轻(-ΔΔCT方法)中的表达特征:结果:H19通过作为ceRNA回路拮抗miR-17-5p的功能,阻止了miR-17-5p诱导的STAT3下调;这一机制进一步促进了BC的发病机制。与模拟细胞相比,在MDA-MB-231细胞中异位表达miR-17-5p能显著抑制致癌介质STAT3和致癌lncRNA H19的表达水平,并诱导TNBC细胞株中ULBP2的表达水平提高3倍,从而显示出它作为NK细胞间接潜在激活剂的突出作用。此外,敲除 STAT3 可抑制 lncRNA H19 并提高 ULBP2 的表达水平,而针对 H19 的 siRNA 可提高 ULBP2 的表达水平:本研究强调了由 miR-17-5p、H19 和 STAT3 组成的新型调控网络之间的相互影响,以及它们对 BC 中 ULBP2 的影响。此外,本研究还强调了 miR-17-5p 通过调节 STAT3/H19/ULBP2 调控轴,在对抗免疫逃避策略,尤其是年轻的 BC 患者的 ULBP2 脱落中的潜在作用。因此,以这一新型调控网络为靶点有可能加深我们对先天系统介导的免疫疗法的理解并推动其在 BC 中的应用。
{"title":"miR-17–5p/STAT3/H19: A novel regulatory axis tuning ULBP2 expression in young breast cancer patients","authors":"A.M. Abdelhamid ,&nbsp;Y. Zeinelabdeen ,&nbsp;T. Manie ,&nbsp;E. Khallaf ,&nbsp;R.A. Assal ,&nbsp;R.A. Youness","doi":"10.1016/j.prp.2024.155638","DOIUrl":"10.1016/j.prp.2024.155638","url":null,"abstract":"<div><h3>Background and aim</h3><div>UL-16 binding protein 2 (ULBP2) is a highly altered ligand for the activating receptor, NKG2D in breast cancer (BC). However, the mechanism behind its de-regulation in BC patients remains to be explored. The sophisticated crosstalk between miR-17–5p, the lncRNA H19, and STAT3 as a possible upstream regulatory loop for ULBP2 in young BC patients and cell lines remains as an unexplored area. Therefore, this study aimed at unravelling the ncRNA circuit regulating ULBP2 in young BC patients and cell lines.</div></div><div><h3>Patients and methods</h3><div>A total of 30 BC patients were recruited for this study. The expression levels of miR-17–5p, lncRNA H19, and STAT3 were examined in 30 BC tissues compared to their normal counterparts. In addition, the expression signatures of those transcripts were compared in young (&lt;40 years) and old BC (≥40 years) patients. miR-17–5p oligonucleotides, STAT3 and H19 siRNAs were transfected in MDA-MB-231 cells using HiPerfect® Transfection Reagent. miR-17–5p and the transcripts of the target genes quantified using RT-qPCR. Their relative expression was calculated using the 2<sup>–ΔΔCT</sup> method.</div></div><div><h3>Results</h3><div>Through acting as a ceRNA circuit that antagonizes the function of miR-17–5p, H19 prevented the miR-17–5p-induced downregulation of STAT3; this mechanism further contributes to the pathogenesis of BC. Ectopic expression of miR-17–5p in MDA-MB-231 cells displayed its prominent role as an indirect potential activator of NK cells by significantly repressing the expression levels of the oncogenic mediator STAT3 and the oncogenic lncRNA H19 and inducing ULBP2 expression level by 3 folds in TNBC cell lines compared to mock cells. Furthermore, knocking down of STAT3 repressed the lncRNA H19 and increased ULBP2 expression levels, whereas siRNAs against H19 increased the expression levels of ULBP2.</div></div><div><h3>Conclusion</h3><div>This study highlighted the crosstalk between the novel regulatory network composed of miR-17–5p, H19 and STAT3, and their impact on ULBP2 in BC. Moreover, this study underscored the potential role of miR-17–5p in counteracting the immune evasion tactics, particularly the shedding of ULBP2 in young BC patients, through the modulation of the STAT3/H19/ULBP2 regulatory axis. Thus, targeting this novel regulatory network could potentially enhance our understanding and advance the future application of the innate system-mediated immunotherapy in BC.</div></div>","PeriodicalId":19916,"journal":{"name":"Pathology, research and practice","volume":"263 ","pages":"Article 155638"},"PeriodicalIF":2.9,"publicationDate":"2024-10-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142400950","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
Sarcoma diagnosis by DNA methylation classifier: A systematic review, current status and future prospects 通过 DNA 甲基化分类器诊断肉瘤:系统综述、现状和前景。
IF 2.9 4区 医学 Q2 PATHOLOGY Pub Date : 2024-10-04 DOI: 10.1016/j.prp.2024.155634
Adil Aziz Khan , Naveen Kumar R , Sushanta Chakma , Sumanta Das
Sarcomas, a diverse group of malignant tumors originating from connective tissues, present substantial diagnostic challenges due to their histological heterogeneity. Traditional diagnostic methods include histomorphology along with immunohistochemistry is necessary for primary evaluation. Fluorescence in situ hybridization (FISH) is a supplementary tool that helps with additional findings. However it is very difficult sometimes to accurately classify sarcoma subtypes despite all these tools. Recent advancements in DNA methylation profiling have emerged as a promising approach to enhance the precision of sarcoma diagnosis. This paper delves into the role of DNA methylation classifiers in diagnosing sarcomas, emphasizing their potential to improve diagnostic accuracy, inform treatment decisions, and ultimately enhance patient outcomes.
肉瘤是一种起源于结缔组织的多种恶性肿瘤,由于其组织学异质性,给诊断带来了巨大挑战。传统的诊断方法包括组织形态学和免疫组化,是初诊评估的必要方法。荧光原位杂交(FISH)是一种辅助工具,有助于获得更多发现。然而,尽管有这些工具,有时仍很难对肉瘤亚型进行准确分类。DNA 甲基化分析的最新进展已成为提高肉瘤诊断精确度的一种有前途的方法。本文深入探讨了 DNA 甲基化分类器在肉瘤诊断中的作用,强调了它们在提高诊断准确性、为治疗决策提供信息以及最终改善患者预后方面的潜力。
{"title":"Sarcoma diagnosis by DNA methylation classifier: A systematic review, current status and future prospects","authors":"Adil Aziz Khan ,&nbsp;Naveen Kumar R ,&nbsp;Sushanta Chakma ,&nbsp;Sumanta Das","doi":"10.1016/j.prp.2024.155634","DOIUrl":"10.1016/j.prp.2024.155634","url":null,"abstract":"<div><div>Sarcomas, a diverse group of malignant tumors originating from connective tissues, present substantial diagnostic challenges due to their histological heterogeneity. Traditional diagnostic methods include histomorphology along with immunohistochemistry is necessary for primary evaluation. Fluorescence in situ hybridization (FISH) is a supplementary tool that helps with additional findings. However it is very difficult sometimes to accurately classify sarcoma subtypes despite all these tools. Recent advancements in DNA methylation profiling have emerged as a promising approach to enhance the precision of sarcoma diagnosis. This paper delves into the role of DNA methylation classifiers in diagnosing sarcomas, emphasizing their potential to improve diagnostic accuracy, inform treatment decisions, and ultimately enhance patient outcomes.</div></div>","PeriodicalId":19916,"journal":{"name":"Pathology, research and practice","volume":"263 ","pages":"Article 155634"},"PeriodicalIF":2.9,"publicationDate":"2024-10-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142392389","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
Recent update on anti-tumor mechanisms of valproic acid in glioblastoma multiforme 丙戊酸在多形性胶质母细胞瘤中抗肿瘤机制的最新进展
IF 2.9 4区 医学 Q2 PATHOLOGY Pub Date : 2024-10-03 DOI: 10.1016/j.prp.2024.155636
Abulfazl Vatankhah , Sepehr Hoseinzadeh Moghaddam , Sadaf Afshari , Amir R. Afshari , Prashant Kesharwani , Amirhossein Sahebkar
Glioblastoma multiforme (GBM) is a malignant tumor of the brain that is considered to be incurable. Currently, surgical removal of tumors, chemotherapy with temozolomide, and radiation treatment remain established options for treatment. Nevertheless, the prognosis of those with GBM continues to be poor owing to the inherent characteristics of tumor growth and spread, as well as the resistance to treatment. To effectively deal with the present circumstances, it is vital to do extensive study to understand GBM thoroughly. The following piece provides a concise overview of the most recent advancements in using valproic acid, an antiseizure medication licensed by the FDA, for treating GBM. In this review, we outline the most recent developments of valproic acid in treating GBM, as well as its fundamental mechanisms and practical consequences. Our goal is to provide a greater understanding of the clinical use of valproic acid as a potential therapeutic agent for GBM.
多形性胶质母细胞瘤(GBM)是一种被认为无法治愈的脑部恶性肿瘤。目前,手术切除肿瘤、替莫唑胺化疗和放射治疗仍是治疗的既定方案。然而,由于肿瘤生长和扩散的固有特性,以及对治疗的耐药性,GBM 患者的预后仍然不佳。要有效应对目前的情况,就必须进行广泛的研究,深入了解 GBM。下面的文章简要概述了使用丙戊酸(一种经 FDA 许可的抗癫痫药物)治疗 GBM 的最新进展。在这篇综述中,我们概述了丙戊酸治疗 GBM 的最新进展及其基本机制和实际后果。我们的目标是让大家更深入地了解丙戊酸作为一种潜在的 GBM 治疗药物在临床上的应用。
{"title":"Recent update on anti-tumor mechanisms of valproic acid in glioblastoma multiforme","authors":"Abulfazl Vatankhah ,&nbsp;Sepehr Hoseinzadeh Moghaddam ,&nbsp;Sadaf Afshari ,&nbsp;Amir R. Afshari ,&nbsp;Prashant Kesharwani ,&nbsp;Amirhossein Sahebkar","doi":"10.1016/j.prp.2024.155636","DOIUrl":"10.1016/j.prp.2024.155636","url":null,"abstract":"<div><div>Glioblastoma multiforme (GBM) is a malignant tumor of the brain that is considered to be incurable. Currently, surgical removal of tumors, chemotherapy with temozolomide, and radiation treatment remain established options for treatment. Nevertheless, the prognosis of those with GBM continues to be poor owing to the inherent characteristics of tumor growth and spread, as well as the resistance to treatment. To effectively deal with the present circumstances, it is vital to do extensive study to understand GBM thoroughly. The following piece provides a concise overview of the most recent advancements in using valproic acid, an antiseizure medication licensed by the FDA, for treating GBM. In this review, we outline the most recent developments of valproic acid in treating GBM, as well as its fundamental mechanisms and practical consequences. Our goal is to provide a greater understanding of the clinical use of valproic acid as a potential therapeutic agent for GBM.</div></div>","PeriodicalId":19916,"journal":{"name":"Pathology, research and practice","volume":"263 ","pages":"Article 155636"},"PeriodicalIF":2.9,"publicationDate":"2024-10-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142419627","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
Keratin 17 and A2ML1 are negative prognostic biomarkers in non-small cell lung cancer 角蛋白 17 和 A2ML1 是非小细胞肺癌的阴性预后生物标志物
IF 2.9 4区 医学 Q2 PATHOLOGY Pub Date : 2024-10-03 DOI: 10.1016/j.prp.2024.155643
Sruthi Babu , Michael Horowitz , Lyanne A. Delgado-Coka , Lucia Roa-Peña , Ali Akalin , Luisa F. Escobar-Hoyos , Kenneth R. Shroyer
Although the overall prognosis for patients with non-small cell lung cancer (NSCLC) has improved over the past several decades, there are still survival differences that are not accurately defined by clinicopathological factors. Thus, there is an unmet clinical need to develop novel approaches to enhance prognostic accuracy for these patients. Keratin 17 (K17) is a negative prognostic biomarker in a wide range of cancer types, including pancreatic ductal adenocarcinoma, head and neck squamous cell carcinoma, and pulmonary adenocarcinoma (LUAD), but has yet to be investigated as a prognostic biomarker in primary lung squamous cell carcinoma (LSCC). Based on TCGA RNA-seq data, alpha-2-macroglobulin like 1 (A2ML1), a protease inhibitor, is highly correlated with K17 in other solid tumors, including pancreatic ductal adenocarcinoma and is also a prognostic biomarker for LSCC, although the prognostic accuracy of A2ML1 for LUAD has not been tested. Thus, we hypothesized that A2ML1 expression correlates with K17 expression and that K17/A2ML1 co-testing could provide complementary prognostic data for NSCLC. The aims of this study were to explore K17 and A2ML1 as dual prognostic biomarkers, using publicly available gene expression databases [The Cancer Genome Atlas (TCGA)] LSCC (n=266), LUAD (n=271)] and multiplexed immunohistochemistry (mIHC) on representative sections of LSCC (n=104) and LUAD (n=107) from two major academic medical centers. Our results suggest that using either mRNA or mIHC-based methods, combined K17 and A2ML1 testing provides information, independent of other clinicopathologic variables, that could impact treatment decisions for patients with NSCLC.
尽管非小细胞肺癌(NSCLC)患者的总体预后在过去几十年中有所改善,但临床病理因素仍无法准确界定患者的生存差异。因此,临床上需要开发新的方法来提高这些患者的预后准确性。角蛋白17(K17)是包括胰腺导管腺癌、头颈部鳞状细胞癌和肺腺癌(LUAD)在内的多种类型癌症的阴性预后生物标志物,但尚未作为原发性肺鳞状细胞癌(LSCC)的预后生物标志物进行研究。根据TCGA RNA-seq数据,蛋白酶抑制剂α-2-巨球蛋白样1(A2ML1)与其他实体瘤(包括胰腺导管腺癌)中的K17高度相关,也是LSCC的预后生物标志物,但A2ML1对LUAD的预后准确性尚未得到检验。因此,我们假设 A2ML1 的表达与 K17 的表达相关,K17/A2ML1 联合检测可为 NSCLC 提供互补的预后数据。本研究的目的是利用公开的基因表达数据库[The Cancer Genome Atlas (TCGA)]LSCC(n=266)、LUAD(n=271)]和来自两大学术医疗中心的具有代表性的LSCC(n=104)和LUAD(n=107)切片的多重免疫组织化学(mIHC),探讨K17和A2ML1作为双重预后生物标志物的作用。我们的研究结果表明,使用基于 mRNA 或 mIHC 的方法,K17 和 A2ML1 联合检测可提供独立于其他临床病理变量的信息,从而影响 NSCLC 患者的治疗决策。
{"title":"Keratin 17 and A2ML1 are negative prognostic biomarkers in non-small cell lung cancer","authors":"Sruthi Babu ,&nbsp;Michael Horowitz ,&nbsp;Lyanne A. Delgado-Coka ,&nbsp;Lucia Roa-Peña ,&nbsp;Ali Akalin ,&nbsp;Luisa F. Escobar-Hoyos ,&nbsp;Kenneth R. Shroyer","doi":"10.1016/j.prp.2024.155643","DOIUrl":"10.1016/j.prp.2024.155643","url":null,"abstract":"<div><div>Although the overall prognosis for patients with non-small cell lung cancer (NSCLC) has improved over the past several decades, there are still survival differences that are not accurately defined by clinicopathological factors. Thus, there is an unmet clinical need to develop novel approaches to enhance prognostic accuracy for these patients. Keratin 17 (K17) is a negative prognostic biomarker in a wide range of cancer types, including pancreatic ductal adenocarcinoma, head and neck squamous cell carcinoma, and pulmonary adenocarcinoma (LUAD), but has yet to be investigated as a prognostic biomarker in primary lung squamous cell carcinoma (LSCC). Based on TCGA RNA-seq data, alpha-2-macroglobulin like 1 (A2ML1), a protease inhibitor, is highly correlated with K17 in other solid tumors, including pancreatic ductal adenocarcinoma and is also a prognostic biomarker for LSCC, although the prognostic accuracy of A2ML1 for LUAD has not been tested. Thus, we hypothesized that A2ML1 expression correlates with K17 expression and that K17/A2ML1 co-testing could provide complementary prognostic data for NSCLC. The aims of this study were to explore K17 and A2ML1 as dual prognostic biomarkers, using publicly available gene expression databases [The Cancer Genome Atlas (TCGA)] LSCC (n=266), LUAD (n=271)] and multiplexed immunohistochemistry (mIHC) on representative sections of LSCC (n=104) and LUAD (n=107) from two major academic medical centers. Our results suggest that using either mRNA or mIHC-based methods, combined K17 and A2ML1 testing provides information, independent of other clinicopathologic variables, that could impact treatment decisions for patients with NSCLC.</div></div>","PeriodicalId":19916,"journal":{"name":"Pathology, research and practice","volume":"263 ","pages":"Article 155643"},"PeriodicalIF":2.9,"publicationDate":"2024-10-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142441511","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
期刊
Pathology, research and practice
全部 Acc. Chem. Res. ACS Applied Bio Materials ACS Appl. Electron. Mater. ACS Appl. Energy Mater. ACS Appl. Mater. Interfaces ACS Appl. Nano Mater. ACS Appl. Polym. Mater. ACS BIOMATER-SCI ENG ACS Catal. ACS Cent. Sci. ACS Chem. Biol. ACS Chemical Health & Safety ACS Chem. Neurosci. ACS Comb. Sci. ACS Earth Space Chem. ACS Energy Lett. ACS Infect. Dis. ACS Macro Lett. ACS Mater. Lett. ACS Med. Chem. Lett. ACS Nano ACS Omega ACS Photonics ACS Sens. ACS Sustainable Chem. Eng. ACS Synth. Biol. Anal. Chem. BIOCHEMISTRY-US Bioconjugate Chem. BIOMACROMOLECULES Chem. Res. Toxicol. Chem. Rev. Chem. Mater. CRYST GROWTH DES ENERG FUEL Environ. Sci. Technol. Environ. Sci. Technol. Lett. Eur. J. Inorg. Chem. IND ENG CHEM RES Inorg. Chem. J. Agric. Food. Chem. J. Chem. Eng. Data J. Chem. Educ. J. Chem. Inf. Model. J. Chem. Theory Comput. J. Med. Chem. J. Nat. Prod. J PROTEOME RES J. Am. Chem. Soc. LANGMUIR MACROMOLECULES Mol. Pharmaceutics Nano Lett. Org. Lett. ORG PROCESS RES DEV ORGANOMETALLICS J. Org. Chem. J. Phys. Chem. J. Phys. Chem. A J. Phys. Chem. B J. Phys. Chem. C J. Phys. Chem. Lett. Analyst Anal. Methods Biomater. Sci. Catal. Sci. Technol. Chem. Commun. Chem. Soc. Rev. CHEM EDUC RES PRACT CRYSTENGCOMM Dalton Trans. Energy Environ. Sci. ENVIRON SCI-NANO ENVIRON SCI-PROC IMP ENVIRON SCI-WAT RES Faraday Discuss. Food Funct. Green Chem. Inorg. Chem. Front. Integr. Biol. J. Anal. At. Spectrom. J. Mater. Chem. A J. Mater. Chem. B J. Mater. Chem. C Lab Chip Mater. Chem. Front. Mater. Horiz. MEDCHEMCOMM Metallomics Mol. Biosyst. Mol. Syst. Des. Eng. Nanoscale Nanoscale Horiz. Nat. Prod. Rep. New J. Chem. Org. Biomol. Chem. Org. Chem. Front. PHOTOCH PHOTOBIO SCI PCCP Polym. Chem.
×
引用
GB/T 7714-2015
复制
MLA
复制
APA
复制
导出至
BibTeX EndNote RefMan NoteFirst NoteExpress
×
0
微信
客服QQ
Book学术公众号 扫码关注我们
反馈
×
意见反馈
请填写您的意见或建议
请填写您的手机或邮箱
×
提示
您的信息不完整,为了账户安全,请先补充。
现在去补充
×
提示
您因"违规操作"
具体请查看互助需知
我知道了
×
提示
现在去查看 取消
×
提示
确定
Book学术官方微信
Book学术文献互助
Book学术文献互助群
群 号:481959085
Book学术
文献互助 智能选刊 最新文献 互助须知 联系我们:info@booksci.cn
Book学术提供免费学术资源搜索服务,方便国内外学者检索中英文文献。致力于提供最便捷和优质的服务体验。
Copyright © 2023 Book学术 All rights reserved.
ghs 京公网安备 11010802042870号 京ICP备2023020795号-1