Pub Date : 2024-09-14DOI: 10.1016/j.prp.2024.155571
Liquid biopsy for CNS tumors is in its nascent phase, hindered by the low levels of circulating tumor DNA (ctDNA). Overcoming this challenge requires highly sensitive molecular techniques. DD-PCR emerges as a standout technique due to its ability to identify rare mutations, copy number variations, and circulating nucleic acids, making it one of the best methods for identifying somatic mutations in cell-free DNA (cfDNA). Despite promising results from various studies demonstrating the feasibility of obtaining informative ctDNA profiles from liquid biopsy samples, challenges persist, including the need to standardize sample collection, storage, and processing methods, define clear assay positivity thresholds, and address the overall low assay sensitivity. Our two-phase study began by assessing DD-PCR efficacy in FFPE tissues, revealing robust concordance with immunohistochemistry. In Phase 1 (85 cases), DD-PCR on FFPE tissues demonstrated 100 % sensitivity and specificity for IDH1 R132H mutations. In Phase 2 (100 cases), analysis extended to cfDNA, maintaining high specificity (100 %) with moderate sensitivity (44.2 %). Overall concordance with immunohistochemistry was 61 %, highlighting liquid biopsy's potential in glioma management. The findings emphasized DD-PCR's clinical utility in both tissue and liquid biopsy, underscoring its role in early detection, diagnosis, and therapeutic monitoring of diffuse gliomas.
{"title":"Clinical utility of plasma cell-free DNA (cfDNA) in diffuse gliomas for the detection of IDH1 R132H mutation","authors":"","doi":"10.1016/j.prp.2024.155571","DOIUrl":"10.1016/j.prp.2024.155571","url":null,"abstract":"<div><p>Liquid biopsy for CNS tumors is in its nascent phase, hindered by the low levels of circulating tumor DNA (ctDNA). Overcoming this challenge requires highly sensitive molecular techniques. DD-PCR emerges as a standout technique due to its ability to identify rare mutations, copy number variations, and circulating nucleic acids, making it one of the best methods for identifying somatic mutations in cell-free DNA (cfDNA). Despite promising results from various studies demonstrating the feasibility of obtaining informative ctDNA profiles from liquid biopsy samples, challenges persist, including the need to standardize sample collection, storage, and processing methods, define clear assay positivity thresholds, and address the overall low assay sensitivity. Our two-phase study began by assessing DD-PCR efficacy in FFPE tissues, revealing robust concordance with immunohistochemistry. In Phase 1 (85 cases), DD-PCR on FFPE tissues demonstrated 100 % sensitivity and specificity for IDH1 R132H mutations. In Phase 2 (100 cases), analysis extended to cfDNA, maintaining high specificity (100 %) with moderate sensitivity (44.2 %). Overall concordance with immunohistochemistry was 61 %, highlighting liquid biopsy's potential in glioma management. The findings emphasized DD-PCR's clinical utility in both tissue and liquid biopsy, underscoring its role in early detection, diagnosis, and therapeutic monitoring of diffuse gliomas.</p></div>","PeriodicalId":19916,"journal":{"name":"Pathology, research and practice","volume":null,"pages":null},"PeriodicalIF":2.9,"publicationDate":"2024-09-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142241049","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-09-10DOI: 10.1016/j.prp.2024.155591
Acute kidney injury (AKI) has a high rate of morbidity, death, and medical expenses, making it a worldwide public health problem. There are still few viable treatment plans for AKI despite medical advancements. A subclass of non-coding RNAs with over 200 nucleotides in length, long non-coding RNAs (lncRNAs) have a wide range of biological roles. Lately, lncRNAs have become important mediators of AKI and prospective biomarkers. However, current studies show that, via constructing the lncRNA/microRNA/target gene regulatory axis, abnormal expression of lncRNAs has been connected to significant pathogenic processes associated with AKI, such as the inflammatory response, cell proliferation, and apoptosis. In order to compete with mRNAs for binding to the same miRNAs and affect the expression of transcripts targeted by miRNAs, lncRNAs may function as competing endogenous RNAs (ceRNAs). The most widely used approach for researching the biological roles of lncRNAs is the construction of ceRNA regulation networks. Our goal in this article is to deliver an updated review of lncRNAs in AKI and to provide more knowledge on their possible applications as therapeutic targets and AKI biomarkers.
急性肾损伤(AKI)的发病率、死亡率和医疗费用都很高,是一个世界性的公共卫生问题。尽管医学在不断进步,但治疗急性肾损伤的可行方案仍然很少。作为长度超过 200 个核苷酸的非编码 RNA 的一个亚类,长非编码 RNA(lncRNA)具有广泛的生物学作用。最近,lncRNAs 已成为 AKI 的重要介质和前瞻性生物标志物。然而,目前的研究表明,通过构建 lncRNA/microRNA/目标基因调控轴,lncRNA 的异常表达与 AKI 相关的重要致病过程有关,如炎症反应、细胞增殖和凋亡。为了与 mRNA 竞争与相同的 miRNA 结合,并影响 miRNA 靶向转录本的表达,lncRNA 可作为竞争性内源性 RNA(ceRNA)发挥作用。研究 lncRNAs 生物作用最广泛使用的方法是构建 ceRNA 调控网络。本文旨在对 AKI 中的 lncRNA 进行最新综述,并就其作为治疗靶点和 AKI 生物标志物的可能应用提供更多知识。
{"title":"Long journey on the role of long non-coding RNA (lncRNA) in acute kidney injury (AKI)","authors":"","doi":"10.1016/j.prp.2024.155591","DOIUrl":"10.1016/j.prp.2024.155591","url":null,"abstract":"<div><p>Acute kidney injury (AKI) has a high rate of morbidity, death, and medical expenses, making it a worldwide public health problem. There are still few viable treatment plans for AKI despite medical advancements. A subclass of non-coding RNAs with over 200 nucleotides in length, long non-coding RNAs (lncRNAs) have a wide range of biological roles. Lately, lncRNAs have become important mediators of AKI and prospective biomarkers. However, current studies show that, via constructing the lncRNA/microRNA/target gene regulatory axis, abnormal expression of lncRNAs has been connected to significant pathogenic processes associated with AKI, such as the inflammatory response, cell proliferation, and apoptosis. In order to compete with mRNAs for binding to the same miRNAs and affect the expression of transcripts targeted by miRNAs, lncRNAs may function as competing endogenous RNAs (ceRNAs). The most widely used approach for researching the biological roles of lncRNAs is the construction of ceRNA regulation networks. Our goal in this article is to deliver an updated review of lncRNAs in AKI and to provide more knowledge on their possible applications as therapeutic targets and AKI biomarkers.</p></div>","PeriodicalId":19916,"journal":{"name":"Pathology, research and practice","volume":null,"pages":null},"PeriodicalIF":2.9,"publicationDate":"2024-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142240883","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-09-08DOI: 10.1016/j.prp.2024.155589
The 2019 widespread contagion of the human coronavirus novel type (SARS-CoV-2) led to a pandemic declaration by the World Health Organization. A daily increase in patient numbers has formed an urgent necessity to find suitable targets and treatment options for the novel coronavirus (COVID-19). Despite scientists’ struggles to discover quick treatment solutions, few effective specific drugs are approved to control SARS-CoV-2 infections thoroughly. Drug repositioning or Drug repurposing and target-based approaches are promising strategies for facilitating the drug discovery process. Here, we review current in silico, in vitro, in vivo, and clinical updates regarding proposed drugs for prospective treatment options for COVID-19. Drug targets that can direct pharmaceutical sciences efforts to discover new drugs against SARS-CoV-2 are divided into two categories: Virus-based targets, for example, Spike glycoprotein and Nucleocapsid Protein, and host-based targets, for instance, inflammatory cytokines and cell receptors through which the virus infects the cell. A broad spectrum of drugs has been found to show anti-SARS-CoV-2 potential, including antiviral drugs and monoclonal antibodies, statins, anti-inflammatory agents, and herbal products.
{"title":"Molecular targets in SARS-CoV-2 infection: An update on repurposed drug candidates","authors":"","doi":"10.1016/j.prp.2024.155589","DOIUrl":"10.1016/j.prp.2024.155589","url":null,"abstract":"<div><p>The 2019 widespread contagion of the human coronavirus novel type (SARS-CoV-2) led to a pandemic declaration by the World Health Organization. A daily increase in patient numbers has formed an urgent necessity to find suitable targets and treatment options for the novel coronavirus (COVID-19). Despite scientists’ struggles to discover quick treatment solutions, few effective specific drugs are approved to control SARS-CoV-2 infections thoroughly. Drug repositioning or Drug repurposing and target-based approaches are promising strategies for facilitating the drug discovery process. Here, we review current in silico, in vitro, in vivo, and clinical updates regarding proposed drugs for prospective treatment options for COVID-19. Drug targets that can direct pharmaceutical sciences efforts to discover new drugs against SARS-CoV-2 are divided into two categories: Virus-based targets, for example, Spike glycoprotein and Nucleocapsid Protein, and host-based targets, for instance, inflammatory cytokines and cell receptors through which the virus infects the cell. A broad spectrum of drugs has been found to show anti-SARS-CoV-2 potential, including antiviral drugs and monoclonal antibodies, statins, anti-inflammatory agents, and herbal products.</p></div>","PeriodicalId":19916,"journal":{"name":"Pathology, research and practice","volume":null,"pages":null},"PeriodicalIF":2.9,"publicationDate":"2024-09-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142172552","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-09-07DOI: 10.1016/j.prp.2024.155592
Among gynecological malignancies, ovarian cancer (OC) presents the most challenging diagnostic scenario. Despite exhaustive efforts, up to 90 % of patients treated with taxane/platinum-based chemotherapy experience relapse, leading to poor survival rates. Identifying new molecular markers that can characterize disease aggressiveness, chemoresistance, recurrence risk, and metastasis is crucial. This study aimed to assess the susceptibility of three ovarian tumor cell lines (TOV-21G, SKOV-3, and OV-90) to cisplatin and paclitaxel, and to investigate the influence of these treatments on the mRNA expression of TANK, RIPK1, NFKB1, TNFRSF10D, and TRAF2. Among the cell lines, SKOV-3 ovarian adenocarcinoma cells demonstrated the highest resistance to cisplatin treatment (0.125 mg/mL), followed by TOV-21G (0.076 mg/mL) and OV-90 cells (0.028 mg/mL). Regarding paclitaxel treatment, the SKOV-3 cell line exhibited the highest resistance (1.4 µg/mL), followed by OV-90 (1.3 µg/mL) and TOV-21G cells (0.9 µg/mL). Gene expression analysis after paclitaxel treatment remained unchanged; however, after cisplatin treatment, TNFRSF10D was observed to be upregulated nearly 100-fold in SKOV-3 compared to all other cell lines studied. SKOV-3 is described as cisplatin and tumor necrosis factor-resistant. Despite the defective signaling of the TNFRSF10D receptor for apoptosis, it can activate the NFKB transcription factor through non-canonical TRAIL signaling, contributing to a pro-inflammatory immune response. In light of this, damage associated with cisplatin increases TNFRSF10D expression and may promote cell survival through non-canonical NFKB pathway activation. This suggests that resistance to TRAIL-induced apoptosis in these cells could serve as a promising chemoresistance biomarker in OC.
{"title":"TNFRSF10D expression as a potential biomarker for cisplatin-induced damage and ovarian tumor relapse prediction","authors":"","doi":"10.1016/j.prp.2024.155592","DOIUrl":"10.1016/j.prp.2024.155592","url":null,"abstract":"<div><p>Among gynecological malignancies, ovarian cancer (OC) presents the most challenging diagnostic scenario. Despite exhaustive efforts, up to 90 % of patients treated with taxane/platinum-based chemotherapy experience relapse, leading to poor survival rates. Identifying new molecular markers that can characterize disease aggressiveness, chemoresistance, recurrence risk, and metastasis is crucial. This study aimed to assess the susceptibility of three ovarian tumor cell lines (TOV-21G, SKOV-3, and OV-90) to cisplatin and paclitaxel, and to investigate the influence of these treatments on the mRNA expression of <em>TANK</em>, <em>RIPK1</em>, <em>NFKB1</em>, <em>TNFRSF10D</em>, and <em>TRAF2</em>. Among the cell lines, SKOV-3 ovarian adenocarcinoma cells demonstrated the highest resistance to cisplatin treatment (0.125 mg/mL), followed by TOV-21G (0.076 mg/mL) and OV-90 cells (0.028 mg/mL). Regarding paclitaxel treatment, the SKOV-3 cell line exhibited the highest resistance (1.4 µg/mL), followed by OV-90 (1.3 µg/mL) and TOV-21G cells (0.9 µg/mL). Gene expression analysis after paclitaxel treatment remained unchanged; however, after cisplatin treatment, <em>TNFRSF10D</em> was observed to be upregulated nearly 100-fold in SKOV-3 compared to all other cell lines studied. SKOV-3 is described as cisplatin and tumor necrosis factor-resistant. Despite the defective signaling of the TNFRSF10D receptor for apoptosis, it can activate the NFKB transcription factor through non-canonical TRAIL signaling, contributing to a pro-inflammatory immune response. In light of this, damage associated with cisplatin increases <em>TNFRSF10D</em> expression and may promote cell survival through non-canonical NFKB pathway activation. This suggests that resistance to TRAIL-induced apoptosis in these cells could serve as a promising chemoresistance biomarker in OC.</p></div>","PeriodicalId":19916,"journal":{"name":"Pathology, research and practice","volume":null,"pages":null},"PeriodicalIF":2.9,"publicationDate":"2024-09-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142158191","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-09-04DOI: 10.1016/j.prp.2024.155577
Majority of the lung adenocarcinomas show a mixture of different histological patterns. The possibility of histologically heterogeneous areas of the adenocarcinoma showing genetic heterogeneity and harboring different driver mutations, with potentially significant clinical impact, has not been adequately addressed. Currently, there are no guidelines to suggest how to submit tumor tissue in adenocarcinomas with mixed histological features for molecular testing.
The objective of this study is to assess intra-tumoral heterogeneity in prominent driver mutations among different morphological patterns of lung adenocarcinoma, its implications on the future of molecular testing as well as its potential impact on patient management.
Twenty-three cases of mixed histology lung adenocarcinoma resected between 2018 and 2023 were retrieved from the archives. H&E slides were reviewed to identify the predominant and second most predominant histological patterns. The morphologically different tumor areas were manually macro-dissected for DNA extraction. Next-Generation Sequencing with Ion AmpliSeq™ Cancer Hotspot Panel v2 (Thermo Fisher Scientific, USA).
Thirteen cases showed the same pathological variant in both histological components tested. Three cases (13 %) exhibited disparities in the variants detected across the different histological patterns tested (p=0.025). The discrepant findings had a direct therapeutic impact in 4.3 % cases. Seven cases showed no pathogenic variants detected on either of the histological components tested.
This study elucidates the presence of infrequent yet significant intra-tumoral heterogeneity in the molecular profiles of mixed histology adenocarcinomas, highlighting the need for guidelines directing tissue selection for molecular testing to avoid missed therapeutic opportunities and mitigate disease relapse.
大多数肺腺癌显示出不同组织学形态的混合。腺癌的组织学异质性区域可能表现出遗传异质性,并携带不同的驱动基因突变,可能对临床产生重大影响,但这一问题尚未得到充分解决。本研究旨在评估肺腺癌不同形态模式中突出驱动基因突变的瘤内异质性、其对未来分子检测的影响以及对患者管理的潜在影响。对H&E切片进行了审查,以确定主要和次要的组织学模式。对形态各异的肿瘤区域进行人工宏观解剖,以提取DNA。使用 Ion AmpliSeq™ Cancer Hotspot Panel v2(赛默飞世尔科技公司,美国)进行下一代测序。三个病例(13%)在不同组织学模式下检测到的变异存在差异(P=0.025)。在 4.3% 的病例中,不同的检测结果对治疗产生了直接影响。这项研究阐明了混合组织学腺癌的分子图谱中存在不常见但却很重要的瘤内异质性,突出表明需要制定指导组织选择进行分子检测的指南,以避免错过治疗机会并减少疾病复发。
{"title":"Intratumoral heterogeneity of oncogenic drivers in mixed histology lung adenocarcinomas: How tissue selection impacts molecular testing?","authors":"","doi":"10.1016/j.prp.2024.155577","DOIUrl":"10.1016/j.prp.2024.155577","url":null,"abstract":"<div><p>Majority of the lung adenocarcinomas show a mixture of different histological patterns. The possibility of histologically heterogeneous areas of the adenocarcinoma showing genetic heterogeneity and harboring different driver mutations, with potentially significant clinical impact, has not been adequately addressed. Currently, there are no guidelines to suggest how to submit tumor tissue in adenocarcinomas with mixed histological features for molecular testing.</p><p>The objective of this study is to assess intra-tumoral heterogeneity in prominent driver mutations among different morphological patterns of lung adenocarcinoma, its implications on the future of molecular testing as well as its potential impact on patient management.</p><p>Twenty-three cases of mixed histology lung adenocarcinoma resected between 2018 and 2023 were retrieved from the archives. H&E slides were reviewed to identify the predominant and second most predominant histological patterns. The morphologically different tumor areas were manually macro-dissected for DNA extraction. Next-Generation Sequencing with Ion AmpliSeq™ Cancer Hotspot Panel v2 (Thermo Fisher Scientific, USA).</p><p>Thirteen cases showed the same pathological variant in both histological components tested. Three cases (13 %) exhibited disparities in the variants detected across the different histological patterns tested (p=0.025). The discrepant findings had a direct therapeutic impact in 4.3 % cases. Seven cases showed no pathogenic variants detected on either of the histological components tested.</p><p>This study elucidates the presence of infrequent yet significant intra-tumoral heterogeneity in the molecular profiles of mixed histology adenocarcinomas, highlighting the need for guidelines directing tissue selection for molecular testing to avoid missed therapeutic opportunities and mitigate disease relapse.</p></div>","PeriodicalId":19916,"journal":{"name":"Pathology, research and practice","volume":null,"pages":null},"PeriodicalIF":2.9,"publicationDate":"2024-09-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142169267","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-08-31DOI: 10.1016/j.prp.2024.155574
Human Papillomavirus (HPV) is a widespread infection associated with various cancers, including cervical, oropharyngeal, anal, and genital cancers. This infection contributes to 5 % of global cancer cases annually, affecting approximately 625,600 women and 69,400 men. Cervical cancer remains the most prevalent HPV-linked cancer among females, with the highest incidence seen in low and middle-income countries (LMICs). While most HPV infections are transient, factors such as HPV variants, age, gender, and socioeconomic status influence transmission risks. HPV is categorized into high-risk (HR-HPV) and low-risk types, with strains like HPV 16 and 18 displaying distinct demographic patterns. The intricate pathogenesis of HPV involves genetic and epigenetic interactions, with HPV oncogenes (E6 and E7) and integration into host DNA playing a pivotal role in driving malignancies. Early diagnostics, utilizing HPV DNA testing with surrogate markers such as p16, and advanced molecular techniques like PCR, liquid biopsy, and NGS, significantly impact the management of HPV-induced cancers. Effectively managing HPV-related cancers demands a multidisciplinary approach, including immunotherapy, integrating current therapies, ongoing trials, and evolving treatments. Prevention via HPV vaccination and the inclusion of cervical cancer screening in national immunization programs by conventional Pap smear examination and HPV DNA testing remains fundamental.Despite the preventability of HPV-related cancers, uncertainties persist in testing, vaccination, and treatment. This review article covers epidemiology, pathogenesis, diagnostics, management, prevention strategies, challenges, and future directions. Addressing issues like vaccine hesitancy, healthcare disparities, and advancing therapies requires collaboration among researchers, healthcare providers, policymakers, and the public. Advancements in understanding the disease's molecular basis and clinical progression are crucial for early detection, proper management, and improved outcomes.
{"title":"Navigating the landscape of HPV-associated cancers: From epidemiology to prevention","authors":"","doi":"10.1016/j.prp.2024.155574","DOIUrl":"10.1016/j.prp.2024.155574","url":null,"abstract":"<div><p>Human Papillomavirus (HPV) is a widespread infection associated with various cancers, including cervical, oropharyngeal, anal, and genital cancers. This infection contributes to 5 % of global cancer cases annually, affecting approximately 625,600 women and 69,400 men. Cervical cancer remains the most prevalent HPV-linked cancer among females, with the highest incidence seen in low and middle-income countries (LMICs). While most HPV infections are transient, factors such as HPV variants, age, gender, and socioeconomic status influence transmission risks. HPV is categorized into high-risk (HR-HPV) and low-risk types, with strains like HPV 16 and 18 displaying distinct demographic patterns. The intricate pathogenesis of HPV involves genetic and epigenetic interactions, with HPV oncogenes (E6 and E7) and integration into host DNA playing a pivotal role in driving malignancies. Early diagnostics, utilizing HPV DNA testing with surrogate markers such as p16, and advanced molecular techniques like PCR, liquid biopsy, and NGS, significantly impact the management of HPV-induced cancers. Effectively managing HPV-related cancers demands a multidisciplinary approach, including immunotherapy, integrating current therapies, ongoing trials, and evolving treatments. Prevention via HPV vaccination and the inclusion of cervical cancer screening in national immunization programs by conventional Pap smear examination and HPV DNA testing remains fundamental.Despite the preventability of HPV-related cancers, uncertainties persist in testing, vaccination, and treatment. This review article covers epidemiology, pathogenesis, diagnostics, management, prevention strategies, challenges, and future directions. Addressing issues like vaccine hesitancy, healthcare disparities, and advancing therapies requires collaboration among researchers, healthcare providers, policymakers, and the public. Advancements in understanding the disease's molecular basis and clinical progression are crucial for early detection, proper management, and improved outcomes.</p></div>","PeriodicalId":19916,"journal":{"name":"Pathology, research and practice","volume":null,"pages":null},"PeriodicalIF":2.9,"publicationDate":"2024-08-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142147806","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-08-30DOI: 10.1016/j.prp.2024.155576
Cancer-associated fibroblasts are the most important cellular component of the tumor microenvironment, controlling cancer progression and therapeutic response. These cells in the tumor microenvironment regulate tumor progression and development as oncogenic or tumor suppressor agents. However, the mechanisms by which CAFs communicate with cancer cells remain to investigate. Here, we review evidence that extracellular vesicles, particularly exosomes, serve as vehicles for the intercellular transfer of bioactive cargos, notably microRNAs and long non-coding RNAs, from CAFs to cancer cells. We try to highlight molecular pathways of non-coding RNAs and the interaction among these molecules. Together, these findings elucidate a critical exosome-based communication axis by which CAFs create mostly a supportive pro-tumorigenic microenvironment and highlight therapeutic opportunities for disrupting this intercellular crosstalk.
{"title":"Dissecting the roles of exosomal cancer-associated fibroblasts-derived non-coding RNAs in tumor progression: A complete guide","authors":"","doi":"10.1016/j.prp.2024.155576","DOIUrl":"10.1016/j.prp.2024.155576","url":null,"abstract":"<div><p>Cancer-associated fibroblasts are the most important cellular component of the tumor microenvironment, controlling cancer progression and therapeutic response. These cells in the tumor microenvironment regulate tumor progression and development as oncogenic or tumor suppressor agents. However, the mechanisms by which CAFs communicate with cancer cells remain to investigate. Here, we review evidence that extracellular vesicles, particularly exosomes, serve as vehicles for the intercellular transfer of bioactive cargos, notably microRNAs and long non-coding RNAs, from CAFs to cancer cells. We try to highlight molecular pathways of non-coding RNAs and the interaction among these molecules. Together, these findings elucidate a critical exosome-based communication axis by which CAFs create mostly a supportive pro-tumorigenic microenvironment and highlight therapeutic opportunities for disrupting this intercellular crosstalk.</p></div>","PeriodicalId":19916,"journal":{"name":"Pathology, research and practice","volume":null,"pages":null},"PeriodicalIF":2.9,"publicationDate":"2024-08-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142128762","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-08-30DOI: 10.1016/j.prp.2024.155572
Breast cancer, a pervasive and complex disease, continues to pose significant challenges in the field of oncology. Its heterogeneous nature and diverse molecular profiles necessitate a nuanced understanding of the underlying mechanisms driving tumorigenesis and progression. MicroRNA-21 (miR-21) has emerged as a crucial player in breast cancer development and progression by modulating apoptosis, a programmed cell death mechanism that eliminates aberrant cells. MiR-21 overexpression is a hallmark of breast cancer, and it is associated with poor prognosis and resistance to conventional therapies. This miRNA exerts its oncogenic effects by targeting various pro-apoptotic genes, including Fas ligand (FasL), programmed cell death protein 4 (PDCD4), and phosphatase and tensin homolog (PTEN). By suppressing these genes, miR-21 promotes breast cancer cell survival, proliferation, invasion, and metastasis. The identification of miR-21 as a critical regulator of apoptosis in breast cancer has opened new avenues for therapeutic intervention. This review investigates the intricate mechanisms through which miR-21 influences apoptosis, offering insights into the molecular pathways and signaling cascades involved. The dysregulation of apoptosis is a hallmark of cancer, and understanding the role of miR-21 in this context holds immense therapeutic potential. Additionally, the review highlights the clinical significance of miR-21 as a diagnostic and prognostic biomarker in breast cancer, underscoring its potential as a therapeutic target.
{"title":"MicroRNA-21 (miR-21) in breast cancer: From apoptosis dysregulation to therapeutic opportunities","authors":"","doi":"10.1016/j.prp.2024.155572","DOIUrl":"10.1016/j.prp.2024.155572","url":null,"abstract":"<div><p>Breast cancer, a pervasive and complex disease, continues to pose significant challenges in the field of oncology. Its heterogeneous nature and diverse molecular profiles necessitate a nuanced understanding of the underlying mechanisms driving tumorigenesis and progression. MicroRNA-21 (miR-21) has emerged as a crucial player in breast cancer development and progression by modulating apoptosis, a programmed cell death mechanism that eliminates aberrant cells. MiR-21 overexpression is a hallmark of breast cancer, and it is associated with poor prognosis and resistance to conventional therapies. This miRNA exerts its oncogenic effects by targeting various pro-apoptotic genes, including Fas ligand (FasL), programmed cell death protein 4 (PDCD4), and phosphatase and tensin homolog (PTEN). By suppressing these genes, miR-21 promotes breast cancer cell survival, proliferation, invasion, and metastasis. The identification of miR-21 as a critical regulator of apoptosis in breast cancer has opened new avenues for therapeutic intervention. This review investigates the intricate mechanisms through which miR-21 influences apoptosis, offering insights into the molecular pathways and signaling cascades involved. The dysregulation of apoptosis is a hallmark of cancer, and understanding the role of miR-21 in this context holds immense therapeutic potential. Additionally, the review highlights the clinical significance of miR-21 as a diagnostic and prognostic biomarker in breast cancer, underscoring its potential as a therapeutic target.</p></div>","PeriodicalId":19916,"journal":{"name":"Pathology, research and practice","volume":null,"pages":null},"PeriodicalIF":2.9,"publicationDate":"2024-08-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142122771","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-08-30DOI: 10.1016/j.prp.2024.155575
Objective
Immune-related gene expression levels in the tumor microenvironment (TM) of head and neck squamous cell carcinoma (HNSCC) patients was compared.
Materials and methods
The CD163, CD274, CD86, FUT4, FOXP3, and ITGAX levels of HNSCC patients in their tumor tissues (n =76) and surrounding tissues adjacent to the tumor (n =76) were determined using quantitative real-time PCR (qRT-PCR). Changes in these genes were also evaluated by associating with demographical data of the patients.
Results
CD163, CD274, FUT4, and FOXP3 gene expression levels were significantly higher in tumor tissue than in surrounding tissue. FUT4 fold change was statistically higher in patients with lymph node involvement. CD86 expression was statistically lower in smokers of 50 boxes per year or more. CD163, CD274, and FUT4 expressions were increased in response to the presence of extranodal extension (ENE).
Conclusions
These preliminary results demonstrate the alterations in expression levels of immunologic markers are associated with the clinical presentations of HNSCC.
Availability of data and materials
The datasets used and/or analysed during the current study available from the corresponding author on reasonable request.
{"title":"Focusing on tumor and it’s microenvironmental immune members for head and neck cancer patients","authors":"","doi":"10.1016/j.prp.2024.155575","DOIUrl":"10.1016/j.prp.2024.155575","url":null,"abstract":"<div><h3>Objective</h3><p>Immune-related gene expression levels in the tumor microenvironment (TM) of head and neck squamous cell carcinoma (HNSCC) patients was compared.</p></div><div><h3>Materials and methods</h3><p>The <em>CD163</em>, <em>CD274</em>, <em>CD86</em>, <em>FUT4</em>, <em>FOXP3</em>, and <em>ITGAX</em> levels of HNSCC patients in their tumor tissues (n =76) and surrounding tissues adjacent to the tumor (n =76) were determined using quantitative real-time PCR (qRT-PCR). Changes in these genes were also evaluated by associating with demographical data of the patients.</p></div><div><h3>Results</h3><p><em>CD163</em>, <em>CD274</em>, <em>FUT4,</em> and <em>FOXP3</em> gene expression levels were significantly higher in tumor tissue than in surrounding tissue. <em>FUT4</em> fold change was statistically higher in patients with lymph node involvement. <em>CD86</em> expression was statistically lower in smokers of 50 boxes per year or more. <em>CD163</em>, <em>CD274</em>, and <em>FUT4</em> expressions were increased in response to the presence of extranodal extension (ENE).</p></div><div><h3>Conclusions</h3><p>These preliminary results demonstrate the alterations in expression levels of immunologic markers are associated with the clinical presentations of HNSCC.</p></div><div><h3>Availability of data and materials</h3><p>The datasets used and/or analysed during the current study available from the corresponding author on reasonable request.</p></div>","PeriodicalId":19916,"journal":{"name":"Pathology, research and practice","volume":null,"pages":null},"PeriodicalIF":2.9,"publicationDate":"2024-08-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142136485","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-08-29DOI: 10.1016/j.prp.2024.155568
This review investigates the regulatory role of non-coding RNAs (ncRNAs) in estrogen receptor (ER) signaling pathways, particularly in the context of breast cancer therapy, with an emphasis on the emerging potential of nanotechnology for drug delivery. The information was obtained from reputable databases, including PubMed, Elsevier, Springer, Wiley, Taylor, and Francis, which contain past and present research. Breast cancer remains the most prevalent cancer among women worldwide, and ER signaling mechanisms heavily influence its progression. Treatment options have traditionally encompassed surgery, chemotherapy, radiation therapy, targeted therapy, and hormone therapy. In recent decades, nanomedicine has emerged as a promising approach to breast cancer treatment. By passively targeting tumor cells and reducing toxicity, nanodrugs can overcome the challenges of conventional chemotherapy. Additionally, nanocarriers can stimulate tumor cells, enhancing treatment efficacy. Recent advancements in nanomedicine offer promising approaches for targeted cancer therapy, potentially overcoming the limitations of conventional treatments. This review explores the interactions between long non-coding RNAs (lncRNAs) and microRNAs (miRNAs) with ER pathways, their impact on breast cancer progression, and how these interactions can be leveraged to enhance therapeutic efficacy through nanotechnology-based drug delivery systems.
这篇综述探讨了非编码 RNA(ncRNA)在雌激素受体(ER)信号通路中的调控作用,尤其是在乳腺癌治疗中的作用,重点是纳米技术在药物递送方面的新兴潜力。这些信息来自著名的数据库,包括 PubMed、Elsevier、Springer、Wiley、Taylor 和 Francis,其中包含过去和现在的研究。乳腺癌仍然是全球妇女中发病率最高的癌症,ER 信号机制严重影响着乳腺癌的发展。传统的治疗方法包括手术、化疗、放疗、靶向治疗和激素治疗。近几十年来,纳米医学已成为治疗乳腺癌的一种前景广阔的方法。通过被动靶向肿瘤细胞和降低毒性,纳米药物可以克服传统化疗的挑战。此外,纳米载体还能刺激肿瘤细胞,提高治疗效果。纳米医学的最新进展为癌症靶向治疗提供了前景广阔的方法,有可能克服传统疗法的局限性。本综述探讨了长非编码 RNA(lncRNA)和 microRNA(miRNA)与 ER 通路之间的相互作用、它们对乳腺癌进展的影响,以及如何利用这些相互作用通过基于纳米技术的给药系统提高疗效。
{"title":"Non-coding RNAs and estrogen receptor signaling in breast cancer: Nanotechnology-based therapeutic approaches","authors":"","doi":"10.1016/j.prp.2024.155568","DOIUrl":"10.1016/j.prp.2024.155568","url":null,"abstract":"<div><p>This review investigates the regulatory role of non-coding RNAs (ncRNAs) in estrogen receptor (ER) signaling pathways, particularly in the context of breast cancer therapy, with an emphasis on the emerging potential of nanotechnology for drug delivery. The information was obtained from reputable databases, including PubMed, Elsevier, Springer, Wiley, Taylor, and Francis, which contain past and present research. Breast cancer remains the most prevalent cancer among women worldwide, and ER signaling mechanisms heavily influence its progression. Treatment options have traditionally encompassed surgery, chemotherapy, radiation therapy, targeted therapy, and hormone therapy. In recent decades, nanomedicine has emerged as a promising approach to breast cancer treatment. By passively targeting tumor cells and reducing toxicity, nanodrugs can overcome the challenges of conventional chemotherapy. Additionally, nanocarriers can stimulate tumor cells, enhancing treatment efficacy. Recent advancements in nanomedicine offer promising approaches for targeted cancer therapy, potentially overcoming the limitations of conventional treatments. This review explores the interactions between long non-coding RNAs (lncRNAs) and microRNAs (miRNAs) with ER pathways, their impact on breast cancer progression, and how these interactions can be leveraged to enhance therapeutic efficacy through nanotechnology-based drug delivery systems.</p></div>","PeriodicalId":19916,"journal":{"name":"Pathology, research and practice","volume":null,"pages":null},"PeriodicalIF":2.9,"publicationDate":"2024-08-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142241122","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}