Pathology, research and practice最新文献_第10页

Interleukin-12 treatment reduces tumor growth and modulates the expression of CASKA and MIR-203 in athymic mice bearing tumors induced by the HGC-27 gastric cancer cell line 白细胞介素-12治疗可减少肿瘤生长，并调节由HGC-27胃癌细胞系诱发肿瘤的无胸腺小鼠体内CASKA和MIR-203的表达。

IF 2.9 4区医学 Q2 PATHOLOGY

Pathology, research and practice

Pub Date : 2024-10-03 DOI: 10.1016/j.prp.2024.155625

Renata Dellalibera-Joviliano , Marcelo E. Garcia , Mozart Marins , Ana L.úcia Fachin , Lucélio B. Couto , Edgar Mesquita , Tatiana T. Komoto , Gabriel Silva , Walter Campos Neto , Leonardo Orlando , Marina Durand , Suzelei C. França , Reinaldo B. Bestetti

Gastric cancer (GC) is one of the most common malignant tumors in the digestive system and due to its poor prognosis, there is an increase in the demand for more effective anticancer therapies. Interleukins are potential anticancer agents which can modulate expression of cancer related genes and have therapeutic effects. Interleukin 12 (IL-12) exhibits potent anti-tumor, anti-angiogenic and anti-metastatic activities and represents the ideal candidate for tumor immunotherapy, due to its ability to activate both innate and adaptive immunities. The aim of this study was to evaluate the effect of IL-12 administration on GC tumor growth induced in the cancer xenograft nude mouse model. Tumor development was analyzed weekly and after 8 weeks, the animals were sacrificed for cytokine analysis (IL-4, TNF-alfa, IL-2, INF-gamma, IL-12, IL-10, TGF-beta) by ELISA. The tumor cells in the implanted areas of the animals that developed solid growth of the tumor (anatomopathological analysis was performed). We have also evaluated CASK and miR203 expression, two related cell invasion factors, in the induced tumors after administration of 6 n/kg IL-12. The development of tumor masses was observed in all groups of animals inoculated with HGC-27 neoplastic cells. In animals treated with 6 n/kg IL-12, there was no tumor development confirmed by anatomopathological analysis. Changes in the levels of pro and anti-inflammatory cytokines were also observed. Our results indicated that miR203 expression was elevated while CASK was downregulated. These results suggest that IL-12 treatment repress the tumor growth by induction of miR203 expression which in turn repress CASK expression.

胃癌（GC）是消化系统中最常见的恶性肿瘤之一，由于其预后较差，对更有效抗癌疗法的需求不断增加。白细胞介素是一种潜在的抗癌剂，可以调节癌症相关基因的表达，并具有治疗效果。白细胞介素 12（IL-12）具有强大的抗肿瘤、抗血管生成和抗转移活性，能够激活先天性免疫和适应性免疫，是肿瘤免疫疗法的理想候选药物。本研究的目的是评估在癌症异种移植裸鼠模型中施用 IL-12 对 GC 肿瘤生长的影响。每周分析肿瘤的生长情况，8周后，动物被处死，用ELISA法分析细胞因子（IL-4、TNF-alfa、IL-2、INF-gamma、IL-12、IL-10、TGF-beta）。对肿瘤实体生长的动物植入部位的肿瘤细胞进行解剖病理学分析。我们还评估了 6 n/kg IL-12 给药后诱导肿瘤中两种相关细胞侵袭因子 CASK 和 miR203 的表达情况。在接种了 HGC-27 肿瘤细胞的所有动物组中都观察到了肿瘤肿块的发展。经解剖病理学分析证实，接受 6 n/kg IL-12 治疗的动物没有肿瘤发生。我们还观察到促炎和抗炎细胞因子水平的变化。我们的结果表明，miR203 的表达升高，而 CASK 的表达下调。这些结果表明，IL-12 治疗通过诱导 miR203 的表达进而抑制 CASK 的表达来抑制肿瘤的生长。

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引用次数: 0

Impact of estradiol in inducing endometrial cancer using RL95-2 雌二醇对使用 RL95-2 诱导子宫内膜癌的影响

IF 2.9 4区医学 Q2 PATHOLOGY

Pathology, research and practice

Pub Date : 2024-10-03 DOI: 10.1016/j.prp.2024.155640

Anuja Pant, Kareena Moar, Pawan Kumar Maurya

Background

Endometrial cancer is the most common gynecological malignancy that originates from the inner lining of the uterus and predominantly affects postmenopausal women. Prolonged exposure to estrogen, family history of endometrial cancer, obesity, and hormonal imbalance are some of the risk factors associated with endometrial cancer. In our study, we investigated the effect of estradiol, a potent form of estrogen at various concentrations on endometrial cell line RL95–2.

Methods

Endometrial cell RL95–2 were cultured in DMEM medium with optimal conditions required to maintain the cells. MTT assay and colony formation assay were further performed after treating the cells with different concentrations of estradiol (1, 10, and 100 nM) and TAM (100 nM). Moreover, the effect of genes regulated by estradiol was also examined using microarray and validated using real-time polymerase chain reaction (qRT-PCR).

Results

Time-dependent MTT assay shows a significant change in the ability of the cells to survive relative to concentrations. Colony formation was found to be directly proportional to the concentration of the estradiol (p < 0.05). Among genes, MMP14 (p = 0.03), SPARCL1 (p = 0.005), and CLU (p = 0.06) showed a significant up-regulation in their expression after estradiol treatment while NRN1 (p < 0.001) showed significant downregulation in expression pattern compared to control. However, the TAM treatment was found to be significantly effective after 72 h (p < 0.001) compared to control and 100 nM E2 (p = 0.0206).

Conclusion

Our study suggests that estradiol significantly contributes to regulating the viability, colony formation, and expression of genes associated with endometrial cancer.

背景：子宫内膜癌是最常见的妇科恶性肿瘤，起源于子宫内膜，主要影响绝经后妇女。长期接触雌激素、子宫内膜癌家族史、肥胖和内分泌失调是与子宫内膜癌相关的一些风险因素。在我们的研究中，我们调查了不同浓度的雌二醇（一种强效雌激素）对子宫内膜细胞株 RL95-2 的影响：方法：将子宫内膜细胞 RL95-2 培养在 DMEM 培养基中，以维持细胞所需的最佳条件进行培养。用不同浓度的雌二醇（1、10 和 100 nM）和 TAM（100 nM）处理细胞后，进一步进行 MTT 检测和集落形成检测。此外，还使用芯片检测了雌二醇调控基因的影响，并使用实时聚合酶链反应（qRT-PCR）进行了验证：结果：时间依赖性 MTT 检测显示，相对于浓度，细胞的存活能力发生了显著变化。发现菌落的形成与雌二醇的浓度成正比（p < 0.05）。在基因中，MMP14（p = 0.03）、SPARCL1（p = 0.005）和 CLU（p = 0.06）的表达在雌二醇处理后显著上调，而 NRN1（p < 0.001）的表达模式与对照组相比显著下调。然而，与对照组和 100 nM E2（p = 0.0206）相比，72 h 后发现 TAM 处理明显有效（p < 0.001）：我们的研究表明，雌二醇对子宫内膜癌相关基因的活力、集落形成和表达有明显的调节作用。

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引用次数: 0

miRNA-21, an oncomiR that regulates cell proliferation, migration, invasion and therapy response in lung cancer 调控肺癌细胞增殖、迁移、侵袭和治疗反应的 oncomiR - miRNA-21

IF 2.9 4区医学 Q2 PATHOLOGY

Pathology, research and practice

Pub Date : 2024-10-03 DOI: 10.1016/j.prp.2024.155601

Roberta Queiroz da Silvia Lima , César Freire Melo Vasconcelos , João Pedro Alves Gomes , Erika da Silva Bezerra de Menezes , Barbara de Oliveira Silva , Claudio Montenegro , Sérgio de Sá Leitão Paiva Júnior , Michelly Cristiny Pereira

Lung cancer is the leading cause of cancer-related death globally, with poor survival rates due mostly to a lack of early detection. The usual diagnostic technique includes a biopsy, which is frequently performed later in the disease's progression. In order to uncover processes that improve illness detection and prognosis, miRNA-21 emerges as a major miRNA identified in a variety of cancer types, including lung cancer. This review compiles insights into the involvement of miRNA-21 within the distinct cellular processes underlying lung cancer. To achieve this, we conducted an extensive literature review, drawing from published in vitro, in vivo and clinical trials studies. Searches were performed in the PubMed, Scielo, CAPES Journal Portal, BVS, INCA, and Clinical Trials.Gov. Only English written articles were selected. As screening criteria, we selected articles that explored the modulation pathways of miRNA-21, along with the proteins and genes implicated in tumorigenesis, metastasis, therapy resistance to established treatments, and their significance in the diagnosis and prognosis of lung cancer. A total of 3294 articles were identified, and 37 papers were selected to compose the review, after analysing selection criteria. Of these, 57 % studies presented in vitro evaluation, 22 % studies showed in vivo analysis, and 12 clinical trials were found. This study elucidates the principal signaling pathways influenced by miRNA-21, which play a pivotal role in lung cancer development. This comprehensive review sheds light on the potential significance of miRNA-21 as a critical mechanism for improving the prognosis of lung cancer patients, facilitating the transition of experimental data into the clinical phase. Therefore, we summarized published articles of miRNA-21 modulated signal pathways in lung cancer.

肺癌是全球癌症相关死亡的主要原因，其存活率低的主要原因是缺乏早期发现。通常的诊断技术包括活检，但活检往往在疾病进展的后期进行。为了揭示改善疾病检测和预后的过程，miRNA-21 成为在包括肺癌在内的多种癌症类型中发现的主要 miRNA。本综述汇集了有关 miRNA-21 参与肺癌不同细胞过程的见解。为此，我们对已发表的体外、体内和临床试验研究进行了广泛的文献综述。我们在 PubMed、Scielo、CAPES Journal Portal、BVS、INCA 和 Clinical Trials.Gov 中进行了检索。作为筛选标准，我们选择了探讨 miRNA-21 的调节途径、与肿瘤发生、转移、既有疗法的耐药性有关的蛋白质和基因及其在肺癌诊断和预后中的意义的文章。本研究共鉴定了 3294 篇文章，在分析选择标准后，选出 37 篇论文组成综述。其中，57%的研究进行了体外评估，22%的研究进行了体内分析，还发现了 12 项临床试验。本研究阐明了受 miRNA-21 影响的主要信号通路，这些通路在肺癌的发展中起着关键作用。本综述揭示了 miRNA-21 作为改善肺癌患者预后的关键机制的潜在意义，促进了实验数据向临床阶段的过渡。因此，我们总结了已发表的有关 miRNA-21 调节肺癌信号通路的文章。

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引用次数: 0

The combination of p16 and Rb expression pattern is helpful to predict high-risk HPV infection and the primary site in lymph node metastases of squamous cell carcinoma p16 和 Rb 表达模式的组合有助于预测高危 HPV 感染和鳞状细胞癌淋巴结转移的原发部位。

IF 2.9 4区医学 Q2 PATHOLOGY

Pathology, research and practice

Pub Date : 2024-10-03 DOI: 10.1016/j.prp.2024.155642

Ryosuke Kuga , Hidetaka Yamamoto , Fumiya Narutomi , Misa Suzuki , Rina Jiromaru , Takahiro Hongo , Kazuhisa Hachisuga , Nobuko Yasutake , Kiyoko Kato , Takashi Nakagawa , Yoshinao Oda

Identifying the primary site of metastatic squamous cell carcinoma in lymph nodes can be challenging. An immunohistochemistry (IHC) analysis recently revealed that high-risk human papillomavirus (HR-HPV)-associated oropharyngeal squamous cell carcinomas (OPSCCs) typically show overexpression of p16 protein and a partial loss pattern of Rb. Nevertheless, the status of these markers in metastatic lesions is still unclear. In this study, we examined p16 and Rb expression status by IHC and transcriptionally active HR-HPV infection by mRNA in situ hybridization in paired primary and metastatic SCC lesions. A total of 50 patients with OPSCCs (n=17), hypopharyngeal SCCs (n=16), laryngeal SCCs (n=6), or uterine cervical SCCs (n=11) were enrolled. HR-HPV and p16 were positive in 21/50 (42 %) and 23/50 (46 %) patients, respectively. Primary and metastatic lesions showed concordant results for those three markers in individual patients. Among the p16-positive patients (n=23), HPV-positive cases typically showed a partial loss of Rb (n=20) and, rarely, a complete loss of Rb (n=1), whereas HPV-negative cases showed preserved Rb expression (n=2). All 27 p16-negative cases lacked HPV infection, while preserved expression and complete loss of Rb were observed in 26 and 1 of the p16-negative cases, respectively. Compared to standalone p16, the combination of p16 overexpression and Rb-partial/complete loss showed equally excellent sensitivity and negative predictive value (each 100 %) as well as improved specificity (100 % versus 93.1 %) and positive predictive value (100 % versus 91.3 %). Our results suggest that combining p16 and Rb expression patterns may be helpful in screening for HR-HPV infection in metastatic lymph nodes and in estimating the primary site of SCC.

确定淋巴结转移性鳞状细胞癌的原发部位是一项挑战。最近的一项免疫组化（IHC）分析表明，与高危人乳头瘤病毒（HR-HPV）相关的口咽鳞状细胞癌（OPSCC）通常表现为p16蛋白的过度表达和Rb的部分缺失。然而，这些标记物在转移性病灶中的状况仍不清楚。在这项研究中，我们通过IHC检测了p16和Rb的表达状态，并通过mRNA原位杂交检测了配对的原发性和转移性SCC病变中转录活跃的HR-HPV感染。共纳入了50例患有OPSCC（17例）、下咽SCC（16例）、喉SCC（6例）或子宫颈SCC（11例）的患者。21/50（42%）和23/50（46%）的患者HR-HPV和p16分别呈阳性。个别患者的原发病灶和转移病灶显示这三种标记物的结果一致。在p16阳性患者（23例）中，HPV阳性病例通常表现为Rb部分缺失（20例），极少数病例表现为Rb完全缺失（1例），而HPV阴性病例则表现为Rb表达保留（2例）。所有 27 例 p16 阴性病例均未感染 HPV，而在 26 例和 1 例 p16 阴性病例中分别观察到 Rb 的保留表达和完全缺失。与单独的 p16 相比，p16 过表达和 Rb 部分/完全缺失的组合显示出同样出色的灵敏度和阴性预测值（均为 100%），以及更高的特异性（100% 对 93.1%）和阳性预测值（100% 对 91.3%）。我们的研究结果表明，结合 p16 和 Rb 的表达模式可能有助于筛查转移淋巴结中的 HR-HPV 感染和估计 SCC 的原发部位。

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引用次数: 0

Ferroptosis as a hero against oral cancer 抗击口腔癌的英雄--铁蛋白沉积症

IF 2.9 4区医学 Q2 PATHOLOGY

Pathology, research and practice

Pub Date : 2024-10-03 DOI: 10.1016/j.prp.2024.155637

Varshini Vijayarangam , Mangayer karasi Gopalakrishnan Deviparasakthi , Priyanka Balasubramanian , Thirunavukkarasu Palaniyandi , Rekha Ravindran , Muath Suliman , Mohd Saeed , Sudhakar Natarajan , Asha Sivaji , Gomathy Baskar

Cancer is an abnormal condition altering the cells to proliferate out of control simultaneously being susceptible to evolution. The lining which is made up of tissues in the lips, upper throat and mouth can undergo mutations, is recognised as mouth cancer or oral cancer. Substantial number of mouth lesions are identified at a point where it is typically not possible to get effective remedial care. Ferroptosis is a cutting-edge instance of cellular destruction which stands out in distinction to other sorts of cell death. It appears to have distinctive cellular, molecular and gene-level attributes and scavenges on deposits of reactive oxygen species triggered via iron-induced lipid peroxidation. It is said to be involved dichotomously in cancer development. Because the ferroptotic tumour cells put out numerous chemicals that alternatively signal for cancer attenuation or growth. There is increasing proof that researchers are now keenly investigating to stimulate ferroptosis through various inducers and pathways in the intent for oral cancer therapeutics, specifically to kill malignant tumours that refuse to respond well to conventional treatments. Also, it has the ability to reverse chemotherapy and radiotherapy resistance in victims maximising the success rate of the treatments. This review centres on the stimulation of ferroptosis as a stand-alone therapy for oral cancer, or in combination with other medicines, agents and pathways.

癌症是一种不正常的病症，会使细胞失控增殖，同时容易进化。由嘴唇、上喉咙和口腔组织构成的内膜会发生突变，被称为口腔癌或口腔癌。大量口腔病变被发现时，通常无法得到有效的补救治疗。铁细胞凋亡是细胞破坏的一个前沿实例，它有别于其他类型的细胞死亡。它似乎具有独特的细胞、分子和基因层面的属性，并能清除由铁诱导的脂质过氧化引发的活性氧沉积。据说，它与癌症的发展具有二重性。因为铁中毒的肿瘤细胞会释放出许多化学物质，这些化学物质是癌症衰减或生长的交替信号。越来越多的证据表明，研究人员目前正在热衷于研究通过各种诱导剂和途径来刺激铁氧化酶，以寻求口服癌症疗法，特别是杀死对传统疗法反应不佳的恶性肿瘤。此外，它还能逆转化疗和放疗对受害者的抗药性，最大限度地提高治疗的成功率。这篇综述的重点是刺激铁突变作为口腔癌的一种独立疗法，或与其他药物、制剂和途径结合使用。

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引用次数: 0

Non-coding RNAs as therapeutic targets in Parkinson’s Disease: A focus on dopamine 作为帕金森病治疗靶点的非编码 RNA：聚焦多巴胺

IF 2.9 4区医学 Q2 PATHOLOGY

Pathology, research and practice

Pub Date : 2024-10-03 DOI: 10.1016/j.prp.2024.155641

Khalid Saad Alharbi

Parkinson’s Disease is a highly complicated neurological disorder, with a key manifestation of loss of dopaminergic neurons. Despite the plethora of medicines that alleviate the symptoms, there is an urgent need for new treatments acting on the fundamental pathology of PD. Non-coding RNAs are becoming increasingly important in gene regulation and various cellular processes and are found to play a role in PD pathophysiology. This review analyzes the cross-talk of distinct ncRNAs with dopamine signaling. We attempt to constrain the various ncRNA networks that can activate dopamine production. First, we describe the deregulation of miRNAs that target dopamine receptors and have been implicated in PD. Next, we turn to the functions of lncRNAs in dopaminergic neurons and the connections to susceptibility genes for PD. Finally, we will analyze the novel circRNAs, such as ciRS-7, which may modulate dopamine-linked processes and serve as possible PD biomarkers. In this review, we describe recent progress in dopamine neuron revival to treat PD and the therapeutic potential of ncRNA. This review critically evaluates the available data, and we predict the role of some ncRNAs, such as PTBP1, to become candidate treatment targets in the future. Thus, this review aims to summarize the molecular causes for the deficit in dopamine signaling in PD and point to novel ncRNAs-linked therapeutic directions in neuroscience.

帕金森病是一种高度复杂的神经系统疾病，主要表现为多巴胺能神经元的丧失。尽管有大量药物可以缓解症状，但仍迫切需要针对帕金森病根本病理的新疗法。非编码 RNA 在基因调控和各种细胞过程中的作用日益重要，并被发现在帕金森病的病理生理学中发挥作用。本综述分析了不同的 ncRNA 与多巴胺信号传导的交叉作用。我们试图限制可激活多巴胺分泌的各种 ncRNA 网络。首先，我们描述了以多巴胺受体为靶点并与帕金森病有关的 miRNA 的失调。接下来，我们将讨论 lncRNA 在多巴胺能神经元中的功能以及与帕金森病易感基因的联系。最后，我们将分析新型 circRNA（如 ciRS-7），它们可能会调节与多巴胺相关的过程并作为可能的帕金森病生物标志物。在这篇综述中，我们将介绍多巴胺神经元复苏治疗帕金森病的最新进展以及 ncRNA 的治疗潜力。本综述批判性地评估了现有数据，并预测了一些 ncRNA（如 PTBP1）在未来成为候选治疗靶点的作用。因此，本综述旨在总结帕金森病多巴胺信号传导不足的分子原因，并指出神经科学中与 ncRNA 相关的新型治疗方向。

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引用次数: 0

Exploring circulating MiRNA signature for osteosarcoma detection: Bioinformatics-based analyzing and validation 探索用于骨肉瘤检测的循环 MiRNA 标志：基于生物信息学的分析与验证

IF 2.9 4区医学 Q2 PATHOLOGY

Pathology, research and practice

Pub Date : 2024-10-01 DOI: 10.1016/j.prp.2024.155615

Negar Heidari , Massoud Vosough , Abolfazl Bagherifard , Sam Hajialilo Sami , Pedram Asadi Sarabi , Ali Behmanesh , Roshanak Shams

Early detection followed by efficient treatment still remain a considerable challenge for osteosarcoma (OS), indicating the importance of emerging innovative diagnostic methods. Circulating miRNAs offer a promising and non-invasive approach to assess the OS molecular landscapes. This study utilized RNAseq data from OS plasma miRNA expression profiles (PRJEB30542) and PCR Array data (GSE65071) from GEO and ENA databases. In total, 43 miRNAs demonstrated significant differential expression in OS samples of training dataset. A diagnostic model, including hsa-miR-30a-5p, hsa-miR-556–3p, hsa-miR-200a-3p, and hsa-miR-582–5p was identified through multivariate logistic regression analysis and demonstrated significant efficacy in differentiating OS patients from healthy controls in the validation group (AUC: 0.917, sensitivity: 1, specificity: 0.85). The result of target gene prediction and functional enrichment analyses revealed significant associations with terms such as epithelial morphogenesis, P53 and Wnt signaling pathways, and neoplasm metastasis. Further bioinformatics-based evaluations showed that the down-regulation of these miRNAs significantly correlates with poor prognosis and lower survival rate in OS patients and propose their tumor suppressor function in pathogenesis of OS. Furthermore, the study developed a miRNA-mRNA subnetwork that connects these miRNAs to the P53 and Wnt signaling pathways, which are critical pathways with oncogenic effects on OS progression. This comprehensive approach not only presents a promising diagnostic model but also proposes potential molecular markers for OS early diagnosis, making prognosis, and targeted therapy. The identified miRNA-mRNA functional axis holds promise as a valuable resource for further research in understanding OS pathogenesis and establishing therapeutic modalities.

早期检测和有效治疗仍然是骨肉瘤（OS）面临的巨大挑战，这表明了新兴创新诊断方法的重要性。循环 miRNA 为评估 OS 分子图谱提供了一种前景广阔的非侵入性方法。本研究利用了来自 OS 血浆 miRNA 表达谱的 RNAseq 数据（PRJEB30542）和来自 GEO 和 ENA 数据库的 PCR 阵列数据（GSE65071）。在训练数据集中，共有 43 个 miRNA 在 OS 样本中表现出显著的差异表达。通过多变量逻辑回归分析，确定了一个诊断模型，包括 hsa-miR-30a-5p、hsa-miR-556-3p、hsa-miR-200a-3p 和 hsa-miR-582-5p，该模型在区分验证组 OS 患者和健康对照组方面具有显著疗效（AUC：0.917，灵敏度：1，特异性：0.85）。靶基因预测和功能富集分析的结果显示，这些基因与上皮形态发生、P53 和 Wnt 信号通路以及肿瘤转移等术语有显著关联。基于生物信息学的进一步评估表明，这些miRNA的下调与OS患者的不良预后和较低的存活率密切相关，并提出了它们在OS发病机制中的肿瘤抑制功能。此外，研究还建立了一个miRNA-mRNA子网络，将这些miRNA与P53和Wnt信号通路联系起来，而P53和Wnt信号通路是对OS进展具有致癌作用的关键通路。这种综合方法不仅提供了一种有前景的诊断模型，还为 OS 的早期诊断、预后判断和靶向治疗提出了潜在的分子标记。已确定的 miRNA-mRNA 功能轴有望成为进一步研究了解 OS 发病机制和建立治疗模式的宝贵资源。

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引用次数: 0

Expression of claudin 18.2 in poorly cohesive carcinoma and its association with clinicopathologic parameters in East Asian patients 东亚贫粘连癌中 claudin 18.2 的表达及其与临床病理参数的关系。

IF 2.9 4区医学 Q2 PATHOLOGY

Pathology, research and practice

Pub Date : 2024-09-30 DOI: 10.1016/j.prp.2024.155628

Moonsik Kim , Byung Woog Kang , Jihyun Park , Jin Ho Baek , Jong Gwang Kim

Background

Poorly cohesive carcinoma (PCC) is a distinct subtype of gastric cancer with limited therapeutic options. This study investigated claudin (CLDN) 18.2 expression status in PCCs using a 43–13 A clone.

Methods

We retrospectively collected 178 consecutive surgically resected stage Ⅱ–Ⅲ gastric cancer samples. Tissue microarray blocks were constructed for CLDN18.2 immunohistochemical staining. We studied CLDN18.2 expression and its association with clinicopathologic parameters.

Results

CLDN18.2 positivity (defined by ≥ 75 % of tumor cells showing moderate to strong membranous positivity) was found in 34.8 % of the PCC cases (62/178). Approximately half of the CLDN18.2 positive PCCs demonstrated heterogeneous expression (51.6 %, 32/62). CLDN18.2 positivity was not associated with any clinicopathologic parameters examined. However, CLDN18.2 positivity tended to be more frequent in E-cadherin-positive PCCs (no loss of expression) than in E-cadherin-negative PCCs (loss of expression) (50 % vs. 27.7 %). The CLDN18.2 expression level, represented by the H-score, gradually decreased as the paraffin block storage time increased (P = 0.046). Overall survival and disease-free survival analyses showed no significant difference between CLDN18.2-positive and negative PCCs.

Conclusions

A significant portion of surgically resected PCC specimens showed CLDN18.2 positivity. Additionally, since the expression level of CLDN18.2 gradually decreases with increased paraffin block storage time, reflex testing can be considered at the time of the cancer diagnosis.

背景：粘连性差的胃癌（PCC）是胃癌的一个独特亚型，治疗方案有限。本研究利用 43-13 A 克隆研究了 PCC 中 claudin（CLDN）18.2 的表达状况：方法：我们回顾性收集了 178 例连续手术切除的Ⅱ-Ⅲ期胃癌样本。方法：我们回顾性地收集了 178 例手术切除的Ⅱ-Ⅲ期胃癌样本，并构建了组织微阵列块进行 CLDN18.2 免疫组化染色。我们研究了CLDN18.2的表达及其与临床病理参数的关系：34.8%的PCC病例（62/178）发现了CLDN18.2阳性（定义为≥75%的肿瘤细胞显示中度至高度膜阳性）。约有一半的 CLDN18.2 阳性 PCC 呈异质性表达（51.6%，32/62）。CLDN18.2 阳性与任何临床病理参数均无关联。不过，CLDN18.2阳性在E-cadherin阳性PCC（无表达缺失）中的出现率往往高于E-cadherin阴性PCC（表达缺失）（50%对27.7%）。随着石蜡块储存时间的延长，以H-评分表示的CLDN18.2表达水平逐渐降低（P = 0.046）。总生存期和无病生存期分析表明，CLDN18.2阳性和阴性PCC之间无明显差异：结论：相当一部分手术切除的PCC标本显示CLDN18.2阳性。此外，由于 CLDN18.2 的表达水平会随着石蜡块储存时间的延长而逐渐降低，因此在诊断癌症时可考虑进行反射检测。

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引用次数: 0

The impact of exosomes on bone health: A focus on osteoporosis 外泌体对骨骼健康的影响：关注骨质疏松症。

IF 2.9 4区医学 Q2 PATHOLOGY

Pathology, research and practice

Pub Date : 2024-09-29 DOI: 10.1016/j.prp.2024.155618

Amir Mehrvar , Mohammadarian Akbari , Elaheh Mohandesi Khosroshahi , Mehrandokht Nekavand , Khatere Mokhtari , Mojtaba Baniasadi , Majid Aghababaian , Mansour Karimi , Shayan Amiri , Alireza Moazen , Mazaher Maghsoudloo , Mina Alimohammadi , Payman Rahimzadeh , Najma Farahani , Mohammad Eslami Vaghar , Maliheh Entezari , Mehrdad Hashemi

Osteoporosis is a widespread chronic condition. Although standard treatments are generally effective, they are frequently constrained by side effects and the risk of developing drug resistance. A promising area of research is the investigation of extracellular vesicles (EVs), including exosomes, microvesicles, and apoptotic bodies, which play a crucial role in bone metabolism. Exosomes, in particular, have shown significant potential in both the diagnosis and treatment of osteoporosis. EVs derived from osteoclasts, osteoblasts, mesenchymal stem cells, and other sources can influence bone metabolism, while exosomes from inflammatory and tumor cells may exacerbate bone loss, highlighting their dual role in osteoporosis pathology. This review offers a comprehensive overview of EV biogenesis, composition, and function in osteoporosis, focusing on their diagnostic and therapeutic potential. We examine the roles of various types of EVs and their cargo—proteins, RNAs, and lipids—in bone metabolism. Additionally, we explore the emerging applications of EVs as biomarkers and therapeutic agents, emphasizing the need for further research to address current challenges and enhance EV-based strategies for managing osteoporosis.

骨质疏松症是一种普遍存在的慢性疾病。虽然标准疗法普遍有效，但经常受到副作用和产生耐药性风险的限制。细胞外囊泡（EVs），包括外泌体、微囊泡和凋亡体，在骨代谢中发挥着至关重要的作用。外泌体尤其在骨质疏松症的诊断和治疗中显示出巨大的潜力。来自破骨细胞、成骨细胞、间充质干细胞和其他来源的外泌体可影响骨代谢，而来自炎症细胞和肿瘤细胞的外泌体则可能加剧骨质流失，这凸显了它们在骨质疏松症病理学中的双重作用。本综述全面概述了外泌体在骨质疏松症中的生物发生、组成和功能，重点关注其诊断和治疗潜力。我们研究了各种类型的 EV 及其载体（蛋白质、RNA 和脂质）在骨代谢中的作用。此外，我们还探讨了 EVs 作为生物标记物和治疗剂的新兴应用，强调了进一步研究的必要性，以应对当前的挑战并加强基于 EV 的骨质疏松症管理策略。

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引用次数: 0

Comprehensive clinicopathologic features in autoimmune atrophic gastritis: Insights from a European cohort of 57 patients 自身免疫性萎缩性胃炎的综合临床病理特征：从欧洲 57 例患者队列中获得的启示。

IF 2.9 4区医学 Q2 PATHOLOGY

Pathology, research and practice

Pub Date : 2024-09-29 DOI: 10.1016/j.prp.2024.155631

Luiz M. Nova-Camacho , Saul De Burgos , Irune Ruiz Diaz , Katrina Collins

Context

Autoimmune atrophic gastritis (AAG) is a frequently underdiagnosed disease due to its broad-spectrum clinical presentation. The diagnosis is based on histological confirmation of corpus-restricted metaplastic chronic atrophic gastritis.

Objective

To thoroughly describe the histological features of a European cohort of AAG patients.

Design

Clinical and pathological data of 57 out of 676 patients diagnosed with AAG were reviewed.

Results

Thirty-nine patients were female and eighteen were male. The mean age was 62 years. Antibodies were identified in 32/42 patients (76 %). Vitamin B12 levels were low (< 200 pg/mL) in 37/54 patients (69 %). Serum gastrin levels was elevated (> 115 pg/mL) in all cases tested. Associated autoimmune/inflammatory conditions were identified in 20/57 patients (35 %). Histologically, deep chronic inflammation was present in 46/57 (81 %) patients. Complete destruction of oxyntic glands was observed in 45/57 (79 %) patients. Pyloric metaplasia was present in 54/57 (95 %) patients, intestinal metaplasia in 51/57 (89 %) patients, and pancreatic metaplasia in 20/57 (35 %) patients. Among ECL cell proliferation, linear hyperplasia was present in all 57/57 patients, micronodular hyperplasia in 55/57 patients, and adenomatoid hyperplasia in 10/57 patients. ECL cell dysplasia was identified in 5/57 patients, and neuroendocrine microtumor in 4/57 patients.

Conclusions

The diagnosing of AAG remains challenging due to the greater variability in symptoms than previously recognized. It is important to consider chronic AAG, especially with other concurrent autoimmune conditions. The importance of accurate diagnosis and surveillance is based on the potential development of type 1 gastric neuroendocrine tumor and increased risk of gastric adenocarcinoma.

背景：自身免疫性萎缩性胃炎（AAG）是一种经常被漏诊的疾病，因其临床表现广泛。诊断的依据是组织学上对胃体局限性变性慢性萎缩性胃炎的确认：彻底描述欧洲 AAG 患者群的组织学特征：设计：对676名确诊为AAG患者中57名患者的临床和病理数据进行回顾：结果：39 名患者为女性，18 名患者为男性。平均年龄为 62 岁。32/42（76%）名患者体内发现了抗体。37/54 名患者（69%）的维生素 B12 水平较低（< 200 pg/mL）。所有受检病例的血清胃泌素水平均升高（> 115 pg/mL）。在 20/57 例患者（35%）中发现了相关的自身免疫/炎症情况。从组织学角度看，46/57 例患者（81%）存在深度慢性炎症。在 45/57 例（79%）患者中观察到了氧化腺的完全破坏。54/57（95%）例患者出现幽门化生，51/57（89%）例患者出现肠化生，20/57（35%）例患者出现胰腺化生。在 ECL 细胞增生中，57/57 例患者均出现了线状增生，55/57 例患者出现了微粒增生，10/57 例患者出现了腺瘤样增生。在5/57例患者中发现了ECL细胞发育不良，在4/57例患者中发现了神经内分泌微瘤：结论：AAG 的诊断仍然具有挑战性，因为其症状的变异性比以前认识到的更大。重要的是要考虑慢性 AAG，尤其是同时患有其他自身免疫性疾病的患者。准确诊断和监测的重要性在于可能发展为 1 型胃神经内分泌瘤和增加胃腺癌的风险。

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引用次数: 0