metastasis biomarkers

  • 文章类型: Journal Article
    主要的适应性免疫细胞是T和B淋巴细胞,它们在诱导针对犬乳腺肿瘤的免疫应答中起关键作用。研究这些细胞亚群可能会导致对这些恶性肿瘤的更精确诊断。
    CD3+的百分比,将患有恶性乳腺肿瘤的母犬外周血中的CD4和CD8T细胞以及CD21B细胞与健康动物血液中的细胞进行了比较。通过流式细胞术评估外周血白细胞的表型特征。
    健康犬(66.7%)和转移犬(46.1%)之间的CD3淋巴细胞平均百分比存在显着差异,在荷瘤非转移性犬(66.6%)和转移性犬之间。健康犬(40.4%)和转移犬(23.2%)之间的CD4T辅助细胞百分比也存在显着差异,在后者和没有它们的狗之间(35.5%)。在CD21+淋巴细胞亚群的情况下,健康动物(10.9%)和转移动物(20.1%)之间存在显着差异,在后者和没有转移的患者之间(8.5%)。有转移组的CD3+/CD21+比值也有显著差异(3.0),健康组(7.8),和无转移组(8.5)。同样,有转移的动物之间的CD4+/CD8+比率有显著差异(1.4),对照组(2.2)中的母狗,和狗没有转移(1.9)。
    外周血白细胞表型特征是推定的新型生物标志物。这些发现可能对改善乳腺肿瘤诊断程序的未来研究有用。特别是在转移检测中。
    UNASSIGNED: The main adaptive immune cells are T and B lymphocytes and they play key roles in the induction of immune responses against canine mammary tumours. Investigating these cell subpopulations may lead to more precise diagnosis of these malignancies.
    UNASSIGNED: The percentages of CD3+, CD4+ and CD8+ T cells and of CD21+ B cells in the peripheral blood of bitches with malignant mammary tumours were compared with those in the blood of healthy animals. The phenotypic features of peripheral blood leukocytes were evaluated by flow cytometry.
    UNASSIGNED: There was a significant difference in the mean percentages of CD3+ lymphocytes between healthy (66.7%) and metastatic dogs (46.1%), and between tumour-bearing non-metastatic (66.6%) and metastatic dogs. There was also a significant difference in CD4+ T helper cell percentages between healthy dogs (40.4%) and dogs with metastases (23.2%), and between the latter and dogs without them (35.5%). In the case of CD21+ lymphocyte subsets, a significant difference was noted between healthy animals (10.9%) and those with metastases (20.1%), and between the latter and patients without metastases (8.5%). There were also significant differences in CD3+/CD21+ ratios between the group with metastases (3.0), the healthy group (7.8), and the group without metastases (8.5). Similarly, a significant difference was noted in CD4+/CD8+ ratios between animals with metastases (1.4), bitches in the control group (2.2), and dogs without metastases (1.9).
    UNASSIGNED: Peripheral blood leukocyte phenotypic characteristics are putative novel biomarkers. These findings may be useful in future studies improving mammary tumour diagnostic procedures, especially in metastasis detection.
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  • 文章类型: Journal Article
    转移是食管鳞状细胞癌(ESCC)治疗的最大障碍。应用单细胞RNA测序分析来研究在多个时间点从肺转移小鼠模型分离的肺转移性ESCC细胞,以表征早期转移性微环境。鉴定出类似于转移起始细胞(MIC)的小群亲本KYSE30细胞系(簇S),因为它们在肺转移部位存活并定殖。S簇和其他亚群之间的差异表达谱比较确定了一组7个转移起始特征基因(MIS),包括CD44和TACSTD2,代表ESCC中的中等收入国家。功能研究表明,MIC(CD44high)表现出显著增强的细胞存活率(抗氧化应激和凋亡),迁移,入侵,stemness,和体内肺转移能力,虽然生物信息学分析显示器官发育增强,应激反应,和神经元发育,可能重塑早期转移微环境。同时,早期转移细胞表现出准上皮-间质表型,以支持侵袭和锚定。4种MIS的多重免疫组织化学(mIHC)染色(CD44,S100A14,RHOD,和TACSTD2)在ESCC临床样本中证明了差异MIS表达评分(dMIS)可预测淋巴结转移,总生存率,和癌症血栓形成的风险。
    Metastasis is the biggest obstacle to esophageal squamous cell carcinoma (ESCC) treatment. Single-cell RNA sequencing analyses are applied to investigate lung metastatic ESCC cells isolated from pulmonary metastasis mouse model at multiple timepoints to characterize early metastatic microenvironment. A small population of parental KYSE30 cell line (Cluster S) resembling metastasis-initiating cells (MICs) is identified because they survive and colonize at lung metastatic sites. Differential expression profile comparisons between Cluster S and other subpopulations identified a panel of 7 metastasis-initiating signature genes (MIS), including CD44 and TACSTD2, to represent MICs in ESCC. Functional studies demonstrated MICs (CD44high) exhibited significantly enhanced cell survival (resistances to oxidative stress and apoptosis), migration, invasion, stemness, and in vivo lung metastasis capabilities, while bioinformatics analyses revealed enhanced organ development, stress responses, and neuron development, potentially remodel early metastasis microenvironment. Meanwhile, early metastasizing cells demonstrate quasi-epithelial-mesenchymal phenotype to support both invasion and anchorage. Multiplex immunohistochemistry (mIHC) staining of 4 MISs (CD44, S100A14, RHOD, and TACSTD2) in ESCC clinical samples demonstrated differential MIS expression scores (dMISs) predict lymph node metastasis, overall survival, and risk of carcinothrombosis.
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  • 文章类型: Journal Article
    Background: In order to find cytogenetic and molecular metastasis biomarkers detectable in peripheral blood the spontaneous genomic instability expressed as micronuclei and Bmi-1 expression in peripheral blood of breast cancer (BC) patients were studied in different stages of the disease compared with unaffected first-degree relatives (FDRs) and normal control. Methods: The Cytokinesis Block Micronuclei Cytome (CBMN cyt) and nested real-time Reverse Transcription-Polymerase Chain Reaction (RT-PCR) assays, were respectively used to measure genomic instability and Bmi-1 gene expression in 160 Iranian individuals comprised of BC patients in different stages of the disease, unaffected FDRs and normal control groups. Result: The frequency of micronuclei and Bmi-1 expression were dramatically higher in distant metastasis compared with non-metastatic BC. In spite of micronucleus frequency with no association with lymph node (LN) involvement and hormone receptor status, the Bmi-1 expression level was higher in LN positive and triple negative patients. Conclusion: Our results indicate that increased genomic instability expressed as micronuclei and higher Bmi-1 expression in peripheral blood are associated with metastasis in breast cancer. Therefore implementation of micronucleus assay and Bmi-1 expression analysis in blood as possible cytogenetic and molecular biomarkers in clinical level may potentially enhance the quality of management of patients with breast cancer.
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