BrCa, Breast cancer

BrCa,乳腺癌
  • 文章类型: Journal Article
    乳腺癌是全世界女性中最主要的癌症形式。已经对其进行了严格的生物标志物鉴定和治疗靶标研究。然而,各种潜在基因及其与乳腺癌的临床相关性仍未被研究.乳腺癌的异质性是早期检测的主要挑战之一。一些研究报道了碱性磷酸盐(ALP)在不同癌症的发病机理中在肿瘤生长和总体自由生存期的调节中的重要作用。包括可能提供独特治疗靶点的乳腺癌。因此,这些发现需要对ALP基因的生物发生进行全面的研究。这项研究旨在分析碱性磷酸基因在乳腺癌中的表达,并确定乳腺癌增殖和进展的关键通路和分子机制。在这项研究中,对浸润性乳腺癌样本进行转录组分析.我们发现所有ALP基因在侵袭性小叶癌和侵袭性导管癌患者中均下调。了解这些基因在乳腺癌中的潜在分子机制和临床意义,对患者邻近正常组织和肿瘤组织中的基因表达值进行网络分析和功能富集分析。总体分析揭示了ALPL基因在所有四个ALP基因中的高度异常表达。我们确定了RUNX2和WNT3A在解除ALPL调节中的功能意义。因此,我们的研究结果表明,ALPL的下调可能是浸润性乳腺癌进展为骨转移的潜在标记基因.
    Breast Cancer is the most predominant form of cancer among women worldwide. It has been rigorously studied for biomarker identifications and therapeutic targets. However, various potential genes and their clinical relevance to breast cancer remain unexplored. The heterogeneity of breast cancer is one of the major challenges in early detection. Several studies have reported the significant role of alkaline phosphate (ALP) in the regulation of tumor growth and overall free survival in the pathogenesis of different cancer, including breast cancer which may offer unique therapeutic targets. Therefore, these findings demand a comprehensive study for the biogenesis of ALP genes. This study aims to expression profiling of alkaline phosphate genes in breast cancer and to identify the key pathways and molecular mechanisms underlying breast cancer proliferation and progression. In this study, the transcriptome profiling of invasive breast carcinoma samples was performed and analyzed. We identified that all the ALP genes were downregulated in both Invasive Lobular and Invasive Ductal Carcinoma patients. To understand the underlying molecular mechanism and the clinical significance for these genes in breast cancer, the expression values of genes were measured in adjacent normal and tumor tissues of patients followed by network analysis and functional enrichment analysis. The overall analysis revealed the highly aberrant expression of ALPL gene among all four ALP genes. We identified the functional significance of RUNX2 and WNT3A in deregulating ALPL. Therefore, our findings suggests that downregulation of ALPL could be a potential marker gene for invasive breast carcinoma progression towards bone metastasis.
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  • 文章类型: Journal Article
    BRCA1/2突变的女性在其一生中患乳腺癌/卵巢癌的风险增加11-72%。目前的研究调查了有和没有癌症病史的BRCA1/2阳性女性样本与三个没有BRCA1/2突变的美国女性样本之间的社会心理差异。
    60名BRCA1/2阳性女性(有和没有癌症病史)是通过美国多个私人在线支持小组招募的。参与者完成了一项在线调查,概述了社会人口统计学和遗传咨询信息,和焦虑,压力,和健康相关生活质量(HRQoL)结果。通过独立样本t检验分析,将结果与三个相似的美国女性规范样本进行比较。
    在当前BRCA1/2阳性女性样本中,状态和特质焦虑(p=0.00)和压力(p=0.001)与可比的美国女性样本相比明显更差。所有HRQoL域在当前样本中都明显更好,除了能量/活力,在当前样本中显著较低(p=0.02)。结果按癌症和复发状态分层。
    这项研究提供了与三个规范女性人群相比,患有和不患有癌症的BRCA1/2阳性女性样本如何进行遗传咨询。结果推断需要额外的教育,患者提供者培训,和心理健康转介,以支持这一人群,以规避意想不到的后果,并改善接受测试的人的社会心理健康,那些测试呈阳性的人,BRCA1/2基因突变。
    UNASSIGNED: Women with BRCA1/2 mutations have a 11-72% increased risk of breast/ovarian cancers throughout their lifetime. The current study examines psychosocial differences between the current sample of BRCA1/2-positive women with and without cancer histories and three comparable United States (US) female samples without BRCA1/2 mutations.
    UNASSIGNED: Sixty BRCA1/2-positive women (with and without cancer histories) were recruited through multiple private online support groups in the US. Participants completed an online survey outlining sociodemographic and genetic counseling information, and anxiety, stress, and health-related quality of life (HRQoL) outcomes. Outcomes were compared to three similar US female normative samples via independent samples t-test analyses.
    UNASSIGNED: State and trait anxiety (p = 0.00) and stress (p = 0.001) were significantly worse in the current sample of BRCA1/2-positive women compared comparable US female samples. All HRQoL domains were significantly better in the current sample except energy/vitality, which was significantly lower (p = 0.02) in the current sample. Results were stratified by cancer and recurrence status.
    UNASSIGNED: This study provides insight into how a sample of BRCA1/2-positive women both with and without cancer fare post-genetic counseling as compared to three normative female populations. Results infer the need for additional education, patient-provider training, and mental health referrals to support this population in order to circumvent unintended consequences and to improve psychosocial health in those being tested for, and those who test positive for, BRCA1/2 genetic mutations.
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  • 文章类型: Journal Article
    UNASSIGNED:据估计,在其一生中,有12.5%的女性将被诊断出患有乳腺癌,而1.10%的女性将被诊断出患有卵巢癌。虽然不太常见,具有这些突变的女性患乳腺癌/卵巢癌的风险增加11-72%,并且具有遗传性.基因检测/咨询提供了在癌症诊断之前识别BRCA1/2基因突变携带者的机会。
    UNASSIGNED:通过在线国家支持小组招募了34名BRCA1/2阳性女性(有或没有乳腺癌/卵巢癌病史),以更好地了解他们的基因检测/咨询看法和经验。确认合格后,他们被邀请参加电话或网络摄像头采访。使用定性主题文本分析和描述性编码技术对访谈笔录进行了分析。
    未经授权:出现了六大主题,捕捉对这些妇女的基因检测/咨询的看法和经验:1)对结果和遗传咨询的情绪反应,2)未来的建议,3)家庭团结和支持,4)医疗保健系统的经验,5)预防性关注和决定,和6)影响感知风险的来源。在第一个主题中也出现了两个子主题,被称为“前生物”,\"和\"测试直觉。\"
    UNASSIGNED:参与者表示,基因检测/咨询的改善将有助于该人群中围绕优质护理的女性,包括对参与测试/咨询的医疗保健专业人员的敏感性培训,额外的教育资源,增加情感和经济支持。虽然这些建议可能是有益的,在实施之前,可能需要对不同群体进行更广泛的研究,并对不同群体进行更广泛的研究。
    UNASSIGNED: It is estimated that 12.5% of women will be diagnosed with breast cancer and 1.10% with ovarian cancer during their lifetime. Although less common, women with these mutations have a 11-72% increased risk of breast/ovarian cancers and are hereditary. Genetic testing/counseling presents the opportunity to identify carriers of BRCA1/2 genetic mutations before a cancer diagnosis.
    UNASSIGNED: Thirty-four BRCA1/2-positive women (with and without histories of breast/ovarian cancers) were recruited through online national support groups to gain a better understanding of their genetic testing/counseling perceptions and experiences. After confirming eligibility, they were invited to participate in either a telephone or webcam interview. Interview transcripts were analyzed using qualitative thematic text analysis and descriptive coding techniques.
    UNASSIGNED: Six major themes emerged, capturing the perceptions and experiences of genetic testing/counseling for these women: 1) Emotional Reactions to Results and Genetic Counseling, 2) Future Recommendations, 3) Family Solidarity and Support, 4) Experiences with the Healthcare System, 5) Preventive Concerns and Decisions, and 6) Sources Affecting Perceived Risk. Two subthemes also emerged within the first theme, which are termed \"Pre-vivor,\" and \"Testing Intuition.\"
    UNASSIGNED: Participants indicated that genetic testing/counseling improvements would be helpful for women in this population surrounding quality care, including sensitivity training for healthcare professionals involved in testing/counseling, additional educational resources, and increased emotional and financial support. Although these recommendations may be beneficial, more widespread research with greater generalizability to disparate groups may be necessary prior to implementation.
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  • 文章类型: Journal Article
    肿瘤异质性和转移机制不明确是导致三阴性乳腺癌(TNBC)无法获得有效靶向治疗的主要原因。一种乳腺癌(BrCa)亚型,其特征是高死亡率和高频率的远处转移病例。预后生物标志物的鉴定可以改善预后和个性化治疗方案。在这里,我们收集了代表TNBC和非TNBCBrCa的基因表达数据集。从完整的数据集中,还构建了一个仅反映已知癌症驱动基因的子集。采用递归特征消除(RFE)来鉴定将TNBC与其他BrCa亚型区分开的前20、25、30、35、40、45和50个基因标签。在这些选定的特征和模型性能评估的基础上,采用了五种机器学习算法,发现对于完整和驱动程序数据集,XGBoost对25个和20个基因的子集表现最好,分别。在这两个数据集中的45个基因中,发现34个基因受到差异调节。Kaplan-Meier(KM)分析了这34个差异调节基因的远处无转移生存(DMFS),揭示了四个基因,其中两个是新的,可能是潜在的预后基因(POU2AF1和S100B)。最后,我们进行了相互作用组和通路富集分析,以研究已鉴定的潜在预后基因在TNBC中的功能作用.这些基因与MAPK有关,PI3-AkT,Wnt,TGF-β,和其他信号转导途径,在转移级联中至关重要。这些基因标签可以提供对转移的新的分子水平见解。
    Tumor heterogeneity and the unclear metastasis mechanisms are the leading cause for the unavailability of effective targeted therapy for Triple-negative breast cancer (TNBC), a breast cancer (BrCa) subtype characterized by high mortality and high frequency of distant metastasis cases. The identification of prognostic biomarker can improve prognosis and personalized treatment regimes. Herein, we collected gene expression datasets representing TNBC and Non-TNBC BrCa. From the complete dataset, a subset reflecting solely known cancer driver genes was also constructed. Recursive Feature Elimination (RFE) was employed to identify top 20, 25, 30, 35, 40, 45, and 50 gene signatures that differentiate TNBC from the other BrCa subtypes. Five machine learning algorithms were employed on these selected features and on the basis of model performance evaluation, it was found that for the complete and driver dataset, XGBoost performs the best for a subset of 25 and 20 genes, respectively. Out of these 45 genes from the two datasets, 34 genes were found to be differentially regulated. The Kaplan-Meier (KM) analysis for Distant Metastasis Free Survival (DMFS) of these 34 differentially regulated genes revealed four genes, out of which two are novel that could be potential prognostic genes (POU2AF1 and S100B). Finally, interactome and pathway enrichment analyses were carried out to investigate the functional role of the identified potential prognostic genes in TNBC. These genes are associated with MAPK, PI3-AkT, Wnt, TGF-β, and other signal transduction pathways, pivotal in metastasis cascade. These gene signatures can provide novel molecular-level insights into metastasis.
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  • 文章类型: Journal Article
    The changing landscape of gynaecological and breast cancers has involved the development of more targeted and effective therapies, and improved survival. Ultimately, these changes result in an increasing number of women surviving their cancer diagnosis, with increasing emphasis on quality-of-life issues by following treatments. Many of these women experience severe menopausal symptoms associated with cancer treatments, but the hormonal nature of many gynaecological and breast cancers complicates the effective management of these symptoms. Generally, there is a paucity of high-quality data directly examining the safety of menopausal hormone therapy (MHT) following many female cancers, and more research is needed with long term follow-up to ensure the provision of comprehensive, patient-focussed care. This article aims to synthesise and evaluate the current evidence to provide comprehensive yet accessible information to clinicians to help guide treatment decisions about the use of MHT in women, who have experienced, or are at increased risk of, both gynaecological and breast cancers. These treatment decisions should often be made in a multi-disciplinary setting which encourages shared decision-making with patients.
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  • 文章类型: Journal Article
    miR-18a是称为miR-17-92a(C13orf25或MIR17HG)的初级转录物的成员,它还包含五个其他miRNA:miR-17,miR-19a,miR-20a,miR-19b和miR-92a。这个集群作为一个整体显示出特定的特征,miR-18a似乎是独一无二的。与其他成员相比,miR-18a的表达受到额外控制,并可能充当其自身的簇内部控制器.miR-18a调节许多参与增殖的基因,细胞周期,凋亡,对不同压力的反应,自噬和分化。在癌症以及不同的疾病或病理状态中观察到miR-18a表达的紊乱。miR-17-92a簇通常被描述为致癌的,它被称为“oncomiR-1”,但这种说法是一种简化,因为miR-18a既可以作为癌基因又可以作为抑制因子。在这篇综述中,我们总结了有关miR-18a的最新知识,重点是其调控,在癌症生物学中的作用和作为潜在生物标志物的效用。
    miR-18a is a member of primary transcript called miR-17-92a (C13orf25 or MIR17HG) which also contains five other miRNAs: miR-17, miR-19a, miR-20a, miR-19b and miR-92a. This cluster as a whole shows specific characteristics, where miR-18a seems to be unique. In contrast to the other members, the expression of miR-18a is additionally controlled and probably functions as its own internal controller of the cluster. miR-18a regulates many genes involved in proliferation, cell cycle, apoptosis, response to different kinds of stress, autophagy and differentiation. The disturbances of miR-18a expression are observed in cancer as well as in different diseases or pathological states. The miR-17-92a cluster is commonly described as oncogenic and it is known as \'oncomiR-1\', but this statement is a simplification because miR-18a can act both as an oncogene and a suppressor. In this review we summarize the current knowledge about miR-18a focusing on its regulation, role in cancer biology and utility as a potential biomarker.
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  • 文章类型: Journal Article
    OBJECTIVE: The goal of this study was to determine whether a delay in starting treatment via surgery or neoadjuvant chemotherapy is related to a decrease in cancer-specific survival (CSS) in women with operable breast cancer (BrCr).
    BACKGROUND: Limited medical infrastructure and a lack of cancer prevention awareness in low- and middle-income countries have caused high BrCr incidence and mortality rates.
    METHODS: We analyzed a retrospective cohort of 720 women treated at a single center from 2005 to 2012. CSS estimates were obtained by the Kaplan-Meier method. A Cox model of proportional risks was performed to obtain the risk of dying from BrCr. We also obtained the risk according to the category of treatment initiation.
    RESULTS: Women with locally advanced stages and without hormone receptor expression were more likely to initiate treatment after 45 days. Patients in Stage IIIA had a 78.1% survival if treatment was initiated before 45 days (95% CI, 0.70-0.84) and 63.6% survival if treatment was started after 45 days (95% CI, 0.44-0.78; p < 0.001). Patients in Stage IIIB had a 62.9% survival if treatment was initiated before 45 days (95% CI, 0.53-0.72) and 57.4% survival if treatment started after 45 days (95% CI, 0.31-0.89; p < 0.001). Prognostic factors in which lower survival was recognized were Stage IIIA, Stage IIIB, treatment initiation after 45 days, and triple-negative tumors.
    CONCLUSIONS: The initiation of treatment within the first 45 days of diagnosis of BrCr in women portends better survival compared with those who began treatment longer than 45 days from diagnosis.
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  • 文章类型: Journal Article
    Epigenetic changes play significant roles in cancer development. UHRF1, an epigenetic regulator, has been shown to be overexpressed and to coordinate tumor suppressor gene (TSG) silencing in several cancers. In a previous study, we found that UHRF1 promoted gastric cancer (GC) invasion and metastasis. However, the role and underlying mechanism of UHRF1 in GC carcinogenesis remain largely unknown. In the present study, we investigated UHRF1 expression and function in GC proliferation and explored its downstream regulatory mechanism. The results demonstrated that UHRF1 overexpression was an independent and significant predictor of GC prognosis. Downregulation of UHRF1 suppressed GC proliferation and growth in vitro and in vivo, and UHRF1 upregulation showed opposite effects. Furthermore, downregulation of UHRF1 reactivated 7 TSGs, including CDX2, CDKN2A, RUNX3, FOXO4, PPARG, BRCA1 and PML, via promoter demethylation. These results provide insight into the GC proliferation process, and suggest that targeting UHRF1 represents a new therapeutic approach to block GC development.
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