正しい方法がわかる臨床基本手技 : from the New England journal of medicine

The mammary gland is a highly dynamic organ that undergoes profound changes within its epithelium during puberty and the reproductive cycle. These changes are fueled by dedicated stem and progenitor cells. Both short- and long-lived lineage-restricted progenitors have been identified in adult tissue as well as a small pool of multipotent mammary stem cells (MaSCs), reflecting intrinsic complexity within the epithelial hierarchy. While unipotent progenitor cells predominantly execute day-to-day homeostasis and postnatal morphogenesis during puberty and pregnancy, multipotent MaSCs have been implicated in coordinating alveologenesis and long-term ductal maintenance. Nonetheless, the multipotency of stem cells in the adult remains controversial. The advent of large-scale single-cell molecular profiling has revealed striking changes in the gene expression landscape through ontogeny and the presence of transient intermediate populations. An increasing number of lineage cell-fate determination factors and potential niche regulators have now been mapped along the hierarchy, with many implicated in breast carcinogenesis. The emerging diversity among stem and progenitor populations of the mammary epithelium is likely to underpin the heterogeneity that characterizes breast cancer.

https://journals.physiology.org/doi/pdf/10.1152/physrev.00040.2018

Stem Cells and the Differentiation Hierarchy in Mammary Gland Development

As an aggressive subtype of breast cancer with a high risk of recurrence, triple-negative breast cancer (TNBC) lacks available treatment targets. LncRNA MIR100HG promotes cell proliferation in TNBC. However, few studies have investigated the molecular mechanism of MIR100HG in TNBC. Thus, additional in-depth investigations are needed to unravel its associated regulatory mechanism. MIR100HG and miR-5590-3p expression in TNBC tissue samples and cell lines was detected by RT-qPCR. Flow cytometry, transwell, wound-healing, CCK8 and colony formation assays were performed to analyse cell apoptosis, cell cycle, invasion, migration and proliferation. The protein expression of orthodenticle homeobox 1 (OTX1) and proteins in the ERK/MAPK signalling pathway were assessed by western blot analysis. Bioinformatics and luciferase assay were performed to predict and validate the interaction between MIR100HG and miR-5590-3p as well as OTX1 and miR-5590-3p. RNA immunoprecipitation (RIP) was used to detect the interaction between MIR100HG and miR-5590-3p. Subcutaneous tumour growth was observed in nude mice. Immunohistochemistry (IHC) analysis was used to assess OTX1 expression in tumour tissues. MIR100HG expression was upregulated, whereas that of miR-5590-3p was downregulated in TNBC. MIR100HG was shown to directly interact with miR-5590-3p. Furthermore, MIR100HG knockdown could promote TNBC cell apoptosis and cell cycle arrest in G0/G1 phase while inhibiting migration, invasion and proliferation. Furthermore, miR-5590-3p inhibition showed the opposite results and could reverse the effect of MIR100HG knockdown in TNBC cells. MiR-5590-3p downregulated the ERK/MAPK signalling pathway, suppressed the migration, invasion and proliferation of TNBC cells and promoted their apoptosis and cell cycle arrest in G0/G1 phase by targeting OTX1. In addition, MIR100HG knockdown inhibited OTX1 expression by upregulating miR-5590-3p in vivo, thereby inhibiting tumour growth. MIR100HG promotes the progression of TNBC by sponging miR-5590-3p, thereby upregulating OTX1, suggesting a new potential treatment target for TNBC.

/pdf/long-non-coding-rna-mir100hg-promotes-the-migration-invasion-4acdpn01an.pdf

Long non-coding RNA MIR100HG promotes the migration, invasion and proliferation of triple-negative breast cancer cells by targeting the miR-5590-3p/OTX1 axis

Accurate determination of the aberrantly expressed biomarkers such as human epidermal growth factor receptor 2 (HER2), carcinoembryonic antigen (CEA), platelet-derived growth factor (PDGF), mucin 1...

Aptamer-based sensing of breast cancer biomarkers: a comprehensive review of analytical figures of merit.

While the stem cell marker Musashi-1 (MSI-1) has been identified as a key player in a wide array of malignancies, few findings exist on its prognostic relevance and relevance for cancer cell death and therapy resistance in breast cancer. First, we determined prognostic relevance of MSI-1 in database analyses regarding multiple survival outcomes. To substantiate findings, MSI-1 was artificially downregulated in MCF-7 breast cancer cells and implications for cancer stem cell markers, cell apoptosis and apoptosis regulator p21, proliferation and radiation response were analyzed via flow cytometry and colony formation. Radiation-induced p21 expression changes were investigated using a dataset containing patient samples obtained before and after irradiation and own in vitro experiments. MSI-1 is a negative prognostic marker for disease-free and distant metastasis-free survival in breast cancer and tends to negatively influence overall survival. MSI-1 knockdown downregulated stem cell gene expression and proliferation, but increased p21 levels and apoptosis. Similar to the MSI-1 knockdown effect, p21 expression was strongly increased after irradiation and was expressed at even higher levels in MSI-1 knockdown cells after irradiation. Finally, combined use of MSI-1 silencing and irradiation reduced cancer cell survival. MSI-1 is a prognostic marker in breast cancer. MSI-1 silencing downregulates proliferation while increasing apoptosis. The anti-proliferation mediator p21 was upregulated independently after both MSI-1 knockdown and irradiation and even more after both treatments combined, suggesting synergistic potential. Radio-sensitization effects after combining radiation and MSI-1 knockdown underline the potential of MSI-1 as a therapeutic target.

/pdf/knockdown-of-the-prognostic-cancer-stem-cell-marker-musashi-4wzvdwv051.pdf

Knockdown of the prognostic cancer stem cell marker Musashi-1 decreases radio-resistance while enhancing apoptosis in hormone receptor-positive breast cancer cells via p21WAF1/CIP1.

Nestin has been revealed to promote tumorigenesis, progression, metastasis, and angiogenesis of breast cancer. Although the prognostic and clinicopathological impact of nestin expression on breast cancer patients has been assessed in several independent studies, their results remained conflicting. Therefore, we performed this meta-analysis to elucidate the prognostic and clinicopathological association of nestin expression with breast cancer. A comprehensive literature search was performed in the electronic databases PubMed, EMBASE, Web of Science, the Cochrane Library, China National Knowledge Infrastructure (CNKI), and the Wangfang Data. The statistical analysis was conducted using Stata 15.0 and Review Manager 5.3. A total of 15 studies with 6066 breast cancer patients were included in this meta-analysis. Pooled results indicated that positive expression of nestin was significantly associated with reduced breast cancer-specific survival (BCSS, univariate analysis, HR = 2.11, 95% CI [1.79, 2.49], P   0.05). In addition, increased nestin expression was correlated with younger age, higher tumor grade, larger tumor size, positive blood vessel invasion and high vascular proliferation index, but not with lymph node metastasis or lymph vessel invasion. Nestin was preferentially expressed in invasive ductal carcinoma, triple-negative breast cancer and basal-like subtypes. Nestin expression was inversely associated with the expression of ER and PR, but not with HER-2. Conversely, nestin expression was positively correlated with the expression of basal-like markers CK5, P-cadherin and EGFR. Moreover, nestin expression was strongly associated with the presence of five basal-like profiles (BLP1-5). This meta-analysis revealed the prognostic value and clinicopathological significance of nestin expression in breast cancer. Nestin is an independent prognostic factor for worse BCSS and OS of breast cancer patients. Nestin is also a valuable biomarker for unfavorable clinicopathological features and tumor angiogenesis of breast cancer. Therefore, nestin is a promising therapeutic target for malignant breast cancer, especially for TNBC and basal-like phenotype.

/pdf/clinicopathological-and-prognostic-significance-of-nestin-4rpr2wpqe6.pdf

Clinicopathological and prognostic significance of nestin expression in patients with breast cancer: a systematic review and meta-analysis


 Background Evaluation of the feasibility for osteopontin (OPN) to serve as a biomarker in the prognosis and clinical pathological features of prostate cancer patients.Methods The original publications related to osteopontin and prostate cancer were comprehensively searched in the online databases, including PubMed, Embase, Cochrane Library, Web of Science, Medline, Wanfang database and China National Knowledge Infrastructure up to August 2019. Results were analyzed by software Revman 5.3 and Stata 12.0.Results A total of 21 studies were included in the analysis and the result showed that the positive OPN expression group had a lower overall survival than the negative expression group (univariate: HR = 2.32, 95%CI [1.74, 3.10], multivariate: HR = 2.41, 95%CI [1.63, 3.57]) and a lower biochemical relapse-free survival than the negative group (univariate: HR = 1.42, 95%CI [0.92, 2.17], multivariate: HR = 1.61, 95%CI [1.39, 1.87]). In addition, there was a higher expression level of OPN in prostate cancer tissues than in normal prostate tissues (OR = 46.55, 95%CI [12.85, 168.59], p < 0.00001) and benign prostatic hyperplasia tissues (OR = 11.07, 95%CI [3.43, 35.75], p < 0.0001). Moreover, OPN positive expression was also related to high Gleason score (OR = 2.64, 95%CI [1.49, 4.70], p = 0.0009), high TNM stage (OR = 3.15, 95%CI [1.60, 6.20, p = 0.0009), high Whitmore-Jewett stage (OR = 2.53, 95%CI [1.06, 6.03], p = 0.04), high lymph node (OR = 3.69, 95%CI [1.88, 7.23], p = 0.0001), and distant metastasis (OR = 8.10, 95%CI [2.94, 22.35], p = 0.01). There was no difference observed in the differentiation of prostate cancer (OR = 1.79, 95%CI [0.39, 8.33], p = 0.46).Conclusion Osteopontin could be recognized as a promising novel diagnostic and prognostic biomarker for prostate cancer patients.

/pdf/osteopontin-as-a-novel-biomarker-for-the-prognosis-and-35kbu5o6mb.pdf

Osteopontin as a novel biomarker for the prognosis and clinical pathology of prostate cancer: a systematic review and meta-analysis

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Clinicopathological and prognostic significance of nestin expression in patients with breast cancer: a systematic review and meta-analysis

Osteopontin as a novel biomarker for the prognosis and clinical pathology of prostate cancer: a systematic review and meta-analysis