ABSTRACT
The majority of advanced breast cancers exhibit strong aggressiveness, heterogeneity, and drug resistance, and currently, the lack of effective treatment strategies is one of the main challenges that cancer research must face. Therefore, developing a feasible preclinical model to explore tailored treatments for refractory breast cancer is urgently needed. We established organoid biobanks from 17 patients with breast cancer and characterized them by immunohistochemistry (IHC) and next generation sequencing (NGS). In addition, we in the first combination of patient-derived organoids (PDOs) with mini-patient-derived xenografts (Mini-PDXs) for the rapid and precise screening of drug sensitivity. We confirmed that breast cancer organoids are a high-fidelity three-dimension (3D) model in vitro that recapitulates the original tumour's histological and genetic features. In addition, for a heavily pretreated patient with advanced drug-resistant breast cancer, we combined PDO and Mini-PDX models to identify potentially effective combinations of therapeutic agents for this patient who were alpelisib + fulvestrant. In the drug sensitivity experiment of organoids, we observed changes in the PI3K/AKT/mTOR signalling axis and oestrogen receptor (ER) protein expression levels, which further verified the reliability of the screening results. Our study demonstrates that the PDO combined with mini-PDX model offers a rapid and precise drug screening platform that holds promise for personalized medicine, improving patient outcomes and addressing the urgent need for effective therapies in advanced breast cancer.
Subject(s)
Breast Neoplasms , Organoids , Precision Medicine , Humans , Breast Neoplasms/drug therapy , Breast Neoplasms/pathology , Breast Neoplasms/metabolism , Female , Organoids/drug effects , Organoids/pathology , Organoids/metabolism , Precision Medicine/methods , Animals , Xenograft Model Antitumor Assays , Mice , Drug Resistance, Neoplasm/drug effects , Drug Screening Assays, Antitumor/methods , Middle AgedABSTRACT
BACKGROUND: Triple-negative breast cancer (TNBC), the most aggressive subtype of breast cancer, always exhibits a poor prognosis due to high risk of early recurrence and distant metastasis. Long noncoding RNAs (lncRNAs) have been reported as crucial regulators in breast cancer. However, the functions and action mechanisms of lncRNA ST8SIA6-AS1 in TNBC are largely unknown. METHODS: Quantitative real-time PCR and western blot assays were used to measure the expression levels of different genes and proteins. Cell proliferation ability was monitored by CCK-8, colony forming and flow cytometry assays. Wound healing and transwell assays were performed to evaluate cell migration and invasion. The regulatory mechanisms of ST8SIA6-AS1 in TNBC were confirmed by dual luciferase reporter and RIP assays. A mouse xenograft model was established to investigate the role of ST8SIA6-AS1 in TNBC tumor growth. RESULTS: ST8SIA6-AS1 displayed a higher expression in TNBC cells. Silencing ST8SIA6-AS1 impaired cell proliferation, cell cycle progression, migration, and invasion in vitro, and slowed tumor growth in vivo. Mechanistically, ST8SIA6-AS1 could facilitate the expression of its target CDCA3 (cell division cycle associated protein 3) and inactivate the p53/p21 signaling by inhibiting miR-145-5p. Moreover, miR-145-5p exerted a tumor-suppressive activity by targeting CDCA3. The tumor-suppressive effects induced by ST8SIA6-AS1 knockdown were abated by the down-regulation of miR-145-5p or the up-regulation of CDCA3. CONCLUSION: ST8SIA6-AS1 exerts an oncogenic role in TNBC by interacting with miR-145-5p to up-regulate CDCA3 expression and inactivate the p53/p21 signaling, highlighting ST8SIA6-AS1 as a promising molecular target to combat TNBC.
Subject(s)
MicroRNAs , RNA, Long Noncoding , Triple Negative Breast Neoplasms , Animals , Cell Cycle Proteins/metabolism , Cell Line, Tumor , Cell Movement/genetics , Cell Proliferation/genetics , Disease Progression , Gene Expression Regulation, Neoplastic , Humans , Mice , MicroRNAs/genetics , MicroRNAs/metabolism , RNA, Long Noncoding/genetics , RNA, Long Noncoding/metabolism , Sialyltransferases/genetics , Sialyltransferases/metabolism , Signal Transduction/genetics , Triple Negative Breast Neoplasms/genetics , Triple Negative Breast Neoplasms/pathology , Tumor Suppressor Protein p53/genetics , Tumor Suppressor Protein p53/metabolismABSTRACT
Breast cancer, as the most common malignancy, is the second leading cause of cancer-related death in women. One of the kelch family member ENC1 is involved in various pathophysiologic processes. But the role of ENC1 in breast cancer has not been investigated. The present study value the feature, clinical significance and the molecular mechanisms of ENC1 in breast cancer. The expression and prognosis value of ENC1 expression among breast cancer and normal breast tissue were investigated in The Cancer Genome Atlas database and human samples. ENC1 was knockdown to explore its function in various breast cancer cell lines. Western blot was performed to explore the potential molecular mechanisms. We observed that ENC1 was overexpressed in breast cancer tissues. ENC1 overexpression was associated with high metastasis and predicted a poor prognosis in patients with breast cancer. ENC1 Knockdown inhibits the growth, clone formation, migration and invasion of breast cancer cells. Mechanism analysis revealed ENC1 was strong associated with the metastasis by modulating ß-catenin pathway. Our study emphasizes that ENC1 is a potential prognostic and metastasis-related marker of breast cancer, and may function as a possible therapeutic target against breast cancer.
Subject(s)
Biomarkers, Tumor , Breast Neoplasms/metabolism , Breast Neoplasms/mortality , Microfilament Proteins/metabolism , Neuropeptides/metabolism , Nuclear Proteins/metabolism , Wnt Signaling Pathway , Adult , Aged , Breast Neoplasms/diagnosis , Breast Neoplasms/etiology , Cell Line, Tumor , Computational Biology , Databases, Genetic , Female , Gene Expression Regulation, Neoplastic , Humans , Immunohistochemistry , Microfilament Proteins/genetics , Middle Aged , Neoplasm Metastasis , Neoplasm Staging , Neuropeptides/genetics , Nuclear Proteins/genetics , Proportional Hazards Models , ROC CurveABSTRACT
BACKGROUND: The features and survival of stage IV breast cancer patients with different metastatic sites are poorly understood. This study aims to examine the clinicopathological features and survival of stage IV breast cancer patients according to different metastatic sites. METHODS: Using the Surveillance, Epidemiology, and End Results database, we restricted our study population to stage IV breast cancer patients diagnosed between 2010 to 2015. The clinicopathological features were examined by chi-square tests. Breast cancer-specific survival (BCSS) and overall survival (OS) were compared among patients with different metastatic sites by the Kaplan-Meier method with log-rank test. Univariable and multivariable analyses were also performed using the Cox proportional hazard model to identify statistically significant prognostic factors. RESULTS: A total of 18,322 patients were identified for survival analysis. Bone-only metastasis accounted for 39.80% of patients, followed by multiple metastasis (33.07%), lung metastasis (10.94%), liver metastasis (7.34%), other metastasis (7.34%), and brain metastasis (1.51%). The Kaplan-Meier plots showed that patients with bone metastasis had the best survival, while patients with brain metastasis had the worst survival in both BCSS and OS (p < 0.001, for both). Multivariable analyses showed that age, race, marital status, grade, tumor subtype, tumor size, surgery of primary cancer, and a history of radiotherapy or chemotherapy were independent prognostic factors. CONCLUSION: Stage IV breast cancer patients have different clinicopathological characteristics and survival outcomes according to different metastatic sites. Patients with bone metastasis have the best prognosis, and brain metastasis is the most aggressive subgroup.
Subject(s)
Breast Neoplasms/mortality , Breast Neoplasms/pathology , Adult , Aged , Aged, 80 and over , Breast Neoplasms/epidemiology , Breast Neoplasms/therapy , Female , Humans , Kaplan-Meier Estimate , Middle Aged , Neoplasm Metastasis , Neoplasm Staging , Patient Outcome Assessment , Prognosis , Proportional Hazards Models , SEER Program , Survival Analysis , Young AdultABSTRACT
Even though early detection methods and treatment options are greatly improved, chemoresistance is still a tremendous challenge for breast cancer therapy. Breast cancer stem cells (BCSCs) represent a subpopulation that is central to chemoresistance. We aim to investigate the relationship between SLC34A2 and chemoresistance in BCSCs and identify the underlying mechanisms by which SLC34A2 regulates chemoresistance in BCSCs. Fluorescence Activated Cell Sorting (FACS) analysis showed the presence of a variable fraction of CD44(+)CD24(-) cells in 25 out of 25 breast cancer samples. We cultured primary breast cancer sample cells and breast cancer cell line cells to induce sphere formation in serum-free medium. Following sorting of CD44(+)CD24(-) cells from spheres, we showed that CD44(+)CD24(-) cells displayed stem cell-like features and were resistant to chemotherapy drug doxorubicin. Significantly, enhanced SLC34A2 expression correlated with chemoresponse and survival of breast cancer patients. We subsequently indicated that increased SLC34A2 expression in BCSCs directly contributed to their chemoresistance by a series of in vitro and in vivo experiments. Furthermore, we demonstrated that SLC34A2 induced chemoresistance in BCSCs via SLC34A2-Bmi1-ABCC5 signaling. Finally, we showed that ABCC5 was a direct transcriptional target of Bmi1 by chromatin immunoprecipitation (ChIP). In conclusion, our work indicated that decreased SLC34A2 expression sensitized BCSCs to doxorubicin via SLC34A2-Bmi1-ABCC5 signaling and shed new light on understanding the mechanism of chemoresistance in BCSCs. This study not only bridges the missing link between stem cell-related transcription factor (Bmi1) and ABC transporter (ABCC5) but also contributes to development of potential therapeutics against breast cancer.
Subject(s)
Breast Neoplasms/drug therapy , Mitogen-Activated Protein Kinase 7/biosynthesis , Multidrug Resistance-Associated Proteins/biosynthesis , Sodium-Phosphate Cotransporter Proteins, Type IIb/biosynthesis , Adult , Animals , Breast Neoplasms/genetics , Breast Neoplasms/pathology , Doxorubicin/administration & dosage , Drug Resistance, Neoplasm/genetics , Female , Flow Cytometry , Gene Expression Regulation, Neoplastic/drug effects , Humans , Mice , Middle Aged , Mitogen-Activated Protein Kinase 7/genetics , Multidrug Resistance-Associated Proteins/genetics , Neoplastic Stem Cells/metabolism , Neoplastic Stem Cells/pathology , Signal Transduction/drug effects , Sodium-Phosphate Cotransporter Proteins, Type IIb/genetics , Xenograft Model Antitumor AssaysABSTRACT
Breast cancer (BC) is the most prevalent cancer in women globally. The tumor microenvironment (TME), comprising epithelial tumor cells and stromal elements, is vital for breast tumor development. N6-methyladenosine (m6A) modification plays a key role in RNA metabolism, influencing its various aspects such as stability and translation. There is a notable link between m6A methylation and immune cells in the TME, although this relationship is complex and not fully deciphered. In this research, BC expression and clinicopathological data from TCGA were scrutinized to assess expression profiles, mutations, and CNVs of 31 m6A genes and immune microenvironment-related genes, examining their correlations, functions, and prognostic impacts. Lasso and Cox regression identified prognostic genes for constructing a nomogram. Single-cell analyses mapped the distribution and patterns of these genes in BC cell development. We investigated associations between gene-derived risk scores and factors like immune infiltration, TME, checkpoints, TMB, CSC indices, and drug response. As a complement to computational analyses, in vitro experiments were conducted to confirm these expression patterns. We included 31 m6A regulatory genes and discovered a correlation between these genes and the extent of immune cell infiltration. Subsequently, a 7-gene risk score was generated, encompassing HSPA2, TAP1, ULBP2, CXCL1, RBP1, STC2, and FLT3. It was observed that the low-risk group exhibited better overall survival (OS) in BC, with higher immune scores but lower tumor mutational burden (TMB) and cancer stem cell (CSC) indices, as well as lower IC50 values for commonly used drugs. To enhance clinical applicability, age and stage were incorporated into the risk score, and a more comprehensive nomogram was constructed to predict OS. This nomogram was validated and demonstrated good predictive performance, with area under the curve (AUC) values for 1-year, 3-year, and 5-year OS being 0.848, 0.807, and 0.759, respectively. Our findings highlight the profound impact of prognostic-related genes on BC immune response and prognostic outcomes, suggesting that modulation of the m6A-immune pathway could offer new avenues for personalized BC treatment and potentially improve clinical outcomes.
Subject(s)
Adenosine , Breast Neoplasms , Gene Expression Regulation, Neoplastic , Tumor Microenvironment , Humans , Tumor Microenvironment/immunology , Tumor Microenvironment/genetics , Breast Neoplasms/genetics , Breast Neoplasms/immunology , Breast Neoplasms/pathology , Breast Neoplasms/mortality , Adenosine/analogs & derivatives , Adenosine/metabolism , Adenosine/genetics , Female , Prognosis , Biomarkers, Tumor/genetics , Nomograms , Gene Expression ProfilingABSTRACT
BACKGROUND: We assessed the potential role of serial circulating tumor DNA (ctDNA) as a biomarker to monitor treatment response to primary systemic therapy (PST) in breast cancer and evaluated the predictive value of ctDNA to further identify patients with residual disease. METHODS: We prospectively enrolled 208 plasma samples collected at three time points (before PST, after 2 cycles of treatment, before surgery) of 72 patients with stage â ¡-III breast cancer. Somatic mutations in plasma samples were identified using a customized 128-gene capture panel with next-generation sequencing. The correlation between early change in ctDNA levels and treatment response or long-term clinical outcomes was assessed. RESULTS: 37 of 72 (51.4%) patients harbored detectable ctDNA alterations at baseline. Patients with complete response showed a larger decrease in ctDNA levels during PST. The median relative change of variant allele fraction (VAF) was -97.4%, -46.7%, and +21.1% for patients who subsequently had a complete response (n = 11), partial response (n = 11), and no response (n = 15) (p = 0.0012), respectively. In addition, the relative change of VAF between the pretreatment and first on-treatment blood draw exhibited the optimal predictive value to tumor response after PST (area under the curve, AUC = 0.7448, p = 0.02). More importantly, early change of ctDNA levels during treatment have significant prognostic value for patients with BC, there was a significant correlation between early decrease of VAF and longer recurrence-free survival compared to those with an VAF increase (HR = 12.54; 95% CI, 2.084 to 75.42, p = 0.0063). CONCLUSION: Early changes of ctDNA are strongly correlated with therapeutic efficacy to PST and clinical outcomes in BC patients. The integration of preoperative ctDNA evaluation could help improving the perioperative management for BC patients receiving PST.
Subject(s)
Biomarkers, Tumor , Breast Neoplasms , Circulating Tumor DNA , Humans , Female , Circulating Tumor DNA/blood , Circulating Tumor DNA/genetics , Breast Neoplasms/blood , Breast Neoplasms/genetics , Breast Neoplasms/drug therapy , Breast Neoplasms/therapy , Middle Aged , Biomarkers, Tumor/blood , Biomarkers, Tumor/genetics , Prospective Studies , Prognosis , Adult , Aged , Treatment Outcome , Predictive Value of Tests , Mutation , Neoplasm, Residual , High-Throughput Nucleotide Sequencing , Neoplasm StagingABSTRACT
An elliptical monolithic bifocal zone plate as a collimating lens, whose two focal lengths in the orthogonal directions match the different beam waist positions of the fast and slow axes' light from edge-emitting laser diodes, is proposed and experimentally demonstrated by employing femtosecond laser direct writing technology. The high-quality eight-level zone plate exhibits a diffraction efficiency of 92.9%, which is much higher than those ever reported. Shaped by the elliptical lens, the laser diodes' divergence angles are simultaneously reduced from 65° (1134 mrad, fast axis) and 24° (418 mrad, slow axis) to 7.7 and 136.5 mrad, respectively.
ABSTRACT
We report the fabrication of three-dimensional periodic metal nickel nanostructures achieved by the combination of femtosecond laser-induced two-photon polymerization and electroless plating technology. We can control the deposition speed of 10 nm per second by adjusting the reaction time. The thermal stability is good under 500 °C for the three-dimensional graphite-lattice polymer structure with 200 nm nickel film. Optical reflectivity and thermal emission measurements under 550 °C showed that the fabricated metallic structure was thermally excited and emitted light at λ = 4.50, 4.95 µm. The emission peak wavelengths agree with the absorption peaks. These data demonstrate that creating metallic photonic crystals by incorporation of metals to laser-fabricated templates is a simple and cost-efficient method. The emitters can work at such low temperatures, which is more important for realistic operation in applications.
ABSTRACT
BACKGROUND: The mesenchymal stem cell-derived exosome (MSCs-exo) carrying microRNAs have been proved to regulate tumor biological activities. Clarifying molecular mechanism and identifying predictive microRNAs will be of great value in anti-tumor therapy improvement. OBJECTIVE: We aimed to investigate the regulatory role of microRNA-342-3p (miR-342-3p) in MSCs-exo on breast cancer. METHODS: Breast cancer tissues and cell lines were used to evaluate miR-342-3p expression in patients with or without lymph node/distal organ metastasis. The impact of MSCs-exo expression on tumor cell chemo-resistance and invasion/migration was measured. Dual-luciferase reporter gene assay was applied to identify binding site. Inhibitor of differentiation 4 (ID4) siRNA and miR-342-3p inhibitor transfection was conducted to further explore the miR-342-3p/ID4 axis on chemo-resistance and metastasis of breast cancer cells. RESULTS: Breast cancer cells revealed significantly lower level of miR-342-3p in patients with metastatic diseases. miR-342-3p suppressed invasive and chemo-resistant behavior of breast cancer tumor cells. Binding site between miR-342-3p and ID4 was proved. ID4 could reverse the influence of miR-342-3p on chemo-resistance. The tumor inhibition effect of IDA siRNA in vivo was also identified. CONCLUSIONS: This study demonstrated that miR-342-3p acted as potential tumor suppressor by inhibiting metastasis and chemo-resistance of breast cancer cells through targeting ID4. This study might provide potential therapy targets for the treatment of breast cancer.
Subject(s)
Breast Neoplasms , Exosomes , Mesenchymal Stem Cells , MicroRNAs , Breast Neoplasms/genetics , Cell Line, Tumor , Cell Proliferation/genetics , Exosomes/genetics , Female , Humans , Inhibitor of Differentiation Proteins/metabolism , Mesenchymal Stem Cells/metabolism , MicroRNAs/genetics , MicroRNAs/metabolism , RNA, Small InterferingABSTRACT
Hypertension caused by a high-salt (HS) diet is one of the major causes of cardiovascular diseases. Underlining pathology includes oxidative stress and inflammation in the hypothalamic paraventricular nucleus (PVN). This study investigates genistein's (Gen) role in HS-induced hypertension and the underlying molecular mechanism. We placed male Wistar rats on HS (8% NaCl) or normal salt diet (0.3% NaCl). Then, we injected bilateral PVN in rats with Gen, vehicle, or nicotinamide (NAM) for 4 weeks. Tail cuff was used weekly to assess the systolic pressure, diastolic pressure, and mean arterial pressure (MAP). Cardiac hypertrophy was analyzed by heart weight/body weight ratio and wheat germ agglutinin staining. ELISA kits, Western blot, or dihydroethidium staining determined the levels of inflammatory cytokines and oxidative stress markers. Western blot measured protein levels of Sirt1, Ac-FOXO1, Nrf2, NQO-1, HO-1, and gp91phox. Our result showed that PVN infusion of Gen significantly reduced the increase of systolic pressure, diastolic pressure, and MAP induced by an HS diet. Additionally, there was a decrease in cardiac hypertrophy and the levels of inflammatory cytokines in PVN and plasma. Meanwhile, PVN infusion of Gen notably inhibited the levels of oxidized glutathione and superoxide dismutase and improved the glutathione level and total antioxidant capacities and superoxide dismutase activities. It also decreased the level of reactive oxygen species and gp91phox expression in PVN. Furthermore, Gen infusion markedly increases the Sirt1, Nrf2, HO-1, and NQO-1 levels and decreases the Ac-FOXO1 level. However, PVN infusion of NAM could significantly block these changes induced by Gen in HS diet rats. Our results demonstrated that PVN infusion of Gen could inhibit the progression of hypertension induced by an HS diet by activating the Sirt1/Nrf2 pathway.
Subject(s)
Genistein , Hypertension , Oxidative Stress , Paraventricular Hypothalamic Nucleus , Animals , Male , Rats , Antioxidants/metabolism , Cardiomegaly/pathology , Cytokines/metabolism , Genistein/pharmacology , Glutathione Disulfide/metabolism , Hypertension/chemically induced , Hypertension/prevention & control , Hypertension/metabolism , Inflammation/chemically induced , Inflammation/prevention & control , NF-E2-Related Factor 2/metabolism , Niacinamide/pharmacology , Oxidative Stress/drug effects , Paraventricular Hypothalamic Nucleus/physiopathology , Rats, Wistar , Reactive Oxygen Species/metabolism , Sirtuin 1/metabolism , Sodium Chloride, Dietary/adverse effects , Superoxide Dismutase/metabolismABSTRACT
Introduction: Due to the lack of randomized controlled trial, the effectiveness and oncological safety of nipple-excising breast-conserving therapy (NE-BCT) for female breast cancer (FBC) remains unclear. We aimed to explore and investigate the prognostic value of NE-BCT versus nipple-sparing breast-conserving therapy (NS-BCT) for patients with early FBC. Methods: In this cohort study, data between NE-BCT and NS-BCT groups of 276,661 patients diagnosed with tumor-node-metastasis (TNM) stage 0-III FBC from 1998 to 2015 were retrieved from the Surveillance, Epidemiology, and End Results database. Propensity score matching analysis, Kaplan-Meier, X-tile, Cox proportional hazards model, and competing risk model were performed to evaluate the effectiveness and oncological safety for patients in NE-BCT and NS-BCT groups. Results: A total of 1,731 (0.63%) patients received NE-BCT (NE-BCT group) and 274,930 (99.37%) patients received NS-BCT (NS-BCT group); 44,070 subjects died after a median follow-up time of 77 months (ranging from 1 to 227 months). In the propensity score matching (PSM) cohort, NE-BCT was found to be an adversely independent prognostic factor affecting overall survival (OS) [hazard ratio (HR), 1.24; 95% CI, 1.06-1.45, p=0.0078]. Subjects in NE-BCT group had similar breast-cancer-specific survival (BCSS) (HR, 1.15; 95%CI, 0.88-1.52, p=0.30) and worse other-causes-specific death (OCSD) (HR, 1.217; 95%CI, 1.002-1.478, p=0.048<0.05) in comparison with those in the NS-BCT group. Conclusions: Our study demonstrated that the administration of NE-BCT is oncologically safe and reliable and can be widely recommended in clinics for women with non-metastatic breast cancer.
ABSTRACT
MicroRNAs (miRNAs) have been regarded as modulators in vascular pathologies, including hypertension. Dysregulated proliferation and migration of VSMCs (vascular smooth muscle cells) contributes to vascular remodeling during hypertension. miR-634 was reported to be dysregulated in hypertensive patients. The involvement of miR-634 in hypertension and the role of miR-634 on VSMCs proliferation and migration were then evaluated. Firstly, HASMCs (human aortic smooth muscle cells) were incubated with 2 µM angiotensin (Ang) II for 12 hours to establish the cell model of Ang II-induced hypertension. Results showed that Ang II treatment promoted proliferation and migration of HASMCs. Secondly, miR-634 was down-regulated in the hypertensive patients, and reduced in Ang II-induced HASMCs in a time dependent manner. Functional assays revealed that Ang II promoted proliferation and migration of HASMCs were suppressed by miR-634 mimic. Lastly, miR-634 targeted 3' untranslated region (UTR) of Wnt4, and reduced Wnt4 expression in HASMCs. miR-634 inhibited ß-catenin nuclear translocation. Over-expression of Wnt4 counteracted the suppressive effects of miR-634 on Ang II-induced proliferation and migration of HASMCs. In conclusion, miR-634 inhibited HASMCs proliferation and migration through inactivation of Wnt4/ß-catenin pathway.
Subject(s)
Hypertension , MicroRNAs , Myocytes, Smooth Muscle/cytology , Wnt Signaling Pathway , Cell Movement , Cell Proliferation , Cells, Cultured , Humans , Hypertension/chemically induced , Hypertension/genetics , MicroRNAs/genetics , Muscle, Smooth, Vascular , Wnt4 Protein , beta Catenin/geneticsABSTRACT
OBJECTIVE: To assess the expression of ARHGEF19 in human breast cancer, investigate its role in breast cancer, and clarify the mechanism. METHODS: Bioinformatics analysis, immunoblot, quantitative PCR, and immunohistochemical (IHC) assays were performed to assess ARHGEF19 expression in breast cancer. CCK-8 and Edu assays were conducted to reveal its role in breast cancer cell proliferation. Flow cytometry (FCM) assays and immunoblot were performed to confirm its effects on breast cancer apoptosis. Immunoblot was also performed to clarify the mechanism. Finally, tumor growth assays were aimed to confirm the role of ARHGEF19 in mice. RESULTS: We observed that ARHGEF19 was highly expressed in human breast cancer. ARHGEF19 promoted breast cancer cell growth in vitro, and suppressed apoptosis. In addition, we found that ARHGEF19 could activate the MAPK pathway in breast cancer cells. Our findings further confirmed that ARHGEF19 contributed to breast cancer growth in mice. CONCLUSION: We observed that ARHGEF19 promoted the growth of breast cancer in vitro and in vivo via MAPK pathway, and presume it could serve as a breast cancer therapeutic target.
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Background: The role of surgery and surgery type in de novo stage IV breast cancer (BC) is unclear. Methods: We carried out a retrospective cohort study that included the data of 4,108 individuals with de novo stage IV BC abstracted from SEER (Surveillance, Epidemiology, and End Results) data resource from 2010 to 2015. The patients were stratified into the non-surgery group, breast-conserving (BCS) surgery group, and mastectomy group. Inverse probability propensity score weighting (IPTW) was then used to balance clinicopathologic factors. Overall survival (OS), as well as the breast cancer-specific survival (BCSS), was assessed in the three groups using Kaplan-Meier analysis and COX model. Subgroups were stratified by metastatic sites for analysis. Results: Of the 4,108 patients, 48.5% received surgery and were stratified into the BCS group (574 cases) and mastectomy group (1,419 cases). After IPTW balance demographic and clinicopathologic factors, BCS and mastectomy groups had better OS (BCS group: HR, 0.61; 95% CI: 0.49-0.75; mastectomy group: HR, 0.7; 95% CI: 0.63-0.79) and BCSS (BCS group: HR, 0.6; 95% CI, 0.47-0.75; mastectomy group: HR, 0.71; 95% CI, 0.63-0.81) than the non-therapy group. Subgroup analyses revealed that BCS, rather than mastectomy, was linked to better OS (HR, 0.66; 95% CI: 0.48-0.91) and BCSS (HR, 0.63; 95% CI: 0.45-0.89) for patients with bone-only metastasis. For patients with viscera metastasis or bone+viscera metastases, BCS achieved similar OS (viscera metastasis: HR, 1.05; 95% CI: 0.74-1.48; bone+viscera metastases: HR, 1.01; 95% CI: 0.64-1.61) and BCSS (viscera metastasis: HR, 0.94; 95% CI: 0.64-1.38; bone+viscera metastases: HR, 1.06; 95% CI: 0.66-1.73) in contrast with mastectomy. Conclusions: Local surgery for patients with distant metastasis (DS) exhibited a remarkable survival advantage in contrast with non-operative management. BCS may have more survival benefits for patients with de novo stage IV BC with bone-only metastasis than other metastatic sites. Decisions on de novo stage IV BC primary surgery should be tailored to the metastatic pattern.
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This paper demonstrates the embellishment of existing microfluidic devices with integrated three dimensional (3D) micronanostructures via femtosecond laser micronanofabrication, which, for the first time, proves two-photon photopolymerization (TPP) to be a powerful technology for chip functionalization. As representative examples, microsieves with various pore shape and adjustable pore size were successfully fabricated inside a conventional glass-based microfluidic channel prepared by wet etching for microparticle separation. Moreover, a fish scale like microfilter was also fabricated and appointed as a one-way valve, which showed excellent performance as we expected. These results indicate that such embellishment of microfluidic devices is simple, low cost, flexible and easy to access. We believe that, combined with TPP, the application of lab-on-chip devices would be further extended.
Subject(s)
Lab-On-A-Chip Devices , Lasers , Microfluidic Analytical Techniques/methods , Photochemical Processes , Microfluidic Analytical Techniques/instrumentationABSTRACT
In this paper, one simple method to control two-direction anisotropic wetting by regular micropearl arrays was demonstrated. Various micropearl arrays with large area were rapidly fabricated by a kind of improved laser interference lithography. Specially, we found that the parallel contact angle (CA) theta(2) decreased from 93 degrees to 67 degrees as the intensity ratio of four laser beams increased from 2:1 to 30:1, while the perpendicular CA theta(1) determined by the thickness of the resin remained constant. This was interpreted as the decrease of height variations Delta h from 1100 to 200 nm along the parallel direction caused by the increase of the intensity ratio. According to this rule, both theta(1) and theta(2) could be simultaneously controlled by adjusting the height variation Delta h and the resin thickness. Moreover, by combining appropriate design and low surface energy modification, a natural anisotropic rice leaf exhibiting CAs of 146 degrees +/- 2 degrees/153 degrees +/- 3 degrees could be mimicked by our anisotropic biosurface with the CAs 145 degrees +/- 1 degrees/150 degrees +/- 2 degrees. We believe that these controlled anisotropic biosurfaces will be helpful for designing smart, fluid-controllable interfaces that may be applied in novel microfluidic devices, evaporation-driven micro/nanostructures, and liquid microdroplet directional transfer.
Subject(s)
Biomimetics/instrumentation , Microspheres , Anisotropy , Biomimetics/economics , Lasers , Surface Properties , Time Factors , WettabilityABSTRACT
Respiration monitoring equipment has wide applications in daily health monitoring and modern medical diagnosis. Despite significant progress being made in humidity sensors for respiration monitoring, the fabrication of the humidity sensors with low-cost, simple manufacturing process and easy integration remains a challenge. This work reports a facile and inexpensive laser printing fabrication of PEDOT:PSS micron line as a humidity sensor for respiration monitoring. Laser printing technology can process any material into an arbitrary pattern. The PEDOT:PSS micron line humidity sensor has a fast response-recovery time (0.86 s/0.59 s), demonstrating excellent performance for real-time monitoring of human respiration. Furthermore, the PEDOT:PSS micron line humidity sensor can also monitor the respiration of rats under different physiological conditions along with the drug injection. The PEDOT:PSS micron line humidity sensor features simple manufacturing process with commercial materials, and easy integration with wearable devices. This work paves an important step in real-time monitoring of human health and further physiology and pharmacology study.
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BACKGROUND: The homeobox gene family, encoding a specific nuclear protein, is essential for embryonic development, differentiation, and homeostasis. The role of the HOXB3 protein varies in different tumors. This study aims to explore the role of the HOXB3 gene in breast cancer. METHOD: Differentially expressed genes were screened by analyzing metastatic breast cancer gene chip data from TCGA and GEO databases. The function of the selected HOXB3 gene was also analyzed in different databases and through molecular biology methods, such as qRT-PCR, western blot and IF to verify bioinformatics findings. RESULTS: Both bioinformatics analyses and western blot showed that HOXB3 was lost in breast cancer compared to normal breast tissue. Survival analysis also showed that lower expression of HOXB3 was associated with poor prognosis. Bioinformatics analyses further showed that HOXB3 was positively correlated with hormone receptors. Metascape for GO analysis of GEO data provided possible mechanisms that HOXB3 could positively regulate cell adhesion, inhibit cell proliferation and activate immune response in breast cancer; moreover, GSEA included several cancer-associated pathways. CONCLUSION: In summary, HOXB3 expression was decreased in breast cancer, and it was associated with poor prognosis. It might become a new biomarker to predict prognosis of breast cancer.
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OBJECTIVE: Body mass index (BMI) is a risk factor associated with breast cancer in postmenopausal women. This study aimed to identify the associations of BMI with clinical characteristics and management of breast cancer in female Chinese patients. METHODS: Clinicopathological information on 1296 women who were diagnosed with breast cancer was collected at our hospital. We recorded the clinicopathological characteristics, molecular phenotypes, manner of diagnosis, implementation rate of preoperative examinations, and surgical method used. RESULTS: Significant differences were found in the tumor size, disease stage, manner of diagnosis, implementation rate of preoperative examinations, and the surgical method among different BMI groups. In premenopausal patients, significant differences were found in the distribution of molecular phenotypes and surgical approach among different BMI groups. In postmenopausal patients, different BMI groups showed significant differences in the tumor size, disease stage, distribution of molecular phenotypes, manner of diagnosis, rate of implementation of preoperative mammography, and surgical method. CONCLUSION: Higher BMI is associated with a larger tumor size, more advanced disease stage, diagnosis by physical examination, higher implementation rate of preoperative examinations, and lower radical surgery rate in Chinese women with breast cancer. However, the relationship between BMI and molecular phenotypes differs between pre- and postmenopausal women.