Breast cancer is the most common cancer among women and is considered a major public health concern worldwide. Biogeography-based optimization (BBO) is a novel metaheuristic algorithm. This study ...analyzed the relationship between the clinicopathologic variables of breast cancer using Cox proportional hazard (PH) regression on the basis of the BBO algorithm. The dataset is prospectively maintained by the Division of Breast Surgery at Kaohsiung Medical University Hospital. A total of 1896 patients with breast cancer were included and tracked from 2005 to 2017. Fifteen general breast cancer clinicopathologic variables were collected. We used the BBO algorithm to select the clinicopathologic variables that could potentially contribute to predicting breast cancer prognosis. Subsequently, Cox PH regression analysis was used to demonstrate the association between overall survival and the selected clinicopathologic variables. C-statistics were used to test predictive accuracy and the concordance of various survival models. The BBO-selected clinicopathologic variables model obtained the highest C-statistic value (80%) for predicting the overall survival of patients with breast cancer. The selected clinicopathologic variables included tumor size (hazard ratio HR 2.372, p = 0.006), lymph node metastasis (HR 1.301, p = 0.038), lymphovascular invasion (HR 1.606, p = 0.096), perineural invasion (HR 1.546, p = 0.168), dermal invasion (HR 1.548, p = 0.028), total mastectomy (HR 1.633, p = 0.092), without hormone therapy (HR 2.178, p = 0.003), and without chemotherapy (HR 1.234, p = 0.491). This number was the minimum number of discriminators required for optimal discrimination in the breast cancer overall survival model with acceptable prediction ability. Therefore, on the basis of the clinicopathologic variables, the survival prediction model in this study could contribute to breast cancer follow-up and management.
Treatment options for patients with hormone receptor-positive (HR+), HER2-negative (HER2-) breast cancer and resistance to endocrine therapy remain limited. An interesting therapeutic target in these ...patients is fibroblast growth factor receptor 1 (
).
is amplified in approximately 11% of patients with breast cancer, especially those with HR+ disease. This report presents a patient with metastatic HR+ HER2- breast cancer harboring an
amplification who was resistant to endocrine therapy but responded to pazopanib, a multi-tyrosine kinase inhibitor with
-inhibiting activity. Upon pazopanib treatment, the patient's brain lesions nearly disappeared, and she experienced therapeutic changes in the lung and an improvement of liver function. This case suggests that pazopanib may be a promising agent for the treatment of patients with breast cancer and
amplifications.
Deregulated signal transducer and activator of transcription 3 (STAT3) signaling has been well documented in certain cancers. Alterations in specific negative regulators, such as protein inhibitor of ...activated STAT3 (PIAS3), may contribute to cancer development.
The expression of total PIAS3 was determined in 100 paired cancerous and non-cancerous breast tissues by immunoblotting and was statistically analyzed along with the clinicopathological characteristics and overall survival of the patients. XTT, immunoblotting, and chromatin immunoprecipitation (Chip) were used to examine the biological effect of PIAS3 in breast cancer cells.
Hormone therapy failed to improve the overall survival in patients presenting with increased PIAS3 expression. Ectopic PIAS3 overexpression increased the proliferation and expression of cyclin D1 in estrogen receptor (ER)-positive MCF-7 and T47D cells, but decreased those in ER-negative MDA-MB-231 and SKBR3 cells. Furthermore, PIAS3 overexpression attenuated cytotoxicity of tamoxifen and increased proliferation and cyclin D1 expression in MCF-7 cells. PIAS3 also decreased the binding of itself on the cyclin D1 promoter and this decreased binding was not affected by tamoxifen.
PIAS3 may serve as a biomarker for predicting hormone therapy stratification, although it is limited to those breast cancer patients receiving hormone therapy.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Offshore wind turbine selection is a complex multi-attribute decision-making (MADM) problem with multiple variables and schemes. As a result of the intervention of expert judgment and linguistic ...assessment, various uncertainties arise in the process of wind turbine selection. This work presents a novel decision-making system for selecting offshore wind turbine by combining D numbers with principal component analysis (PCA). Firstly, we build five main attribute indexes involving technology, matching with wind resources, economy, historical performance of wind turbine and after-sales service of manufacturer through historical experience and expert advice. Then, to reduce the subjectivity of experts in selecting decision variables, PCA is employed to select twelve secondary indicators and determine the corresponding weights. Secondly, experts evaluate the performance of schemes according to the language set, and give the confidence of judgment. We propose to quantify the evaluation results in the form of D numbers, which can directly express the incomplete information of experts and realize the integration of expert opinions. Finally, the optimal scheme is obtained through the technique for order preference by similarity to ideal solution (TOPSIS). The selection results from an actual case show that the proposed model can effectively realize offshore wind turbine selection.
•A new decision-making system for selecting offshore wind turbine selection is established.•The affecting factors and the corresponding weights are determined by PCA.•D-number theory transforms fuzzy and linguistic assessment into reliable quantitative form.•MADM fused with D numbers addresses the uncertainty cause by expert judgment.
Some withanolides, particularly the family of steroidal lactones, show anticancer effects, but this is rarely reported for withanolide C (WHC)—especially anti-breast cancer effects. The subject of ...this study is to evaluate the ability of WHC to regulate the proliferation of breast cancer cells, using both time and concentration in treatment with WHC. In terms of ATP depletion, WHC induced more antiproliferation to three breast cancer cell lines, SKBR3, MCF7, and MDA-MB-231, than to normal breast M10 cell lines. SKBR3 and MCF7 cells showing higher sensitivity to WHC were used to explore the antiproliferation mechanism. Flow cytometric apoptosis analyses showed that subG1 phase and annexin V population were increased in breast cancer cells after WHC treatment. Western blotting showed that cleaved forms of the apoptotic proteins poly (ADP-ribose) polymerase (c-PARP) and cleaved caspase 3 (c-Cas 3) were increased in breast cancer cells. Flow cytometric oxidative stress analyses showed that WHC triggered reactive oxygen species (ROS) and mitochondrial superoxide (MitoSOX) production as well as glutathione depletion. In contrast, normal breast M10 cells showed lower levels of ROS and annexin V expression than breast cancer cells. Flow cytometric DNA damage analyses showed that WHC triggered γH2AX and 8-oxo-2′-deoxyguanosine (8-oxodG) expression in breast cancer cells. Moreover, N-acetylcysteine (NAC) pretreatment reverted oxidative stress-mediated ATP depletion, apoptosis, and DNA damage. Therefore, WHC kills breast cancer cells depending on oxidative stress-associated mechanisms.
Defect-engineering UiO-66 was synthesized by using a simple hydrothermal method and affords improved adsorption selectivity of toluene and stability and the best capture capacity for the presenting ...VOCs sources such as toluene in all the known UiO-66.
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•Defect-engineering UiO-66 was successfully synthesized.•Acetic acid obviously regulated the adsorbents’ size and morphology.•Acetic acid controllably modulated the amount of defects by ‘missing-linkers’.•UiO-66–1.0HAc showed well improved adsorption selectivity of toluene.•UiO-66–2.0HAc affords the highest toluene capture ability in all the known UiO-66.
The great challenge in capturing harmful volatile organic compounds (VOCs) using Metal-Organic-Frameworks (MOFs) materials still rely on rationally modifying its appreciable microporous character in hydrostable structure. Defected structure in MOFs might be very beneficial for creating expected engineering adsorbent. In this study, defect-engineering UiO-66 via imparting acetic acid (HAc) as an interfering agent was successfully fabricated by a simple hydrothermal method. The physicochemical properties of the obtained materials were intensively ascertained and identified through a series of applicable characterizations. By the proper participation of tuning concentration of HAc (HAc/TAc = 24, molar ratio), the obtained adsorbent UiO-66–1.0HAc was endowed with the highest adsorption capacity for benzene (367.13 mg g−1, 25 °C) in the known UiO-66 materials, which was 41.9% higher than that of the non-defected UiO-66. With a higher optimized added amount of HAc (HAc/TAc = 48, molar ratio), the adsorption capacity of UiO-66–2.0HAc to toluene achieved the highest capture values (410.21 mg g−1, 25 °C), which boosted 93% compared with the original counterpart. This demonstrated improvement was ascribable to the imparted structural defect-engineering derived from the missing-linkers of MOFs increasing the unsaturated adsorption site and concomitant enlarged structural properties of the resultant material. By identifying the DIH (Difference in adsorption heat), the obtained maximum adsorption selectivity of UiO-66–1.0HAc to toluene/water was further enhanced to 64.4, which was 3.7 times the original UiO-66, owing to the existed defect-engineering in adsorbents, indicating the potential differential competitive adsorption effect for benzene and toluene under humid conditions.
The value of postmastectomy radiation therapy for breast cancer patients with T1-2 tumor and one to three positive nodes remains controversial. The purpose of this retrospective study was to compare ...the clinical outcomes of breast cancer patients with T1-2 and one to three positive nodes with and without postmastectomy radiation therapy.
Between May 1990 and June 2008, of 318 breast cancer patients with T1-2 and one to three positive nodes who had undergone modified radical mastectomy, 163 received postmastectomy radiation therapy and 155 did not. The clinico-pathologic characteristics were analyzed for clinical outcomes including loco-regional recurrence, distant metastasis, disease-free survival and overall survival.
During the median follow-up period of 102 months, the clinical outcomes in postmastectomy radiation therapy versus no-postmastectomy radiation therapy groups were as follows: loco-regional recurrence rate (3.1 versus 11.0%, P= 0.006); distant metastasis rate (20.9 versus 27.7%, P= 0.152); 10-year disease-free survival rate (73.8 versus 61.3%, P= 0.001); and 10-year overall survival rate (82.1 versus 76.1%, P= 0.239). Through a multivariate analysis, a positive nodal ratio of ≥25% (hazard ratio= 4.571, P= 0.003) and positive lymphovascular invasion (hazard ratio= 2.738, P= 0.028) were found to be independent poor prognostic predictors of loco-regional recurrence. The reduction in loco-regional recurrence (hazard ratio= 0.208, P= 0.004) by postmastectomy radiation therapy was found to be significant.
On the basis of our results, postmastectomy radiation therapy is highly recommended for breast cancer patients with T1-2 and one to three positive nodes, especially for high-risk subgroups with a positive nodal ratio of ≥25% and positive lymphovascular invasion, not only for reducing loco-regional recurrence but also for improving disease-free survival.
Triple-negative breast cancer (TNBC) remains a significant clinical challenge because of its high vascularity and metastatic and recurrent rates. Tumor angiogenesis is considered an important ...mediator in the regulation of tumor cell survival and metastasis in TNBC. Angiogenesis is induced by the binding of vascular endothelial growth factor to vascular endothelial growth factor receptor 2 (VEGFR2). Focal adhesion kinase (FAK) plays an important role in regulating various cell functions in normal and cancer cells. Previous studies have focused on investigating the function of endothelial FAK in tumor cell angiogenesis. However, the association between tumor FAK and VEGFR2 in tumor angiogenesis and the possible mechanisms of this remain unclear. In this study, we used a public database and human specimens to examine the association between FAK and VEGFR2. At the same time, we verified the association between FAK and VEGFR2 through several experimental methods, such as quantitative real-time polymerase chain reaction, Western blotting, and next-generation sequencing. In addition, we used the endothelial cell model, zebrafish, and xenograft animal models to investigate the role of FAK in TNBC angiogenesis. We found that FAK and VEGFR2 were positively correlated in patients with TNBC. VEGFR2 and several other angiogenesis-related genes were regulated by FAK. In addition, FAK regulated VEGFR2 and VEGF protein expression in TNBC cells. Functional assays showed that FAK knockdown inhibited endothelial tube formation and zebrafish angiogenesis. An animal model showed that FAK inhibitors could suppress tumor growth and tumor vascular formation. FAK promotes angiogenesis in TNBC cells by regulating VEGFR2 expression. Therefore, targeting FAK could be another antiangiogenic strategy for TNBC treatment.
Abstract There are clear discrepancies between ethnicity and geographic area regarding the peak age incidence and mortality of breast cancer. Underlying variances include genetic, environmental, and ...socioeconomic factors. The wild-type p53 codon has two common polymorphic variants from a single-base-pair substitution at codon 72, where either C-C-C encodes proline (p53-p72) or C-G-C encodes arginine (p53-R72). We aim to study the p53 codon 72 genotypes of patients with breast cancer in Taiwan and make a comparison with the published data to ascertain whether any difference exists between Taiwanese and Western patients with breast cancer. We also evaluated the effect of the p53 codon 72 polymorphism on clinicopathologic features. We examined blood from 170 Taiwanese women with breast cancer with polymerase chain reaction–restriction fragment length polymorphism for the genotypes of p53 codon 72. For the p53 codon 72 polymorphism, there were 31 p53-P/P72 (18.2%), 93 p53-R/P72 (54.7%), and 46 p53-R/R72 (27.1%) with the allele frequencies 0.54 for the p53-R72 and 0.46 for p53-P72, respectively. Our results indicate that there was more p53-P72 (40.6% in Asians vs. 26.4% in Caucasians) and twice the incidence of p53-P/P72 homozygotes (18% in Asians vs. 8% in Caucasians) among the Asian population. Patients with the p53-R/R72 variant were more likely to have a t1 tumor size status (55.2%) compared with patients with the P53-P/R72 (30.9%) or P53-P/P72 variant (36%). Our results support the hypothesis that genetic factors may contribute to the difference between Taiwanese or Asian breast cancer and Western breast cancer patient populations.
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