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1.
Int J Cancer ; 2020 Feb 05.
Artigo em Inglês | MEDLINE | ID: mdl-32020593

RESUMO

Resistance to chemotherapy continues to be a critical issue in the clinical therapy of triple-negative breast cancer (TNBC). Epithelial-mesenchymal transition (EMT) is thought to contribute to chemoresistance in several cancer types, including breast cancer. Identification of the key signaling pathway that regulates the EMT program and contributes to chemoresistance in TNBC will provide a novel strategy to overcome chemoresistance in this subtype of cancer. Herein, we demonstrate that Notch1 positively associates with melanoma cell adhesion molecule (MCAM), a unique EMT activator, in TNBC tissue samples both at mRNA and protein levels. High expression of Notch1 and MCAM both predicts a poor survival in basal-like/TNBC patients, particularly in those treated with chemotherapy. The expression of Notch1 and MCAM in MDA-MB-231 cells gradually increases in a time-dependent manner when exposing to low dose cisplatin. Moreover, the expressions of Notch1 and MCAM in cisplatin-resistant MDA-MB-231 cells are significantly higher than wild-type counterparts. Notch1 promotes EMT and chemoresistance, as well as invasion and proliferation of TNBC cells via direct activating MCAM promoter. Inhibition of Notch1 significantly downregulates MCAM expression, resulting in the reversion of EMT and chemoresistance to cisplatin in TNBC cells. Our study reveals the regulatory mechanism of the Notch1 pathway and MCAM in TNBC and suggesting that targeting the Notch1/MCAM axis, in conjunction with conventional chemotherapies, might be a potential avenue to enhance the therapeutic efficacy for patients with TNBC.

2.
J Cell Physiol ; 2020 Feb 11.
Artigo em Inglês | MEDLINE | ID: mdl-32043610

RESUMO

Resistance to tamoxifen remains a prominent conundrum in the therapy of hormone-sensitive breast cancer. Also, the molecular underpinnings leading to tamoxifen resistance remain unclear. In the present study, we utilized the Gene Expression Omnibus database to identify that SOX11 might exert a pivotal function in conferring tamoxifen resistance of breast cancer. SOX11 was found to be markedly upregulated at both the messenger RNA and protein levels in established MCF-7-Tam-R cells compared to the parental counterparts. Moreover, SOX11 was able to activate the transcription of slug via binding to its promoter, resulting in promoting the progress of epithelial-to-mesenchymal transition and suppressing the expression of ESR1. Downregulating SOX11 expression can restore the sensitivity to 4-hydroxytamoxifen in MCF-7-Tam-R cells. Survival analysis from large sample datasets indicated that SOX11 was closely related to poorer survival in patients with breast cancer. These findings suggest a novel feature of SOX11 in contributing to tamoxifen resistance. Hence, targeting SOX11 could be a potential therapeutic strategy to tackle tamoxifen resistance in breast cancer.

3.
J Clin Ultrasound ; 48(1): 29-37, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31566758

RESUMO

PURPOSE: This study aimed to analyze left ventricular (LV) remodeling in patients with LV dilation using three-dimensional (3D) echocardiography, and to compare geometry and systolic function between patients with dilated cardiomyopathy (DCM) and with mitral regurgitation (MR) but similar LV dimension. METHODS: Cross-sectional study of 60 DCM and 60 MR patients with LV end diastolic diameter (LVEDD) > 35 mm/m2 , and of 60 healthy control volunteers. RESULTS: Despite a similar LVEDD, DCM patients showed a significantly higher 3D sphericity index (3D-SI) than MR patients, whereas 3D ejection fraction (3D-EF) was significantly lower (P < .01). There was a linear relationship between 3D-EF and 3D-SI in both DCM and MR patients (r = -0. 745 and r = -0. 642, respectively; both P < .001). Receiver operating characteristic (ROC) curves showed that 3D-SI had could better discriminate between DCM and MR (sensitivity 90%; specificity 73%; AUC 0.852, P < .01) than other variables. The area under the ROC curve of 3D-SI was significantly larger than that of 3D-EF for detecting heart failure in both patients with DCM and MR. CONCLUSIONS: LV geometry appears to be more spherical and associated with worse systolic function in DCM than in MR patients, in spite of similar LV dimensions. Systolic function correlated significantly with 3D-SI, which provided a better description of LV remodeling and could be a stronger indicator of heart failure in patients with LV dilation.


Assuntos
Cardiomiopatia Dilatada/diagnóstico por imagem , Ecocardiografia Tridimensional , Ventrículos do Coração/diagnóstico por imagem , Insuficiência da Valva Mitral/diagnóstico por imagem , Disfunção Ventricular Esquerda/diagnóstico por imagem , Remodelação Ventricular , Adulto , Cardiomiopatia Dilatada/fisiopatologia , Estudos de Casos e Controles , Estudos Transversais , Feminino , Ventrículos do Coração/patologia , Ventrículos do Coração/fisiopatologia , Humanos , Masculino , Pessoa de Meia-Idade , Insuficiência da Valva Mitral/fisiopatologia , Sensibilidade e Especificidade , Disfunção Ventricular Esquerda/etiologia
4.
Zhongguo Zhong Yao Za Zhi ; 44(20): 4448-4453, 2019 Oct.
Artigo em Chinês | MEDLINE | ID: mdl-31872631

RESUMO

Musk,with unique and intense perfume,was a kind of deep brown precious medicinal material in traditional Chinese medicine. However,the immature musk in musk pot was white and stench. Given the fact that bacterial diversity generated odorous metabolites in animal hosts,in this study,musk samples at three different mature stages,including MJ( the end of June),MA( the end of August) and MO( the end of October) were harvested from three male forest musk deer,and then next-generation sequencing was used to intensively survey the bacterial communities in musk harvested at different mature stages. RESULTS: indicated that the average OTUs per sample at the end of June,August and October were 47 116. 00 ± 1 567. 24( SE),52 009. 00 ± 8 958. 75( SE) and50 004. 67±4 135. 57( SE),respectively. Feature of the musk 16 S rRNA gene showed a total of 418 genera belonging to 52 phyla were observed in all samples. The main microbiota was bacteria,which accounted for 98. 82%,99. 95% and 99. 58% in MJ,MA and MO,respectively. At phylum level,Firmicutes was the most abundant bacterial of MA( 32. 75%) and MO( 39. 19%). While,the major bacterial in MJ was Proteobacteria( 49. 14%). PICRUSt analysis revealed the functions of bacterial in MJ were mainly involved in secretion,while bacterial functions of MA and MO were mainly involved in amino acid or other substance metabolism,which was in accord with the musk secretion physiological process of forest musk deer. This is the first study involved in the bacterial diversity in musk of forest musk deer across the maturation process,while may provide a new insight into the musk generation mechanism.


Assuntos
Cervos/microbiologia , Ácidos Graxos Monoinsaturados , Animais , Florestas , Sequenciamento de Nucleotídeos em Larga Escala , Masculino
5.
Math Biosci Eng ; 17(1): 105-121, 2019 Sep 26.
Artigo em Inglês | MEDLINE | ID: mdl-31731342

RESUMO

Public water supply facilities are vulnerable to intentional intrusion. In particular, Water Distribution Network (WDN) has become one of the most important public facilities that are prone to be attacked because of its wide coverage and constant open operation. In recent years, water contamination incidents happen frequently, causing serious losses and impacts to the society. Various measures have been taken to tackle this issue. Pollution or contamination isolation by localizing the contamination via sensors and scheduling certain valves have been regarded as one of the most promising solutions. The main challenge is how to schedule water valves to effectively isolate contamination and reduce the residual concentration of contaminants in WDN. In this paper, we are motivated to propose a reinforcement learning based method for valve real time scheduling by treating the sensing data from the sensors as state, and the valve scheduling as action, thus we can learn scheduling policy from uncertain contamination events without precise characterization of contamination source. Simulation results show that our proposed algorithm can effectively isolate the contamination and reduce the risk exclosure to the customers.

6.
Int J Biol Sci ; 15(12): 2522-2537, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31754326

RESUMO

Despite remarkable advancements in our understanding of breast cancer, it remains the leading cause of cancer deaths in women. Distant recurrence and metastasis is the main reason for death due to breast cancer. It is well recognized that the GATA binding protein 3 (GATA3), a transcription factor, is a tumor suppressor in breast cancer. To date, the mechanistic molecular details of GATA3 remain elusive, because, as a transcription factor, it is not a direct executor in physiological and pathological processes. Here, we demonstrate that GATA3 reduces the ATP level in the breast cancer microenvironment and inhibits breast cancer metastasis by up-regulating ectonucleoside triphosphate diphosphohydrolase 3 (ENTPD3). The extracellular ATP concentration is significantly higher in tumor tissues than in normal tissues and promotes the migration of cancer cells from the primary site. ENTPD3 hydrolyzes ATP in tumor microenvironment and suppresses breast cancer metastasis. Furthermore, ENTPD3 inhibits epithelial-to-mesenchymal transition, a key program responsible for the development of metastatic disease. These findings provide novel insights into the tumor suppressor activity of GATA3.

7.
Chin Med Sci J ; 34(3): 211-220, 2019 Sep 30.
Artigo em Inglês | MEDLINE | ID: mdl-31601304

RESUMO

We review the representatives literatures on chronic osteomyelitis, sum up the new insights in recent years into diagnostic options and treatment regimens, analyze the advantages and disadvantages of various diagnostic approaches and treatment strategies, and propose areas of interest to make current diagnostic and treatment strategies more specific.


Assuntos
Osteomielite/diagnóstico , Osteomielite/metabolismo , Osteomielite/terapia
8.
Chaos ; 29(8): 083103, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31472503

RESUMO

New variable-order fractional chaotic systems are proposed in this paper. A concept of short memory is introduced where the initial point in the Caputo derivative is varied. The fractional order is defined by the use of a piecewise constant function which leads to rich chaotic dynamics. The predictor-corrector method is adopted, and numerical solutions of fractional delay equations are obtained. Then, this concept is extended to fractional difference equations, and generalized chaotic behaviors are discussed numerically. Finally, the new fractional chaotic models are applied to block image encryption and each block has a different fractional order. The new chaotic system improves security of the image encryption and saves the encryption time greatly.

9.
Ying Yong Sheng Tai Xue Bao ; 30(9): 3019-3027, 2019 Sep.
Artigo em Chinês | MEDLINE | ID: mdl-31529877

RESUMO

We examined the role of photosynthesis in regulating soil CO2 emission under nitrogen enrichment in Keerqin sandy grassland. Results showed that nitrogen (N) application could affect soil respiration rate by altering the allocation of photosynthetic products to the belowground. Gross ecosystem photosynthesis rate (GEP) was positively correlated with soil respiration rate (Rs). Nitrogen application reduced slope of the fitting function from 0.236 to 0.161, with the equation intercept difference (0.51 µmol·m-2·s-1) being similar to the nighttime soil respiration rate increment (0.52 µmol·m-2·s-1). From May to October, the difference of photosynthetic rate (differential ratio) caused by nitrogen application was significantly correlated with that of soil respiration (differential ratio). Results from partial correlation confirmed the essential role of photosynthetic rate difference (ΔGEP) in driving soil respiration rate difference (ΔRs) caused by nitrogen application. In the nighttime, soil respiration rate was affected by the aboveground vegetation activities in daytime. The daily mean GEP was an important factor affecting the nighttime soil respiration rate difference (ΔRs) (P<0.01). Photosynthesis, rather than soil temperature, was the main factor affecting soil respiration rate difference (ΔRs) under nitrogen application. Thus, the role of photosynthetic assimilation-regulating may provide a novel supplement for elucidating the responses of soil respiration to nitrogen enrichment.


Assuntos
Pradaria , Nitrogênio , Fotossíntese , Solo/química , Dióxido de Carbono , Ecossistema , Estações do Ano
10.
Oncol Lett ; 18(4): 4144-4152, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31516613

RESUMO

Thymocyte selection-associated high mobility group box (TOX) genes represent a novel family of genes. Deregulated expression of TOXs has been reported in a variety of cancer types, including lung cancer. It has also been reported that TOXs are crucial regulators of the immune system. The present study systematically evaluated the prognostic values of TOX family members using a set of publicly accessible databases, including Oncomine, Kaplan-Meier plotter and cBioPortal. It was revealed that TOX expression profiles differed between lung cancer and normal tissues, and high expression of TOX mRNAs generally predicted improved survival outcomes. Notably, TOX3 expression was significantly increased in lung adenocarcinoma, compared with other pathological subtypes of lung cancer. Survival analysis demonstrated that elevated TOX3 expression was significantly associated with improved progression-free and overall survival in patients with lung adenocarcinoma. Furthermore, correlation analysis indicated that TOX3 expression was negatively correlated with the expression of programmed death-1 receptor (PD-1), PD-ligand 1 and Hepatitis A virus cellular receptor 2 in lung adenocarcinoma. These results indicated that TOX3 is a prognostic indicator and promising immunomodulatory factor in lung adenocarcinoma. Future studies investigating the role of TOX3 in lung cancer immunity are warranted.

11.
Biosci Rep ; 39(7)2019 07 31.
Artigo em Inglês | MEDLINE | ID: mdl-31262972

RESUMO

Patients with type 2 diabetes mellitus (T2DM) have a very high risk of cardiovascular related events, and reducing complications is an important evaluation criterion of efficacy and safety of hypoglycemic drugs. Previous studies have shown that the dipeptidyl peptidase-4 (DPP-4) inhibitors (DPP4i), such as sitagliptin, might reduce the incidence of major cardiovascular events (MACEs). However, the safety and efficacy of sitagliptin remains controversial, especially the safety for cardiovascular related events. Here, a systematic review was conducted to assess the cardiovascular safety of sitagliptin in T2DM patients. The literature research dating up to October 2018 was performed in the electronic database. The clinical trials about sitagliptin for T2DM patients were included. Two reviewers independently screened literature according to the inclusion and exclusion criteria. The primary outcome was the MACE, and the secondary outcome was all-cause mortality. Finally, 32 clinical trials composed of 16082 T2DM patients were included in this meta-analysis. The results showed that: there was no significant difference between sitagliptin group and the control group on MACE (odds ratio (OR) = 0.85, 95% confidence intervals (CIs) = 0.63-1.15), myocardial infarction (MI) (OR = 0.66, 95% CI = 0.38-1.16), stroke (OR = 0.83, 95% CI = 0.44-1.54) and mortality (OR = 0.52, 95% CI = 0.26-1.07). These results demonstrated that sitagliptin did not increase the risk of cardiovascular events in patients with T2DM.

12.
J Vis Exp ; (147)2019 05 17.
Artigo em Inglês | MEDLINE | ID: mdl-31157790

RESUMO

In recent years, emerging databases were designed to lower the barriers for approaching the intricate cancer genomic datasets, thereby, facilitating investigators to analyze and interpret genes, samples and clinical data across different types of cancer. Herein, we describe a practical operation procedure, taking ID1 (Inhibitor of DNA binding proteins 1) as an example, to characterize the expression patterns of biomarker and survival predictors of breast cancer based on pooled clinical datasets derived from online accessible databases, including ONCOMINE, bcGenExMiner v4.0 (Breast cancer gene-expression miner v4.0), GOBO (Gene expression-based Outcome for Breast cancer Online), HPA (The human protein atlas), and Kaplan-Meier plotter. The analysis began with querying the expression pattern of the gene of interest (e.g., ID1) in cancerous samples vs. normal samples. Then, the correlation analysis between ID1 and clinicopathological characteristics in breast cancer was performed. Next, the expression profiles of ID1 was stratified according to different subgroups. Finally, the association between ID1 expression and survival outcome was analyzed. The operation procedure simplifies the concept to integrate multidimensional data types at the gene level from different databases and test hypotheses regarding recurrence and genomic context of gene alteration events in breast cancer. This method can improve the credibility and representativeness of the conclusions, thereby, present informative perspective on a gene of interest.

13.
J Orthop Surg Res ; 14(1): 192, 2019 Jun 26.
Artigo em Inglês | MEDLINE | ID: mdl-31242906

RESUMO

BACKGROUND: Large segmental bone defects can be repaired using the Masquelet technique in conjunction with autologous cancellous bone (ACB). However, ACB harvesting is severely restricted. α-calcium sulfate hemihydrate (α-CSH) is an outstanding bone substitute due to its easy availability, excellent biocompatibility, biodegradability, and osteoconductivity. However, the resorption rate of α-CSH is too fast to match the rate of new bone formation. The objective of this study was to investigate the bone repair capacity of the Masquelet technique in conjunction with isolated α-CSH or an α-CSH/ACB mix in a rabbit critical-sized defect model. METHODS: The rabbits (n = 28) were randomized into four groups: sham, isolated α-CSH, α-CSH/ACB mix, and isolated ACB group. A 15-mm critical-sized defect was established in the left radius, followed by filling with polymethyl methacrylate spacer. Six weeks after the first operation, the spacers were removed and the membranous tubes were grafted with isolated α-CSH, isolated ACB, α-CSH/ACB mix, or none. Twelve weeks later, the outcomes were evaluated by manual assessment, radiography, and spiral-CT. The histopathological and morphological changes were examined by H&E staining. The levels of alkaline phosphatase and osteocalcin were analyzed by immunohistochemistry and immunofluorescence staining. RESULTS: Our results suggest that the bone repair capacity of the α-CSH/ACB mix group was similar to the isolated ACB group, while the isolated α-CSH group was significantly decreased compared to the isolated ACB group. CONCLUSION: These results highlighted a promising strategy in the healing of large segmental bone defect with the Masquelet technique in conjunction with an α-CSH/ACB mix (1:1, w/w) as they possessed the combined effects of sufficient supply and low resorption.


Assuntos
Substitutos Ósseos/administração & dosagem , Sulfato de Cálcio/administração & dosagem , Rádio (Anatomia)/lesões , Rádio (Anatomia)/cirurgia , Procedimentos Cirúrgicos Reconstrutivos/métodos , Animais , Masculino , Coelhos , Rádio (Anatomia)/diagnóstico por imagem
15.
Cancer Manag Res ; 11: 2059-2072, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30881130

RESUMO

Background: Growing evidence has indicated that the long noncoding RNA H19 (lncRNA H19), frequently deregulated in almost all tumor types tested, acted as a pivotal contributor to both cancer initiation and progression. However, the role of lncRNA H19 in human papillary thyroid carcinoma (PTC) remains controversial. The aim of the study was to investigate the expression and potential function of lncRNA H19 in human PTC. Patients and methods: The lncRNA H19 level was determined by quantitative real-time (RT)-PCR analyses in 58 PTC tissue samples and their paired paracancerous tissue samples. RNA interference, RT-PCR analysis, and Western blot assay were used to determine the impact of lncRNA H19 on epithelial-mesenchymal transition (EMT) markers in human PTC cells. The migratory and invasive capacities of PTC cells were determined by wound-healing and transwell migration and invasion assays. Results: lncRNA H19 expression was 2.417-fold higher in PTC tissues than their paired paracancerous tissue (95% CI: 1.898-2.935, P<0.0001). Higher level of lncRNA H19 was correlated to elevated expression of Vimentin, ZEB2, Twist, and Snail2. Inhibition of lncRNA H19 resulted in upregulation of E-cadherin and downregulation of Vimentin both at mRNA and protein levels. Conversely, enforced expression of the exogenous lncRNA H19 led to E-cadherin mRNA and protein downregulation and relative upregulation of Vimentin. Moreover, wound-healing and transwell migration and invasion assays showed that lncRNA H19 could promote the migratory and invasive abilities of PTC cells. Conclusion: The level of lncRNA H19 was significantly higher in PTC tissues than paired paracancerous tissue or normal tissues. Overexpression of lncRNA H19 was correlated with higher tumor burden of PTC. It also contributes to EMT process, as well as promotes migration and invasion of PTC cells.

16.
Micromachines (Basel) ; 10(2)2019 Feb 16.
Artigo em Inglês | MEDLINE | ID: mdl-30781497

RESUMO

The biomechanical properties of single cells show great potential for early disease diagnosis and effective treatments. In this study, a microfluidic device was developed for quantifying the mechanical properties of a single cell. Micropipette aspiration was integrated into a microfluidic device that mimics a classical Wheatstone bridge circuit. This technique allows us not only to effectively alter the flow direction for single-cell trapping, but also to precisely control the pressure exerted on the aspirated cells, analogous to the feature of the Wheatstone bridge that can precisely control bridge voltage and current. By combining the micropipette aspiration technique into the microfluidic device, we can effectively trap the microparticles and Hela cells as well as measure the deformability of cells. The Young's modulus of Hela cells was evaluated to be 387 ± 77 Pa, which is consistent with previous micropipette aspiration studies. The simplicity, precision, and usability of our device show good potential for biomechanical trials in clinical diagnosis and cell biology research.

17.
Genes (Basel) ; 10(2)2019 02 20.
Artigo em Inglês | MEDLINE | ID: mdl-30791673

RESUMO

Transport inhibitor response 1/auxin signaling f-box proteins (TIR1/AFBs) play important roles in the process of plant growth and development as auxin receptors. To date, no information has been available about the characteristics of the TIR1/AFB gene family in Brassica juncea var. tumida. In this study, 18 TIR1/AFB genes were identified and could be clustered into six groups. The genes are located in 11 of 18 chromosomes in the genome of B. juncea var. tumida, and similar gene structures are found for each of those genes. Several cis-elements related to plant response to phytohormones, biotic stresses, and abiotic stresses are found in the promoter of BjuTIR1/AFB genes. The results of qPCR analysis show that most genes have differential patterns of expression among six tissues, with the expression levels of some of the genes repressed by salt stress treatment. Some of the genes are also responsive to pathogen Plasmodiophora brassicae treatment. This study provides valuable information for further studies as to the role of BjuTIR1/AFB genes in the regulation of plant growth, development, and response to abiotic stress.


Assuntos
Brassica/genética , Proteínas de Plantas/genética , Receptores de Superfície Celular/genética , Regulação da Expressão Gênica de Plantas , Família Multigênica , Proteínas de Plantas/metabolismo , Receptores de Superfície Celular/metabolismo , Estresse Fisiológico
18.
Chin J Nat Med ; 17(1): 33-42, 2019 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-30704622

RESUMO

Antrodia camphorata, a well-known and highly valued edible medicinal mushroom with intriguing activities like liver protection, has been traditionally used for the treatment of alcoholic liver disease. A. camphorata shows highly medicinal and commercial values with the demand far exceeds the available supply. Thus, the petri-dish cultured A. camphorata (PDCA) is expected to develope as a substitute. In this paper, nineteen triterpenes were isolated from PDCA, and thirteen of them were the unique anthroic acids in A. camphorata, including the main content antcin K, which suggested that PDCA produced a large array of the same anthroic acids as the wild one. Furthermore, no obvious acute toxicity was found suggesting the edible safety of PDCA. In mice alcohol-induced liver injury model, triglyceride (TG), aspartate aminotransferase (AST), alanine aminotransferase (ALT), and malondialdehyde (MDA) had been reduced by the PDCA powder as well as the main content antcin K, which indicated that the PDCA could protect alcoholic liver injury in mice model and antcin K could be the effective component responsible for the hepatoprotective activities of PDCA against alcoholic liver diseases.


Assuntos
Antrodia/química , Produtos Biológicos/farmacologia , Produtos Biológicos/uso terapêutico , Doença Hepática Induzida por Substâncias e Drogas/prevenção & controle , Fígado/efeitos dos fármacos , Alanina Transaminase/sangue , Aldeído Desidrogenase/sangue , Animais , Aspartato Aminotransferases/sangue , Produtos Biológicos/química , Doença Hepática Induzida por Substâncias e Drogas/etiologia , Colestenos/química , Colestenos/farmacologia , Colestenos/uso terapêutico , VLDL-Colesterol/sangue , Modelos Animais de Doenças , Etanol/toxicidade , Feminino , Carpóforos/química , Fígado/metabolismo , Fígado/patologia , Hepatopatias Alcoólicas/prevenção & controle , Masculino , Malondialdeído/sangue , Camundongos , Estrutura Molecular , Triglicerídeos/sangue , Triterpenos/química , Triterpenos/farmacologia , Triterpenos/uso terapêutico
19.
Oncol Lett ; 17(2): 1505-1516, 2019 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-30675206

RESUMO

Early-onset breast cancer (BC) has been recognized to be more aggressive compared with its later counterparts. Survival models of BC in young patients have rarely been reported in previous studies. The current study aimed to establish and validate prediction models with clinicopathological variables for visceral metastasis-free survival (VFS), disease-free-survival (DFS) and overall survival (OS) time in young patients with BC. Clinicopathological data were obtained for 351 patients with primary breast tumors who were ≤40 years old. Univariate and multivariate analyses were performed and nomograms were established to screen and illustrate the prognostic factors. Risk scores were calculated based on coefficients from the Cox regression analysis. Internal validation of the prediction models was conducted by predicting the prognosis of cases randomly sampled from the cohort used in the current study. Multivariate analysis demonstrated that N stage (P=0.004), molecular subtype (P=0.007) and age (P=0.005) were significant independent prognostic factors for VFS. Similarly, N stage (P=0.002) and molecular subtype (P=0.001) were significantly associated with DFS. In addition, N stage (P=0.006), molecular subtype (P=0.006) and the presence of an initially inoperable tumor (P=0.005) were significant independent prognostic factors for OS. According to the Cox regression analysis, nomograms were generated to illustrate the effect of independent prognostic factors on VFS, DFS and OS. Risk scores were calculated and internal validation demonstrated the reliability of the prediction models. In conclusion, N stage and molecular subtype were identified as predictors for VFS, DFS and OS in early-onset BC. Furthermore, an age of <35 years at diagnosis was revealed to be unfavorable for VFS and the presence of an initially inoperable tumor was identified to reduce OS time.

20.
Cancer Manag Res ; 11: 143-156, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30613163

RESUMO

Background: NPM1 is a multifunctional phosphoprotein that commutes between the cytoplasm and nucleus in cell cycle process, which appears to be actively involved in tumorigenesis. Herein, we sought to investigate the possible role and prognostic value of NPM1 in triple-negative breast cancer (TNBC). Methods: An array of public databases, including bc-GenExMiner v4.0, GOBO, GEPIA, UAL-CAN, ONCOMINE database and Kaplan-Meier plotter, were used to investigate the expression feature and potential function of NPM1 in TNBC. Immunohistochemistry, immunofluorescence, proliferation and colony formation, flow cytometry and western-blotting assays were used to analyze and verify the function and relevant mechanism of NPM1 in TNBC tissues and cells. Results: According to analysis from bc-GenExMiner, the expression level of NPM1 was significantly higher in basal-like subtypes than luminal-A, HER-2 or normal-like subtypes of breast cancer (P<0.0001). GOBO database analysis indicated that the expression of NPM1 in basal-A or basal-B was significantly higher than luminal-like breast cancer cells. Immunohistochemistry assay in 52 TNBC tissue samples showed that positive expression of Ki-67 was 93.5% in the high-NPM1-expression group and 66.7% in the low-NPM1-expression group, respectively (P=0.032). Proliferation and colony formation assays demonstrated that inhibition of NPM1 suppressed cell growth by approximately 2-fold and reduced the number of colonies by 3-4-fold in MDA-MB-231 and BT549 cells. Moreover, inhibition of NPM1 in MDA-MB-231 and BT549 cells increased the percentage of cells at G0/G1 phase and decreased the percentage of cells at both S and G2/M phase, as compared with control counterparts. Western-blotting results showed that down-regulation of NPM1 could elevate CDH1 and p27kip1 expression, while decrease Skp2 expression both in MDA-MB-231 and BT549 cells. In addition, high mRNA expression of NPM1 correlated with shorter RFS (HR=1.64, P=0.00013) and OS (HR=2.45, P=0.00034) in patients with TNBC. Conclusions: NPM1 is significantly high expressed basal-like/triple-negative breast cancer and is correlated with shorter RFS and OS in this subset of patients. Knockdown of NPM1 impairs the proliferative capacity of TNBC cells via activation of the CDH1/Skp2/p27kip1 pathway. Targeting NPM1 is a potential therapeutic strategy against TNBC.

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