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A retrospective study on 90 eligible HER2+ ductal carcinoma in situ with microinvasion (DCIS-MI) patients was performed with a median follow-up time of 57 months. The baseline was consistent between the 4-cycle and 6-cycle chemotherapy groups. There were more patients with multiple foci of micrometastasis in the target therapy group in the two groups with or without target therapy (p < 0.01). Postoperative chemotherapy with a 4-cycle regimen can achieve the expected therapeutic effect in patients with HER2+ DCIS-MI, but the role of target therapy in HER2+ DCIS-MI patients has not been confirmed.
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Neoplasias da Mama , Carcinoma Intraductal não Infiltrante , Receptor ErbB-2 , Humanos , Feminino , Receptor ErbB-2/metabolismo , Neoplasias da Mama/patologia , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/cirurgia , Neoplasias da Mama/metabolismo , Pessoa de Meia-Idade , Estudos Retrospectivos , Quimioterapia Adjuvante , Carcinoma Intraductal não Infiltrante/patologia , Carcinoma Intraductal não Infiltrante/tratamento farmacológico , Carcinoma Intraductal não Infiltrante/cirurgia , Carcinoma Intraductal não Infiltrante/metabolismo , Adulto , Idoso , Invasividade Neoplásica , Resultado do Tratamento , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêuticoRESUMO
The total viable count (TVC) of bacteria is an important index to evaluate the freshness and safety of dishes. To improve the accuracy and robustness of spectroscopic detection of total viable bacteria count in a complex system, a new method based on a near-infrared (NIR) hyperspectral hybrid model and Support Vector Machine (SVM) algorithms was developed to directly determine the total viable count in intact beef dish samples in this study. Diffuse reflectance data of intact and crushed samples were tested by NIR hyperspectral and processed using Multiplicative Scattering Correction (MSC) and Competitive Adaptive Reweighted Sampling (CARS). Kennard-Stone (KS) and Samples Set Partitioning Based on Joint X-Y Distance (SPXY) algorithms were used to select the optimal number of standard samples transferred by the model combined with root mean square error. The crushed samples were transferred into the complete samples prediction model through the Direct Standardization (DS) algorithm. The spectral hybrid model of crushed samples and full samples was established. The results showed that the Determination Coefficient of Calibration (RP2) value of the total samples prediction set increased from 0.5088 to 0.8068, and the value of the Root Mean Square Error of Prediction (RMSEP) decreased from 0.2454 to 0.1691 log10 CFU/g. After establishing the hybrid model, the RMSEP value decreased by 9.23% more than before, and the values of Relative Percent Deviation (RPD) and Reaction Error Relation (RER) increased by 12.12% and 10.09, respectively. The results of this study showed that TVC instewed beef samples can be non-destructively determined based on the DS model transfer method combined with the hybrid model strategy. This study provided a reference for solving the problem of poor accuracy and reliability of prediction models in heterogeneous samples.
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Algoritmos , Espectroscopia de Luz Próxima ao Infravermelho , Animais , Bovinos , Espectroscopia de Luz Próxima ao Infravermelho/métodos , Reprodutibilidade dos Testes , Análise dos Mínimos Quadrados , Máquina de Vetores de SuporteRESUMO
Three-dimensional (3D) porous graphene-based materials have displayed attractive electrochemical catalysis and sensing performances, benefiting from their high porosity, large surface area, and excellent electrical conductivity. In this work, a novel electrochemical sensor based on 3D porous reduced graphene (3DPrGO) and ion-imprinted polymer (IIP) was developed for trace cadmium ion (Cd(II)) detection in water. The 3DPrGO was synthesized in situ at a glassy carbon electrode (GCE) surface using a polystyrene (PS) colloidal crystal template and the electrodeposition method. Then, IIP film was further modified on the 3DPrGO by electropolymerization to make it suitable for detecting Cd(II). Attributable to the abundant nanopores and good electron transport of the 3DPrGO, as well as the specific recognition for Cd(II) of IIP, a sensitive determination of trace Cd(II) at PoPD-IIP/3DPrGO/GCE was achieved. The proposed sensor exhibited comprehensive linear Cd(II) responses ranging from 1 to 100 µg/L (R2 = 99.7%). The limit of detection (LOD) was 0.11 µg/L, about 30 times lower than the drinking water standard set by the World Health Organization (WHO). Moreover, PoPD-IIP/3DPrGO/GCE was applied for the detection of Cd(II) in actual water samples. The satisfying recoveries (97-99.6%) and relative standard deviations (RSD, 3.5-5.7%) make the proposed sensor a promising candidate for rapid and on-site water monitoring.
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FAT10, an ubiquitin-like protein, functions as a potential tumor promoter in several caners. However, the function and clinical significance of FAT10 in breast cancer (BC) remains unclear. Here, we found that high FAT10 expression was detected frequently in primary BC tissues, and was closely associated with malignant phenotype and shorter survival among the BC patients. Multivariate analyses also revealed that FAT10 overexpression was independent prognostic factors for poor outcome of patients with BC. Function assay demonstrated that FAT10 knockdown significantly inhibited the metastasis abilities and the epithelial-mesenchymal transition (EMT) of breast cancer cell. Further investigation revealed that FAT10 directly bound ZEB2 and decreased its ubiquitination to enhance the protein stability of ZEB2 in BC cells. Moreover, our data shown that the pro-metastasis effect of FAT10 in BC is partially dependent on ZEB2 enhancement. Collectively, our data suggest that FAT10 plays a crucial oncogenic role in BC metastasis, and we provide a novel evidence that FAT10 may be serve as a prognostic and therapeutic target for BC patients.
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Neoplasias da Mama/metabolismo , Neoplasias da Mama/patologia , Movimento Celular , Ubiquitinas/metabolismo , Homeobox 2 de Ligação a E-box com Dedos de Zinco/metabolismo , Animais , Neoplasias da Mama/genética , Linhagem Celular Tumoral , Transição Epitelial-Mesenquimal/genética , Feminino , Regulação Neoplásica da Expressão Gênica , Técnicas de Silenciamento de Genes , Humanos , Camundongos , Pessoa de Meia-Idade , Análise Multivariada , Invasividade Neoplásica , Prognóstico , Ligação Proteica , Estabilidade Proteica , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Ubiquitinas/genéticaRESUMO
AIM: This study aims to explore the accuracy, specificity and laws of axillary lymph node metastasis predicted by sentinel lymph node biopsy (SLNB) by comparing axillary lymph node status via SLNB and axillary lymph node dissection (ALND) with nanocarbon as the tracer. METHODS: Forty six patients were retrospectively analyzed. These patients underwent SLNB with nanocarbon as the tracer from March 2013 to April 2014. RESULTS: Two hundred and forty six patients of sentinel lymph node (SLN) were successfully detected. Among these patients, 8 patients had 1 SLN (3.25%), 33 patients had 2 SLN (13.41%), 46 patients had 3 SLN (18.70%), 51 patients had 4 SLN (20.73%), 40 patients had 5 SLN (16.26%), 24 patients had 6 SLN (9.76%) and 24 patients had 7 or more SLN (9.76%). The SLNB success rate of nanocarbon staining in the 246 cases was 99.59%, accuracy rate was 97.06% and sensitivity was 93.22%. Furthermore, false negatives were found in four patients, and the false-negative rate was 6.78%. The number of lymph node metastasis in the SLNB and ALND of early-stage breast cancer was analyzed. When the number of SLN dissection was 1, 2, 3, 4, 5, 6 or 7, the coincidence rate of lymph node metastasis for SLNB and ALND was 80.00, 84.36, 78.57, 88.89, 90.48, 80.00, 73.68 and 78.36, respectively. CONCLUSION: Sentinel lymph node biopsy performed using the nanocarbon staining method is simple, easy and reliable, and it can be used to predict the axillary status of breast cancer in the early stage.
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Neoplasias da Mama/diagnóstico , Carbono , Linfonodos/patologia , Nanopartículas , Biópsia de Linfonodo Sentinela/estatística & dados numéricos , Biópsia de Linfonodo Sentinela/normas , Adulto , Idoso , Axila/patologia , Neoplasias da Mama/patologia , Feminino , Humanos , Pessoa de Meia-Idade , Estudos Retrospectivos , Sensibilidade e EspecificidadeRESUMO
This study investigated the possibility of using visible and near-infrared (VIS/NIR) hyperspectral imaging techniques to discriminate viable and non-viable wheat seeds. Both sides of individual seeds were subjected to hyperspectral imaging (400-1000 nm) to acquire reflectance spectral data. Four spectral datasets, including the ventral groove side, reverse side, mean (the mean of two sides' spectra of every seed), and mixture datasets (two sides' spectra of every seed), were used to construct the models. Classification models, partial least squares discriminant analysis (PLS-DA), and support vector machines (SVM), coupled with some pre-processing methods and successive projections algorithm (SPA), were built for the identification of viable and non-viable seeds. Our results showed that the standard normal variate (SNV)-SPA-PLS-DA model had high classification accuracy for whole seeds (>85.2%) and for viable seeds (>89.5%), and that the prediction set was based on a mixed spectral dataset by only using 16 wavebands. After screening with this model, the final germination of the seed lot could be higher than 89.5%. Here, we develop a reliable methodology for predicting the viability of wheat seeds, showing that the VIS/NIR hyperspectral imaging is an accurate technique for the classification of viable and non-viable wheat seeds in a non-destructive manner.
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Triticum , Germinação , Análise dos Mínimos Quadrados , Sementes , Espectroscopia de Luz Próxima ao Infravermelho , Máquina de Vetores de SuporteRESUMO
BACKGROUND: Extramammary Paget disease is a relatively rare and less malignant intraepithelial adenocarcinoma. t is found in areas with abundant distribution of apocrine sweat glands such as the external genitalia, external genitalia, and perianal area, with fewer armpits. The disease progresses slowly and is prone to misdiagnosis in clinical practice. METHODS: We retrospectively analyzed a female patient. She had a left axillary mass for more than 2 years. Recently, the mass increased and the surface skin was ulcerated. Then she went to Jiangxi Provincial Dermatology Hospital for left axillary lesion resection, and the postoperative pathology showed Paget disease outside the breast. For further diagnosis and treatment, she came to our hospital. We diagnosed a tumor with uncertain or unknown dynamics in the left axillary breast. Under general anesthesia, left subaxillary mass resection, freezing and left breast cancer breast conserving surgery was performed. RESULTS: The postoperative pathology of the left axillary mass combined with morphological and immunohistochemical results was consistent with Paget disease. Postoperative immunohistochemistry showed estrogen receptor (+, 20%), progesterone receptor (-), human epidermal growth factor receptor-2 (3+), Ki-67 (30%), cytokine7 (+), and p63 (-). Following up for 22 months, there has been no local recurrence, no swelling of the right axillary lymph node, no distant metastasis found on follow-up, and no complications such as upper limb lymphedema, upper limb sensory abnormalities, or motor disorders have been observed. CONCLUSION: Paget disease outside the axillary breast is relatively rare, and surgical resection is the best choice. The prognosis is good, and the recurrence rate is low.
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Adenocarcinoma , Neoplasias da Mama , Osteíte Deformante , Doença de Paget Extramamária , Humanos , Feminino , Estudos Retrospectivos , Adenocarcinoma/cirurgia , Doença de Paget Extramamária/diagnóstico , Doença de Paget Extramamária/cirurgia , Doença de Paget Extramamária/patologia , Linfonodos/patologia , Mama , Neoplasias da Mama/diagnóstico , Neoplasias da Mama/cirurgia , Neoplasias da Mama/patologiaRESUMO
This study aimed to explore the mechanism of cooking intensity on the tenderness of stir-fried pork slices from the perspective of the changes in temperature distribution. Infrared thermal imaging was used to monitor the distribution of temperature. Results showed that the high-level heat (HH) treatment could improve tenderness. When the center temperature increased to 100 °C, the shear force of samples from the low-level heat (LH) group increased by around 3-fold, and HH reduced this upward trend. This result was mainly attributed to the shorter heating time undergone by the HH-treated samples compared to the LH treatment, which resulted in less structural shrinkage and faster passing through the protein denaturation interval of the samples. These changes alleviated temperature fluctuations caused by water loss. This explanation could be confirmed by the results of T2 relaxation time and Fourier transform-infrared spectroscopy (FT-IR). However, the LH treatment caused a slower rise in oil temperature due to more moisture migration, which required the samples to undergo longer thermal denaturation, leading to a deterioration in tenderness. Moreover, histological analysis revealed that the greater integrity of endomysium in the HH group inhibited water loss and oil absorption, which contributed to obtain low-fat meat products with higher tenderness. This study provides support for the industrialization of traditional pork cuisines using oil as the heating medium.
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Culinária , Temperatura Alta , Animais , Suínos , Temperatura Alta/efeitos adversos , Espectroscopia de Infravermelho com Transformada de Fourier/métodos , Carne de Porco/análise , ÁguaRESUMO
The limited nutritional information provided by external food representations has constrained the further development of food nutrition estimation. Near-infrared hyperspectral imaging (NIR-HSI) technology can capture food chemical characteristics directly related to nutrition and is widely used in food science. However, conventional data analysis methods may lack the capability of modeling complex nonlinear relations between spectral information and nutrition content. Therefore, we initiated this study to explore the feasibility of integrating deep learning with NIR-HSI for food nutrition estimation. Inspired by reinforcement learning, we proposed OptmWave, an approach that can perform modeling and wavelength selection simultaneously. It achieved the highest accuracy on our constructed scrambled eggs with tomatoes dataset, with a determination coefficient of 0.9913 and a root mean square error (RMSE) of 0.3548. The interpretability of our selection results was confirmed through spectral analysis, validating the feasibility of deep learning-based NIR-HSI in food nutrition estimation.
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Background: Several studies have analyzed the relationship between body mass index (BMI) and the prognosis of breast cancer (BC). However, whether their relationship is linear or curvilinear remains unclear. This cohort study examined the specific relationship between BMI and BC outcomes. Methods: This retrospective cohort study included 1049 BC patients from March 7, 2013 through December 31, 2019 in a hospital. Kaplan-Meier curves, multivariate Cox proportional models, and restricted cubic spline (RCS) was used to analysis the relationship between BMI and overall survival (OS) and breast cancer-specific survival (BCSS) was analyzed. Results: During a median of 4.87 (IQR:3.26-6.84) years of follow-up period, 71 patients (6.77%) died, of which 50 (70.42%) were attributed to BC. RCS analysis revealed a U- shaped relationship between BMI levels and OS and BCSS after adjusting for other variables. The turning points of the U-shaped curves were 23 kg/m2. On the left side of the turning point, the risk of OS (HR, 0.83; 95% CI, 0.70, 0.98) and BCSS (HR, 0.80; 95% CI, 0.65, 0.98) were adversely correlated with BMI. In contrast, to the right of the turning point, the risk of OS (HR, 1.22; 95% CI, 1.10, 1.37) and BCSS (HR, 1.28; 95% CI, 1.13, 1.46) was positively related to BMI. Kaplan-Meier curves and multivariate Cox regression analyses shown consistent results with RCS analyses. Conclusion: BMI was an independent prognostic factor for BC, and had a U-shaped relationship with OS and BCSS. Interventions should be designed to improve patient outcomes based on BMI.
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Agricultural products are frequently contaminated by mycotoxins. Multiplex, ultrasensitive, and rapid determination of mycotoxins is still a challenging problem, which is of great significance to food safety and public health. Herein, a surface-enhanced Raman scattering (SERS) based lateral flow immunoassay (LFA) for the simultaneous on-site determination of aflatoxin B1 (AFB1) and ochratoxin A (OTA) on the same test line (T line) was developed, in this study. In practice, two kinds of Raman reporters 4-mercaptobenzoic acid (4-MBA), and 5,5'-dithiobis-(2-nitrobenzoic acid) (DTNB) encoded silica-encapsulated gold nanotags (Au4-MBA@SiO2 and AuDNTB@SiO2) were used as detection markers to identify the two different mycotoxins. Through systematic optimization of the experimental conditions, this biosensor has high sensitivity and multiplexing with the limits of detection (LODs) at 0.24 pg mL-1 for AFB1 and 0.37 pg mL-1 for OTA. These are far below the regulatory limits set by the European Commission, in which the minimum LODs for AFB1 and OTA are 2.0 and 3.0 µg kg-1. In the spiked experiment, the food matrix are corn, rice, and wheat, and the mean recoveries of the two mycotoxins ranged from 91.0% ± 6.3%-104.8% ± 5.6% for AFB1 and 87.0% ± 4.2%-112.0% ± 3.3% for OTA. These results demonstrate that the developed immunoassay has good stability, selectivity, and reliability, which can be used for routine monitoring of mycotoxin contamination.
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Nanopartículas Metálicas , Micotoxinas , Aflatoxina B1/análise , Dióxido de Silício , Reprodutibilidade dos Testes , Micotoxinas/análise , Imunoensaio , Ouro , Limite de DetecçãoRESUMO
Interleukin-6 (IL-6) is generally used as a biomarker for the evaluation of inflammatory infection in humans and animals. However, there is no approach for the on-site and rapid detection of IL-6 for the monitoring of mastitis in dairy farm scenarios. A rapid and highly sensitive surface enhanced Raman scattering (SERS) immunofiltration assay (IFA) for IL-6 detection was developed in the present study. In this assay, a high sensitivity gold core silver shell SERS nanotag with Raman molecule 4-mercaptobenzoic acid (4-MBA) embedded into the gap was fabricated for labelling. Through the immuno-specific combination of the antigen and antibody, antibody conjugated SERS nanotags were captured on the test zone, which facilitated the SERS measurement. The quantitation of IL-6 was performed by the readout Raman signal in the test region. The results showed that the detection limit (LOD) of IL-6 in milk was 0.35 pg mL-1, which was far below the threshold value of 254.32 pg mL-1. The recovery of the spiking experiment was 87.0-102.7%, with coefficients of variation below 9.0% demonstrating high assay accuracy and precision. We believe the immunosensor developed in the current study could be a promising tool for the rapid assessment of mastitis by detecting milk IL-6 in dairy cows. Moreover, this versatile immunosensor could also be applied for the detection of a wide range of analytes in dairy cow healthy monitoring.
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Background: The solute carrier (SLC) 7 family genes play central roles in cancer cell metabolism as glucose and glutamate transporters. However, their expression and prognostic value in breast cancer (BC) remains to be elucidated. Methods: Clinical data from BC patients were downloaded from The Cancer Genome Atlas (TCGA) and the Kaplan-Meier (KM) plotter database. The mechanisms underlying the association between SLC7A expression and overall survival (OS) were explored using Cox regression and log-rank tests. ESTIMATE gives a measure of the immune-cell infiltrates. Single-sample (ss) Gene Set Enrichment Analysis (GSEA) was conducted to quantify immune cell infiltration. Results: High SLC7A5 expression was associated with a poorer survival time in BC patients according to the TCGA and KM plotter data. SLC7A4 was associated with good progression-free interval (PFI) and disease-specific survival (DSS) according to the TCGA data. Furthermore, SLC7A4 was correlated with good prognosis of OS, distant metastasis-free survival (DMFS), relapse-free survival (RFS), and post-progression survival (PPS) according to the KM plotter data. SLC7A3 expression was positively associated with OS, but was not strongly associated with PFI nor DSS in the TCGA data. However, SLC7A3 was positively correlated with DMFS and RFS in the KM database analysis. SLC7A had excellent diagnostic value in BC patients and was strongly correlated with tumor infiltration. T helper 2 (Th2) cells, CD56 bright natural killer (NK) cells, and NK cells were the most strongly correlated with the SLC7A family genes, suggesting that these genes play a crucial role in BC partly by modulating immune infiltration. Conclusions: SLC7A4 and SLC7A5 expression levels may be sensitive biomarkers for predicting BC outcomes. SLC7A3 may be a potential diagnostic and prognostic biomarker in BC, but further studies are warranted to verify these results.
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INTRODUCTION: Non-islet cell tumor hypoglycemia (NICTH) generally refers to hypoglycemia caused by tumors other than islet cell tumors. Although hypoglycemia is a common clinical emergency, NICTH rarely occurs in patients with breast cancer. PATIENT CONCERNS: A 47-year-old woman presented with repeated hypoglycemia hypoglycemia caused by a lobulated breast tumor. DIAGNOSES: Hypoglycemic symptoms occurred many times during fasting and in the early morning. Insulin and C-peptide levels were decreased; insulin-like growth factor (IGF)-II: IGF-I was greater than 10. Postoperative pathology revealed a lobulated tumor in the breast. After excluding other causes of hypoglycemia, the patient was diagnosed with NICTH due to breast cancer. INTERVENTIONS: Total mastectomy of right breast was performed. OUTCOMES: After 3 years of follow-up, hypoglycemia did not recur. CONCLUSION: Patients with breast cancer may experience recurrent hypoglycemia. After exclusion of insulinomatous and pancreatic origin of hypoglycemia, the possibility of NICTH should be considered, and surgical resection of the primary tumor should be performed as soon as possible.
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Adenoma de Células das Ilhotas Pancreáticas , Neoplasias da Mama/complicações , Hipoglicemia/etiologia , Neoplasias Pancreáticas , Adenoma de Células das Ilhotas Pancreáticas/patologia , Neoplasias da Mama/cirurgia , Feminino , Humanos , Hipoglicemia/cirurgia , Fator de Crescimento Insulin-Like II , Mastectomia , Pessoa de Meia-Idade , Recidiva Local de Neoplasia , Neoplasias Pancreáticas/patologiaRESUMO
INTRODUCTION: The purpose of our research was to evaluate MT1JP in breast cancer. MATERIAL AND METHODS: For clinical purpose, tissues were collected, and a correlation analysis ofMT1JP and miRNA-214 gene expressions was conducted. Using an in vitro study, MDA-MB-231 and MCF-7 cell lines were used as research objects in our research. Colony, flow cytometry, TUNEL, transwell, adhesion and wound healing assay were used to discuss the biological activities of the cells. In an in vivo study, tumor weight and volume were measured, and cell apoptosis was measured by TUNEL assay. The relative mechanism's proteins were evaluated by Western blotting or immunohistochemistry assay. RESULTS: Compared with adjacent tissues, MT1JP and miRNA-214 gene expressions were significantly different (P<0.001, respectively). By in vitro and in vivo studies, the biological activities of the cells were significantly decreased in MDA-MB-231 and MCF-7 cell lines with MT1JP overexpression. The relative mechanism was correlated with miRNA-214/RUNX3 axis. CONCLUSION: The overexpression of MT1JP suppresses the biological activities of breast cancer cells by regulation miRNA-214/RUNX3 axis in vitro and vivo study.
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This paper described a rapid and non-destructive method based on visible near-infrared (Vis-NIR) hyperspectral imaging system (400-1000â¯nm) for detection adulteration with duck meat in minced lamb. The multiple average of the reference spectral and a predicted relative spatial distribution coefficient were applied in this study to reduce the noise of the spectra. The PLSR model with selected wavelengths achieved better results than others with determination of coefficients (R2P) of 0.98, and standard error of prediction (RMSEP) of 2.51%. And the prediction map of the duck minced in lamb meat was generated by applying the prediction model. The results of this study indicate the great potential of the hyperspectral technology applying to rapidly and accurately detect the meat adulteration in minced lamb meat.
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Patos , Carne Vermelha/análise , Ovinos , Espectroscopia de Luz Próxima ao Infravermelho/métodos , Algoritmos , Animais , Contaminação de Alimentos/análiseRESUMO
BACKGROUND: Triple-negative breast cancer (TNBC) is the most aggressive subtype of breast cancer, characterized by advanced disease stage and poor prognosis. Moreover, due to the lack of therapeutic markers, TNBC patients can't benefit fully from currently available targeted therapies. METHODS: To fully understand the molecular basis of TNBC, we used gene set enrichment analysis (GSEA) to screen out the most altered functional module in TNBC, from publicly available microarray data and studied the association of the candidate gene with TNBC development. RESULTS: We found that the proteasome was significantly activated in TNBC. As compared with other breast cancer subtypes and normal tissue, proteasome subunit beta 5 (PSMB5), the key regulator of proteasome function, was overexpressed in TNBC tissue and predictive of poor prognosis. Moreover, we also found that PSMB5 knockdown induced TNBC apoptosis and significantly enhanced cancer cell sensitivity to the chemotherapeutic agents bortezomib and paclitaxel. CONCLUSIONS: Our results suggest a potential role for PSMB5 as a biomarker and therapeutic target for TNBC.
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Biomarcadores Tumorais/genética , Complexo de Endopeptidases do Proteassoma/genética , Neoplasias de Mama Triplo Negativas/tratamento farmacológico , Neoplasias de Mama Triplo Negativas/genética , Idoso , Apoptose/efeitos dos fármacos , Apoptose/genética , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Resistencia a Medicamentos Antineoplásicos/genética , Feminino , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Técnicas de Silenciamento de Genes , Humanos , Pessoa de Meia-Idade , Paclitaxel/administração & dosagem , Neoplasias de Mama Triplo Negativas/patologiaRESUMO
During the past two decades, cytokines have emerged as key molecules to modulate innate and adaptive immunity and mediate anti-tumor activity. Although multiple cytokine types are implicated for such anti-tumor activity in several cancer types, it remains largely unknown in breast cancer. In this study, cytokines that are prior known for antitumor activity in different cancer types were examined against breast cancer using a 4T1 cells based xenograft-model. Our results showed Interleukin-12 (IL-12) (500ng/mouse) significantly suppressed the growth of tumors, while other cytokines showed minimal suppression. Subsequent molecular analysis by flow cytometry and immunohistochemistry confirmed the CD8+ cells infiltration and Interferon-γ (IFN-γ) production by them in tumor environment. In addition, we observed that IFN-γ production by activated CD8+ cells directly induced apoptosis in tumor cells, which together indicate that IL-12 causes CD8+ cells to infiltrate and secrete IFN-γ in tumor environment, which induce apoptosis in them and causes tumor growth suppression. Furthermore, we showed that lower dosage of IL-12 and chemotherapy drug tamoxifen combinations enhanced the tumor suppression as opposed to single treatments, and thereby propose an alternate option for high dosage associated effects for both drug and cytokine treatments.