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1.
Environ Geochem Health ; 45(12): 9639-9652, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37787830

RESUMO

Fine particulate matter (PM2.5) has health effects that may depend on its sources and chemical composition. In this study, characteristics of PM2.5 chemical composition and health risk assessment from Songyuan, China, were investigated during day and night in indoor and outdoor from February 4 to 19, 2021. Relative high concentrations of PM2.5 were obtained in indoor environment than outdoor, with 503.95 ± 209.62 µg/m3 during the day and 357.52 ± 232.81 µg/m3 at night for the indoor environment. Relatively high total carbon, organic carbons, elemental carbons, polycyclic aromatic hydrocarbons (PAHs), and oxygenated polycyclic aromatic hydrocarbons (OPAHs) were obtained in indoor environment. However, the average concentrations of PAHs were higher during night (73.57 ± 43.09 ng/m3) in indoor and OPAHs during day (6.027 ± 2.960 ng/m3) in outdoor. They had different I/O distributions of these compounds during day and night. Indeno(1,2,3-cd) pyrene was the dominant PAHs, and benzanthrone was the dominant OPAHs; this is different with the previous studies. The high indoor/outdoor ratios showed the indoor coal and biomass burning greatly affect the indoor pollutants. Average ILCR health risk assessment for PAHs was all higher than 10-6 for different age gender, suggesting there has potential cancer risk existed for populations living in the rural coal and biomass burning area Songyuan, China.


Assuntos
Poluentes Atmosféricos , Poluição do Ar em Ambientes Fechados , Hidrocarbonetos Policíclicos Aromáticos , Poluentes Atmosféricos/análise , Monitoramento Ambiental , Carvão Mineral/análise , Biomassa , Material Particulado/análise , China , Hidrocarbonetos Policíclicos Aromáticos/toxicidade , Hidrocarbonetos Policíclicos Aromáticos/análise , Medição de Risco , Poluição do Ar em Ambientes Fechados/análise
2.
Breast Cancer Res Treat ; 201(1): 27-41, 2023 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-37311933

RESUMO

Neoadjuvant chemotherapy (NCT) is the standard treatment for patients with locally advanced breast cancer (LABC). The predictive value of heterogeneous circulating tumor cells (CTCs) in NCT response has not been determined. All patients were staged as LABC, and blood samples were collected at the time of biopsy, and after the first and eighth NCT courses. Patients were divided into High responders (High-R) and Low responders (Low-R) according to Miller-Payne system and changes in Ki-67 levels after NCT treatment. A novel SE-i·FISH strategy was applied to detect CTCs. Heterogeneities were successfully analyzed in patients undergoing NCT. Total CTCs increased continuously and were higher in Low-R group, while in High-R group, CTCs increased slightly during NCT before returning to baseline levels. Triploid and tetraploid chromosome 8 increased in Low-R but not High-R group. The number of small CTCs in Low-R group increased significantly until the last sample, however, remained constant in High-R group. The patients with more CTCs had shorter PFS and OS than those with less CTCs after the eighth course of NCT. Total CTCs following NCT could predict patients' responses. More detailed characterizations of CTC blood profiles may improve predictive capacity and treatments of LABC.


Assuntos
Neoplasias da Mama , Células Neoplásicas Circulantes , Humanos , Feminino , Neoplasias da Mama/patologia , Células Neoplásicas Circulantes/patologia , Terapia Neoadjuvante , Biomarcadores Tumorais , Prognóstico
3.
Int J Biol Sci ; 19(1): 89-103, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36594100

RESUMO

Chemoresistance is a major obstacle in the neoadjuvant chemotherapy (NCT) of locally advanced breast cancer (LABC). Identification of miRNAs as prognostic biomarkers may help overcome chemoresistance of breast cancer (BC). This study aimed to evaluate the expression level of miR-1275 in plasma samples and its biological functions in the chemoresistance of BC. The expression levels of miR-1275 in plasma samples and cells were measured by RT-qPCR. CRISPR/Cas9-mediated gene editing was used to construct miR-1275 knock-out cells in MCF-7. We found that miR-1275 was significantly downregulated in plasma from patients resistant to chemotherapy and in chemoresistant BC cell lines, while patients with low levels of miR-1275 showed poor overall survival. miR-1275 knock-out promoted chemoresistance in BC cells by increasing the properties of cancer stem cells (CSCs). Mechanistically, we identified that MDK was determined to be direct downstream protein of miR-1275 which initiated PI3K/Akt signaling in breast cancer cells. We demonstrated that the high expression level of miR-1275 in plasma predicted better response to NCT. The reduction of miR-1275 promoted BC cells chemoresistance by increasing CSCs properties via targeting MDK/AKT axis. The potential of miR-1275 as a new prognostic biomarker and therapeutic target of BC patients was identified.


Assuntos
Neoplasias da Mama , MicroRNAs , Humanos , Feminino , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/genética , Neoplasias da Mama/metabolismo , Proteínas Proto-Oncogênicas c-akt/genética , Proteínas Proto-Oncogênicas c-akt/metabolismo , Resistencia a Medicamentos Antineoplásicos/genética , Fosfatidilinositol 3-Quinases/genética , Fosfatidilinositol 3-Quinases/metabolismo , MicroRNAs/metabolismo , Células-Tronco Neoplásicas/metabolismo , Regulação Neoplásica da Expressão Gênica/genética
4.
Environ Geochem Health ; 45(3): 1027-1044, 2023 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-35978258

RESUMO

The PM2.5-bounded elements were measured in outdoor and indoor from two urban middle schools in Xi'an. The PM2.5 mass was from 42.4 to 283.7 µg/m3 with bounded element from 3.4 to 41.7 µg/m3. Both the particle mass and the bounded elements displayed higher levels compared with previous studies in school environments. The most abundant elements were Ca, K, Fe, S, Zn and Cl both indoor and outdoor in two schools, which accounted for about 90% of the total elements. Strong correlations between indoor and outdoor were obtained along with relative effect from students' and teachers' activities on the indoor distributions between workdays and weekends. There had different indoor/outdoor (I/O) distributions for the two schools. It revealed the main outdoor sources for elements in JT and predominance of indoor sources in HT. The principal component analysis investigated main sources of elements in this study were coal combustion, geogenic dust and industrial emission, even though there displayed differences in the two school classrooms. The health risk assessment showed that the cancer risk for Ni and Pb was below the safe value while As and Cr might pose acceptable potential threat to both students' and teachers' health. The total non-cancer risks of accumulative multi-metals in JT exhibited to be higher than 1, indicating that there existed the potential non-carcinogenic health risks of exposure metals.


Assuntos
Poluentes Atmosféricos , Poluição do Ar em Ambientes Fechados , Oligoelementos , Humanos , Poluentes Atmosféricos/análise , Poluição do Ar em Ambientes Fechados/análise , Oligoelementos/análise , Poeira/análise , Medição de Risco , Instituições Acadêmicas , China , Monitoramento Ambiental , Material Particulado/análise
5.
Toxics ; 10(12)2022 Dec 19.
Artigo em Inglês | MEDLINE | ID: mdl-36548632

RESUMO

BACKGROUND: Per- and polyfluoroalkyl substances (PFAS) are human-made compounds with a widespread presence in human blood and other organs. PFAS have been associated with multiple health effects, including higher serum cholesterol and LDL cholesterol. OBJECTIVE: Potential population differences in serum PFAS attributable to ezetimibe, a medication that inhibits cholesterol absorption, are of interest for several reasons. The "C8" Health Project survey data from six contaminated water districts in the mid-Ohio Valley of the United States provide a wide enough range of serum PFAS and a sufficient number of ezetimibe takers to explore this topic. METHODS: A total of 44,126 adult participants of the C8 Health Survey were included in the community-based study. The status of taking (1075) or non-taking of ezetimibe, alone or in combination with another lipid-lowering agent, was acquired. The geometric mean serum concentrations of the four most commonly detected serum PFAS were compared based on the status of ezetimibe use. RESULTS: There is no significant difference in serum concentrations of perfluorohexanesulfonic acid (PFHxS), perfluorooctanoic acid (PFOA), perfluorooctanesulfonic acid (PFOS), and perfluorononanoic acid (PFNA) between ezetimibe users and non-users after adjustment for age, sex, body mass index, estimated glomerular filtration rate (eGFR), cigarette smoking, education, and average household income. CONCLUSION: The sterol absorption-inhibiting medication ezetimibe does not appear to affect serum PFAS concentrations. We sought but did not find direct evidence that ezetimibe could inhibit PFAS uptake nor inferential evidence that inter-individual differences in sterol absorption could provide a confounding factor explanation for the association of serum total- and LDL-cholesterol with serum PFAS.

6.
Environ Sci Pollut Res Int ; 29(50): 76378-76393, 2022 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-35668257

RESUMO

Polycyclic aromatic hydrocarbons (PAHs) are widespread toxic pollutants in the atmosphere and have attracted much attention for decades. In this study, we compared the health risks of PAHs based on different toxic equivalent factors (TEFs) in a heavily polluted area during heating and non-heating periods. We also pay attention to occupancy probability (OP) in different polluted areas. The results showed that there were big differences for calculations by different TEFs, and also by OP or not. Age groups except adults were all lower calculated by OP than not. The sensitivity analysis results on the incremental lifetime cancer risks (ILCR) for population groups by Monte Carlo simulation identified that the cancer slope factor extremely affected the health risk assessment in heating periods, followed by daily inhalation exposure levels. However, daily inhalation exposure levels have dominated the effect on the inhalation ILCR and then followed by the cancer slope factor in non-heating periods. The big differences by different calculations investigated that it is important to set up the correlations between the pollution level and health risks, especially for the longtime health assessment.


Assuntos
Poluentes Atmosféricos , Neoplasias , Hidrocarbonetos Policíclicos Aromáticos , Adulto , Poluentes Atmosféricos/análise , China/epidemiologia , Monitoramento Ambiental , Humanos , Exposição por Inalação/análise , Neoplasias/induzido quimicamente , Neoplasias/epidemiologia , Material Particulado/análise , Hidrocarbonetos Policíclicos Aromáticos/análise , Probabilidade , Medição de Risco
7.
Int J Clin Oncol ; 27(5): 889-898, 2022 May.
Artigo em Inglês | MEDLINE | ID: mdl-35122586

RESUMO

BACKGROUND: Circulating tumor cells (CTCs) have been shown to be associated with the response to neoadjuvant chemotherapy (NCT) and the prognosis of locally advanced breast cancer (LABC) patients. Our study aimed to investigate whether the change of CTC status during NCT could serve as a supplement to the Response Evaluation Criteria in Solid Tumors (RECIST) in the treatment and evaluation of LABC patients. METHODS: 6 ml of blood samples were collected before NCT, after the first cycle of NCT and after the completion of NCT, respectively. According to the change of CTC number during NCT, the patients were divided into "CTC low-response (low-R)" group and "CTC high-response (high-R)" group. Survival data of each group of patients were obtained through long-term follow-up. RESULTS: A total of 35 patients diagnosed with LABC were enrolled. The median follow-up for distant metastasis was 27 months (range 7-36 months). There was no significant difference in distant metastasis-free survival (DMFS) between PR/CR group and PD/SD group (P = 0.0914), while CTC low-R group had a worse DMFS than CTC high-R group (P = 0.0199). In PR/CR subgroup, patients with CTC low-R showed a lower DMFS compared with those with CTC high-R (P = 0.0159). However, in PD/SD subgroup, there was no significant difference in DMFS between CTC low-R and CTC high-R group (P = 0.7521). In terms of assessing response to NCT, CTC change or RECIST classification alone had an AUC of 0.533 (95% CI 0.277-0.790) and 0.700 (95% CI 0.611-0.789), respectively. When combining the two, the AUC slightly increased to 0.713 (95% CI 0.532-0.895). CONCLUSION: The change of CTC number during NCT has a potential to serve as a supplement to RECIST in the assessment of NCT efficacy and the prognosis of LABC patients.


Assuntos
Neoplasias da Mama , Células Neoplásicas Circulantes , Biomarcadores Tumorais , Neoplasias da Mama/patologia , Feminino , Humanos , Terapia Neoadjuvante , Células Neoplásicas Circulantes/patologia , Prognóstico , Critérios de Avaliação de Resposta em Tumores Sólidos
8.
Environ Sci Pollut Res Int ; 29(21): 31426-31440, 2022 May.
Artigo em Inglês | MEDLINE | ID: mdl-35006560

RESUMO

Diet is an important exposure pathway of phthalate esters (PAEs) for humans. A total of 174 food samples covering 11 food groups were collected from Xi'an, a typical valley city in Northwest China, and analyzed to assess the occurrence and exposure risks for PAEs in the food. Twenty-two PAEs were detected. The sum of the 22 PAEs (∑22PAEs) varied between 0.0340 and 56.8 µg/g, with a mean of 3.94 µg/g. The major PAEs were di-iso-butyl phthalate (DiBP), di-n-butyl phthalate (DnBP), bis(2-ethylhexyl) phthalate (DEHP), di-iso-nonyl phthalate (DiNP), and di-iso-decyl phthalate (DiDP), which were associated mainly with the usage of plasticizers. Bio-availability of the PAEs in the combined gastro-intestinal fluid simulant of digestion was higher than that in the single gastric or intestinal fluid simulant. Bis(2-methoxyethyl) phthalate exhibited the highest bio-availability in each of the three simulants. Bio-availability of the PAEs was negatively correlated with the molecular weight and octanol-water partition coefficient of the PAEs and positively correlated with the solubility and vapor pressure of the PAEs. The estimated daily intake (EDI) of PAEs based on national and municipal food consumption data was lower than the reference dose (RfD) of the United States Environmental Protection Agency and the tolerable dairy intake (TDI) of European Food Safety Authority (EFSA), except for the EDI of DnBP and DiBP being higher than the TDI of EFSA. Grains and vegetables were the major sources of human dietary exposure to PAEs. The hazardous quotient for human dietary exposure to PAEs was less than the critical value of 1 and the cancer risk of butyl benzyl phthalate and DEHP was in the range of 10-11-10-6, suggesting relatively low health risks. The results indicated that human exposure to DnBP, DiBP, DEHP, DiNP, and DiDP in food is considerable and a health concern.


Assuntos
Dietilexilftalato , Ácidos Ftálicos , China , Cidades , Dibutilftalato , Exposição Dietética , Ésteres , Humanos
9.
SAGE Open Med Case Rep ; 10: 2050313X211068646, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35024148

RESUMO

This case report describes a 22-year-old man with a pharyngeal foreign body sensation arising from the left side of the postpharyngeal wall. Histological examination showed a biphasic pattern of epithelioid and spindle cells including glandular differentiation. The tumour was positive for vimentin and SS18-SSX, and the spindle cells were positive for bcl-2; in contrast, the epithelioid tumour cells were positive for pan-cytokeratin, epithelial membrane antigen and CD99. There was no INI-loss in tumour cells. Then, the presence of the SYT-SSX gene fusion was demonstrated by fluorescence in situ hybridization. In addition, androgen receptor gene somatic mutations were detected by next-generation sequencing. However, 6 months postoperatively, the patient had neither developed a recurrence nor received adjuvant radiotherapy and chemotherapy. Accurate diagnosis depends on morphological and immunohistochemical examination and a proper molecular analysis, and novel technologies can detect a wide variety of genetic alterations. Although androgen receptor somatic mutations cannot provide addition treatment at present, surgical resection with a clean margin and follow-up is an appropriate approach.

10.
ACS Appl Mater Interfaces ; 13(36): 42763-42772, 2021 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-34472837

RESUMO

In this work, ruthenium nanoparticle-decorated ultrathin nickel phosphide nanosheets on nickel foam substrate (Ru/Ni2P/NF) nanocomposites are synthesized conveniently by a cyanogel-NaBH4 method and a subsequent phosphating process, which displays excellent electroactivity for both the hydrogen evolution reaction (HER) and ethylene glycol electro-oxidation reaction (EGEOR) in an alkaline solution. Concretely, at Ru/Ni2P/NF nanocomposites, only 1.37 and -0.13 V potentials are required to obtain a current density of 100 mA cm-2 for EGEOR and HER, respectively. Meanwhile, Ru/Ni2P/NF nanocomposites also exhibit pre-eminent electrocatalytic performance of the long-running process for both EGEOR and HER. Density functional theory calculations demonstrate that the introduction of Ru nanoparticles results in an optimization of the surface adsorption energy and construction of a synergistic catalysis interface, which improve the electrocatalytic performance of nickel phosphide nanosheets. Notably, a symmetric Ru/Ni2P/NF||Ru/Ni2P/NF ethylene glycol electrolyzer needs only 1.14 V electrolysis voltage to obtain 10 mA cm-2 for hydrogen production, which effectively eliminates the H2/O2 explosion risk and highlights an energy-saving mode for electrochemical hydrogen production.

11.
Diagn Interv Radiol ; 27(3): 418-423, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-33769287

RESUMO

PURPOSE: We aimed to determine the ablation characteristics of discontinuous moving shot technique (DMST) in microwave ablation (MWA), radiofrequency ablation (RFA) and laser ablation (LA), and analyze the differences compared with fixed electrode technique (FET) in an ex vivo porcine liver model. METHODS: FET was defined as the ablation needle remaining fixed during ablation. In DMST, ablation needle moved backward for a fixed distance twice along the long axis during ablation. Four moving distances (0.5 cm, 0.75 cm, 1 cm and 2 cm) were used in DMST. Long-axis diameter (LAD) and short-axis diameter (SAD) of ablation zones were measured. The ratio of LAD/SAD was calculated. RESULTS: The shape and size of ablation zones were different between DMST and FET. Compared with FET, DMST could achieve greater LAD when the moving distance became long enough. In MWA with DMST, SAD decreased with the extension of moving distance and finally became smaller than the SAD in FET. While in LA and RFA, the change of moving distance did not affect SAD significantly. CONCLUSION: In MWA, RFA and LA, the characteristics of ablation zone of DMST were different from that of FET. This unique ablation technique may be suitable for conformal thermal ablation.


Assuntos
Técnicas de Ablação , Ablação por Cateter , Hipertermia Induzida , Ablação por Radiofrequência , Animais , Fígado/diagnóstico por imagem , Fígado/cirurgia , Micro-Ondas , Suínos
12.
JAMA Netw Open ; 4(3): e211809, 2021 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-33724394

RESUMO

Importance: There is a lack of studies exploring whether the survival of patients with distant lymph node metastases (DLNM) is different from that of patients with ipsilateral supraclavicular lymph node metastases (ISLM) and other stage IV breast cancer. Objective: To assess the survival of patients with DLNM from breast cancer vs ISLM and other stage IV breast cancer. Design, Setting, and Participants: This cohort study included 2033 patients diagnosed with breast cancer between January 1, 2010, and December 31, 2014, from the Surveillance, Epidemiology and End Results registries database. Three groups of patients were included: (1) patients with ISLM without any distant metastasis, (2) patients with DLNM, and (3) patients with distant metastases (DLNM excluded). Patients younger than 18 years or older than 100 years were excluded. The data were analyzed in February 2020. Exposures: Surgery for primary tumor, surgery for distant lymph nodes, and radiotherapy. Main Outcomes and Measures: Overall survival (OS) and breast cancer-specific survival (BCSS). Results: Of the 2033 women (mean [SD] age, 62.03 [14.62] years [range, 23.00-99.00 years]; 1510 White participants [74.3%]) with breast cancer included in the study, 346 patients (17.0%) had DLNM, 212 (10.4%) had ISLM, and 1475 (72.6%) had distant metastases (DLNM excluded). The 3-year BCSS rates were 63.24% for ISLM, 64.54% for DLNM, and 41.20% for distant metastases. The 3-year OS rates were 53.46% for ISLM, 62.67% for DLNM, and 38.21% for distant metastases. Compared with patients with ISLM, patients with DLNM showed similar BCSS (hazard ratio [HR], 0.81; 95% CI, 0.52-1.25; P = .34) and OS (HR, 0.73; 95% CI, 0.51-1.05; P = .09), whereas patients with distant metastases showed significantly poorer BCSS (HR, 1.99; 95% CI, 1.43-2.78; P < .001) and OS (HR, 1.79; 95% CI, 1.35-2.38; P < .001). Of the 346 patients with DLNM, primary surgery (HR, 0.21; 95% CI, 0.12-0.39; P < .001) and radiotherapy (HR, 0.46; 95% CI, 0.25-0.87; P = .02) were significantly associated with improved OS. Conclusions and Relevance: The results of this cohort study suggest that DLNM of breast cancer, with similar survival to N3c disease (indicating metastases to the ipsilateral supraclavicular lymph nodes), might be a regional disease, and reassessment of the role of lymph node metastases in breast cancer may be necessary. Given these findings, aggressive locoregional therapies for this disease are recommended, although future studies are still needed to confirm these results.


Assuntos
Neoplasias da Mama/mortalidade , Sistema de Registros , Programa de SEER , Adulto , Idoso , Idoso de 80 Anos ou mais , Neoplasias da Mama/diagnóstico , Neoplasias da Mama/secundário , China/epidemiologia , Clavícula , Feminino , Seguimentos , Humanos , Metástase Linfática , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Estudos Retrospectivos , Taxa de Sobrevida/tendências , Adulto Jovem
13.
Chem Commun (Camb) ; 57(18): 2289-2292, 2021 Mar 04.
Artigo em Inglês | MEDLINE | ID: mdl-33533382

RESUMO

Herein, a novel pathway to prepare a porous structured DNA hybrid hydrogel has been described, using a transiently existing Pickering emulsion that is continuously generated during the reaction. The as-prepared highly porous gel features significantly improved capability for trace amounts of PAH removal.


Assuntos
Materiais Biocompatíveis/química , DNA/química , Hidrogéis/química , Nanotubos de Carbono/química , Hidrocarbonetos Policíclicos Aromáticos/isolamento & purificação , Poluentes Químicos da Água/isolamento & purificação , Adsorção , Emulsões/química , Hidrocarbonetos Policíclicos Aromáticos/química , Porosidade , Poluentes Químicos da Água/química , Purificação da Água/métodos
14.
NPJ Breast Cancer ; 7(1): 4, 2021 Jan 05.
Artigo em Inglês | MEDLINE | ID: mdl-33402674

RESUMO

Liquid biopsy is noninvasive and convenient to detect cancer-derived materials in blood or other body fluids. The aim of this study was to identify tRNA-derived small RNAs (tsRNAs) in plasma that could distinguish patients with breast cancer (BC) from healthy controls. Basing on high-throughput sequencing, 15 significantly upregulated tsRNAs were selected and assessed in cell supernatants and cell lines. 6 tsRNAs were identified and verified in a large cohort of 120 patients with BC and 112 healthy controls. tRF-Arg-CCT-017, tRF-Gly-CCC-001, and tiRNA-Phe-GAA-003 could serve as novel diagnostic biomarkers. Meanwhile, tRF-Arg-CCT-017 and tiRNA-Phe-GAA-003 could also act as prognostic biomarkers. Target genes of these tsRNAs were related to the development of cancers. These results suggested that specific tsRNAs in plasma might serve as diagnostic and prognostic biomarkers of BC.

15.
J Mass Spectrom ; 56(4): e4691, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33295108

RESUMO

In this study, the gas-phase fragmentations of protonated benzyl phenyl sulfones were investigated by electrospray ionization tandem mass spectrometry (ESI-MSn ). Upon collisional activation, several characteristic fragment ions were observed, and the similar results occurred with different substituted benzyl phenyl sulfones. A mechanism involving an intramolecular benzyl cation transfer and the formation of intermediate ion was proposed and further identified by density functional theory (DFT) calculations. In addition, a reference compound, benzenesulfinic acid benzyl ester, has been synthesized, and its protonated ion has the same gas-phase behavior as compared to the protonated benzyl phenyl sulfone. This work provides access to some insight into the intramolecular benzyl-transfer reactions of benzyl phenyl sulfones in the gas phase and orients the characteristic peaks in collision-induced dissociation spectrometry (CID-MS).

16.
Cell Mol Immunol ; 18(9): 2153-2164, 2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-32385362

RESUMO

Surgery is essential for controlling the symptoms and complications of stage IV breast cancer. However, locoregional treatment of primary tumors often results in distant progression, including lung metastasis, the most common type of visceral metastasis. As a minimally invasive thermal therapy, microwave ablation (MWA) has been attempted in the treatment of breast cancer, but the innate immune response after MWA has not yet been reported. Using two murine models of stage IV breast cancer, we found that MWA of primary breast cancer inhibited the progression of lung metastasis and improved survival. NK cells were activated after MWA of the primary tumor and exhibited enhanced cytotoxic functions, and the cytotoxic pathways of NK cells were activated. Depletion experiments showed that NK cells but not CD4+ or CD8+ T cells played a pivotal role in prolonging survival. Then, we found that compared with surgery or control treatment, MWA of the primary tumor induced completely different NK-cell-related cytokine profiles. Macrophages were activated after MWA of the primary tumor and produced IL-15 that activated NK cells to inhibit the progression of metastasis. In addition, MWA of human breast cancer stimulated an autologous NK-cell response. These results demonstrate that MWA of the primary tumor in metastatic breast cancer inhibits metastatic progression via the macrophage/IL-15/NK-cell axis. MWA of the primary tumor may be a promising treatment strategy for de novo stage IV breast cancer, although further substantiation is essential for clinical testing.


Assuntos
Neoplasias da Mama , Ablação por Radiofrequência , Animais , Neoplasias da Mama/terapia , Linfócitos T CD8-Positivos , Feminino , Humanos , Células Matadoras Naturais , Camundongos , Micro-Ondas/uso terapêutico , Resultado do Tratamento
18.
Mol Ther Nucleic Acids ; 21: 954-964, 2020 Sep 04.
Artigo em Inglês | MEDLINE | ID: mdl-32814252

RESUMO

Small RNAs derived from tRNAs are attracting considerable attention; however, the effects of tRNA-derived fragments (tRFs) and tRNA halves (tiRNAs) as biomarkers have not been investigated in early-stage breast cancer (EBC). The study aimed to explore whether tRFs and tiRNAs could be detected in plasma and whether they could serve as diagnostic biomarkers. The study was conducted in four phases. Thirty tRFs and tiRNAs were selected by high-throughput sequencing in screening phase and then assessed in training, testing, and external validation phases by qRT-PCR. Six tRFs (tRF-Glu-CTC-003, tRF-Gly-CCC-007, tRF-Gly-CCC-008, tRF-Leu-CAA-003, tRF-Ser-TGA-001, and tRF-Ser-TGA-002) were found significantly downregulated in plasma samples of patients with EBC compared with normal controls, and all were derived from 5' ends of tRNAs. Patients with HER2+ EBC with low expression levels of tRF-Glu-CTC-003 were related to worse disease-free survival and overall survival. The identified tRFs were further examined in cell supernatants, exosomes isolated from plasma, and tissues. In conclusion, our study identified six tRFs from the 5' ends of tRNAs as novel diagnostic biomarkers for EBC, providing additional evidence for, and a better understanding of, circulating tRFs and EBC.

19.
Cell Death Dis ; 11(7): 500, 2020 07 03.
Artigo em Inglês | MEDLINE | ID: mdl-32620748

RESUMO

Triple-negative breast cancer (TNBC), characterized by high aggression and invasiveness, has a worse prognosis than other subtypes of breast cancer. Establishing a novel animal model is helpful to understand the mechanisms involved in the progress of TNBC metastasis. In a self-established mouse model consisting normal human breast tissues and normal human bone tissues, TNBC cell line SUM-1315 could spontaneously form species-specific bone metastasis. The expression level of miR-1976 in SUM-1315-bo (derived from metastatic bone tumor) was found lower than that in SUM-1315-br (derived from orthotopic breast tumor). MiR-1976 was found to be downregulated in TNBC tissues, and lower expression of miR-1976 was correlated with worse overall survival in a patient cohort obtained from TCGA database. MiR-1976 knockdown promoted epithelial-mesenchymal transition (EMT) and cancer stem cell (CSC) properties in vitro and in vivo. Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit gamma (PIK3CG) was verified as a target gene by sequencing, biotinylated miRNA pull-down, and luciferase reporter assay. Moreover, overexpression and suppression analysis implicated PIK3CG as a mediator of the biological effects of miR-1976. Our study demonstrated that miR-1976 knockdown could promote EMT and CSCs by PIK3CG. These findings may reveal mechanisms of TNBC metastasis, and represent a potential treatment target for patients with TNBC.


Assuntos
Transição Epitelial-Mesenquimal/genética , Técnicas de Silenciamento de Genes , MicroRNAs/genética , Células-Tronco Neoplásicas/patologia , Neoplasias de Mama Triplo Negativas/genética , Neoplasias de Mama Triplo Negativas/patologia , Animais , Sequência de Bases , Linhagem Celular Tumoral , Movimento Celular/genética , Classe Ib de Fosfatidilinositol 3-Quinase/metabolismo , Regulação para Baixo/genética , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Camundongos Endogâmicos BALB C , Camundongos Nus , MicroRNAs/metabolismo , Invasividade Neoplásica , Metástase Neoplásica , Células-Tronco Neoplásicas/metabolismo , Prognóstico
20.
Aging (Albany NY) ; 12(13): 13115-13127, 2020 07 02.
Artigo em Inglês | MEDLINE | ID: mdl-32614787

RESUMO

The receptor tyrosine kinase like orphan receptor 2 (ROR2) has been implicated in the pathogenesis of a variety of human cancers, including breast cancer. Here, we analyzed the clinical significance of ROR2 in breast cancer (BC) progression, and its function in the regulation of BC cell proliferation and growth. Analysis of ROR2 mRNA levels in 45 BC tissues and adjacent non-tumor tissues revealed that ROR2 expression was significantly increased in BC tissues, and that it correlated with tumor diameter. Kaplan-Meier disease-free survival (DFS) analysis demonstrated that BC patients with higher ROR2 expression had lower DFS. Knockdown of ROR2 suppressed in vitro proliferation of BC cells and promoted apoptosis, while ROR2 overexpression induced BC cell proliferation and suppressed apoptosis. Importantly, ROR2 suppression also reduced the tumor growth in mouse BC xenografts, indicating that ROR2 promotes BC tumorigenesis in vivo. In addition, our data revealed that ROR2 promotes proliferation of BC cells by activating the PI3K/AKT signaling pathway. Together, our results indicate that ROR2 acts as an oncogenic gene in breast cancer, and suggest that the ROR2/PI3K/AKT regulatory network contributes to breast cancer progression.


Assuntos
Neoplasias da Mama , Fosfatidilinositol 3-Quinases/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Receptores Órfãos Semelhantes a Receptor Tirosina Quinase , Animais , Mama/metabolismo , Mama/patologia , Neoplasias da Mama/genética , Neoplasias da Mama/mortalidade , Neoplasias da Mama/patologia , Linhagem Celular Tumoral , Feminino , Técnicas de Silenciamento de Genes , Humanos , Camundongos , Camundongos Endogâmicos BALB C , Pessoa de Meia-Idade , Fosfatidilinositol 3-Quinases/genética , Proteínas Proto-Oncogênicas c-akt/genética , Receptores Órfãos Semelhantes a Receptor Tirosina Quinase/genética , Receptores Órfãos Semelhantes a Receptor Tirosina Quinase/metabolismo , Transdução de Sinais/genética
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