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1.
J Immunother Cancer ; 9(4)2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33795388

RESUMO

BACKGROUND: Despite great advances in the treatment of breast cancer, innovative approaches are still needed to reduce metastasis. As a minimally invasive local therapy (not standard therapy for breast cancer), microwave ablation (MWA) has been attempted to treat breast cancer, but the local effect and immune response induced by MWA have seldom been reported. METHODS: The clinical study was performed to determine the complete ablation rate of MWA for early-stage breast cancer. Secondary endpoints included safety and antitumor immune response. 35 subjects from this clinical study were enrolled in the current report, and the local effect was determined by pathological examinations or follow-up. To investigate MWA-induced immune response, patients treated with surgery (n=13) were enrolled as control, and blood samples were collected before and after MWA or surgery. The immune cell populations, serum cytokines, secretory immune checkpoint molecules, and T-cell receptor sequencing were analyzed. RESULTS: Of 35 enrolled patients, 32 (91.4%) showed complete ablation. Compared with surgery, MWA induced significantly increased levels of inducible co-stimulator (ICOS)+ activated CD4+ T cells and serum interferon gamma, indicating a shift in the Th1/Th2 balance toward Th1. The activated ICOS pathway was involved in the MWA-induced adaptive immune response. T-cell receptor sequencing revealed MWA of primary tumor activated T lymphocytes expansion and recognized some cancer-specific antigens. Moreover, CD4+ effector memory T-cell response was induced by MWA, and the immune response still existed after surgical resection of the ablated tumor. CONCLUSIONS: MWA may not only be a promising local therapy but also a trigger of antitumor immunity for breast cancer, opening new avenues for the treatment of breast cancer. Combinatorial strategy using additional agents which boost MWA-induced immune response could be considered as potential treatment for clinical study for early breast cancer therapy.

2.
Cancer Biol Med ; 18(1): 74-87, 2021 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-33628586

RESUMO

Objective: The newly defined cancer-testis (CT) gene, MEIOB, was previously found to play key roles in DNA double-strand break (DSB) repair. In this study, we aimed to investigate the effects and mechanisms of MEIOB in the carcinogenesis of triple-negative breast cancers (TNBCs). Methods: The Cancer Genome Atlas database was used to quantify the expression of MEIOB. Cox regression analysis was used to evaluate the association between MEIOB expression and the prognosis of human TNBC. The effects of MEIOB on cell proliferation and migration in TNBCs were also assessed in vitro. Patient-derived xenograft (PDX) models were used to assess the sensitivity of breast cancers with active MEIOB to PARP1 inhibitors. Results: We confirmed MEIOB as a CT gene whose expression was restricted to the testes and breast tumors, especially TNBCs. Its activation was significantly associated with poor survival in breast cancer patients [overall, hazard ratio (HR) = 1.90 (1.16-2.06); TNBCs: HR = 7.05 (1.16-41.80)]. In addition, we found that MEIOB was oncogenic and significantly promoted the proliferation of TNBC cells. Further analysis showed that MEIOB participated in DSB repair in TNBCs. However, in contrast to its function in meiosis, it mediated homologous recombination deficiency (HRD) through the activation of polyADP-ribose polymerase (PARP)1 by interacting with YBX1. Furthermore, activated MEIOB was shown to confer sensitivity to PARP inhibitors, which was confirmed in PDX models. Conclusions: MEIOB played an oncogenic role in TNBC through its involvement in HRD. In addition, dysregulation of MEIOB sensitized TNBC cells to PARP inhibitors, so MEIOB may be a therapeutic target of PARP1 inhibitors in TNBC.

3.
Eur J Radiol ; 135: 109512, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-33429302

RESUMO

PURPOSE: To develop a combined nomogram by incorporating the Memorial Sloan Kettering Cancer Center (MSKCC) nomogram and ultrasound (US)-based radiomics score (Radscore) for predicting sentinel lymph node (SLN) metastasis in invasive breast cancer. MATERIALS AND METHODS: This retrospective study was approved by the ethics committee of our institution, and written informed consent was waived. A total of 452 patients with invasive breast cancer who received SLN Biopsy in a single center were included between January 2016 and December 2019. The patients were divided into a training set (n = 318) and a validation set (n = 134). A total of 1216 features were extracted from the regions of interest (ROIs) of the tumors on conventional ultrasound. The maximum relevance minimum redundancy (mRMR) and the least absolute shrinkage and selection operator (LASSO) algorithm were used to build the Radscore. Afterward, the diagnostic performance was assessed and validated. Comparison of receiver operating characteristic (ROC) curves and decision curve analysis (DCA) were performed to evaluate the incremental value of the combined model. RESULTS: Obtained from 18 features, the Radscore indicated a favorable discriminatory capability in the training set with an area under the curve (AUC) of 0.834, whereas a value of 0.770 was observed in the validation set. The AUC of the combined model was 0.901 (95 % confidence interval (95 % CI): 0.865-0.938) in the training set and 0.833 (95 % CI: 0.788-0.878) in the validation set. Both of them were superior to MSKCC or imaging Radscore alone (P < 0.05). DCA demonstrated that the combined model was superior to the others in terms of clinical practicability. CONCLUSION: Preoperative US-based Radscore can improve the accuracy of clinical MSKCC nomogram for SLN metastasis prediction in breast cancer.

4.
Environ Microbiol ; 2020 Nov 10.
Artigo em Inglês | MEDLINE | ID: mdl-33169936

RESUMO

Degradation of the fungicide iprodione by the Paenarthrobacter sp. strain YJN-5 is initiated via hydrolysis of its N1 amide bond to form N-(3,5-dichlorophenyl)-2,4-dioxoimidazolidine. In this study, another iprodione-degrading strain, Paenarthrobacter sp. YJN-D, which harbours the same metabolic pathway as strain YJN-5 was isolated and characterized. The genes that encode the conserved iprodione catabolic pathway were identified based on comparative analysis of the genomes of the two iprodione-degrading Paenarthrobacter sp. and subsequent experimental validation. These genes include an amidase gene, ipaH (previously reported in AEM e01150-18); a deacetylase gene, ddaH, which is responsible for hydantoin ring cleavage of N-(3,5-dichlorophenyl)-2,4-dioxoimidazolidine, and a hydrolase gene, duaH, which is responsible for cleavage of the urea side chain of (3,5-dichlorophenylurea)acetic acid, thus yielding 3,5-dichloroaniline as the end product. These iprodione-catabolic genes are distributed on three plasmids in strain YJN-5 and are highly conserved between the two iprodione-degrading Paenarthrobacter strains. However, only the ipaH gene is flanked by a mobile genetic element. Two iprodione degradation cassettes bearing ipaH-ddaH-duaH were constructed and expressed in strains Pseudomonas putida KT2440 and Bacillus subtilis SCK6 respectively. Our findings enhance the current understanding of the microbial degradation mechanism of iprodione.

5.
Cancer Manag Res ; 12: 8397-8408, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32982433

RESUMO

Purpose: Chemotherapy is a comprehensive therapy for breast cancer; nevertheless, its associated adverse effects are drawing increasing attention with the continuous improvement of the efficacy. The changes in serum lipids of breast cancer patients caused by chemotherapy have been reported by previous studies, whereby the former increase the incidence rate of cardiovascular disorders. However, the variations in the changes of serum lipids with different chemotherapy regimens have seldom been reported. Methods: From January 2011 to December 2017, 1740 breast cancer patients treated with chemotherapy were recruited at the First Affiliated Hospital of Nanjing Medical University. The chemotherapy regimens included anthracycline-based, taxane-based, and anthracycline-plus-taxane-based regimens, dose-dense and standard-interval regimens. Lipid profiles that contained TG (triglyceride), TC (total cholesterol), HDL-C (high-density lipoprotein cholesterol), LDL-C (low-density lipoprotein cholesterol) and Lpa (lipoprotein a) levels were collected prior to the first, second and last cycles of chemotherapy. The changes of serum lipids with the same or different chemotherapy regimens were analyzed and compared. Results: It was observed that the levels of TG, TC, LDL-C and Lpa increased significantly while that of HDL-C decreased after adjuvant chemotherapy in breast cancer patients (P<0.05). Besides, dose-dense regimens had more influence in TG and HDL-C and less influence in TC and LDL-C than standard-interval regimens. HDL-C was more sensitive to anthracycline-based regimens than taxane-based regimens. The level of TG with anthracycline-plus-taxane-based regimens was higher than that with only anthracycline-based or taxane-based regimens, and the level of HDL-C with anthracycline-plus-taxane-based regimen showed lower than that with taxane-based regimen. Conclusion: In summary, this study proposed that dyslipidemia was strongly associated with chemotherapy in Chinese breast cancer patients after operative treatment. Furthermore, the changes in levels of serum lipids varied among patients with different chemotherapy regimens and taxane had less effect on dyslipidemia than anthracycline.

6.
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.

7.
Ther Adv Med Oncol ; 12: 1758835920918470, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32489429

RESUMO

Background: Neoadjuvant chemotherapy (NCT) is the standard treatment for patients with locally advanced breast cancer (LABC). The aim of this study was to verify this relationship, and to estimate the clinical value of aneuploid circulating endothelial cells (CECs) in LABC patients with different NCT responses. Methods: Breast cancer patients received an EC4-T4 NCT regimen. Peripheral blood mononuclear cells were obtained before NCT, and after the first and last NCT courses. A novel subtraction enrichment and immunostaining fluorescence in situ hybridization (SE-iFISH) strategy was applied for detection of circulating rare cells (CRCs). CECs (CD45-/CD31+/DAPI+) and circulating tumor cells (CTCs) with different cytogenetic abnormalities related to chromosome 8 aneuploidy were analyzed in LABC patients subjected to NCT. Results: A total of 41 patients were enrolled. Firstly, CD31+/EpCAM+ aneuploid endothelial-epithelial fusion cells were observed in LABC patients. Further, aneuploid CECs in the peripheral blood showed a biphasic response during NCT, as they initially increased and then decreased, whereas a strong positive correlation was observed between aneuploid CECs and CTC numbers. Conclusion: We determined that aneuploid CEC dynamics vary in patients with different response to chemotherapy. Elucidating the potential cross-talk between CTCs and aneuploid CECs may help characterize the process associated with the development of chemotherapy resistance and metastasis.

8.
Clin Rheumatol ; 39(7): 2025-2029, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32406001

RESUMO

The coronavirus disease 2019 (COVID-19), the result of an infection with the new virus, SARS-CoV-2, is rapidly spreading worldwide. It is largely unknown whether the occurrence of COVID-19 in patients with rheumatic immune diseases has some specific manifestations, or makes them more prone to rapidly progress into severe COVID-19. In this case report, we describe the clinical features of 5 rheumatic immune disease patients with the concomitant presence of COVID-19. Amongst these patients, 4 had rheumatoid arthritis (RA) and 1 had systemic sclerosis (SSc). Two patients had a history of close contact with a COVID-19 patient. The age of the patients ranged between 51 and 79 years. Fever (80%), cough (80%), dyspnea (40%), and fatigue (20%) were the most common presenting symptoms. Laboratory investigations revealed leukopenia and lymphopenia in 2 patients. In all the patients, chest computerized tomography (CT) revealed patchy ground glass opacities in the lungs. During the hospital stay, the condition of two patients remained the same (i.e., mild COVID-19), two patients progressed to the severe COVID-19, and one patient worsened to the critically ill COVID-19. These patients were treated with antiviral agents for COVID-19, antibiotics for secondary bacterial infections, and immunomodulatory agents for rheumatic immune diseases. All the patients responded well, were cured of COVID-19, and subsequently discharged.


Assuntos
Antivirais/uso terapêutico , Artrite Reumatoide , Infecções por Coronavirus , Imunomodulação , Pandemias , Pneumonia Viral , Escleroderma Sistêmico , Idoso , Artrite Reumatoide/diagnóstico , Artrite Reumatoide/epidemiologia , Artrite Reumatoide/terapia , Betacoronavirus/isolamento & purificação , Contagem de Células Sanguíneas/métodos , Infecções por Coronavirus/diagnóstico , Infecções por Coronavirus/epidemiologia , Infecções por Coronavirus/imunologia , Infecções por Coronavirus/terapia , Estado Terminal/terapia , Progressão da Doença , Feminino , Humanos , Pulmão/diagnóstico por imagem , Masculino , Pessoa de Meia-Idade , Pneumonia Viral/diagnóstico , Pneumonia Viral/epidemiologia , Pneumonia Viral/imunologia , Pneumonia Viral/terapia , Escleroderma Sistêmico/diagnóstico , Escleroderma Sistêmico/epidemiologia , Escleroderma Sistêmico/terapia , Avaliação de Sintomas/métodos , Tomografia Computadorizada por Raios X/métodos , Resultado do Tratamento
9.
Int J Syst Evol Microbiol ; 70(3): 1793-1799, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31958054

RESUMO

A Gram-stain-positive, aerobic, non-motile and coccoid-shaped bacterium, designated XNB-1T, was isolated from farmland soil in Taian, Shandong province, China. Strain XNB-1T contained iso-C15 : 0 and iso-C16 : 0 as the predominant fatty acids. The diagnostic diamino acid of the peptidoglycan was ornithine, and the interpeptide bridge was l-Orn←Gly(1, 2)←d-Glu. The polar lipid profile of strain XNB-1T consisted of diphosphatidylglycerol, phosphatidylglycerol, an unidentified phosphoglycolipid and three unidentified phospholipids. The predominant menaquinone of strain XNB-1T was MK-8(H4) and the DNA G+C content was 70.1 mol%. Phylogenetic analysis based on 16S rRNA gene sequences showed that strain XNB-1T belonged to the genus Ornithinicoccus, and shared the highest similarity with Ornithinicoccus hortensis HKI 0125T (96.0 %), followed by Ornithinicoccus halotolerans EGI 80423T (95.5 %). Genome-based analysis of average nucleotide identity of strain XNB-1T with O. hortensis HKI 0125T and O. halotolerans EGI 80423T yielded values of 73.1 and 73.3 %, respectively, while the digital DNA-DNA hybridization values were 19.5 and 19.9 %, respectively. On the basis of phenotypic, chemotaxonomic and phylogenetic data, strain XNB-1T is considered to represent a novel species of the genus Ornithinicoccus, for which the name Ornithinicoccus soli sp. nov. is proposed. The type strain is XNB-1T (=CCTCC AB 2019099T=KCTC 49259T).


Assuntos
Actinobacteria/classificação , Fazendas , Filogenia , Microbiologia do Solo , Actinobacteria/isolamento & purificação , Técnicas de Tipagem Bacteriana , Composição de Bases , China , DNA Bacteriano/genética , Ácidos Graxos/química , Hibridização de Ácido Nucleico , Peptidoglicano/química , Fosfolipídeos/química , RNA Ribossômico 16S/genética , Análise de Sequência de DNA , Vitamina K 2/análogos & derivados , Vitamina K 2/química
10.
Sci Total Environ ; 706: 135726, 2020 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-31837849

RESUMO

A bacterial strain, Rhodococcus sp. WH99, capable of degrading phenazine-1-carboxylic acid (PCA) was isolated and characterized. Genome comparison revealed that a 21499-bp DNA fragment containing a putative angular dioxygenase gene cluster consisting of the dioxygenase-, ferredoxin reductase- and ferredoxin-encoding genes (pzcA1A2, pzcC and pzcD) is missed in the PCA degradation-deficient mutant WH99M. The pzcA1A2CD genes were expressed in Escherichia coli respectively and hydroxylation of PCA to 1,2-dihydroxyphenazine occurred in vitro only when all components were present. However, in vivo analyses showed that pzcA1A2 and pzcD were indispensable for PCA degradation, while PzcC can be partially replaced by other ferredoxin reductases. Hydroxylation of PCA not only initiates degradation of PCA in strain WH99 but also provides protection to sensitive organisms that would otherwise be inhibited by PCA toxicity. This study illustrates a new initial PCA degradation step in Gram-positive bacteria and enhances our understanding of the genes responsible for PCA hydroxylation, thus enabling targeted studies on protection by PCA degradation in diverse environments.


Assuntos
Rhodococcus , Dioxigenases , Família Multigênica , Fenazinas
11.
Int J Syst Evol Microbiol ; 70(2): 1152-1157, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31800385

RESUMO

A Gram-stain-positive, strictly aerobic, non-motile, non-spore-forming and rod-shaped bacterium, designated as strain G-1T, was isolated from farmland soil sampled in in Fuyang, Anhui Province, PR China. Phylogenetic analysis based on 16S rRNA gene sequences showed that strain G-1T was closely related to Cumulibacter manganitolerans 2-36T (97.7 % similarity). Strain G-1T contained iso-C16 : 0, C17 : 1ω6c, iso-C15 : 0 and iso-C14 : 0 as the predominant fatty acids. The polar lipids of strain G-1T were diphosphatidylglycerol, phosphatidylethanolamine, an unidentified phospholipid, an unidentified lipid and two unidentified glycolipids. The predominant respiratory quinone of strain G-1T was MK-9(H4). The cell wall contained meso-diaminopimelic acid as the diagnostic diamino acid. The G+C content of the genomic DNA based on genome calculations was 64.2 mol%. Average nucleotide identity and the digital DNA-DNA hybridization values for the draft genomes between strain G-1T and strain 2-36T were 75.7 and 20.2 %, respectively. On the basis of phenotypic and phylogenetic data, strain G-1T is considered to represent a novel species of the genus Cumulibacter, for which the name Cumulibacter soli sp. nov. is proposed. The type strain is G-1T (=CCTCC AB2019021T=KCTC 49258T).


Assuntos
Actinobacteria/classificação , Fazendas , Filogenia , Microbiologia do Solo , Actinobacteria/isolamento & purificação , Técnicas de Tipagem Bacteriana , Composição de Bases , China , DNA Bacteriano/genética , Ácido Diaminopimélico/química , Ácidos Graxos/química , Glicolipídeos/química , Hibridização de Ácido Nucleico , Fosfolipídeos/química , RNA Ribossômico 16S/genética , Análise de Sequência de DNA , Vitamina K 2/análogos & derivados , Vitamina K 2/química
12.
Ecotoxicol Environ Saf ; 189: 109938, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31759739

RESUMO

A novel carbofuran-degrading strain CFD-1 was isolated and preliminarily identified as Sphingbium sp. This strain was able to utilize carbofuran as the sole carbon source for growth. The carbofuran hydrolase gene cehA was cloned from strain CFD-1 and expressed in Escherichia coli. CehA could hydrolyze carbamate pesticides including carbofuran and carbaryl efficiently, while it showed poor hydrolysis ability against isoprocarb, propoxur, oxamyl and aldicarb. CehA displayed maximal enzymatic activity at 40 °C and pH 7.0. The apparent Km and Kcat values of CehA for carbofuran were 133.22 ±â€¯5.70 µM and 9.48 ±â€¯0.89 s-1, respectively. The site-directed mutation experiment showed that His313, His315, His453 and His495 played important roles in the hydrolysis of carbofuran by CehA. Furthermore, the sequence of cehA is highly conserved among different carbofuran-degrading strains, and there are mobile elements around cehA, indicating that it may be transferred horizontally between different strains.


Assuntos
Carbofurano/metabolismo , Praguicidas/metabolismo , Sphingomonadaceae/fisiologia , Aminoácidos/metabolismo , Biodegradação Ambiental , Carbamatos , Carbaril/metabolismo , Hidrolases/metabolismo , Hidrólise
13.
ACS Appl Mater Interfaces ; 11(50): 46497-46503, 2019 Dec 18.
Artigo em Inglês | MEDLINE | ID: mdl-31738505

RESUMO

A material that possesses high loading efficiency (in terms of delivering small molecular drugs, nucleic acids, peptides, and proteins) has various medical applications, such as in tumor diagnosis and gene therapy or chemotherapy of tumors. Mesoporous silica nanoparticles are ideal nanocarriers for constructing drug delivery systems because of the unique mesoporous channels for encapsulation and the sustainable release of anticancer drugs. Herein, we demonstrate a doxorubicin (DOX)-peptides double-loaded and -response nanodrug (DMK nanoplatforms) as a multifunctional nanoplatform for chemotherapy of tumors. The nanoparticles are prepared by a surface modification strategy. The KLAK and DOX release in an acidic/reductive tumor microenvironment, which efficiently penetrate cell nuclei and generate the antitumor effect. Our study provides a new approach for developing a smart drug delivery nanosystem, particularly for peptides-guided pH-sensitive chemotherapy.


Assuntos
Antineoplásicos/farmacologia , Neoplasias da Mama/tratamento farmacológico , Doxorrubicina/farmacologia , Sistemas de Liberação de Medicamentos , Peptídeos/farmacologia , Antineoplásicos/química , Neoplasias da Mama/patologia , Linhagem Celular Tumoral , Doxorrubicina/química , Liberação Controlada de Fármacos , Feminino , Humanos , Concentração de Íons de Hidrogênio , Nanopartículas Metálicas/química , Peptídeos/química , Porosidade , Dióxido de Silício/química , Dióxido de Silício/farmacologia , Microambiente Tumoral/efeitos dos fármacos
14.
Diagn Interv Radiol ; 25(4): 291-297, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31120427

RESUMO

PURPOSE: We aimed to investigate the exact role of residual thermal energy following microwave ablation (MWA) and radiofrequency ablation (RFA) at the final ablation and transition zones and determine whether residual thermal energy could be dissipated by subsequent cooling-circulation. METHODS: In an ex vivo study, MWA and RFA were performed on fresh porcine liver, and central and border temperatures were compared. In an in vivo study, MWA and RFA were performed to the livers of New Zealand white rabbits. Tissue samples were stained with α-NADH-diaphorase. The coagulation zones (NADH-negative) and transition zones (lightly NADH-stained) of different groups were compared at different time points. RESULTS: In the ex vivo model, the residual thermal energy after MWA and RFA could be dispersed by subsequent cooling-circulation due to the temperature decreasing rapidly. In the in vivo study, the coagulation volume in the ablation group was larger than that in the cooling-circulation group (P < 0.05) 2 days after ablation. In the ablation group, the damaged zone (the transition zone plus the coagulation zone) on α-NADH-diaphorase-stained images increased rapidly within 2 hours after ablation and slowly reached the maximum on day 2. However, the damaged zones did not change significantly at the three time points observed in the cooling-circulation group. CONCLUSION: The residual thermal energy in MWA and RFA induced secondary damage beyond the direct coagulation zone, and it could be dissipated by subsequent cooling-circulation, contributing to smaller ablation and transition zones.


Assuntos
Ablação por Cateter/efeitos adversos , Fígado/metabolismo , Micro-Ondas/efeitos adversos , Ablação por Radiofrequência/efeitos adversos , Animais , Temperatura Corporal , Ablação por Cateter/métodos , Di-Hidrolipoamida Desidrogenase/metabolismo , Modelos Animais de Doenças , Hipertermia Induzida/efeitos adversos , Fígado/irrigação sanguínea , Fígado/lesões , Masculino , Coelhos , Ablação por Radiofrequência/métodos , Suínos
15.
Gene ; 706: 140-145, 2019 Jul 20.
Artigo em Inglês | MEDLINE | ID: mdl-31078657

RESUMO

BACKGROUND: Alternative splicing regulates most of protein-coding genes by producing diverse messenger RNA transcripts; and mis-splicing events can induce aberrant protein isoforms that contribute to cancer development. It is possible that genetic variations in splicing associated genes may regulate the formation of transcripts and multiple protein isoforms by affecting the splice regulatory elements. In this study, we aimed to determine whether genetic variations in the crucial alternative-splicing genes were associated with breast cancer risk. MATERIALS AND METHODS: A case-control study was conducted with 1064 breast cancer cases and 1073 healthy controls from China. A total of 16 tagging polymorphisms within three splicing factor-associated genes (SFRS3, ESRP1 and ESRP2) were genotyped by using Infinium BeadChip. The association between the polymorphisms and risk of breast cancer was evaluated by computing odds ratios (OR) and 95% confidence intervals (CIs). RESULTS: The genotype distribution of rs2145048 in SFRS3 was different between cases and controls (Bonferroni corrected P = 0.022). After adjusting for age, age at menarche and menopausal status, the A allele of rs2145048 showed an inverse association with breast cancer risk in the additive model (adjusted OR = 0.81, 95% CI = 0.71-0.92, P = 0.001, Bonferroni corrected P = 0.016). In the stratification analysis, the association between rs2145048 A allele and breast cancer remained significant in subgroups of earlier menarche, older first born, premenopausal status, and ER/PR negative status. CONCLUSIONS: This study provided the first evidence that SFRS3 rs2145048 was associated with breast cancer susceptibility in Chinese women, which might represent a biomarker to improve the identification of individuals at high risk of this malignancy.


Assuntos
Neoplasias da Mama/genética , Fatores de Processamento de Serina-Arginina/genética , Adulto , Alelos , Processamento Alternativo/genética , Grupo com Ancestrais do Continente Asiático/genética , Estudos de Casos e Controles , China , Feminino , Frequência do Gene/genética , Predisposição Genética para Doença/genética , Variação Genética/genética , Genótipo , Humanos , Pessoa de Meia-Idade , Razão de Chances , Polimorfismo de Nucleotídeo Único/genética , Proteínas de Ligação a RNA/genética , Proteínas de Ligação a RNA/fisiologia , Fatores de Risco , Fatores de Processamento de Serina-Arginina/fisiologia
16.
J Agric Food Chem ; 67(15): 4170-4176, 2019 Apr 17.
Artigo em Inglês | MEDLINE | ID: mdl-30912660

RESUMO

In this study, we isolated and characterized the bacterial strain Pseudomonas sp. BYT-1, which is capable of degrading pymetrozine and using it as the sole carbon source for growth. Strain BYT-1 could degrade 2.30 mM pymetrozine within 20 h under the optimal conditions of 30 °C and pH 7.0. Investigation of the degradation pathway showed that pymetrozine was oxidatively hydrolyzed to 4-amino-6-methyl-4,5-dihydro-2 H-[1,2,4]triazin-3-one (AMDT) and nicotinic acid (NA). The former accumulates as the end product in the culture, whereas the latter was hydroxylated to 6-hydroxynicotinic acid (6HNA) and subjected to further degradation. The transformation of pymetrozine to AMDT and NA by the cell-free extracts of strain BYT-1 also supported that the oxidative hydrolysis of the C═N double bond in pymetrozine was the initial degradation step. This is the first report on a pure bacterial culture with the ability to degrade pymetrozine. These findings enhance our understanding of the microbial degradation mechanism of pymetrozine.


Assuntos
Pseudomonas/isolamento & purificação , Pseudomonas/metabolismo , Triazinas/metabolismo , Biodegradação Ambiental , Niacina/metabolismo , Pseudomonas/genética , Pseudomonas/crescimento & desenvolvimento , Esgotos/microbiologia , Triazinas/química
17.
Mol Med Rep ; 17(6): 8137-8144, 2018 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-29658570

RESUMO

Breast cancer is the second leading cause of cancer­associated mortality, and metastatic breast cancer is responsible for 90% of patient mortalities. Given that JWA represses the proliferation, invasion and metastasis of a number of other human tumor cells, including melanoma, esophageal, hepatocellular and gastric carcinomas, via mitogen­activated protein kinase or integrin signaling, the present study investigated the expression and function of JWA in human breast cancers. The results showed that the expression level of JWA was significantly reduced in human primary breast cancers when compared with the paired adjacent tissues. Downregulating JWA enhanced, while overexpressing JWA suppressed, the migration and invasion abilities of the two breast cancer cell lines, MDA­MB­468 and MDA­MB­231, without affecting their proliferations in vitro. In addition, JWA negatively regulated the surface expression of CXCR4 in the two cell lines via proteasome degradation, though not via transcriptional inhibition. Functionally, normalizing the disturbed expressions of CXCR4 largely reversed the inhibitory effect of JWA on cell invasion. These data demonstrated that JWA suppressed the migration/invasion of breast carcinoma cells by downregulating the expression of CXCR4, and suggested that JWA may harbor prognostic and therapeutic potential in patients with breast cancer.


Assuntos
Neoplasias da Mama/genética , Neoplasias da Mama/metabolismo , Regulação Neoplásica da Expressão Gênica , Proteínas de Choque Térmico/metabolismo , Peptídeos e Proteínas de Sinalização Intracelular/metabolismo , Receptores CXCR4/genética , Biomarcadores , Biomarcadores Tumorais , Linhagem Celular Tumoral , Movimento Celular , Feminino , Humanos , Proteínas de Membrana Transportadoras , Proteólise
18.
Onco Targets Ther ; 11: 1423-1432, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29588597

RESUMO

Introduction: Neoadjuvant chemotherapy (NAC) has become a standard treatment for locally advanced breast cancer. The present study was designed to investigate the predictive value of different peripheral inflammation/immune biomarker responses to NAC and prognosis in breast cancer patients. Materials and methods: A total of 180 breast cancer patients treated with NAC in the First Affiliated Hospital with Nanjing Medical University between January 2008 and March 2015 were enrolled in the study. The associations between inflammation/immune indicators and pathological complete response (pCR) were determined, and the prognostic value of inflammation/immune indicators was also evaluated. Results: In the univariate analysis, patients with a high pretreatment peripheral lymphocyte count (.2.06×109/L) showed a higher pCR rate than those with a low lymphocyte count (23.9% vs 10.4%, P=0.023). The pCR rate of patients with a neutrophil: lymphocyte ratio ≤2.15 was significantly higher than that of patients with a high neutrophil: lymphocyte ratio (20% vs 7.8%; P=0.03). However, multivariate analysis revealed that only the high lymphocyte count was predictive for pCR (odds ratio: 4.375, 95% CI: 1.429-13.392, P=0.010). In the survival analysis, patients with a higher neutrophil count (.2.65×109/L) were confirmed to have a shorter disease-free survival (hazard ratio: 4.322, 95% CI: 1.028-18.174, P=0.046), and the high neutrophil count was significantly associated with lymphovascular invasion (P=0.037). Conclusion: We demonstrated that a high level of baseline peripheral lymphocyte count can be a predictor for high efficacy of NAC for breast cancer patients, and low baseline peripheral neutrophil count may contribute to the favorable disease-free survival.

19.
Mol Cancer ; 17(1): 4, 2018 01 08.
Artigo em Inglês | MEDLINE | ID: mdl-29310680

RESUMO

BACKGROUND: Triple-negative breast cancer (TNBC) is highly invasive and aggressive and lacks specific molecular targets to improve the prognosis. MiR-25-3p promotes proliferation of many tumors and its role and underlying mechanisms in TNBC remain to be well elucidated. METHODS: Differential expression of miR-25-3p in TNBC was measured with quantitative real-time PCR (qRT-PCR) in both TNBC tissues and cell lines and was validated in the Cancer Genome Atlas (TCGA) database. The effects of miR-25-3p on proliferation, apoptosis capacity of TNBC were evaluated using Cell counting kit-8 (CCK-8), colony formation assay and Annexin V-FITC/PI analyses. The tumor growth in vivo was observed in xenograft model. Luciferase reporter assay, qPCR and western blot were performed to validate a potential target of miR-25-3p in TNBC. Involvement of the AKT and MAPK pathways was investigated by western blot. RESULTS: MiR-25-3p was found to be upregulated in TNBC in tissues and cell lines. MiR-25-3p promoted TNBC cell proliferation in vitro and tumor growth in xenograft model, while suppression of miR-25-3p induced cell apoptosis. The luciferase reporter assay confirmed that B-cell translocation gene 2 (BTG2) might be a direct target of miR-25-3p, and its expression was negatively regulated by miR-25-3p. Moreover, inhibition of BTG2 expression accounted for the role of miR-25-3p in TNBC. Furthermore, BTG2 suppression might indirectly activate the AKT and ERK-MAPK signaling pathways to mediate the downstream effects of miR-25-3p. CONCLUSIONS: This study demonstrates that miR-25-3p promotes proliferation by targeting tumor suppressor BTG2 and may identify new diagnostic and therapeutic targets in TNBC.


Assuntos
Biomarcadores Tumorais , Regulação Neoplásica da Expressão Gênica , Proteínas Imediatamente Precoces/genética , MicroRNAs/genética , Interferência de RNA , Neoplasias de Mama Triplo Negativas/genética , Proteínas Supressoras de Tumor/genética , Animais , Apoptose/genética , Linhagem Celular Tumoral , Movimento Celular/genética , Proliferação de Células , Replicação do DNA , Modelos Animais de Doenças , Feminino , Expressão Gênica , Genes Reporter , Xenoenxertos , Humanos , Sistema de Sinalização das MAP Quinases , Camundongos , Prognóstico , Proteínas Proto-Oncogênicas c-akt/metabolismo , Neoplasias de Mama Triplo Negativas/patologia
20.
J Ocul Pharmacol Ther ; 33(9): 693-703, 2017 11.
Artigo em Inglês | MEDLINE | ID: mdl-28933986

RESUMO

Abstracts Purpose: Pirfenidone is mostly used in antifibrotic and anti-inflammatory therapies. We have previously demonstrated that pirfenidone had antifibrotic and anti-inflammatory effects on the wound healing process after glaucoma filtration surgery in vitro and in vivo. Since the wound healing and reactive scarring process simultaneously involves inflammation, fibrosis, and angiogenesis, and angiogenesis plays a more important role in chronic or prolonged wound healing, we tried to explore the antiangiogenesis effect in pirfenidone and its potential multitarget function in regulating excessive scarring. The aim of the present study was to investigate the antiangiogenesis effect of pirfenidone. METHODS: The proliferation of human umbilical vein endothelial cells (HUVECs) and human Tenon's fibroblasts (HTFs) were detected by WST-1 assay. The cell viability of HUVECs was measured by Trypan Blue together with lactate dehydrogenase, Annexin 5 experiment, and Ki-67 immunofluorescence assay. The functions of HUVECs and HTFs were demonstrated using cell migration assay, transwell invasion assay, and tube formation assay. The expression levels of vascular endothelial growth factor-A (VEGF-A), VEGF receptor-2 (VEGFR-2), neuropilin-1(NRP-1), and their downstream signaling proteins p-PI3K, PI3K, p-AKT, AKT, p-mTOR, and mechanistic target of rapamycin (mTOR) were indicated by western blot assay. The secretion of VEGF-A was detected by enzyme-linked immunosorbent assay. RESULTS: Pirfenidone inhibited proliferation, migration, invasion, and tube formation of HUVECs in vitro, and had an equivalent antiangiogenesis effect when compared with Ranibizumab in HUVECs and HTFs. Pirfenidone downregulated VEGF-A/VEGFR-2, VEGF-A/NRP-1, and its downstream signaling pathway protein expression. CONCLUSIONS: Pirfenidone has an antiangiogenesis effect in the wound healing process and may become an ideal multitarget antiscarring agent after glaucoma filtration surgery.


Assuntos
Inibidores da Angiogênese/farmacologia , Anti-Inflamatórios não Esteroides/farmacologia , Piridonas/farmacologia , Cicatrização/efeitos dos fármacos , Anexina A5/metabolismo , Western Blotting , Movimento Celular/fisiologia , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Ensaio de Imunoadsorção Enzimática , Fibroblastos/efeitos dos fármacos , Citometria de Fluxo , Células Endoteliais da Veia Umbilical Humana/efeitos dos fármacos , Humanos , Antígeno Ki-67/metabolismo , L-Lactato Desidrogenase/metabolismo , Neurofisinas/metabolismo , Cápsula de Tenon/citologia , Fator A de Crescimento do Endotélio Vascular/metabolismo , Receptor 2 de Fatores de Crescimento do Endotélio Vascular/metabolismo
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