RESUMEN
Neutrophil and neutrophil extracellular traps (NETs) were reported to be associated with tumor development, but the exact role and concrete mechanisms are still poorly understood, especially in triple negative breast cancer (TNBC). In this study, our results exhibited that NETs formation in TNBC tissues was higher than that in non-TNBC tissues, and NETs formation was distinctly correlated with tumor size, ki67 level and lymph node metastasis in TNBC patients. Subsequent in vivo experiments demonstrated that NETs inhibition could suppress TNBC tumor growth and lung metastasis. Further in vitro experiments uncovered that oncogenic function of NETs on TNBC cells were possibly dependent on TLR9 expression. We also found that neutrophils from peripheral blood of TNBC patients with postoperative fever were prone to form NETs and could enhance the proliferation and invasion of TNBC cells. Mechanistically, we revealed that NETs could interact with TLR9 to decrease Merlin phosphorylation which contributed to TNBC cell ferroptosis resistance. Our work provides a novel insight into the mechanism of NETs promoting TNBC progression and blocking the key modulator of NETs might be a promising therapeutic strategy in TNBC.
Asunto(s)
Trampas Extracelulares , Ferroptosis , Neoplasias de la Mama Triple Negativas , Humanos , Trampas Extracelulares/metabolismo , Receptor Toll-Like 9/genética , Receptor Toll-Like 9/metabolismo , Neurofibromina 2/metabolismo , Ferroptosis/genética , Línea Celular Tumoral , Neoplasias de la Mama Triple Negativas/patología , Apoptosis , Neutrófilos/patología , Proliferación CelularRESUMEN
Autophagy, as a special programmed cell death, is a critical degradative process that eliminates intracellular abnormal proteins or damage organelles to balance cell energy and favor cell metabolism with autophagy-related (ATG) proteins. Autophagy activation is being increasingly recognized as an essential hallmark in tumorigenesis through influencing the metabolism of stromal cells in the tumor microenvironment (TME) which comprises of tumor cells, cancer-associated fibroblasts (CAFs), cancer-associated endothelial cells (CAEs), immune cells and adipocytes. Tumor cells can reuse autophagy-involved recycling to maintain mitochondrial function and energy supply to meet the metabolic demand of their growth and proliferation. However, the mechanism through which autophagy can promote a crosstalk between tumor and stroma cells is not clear. Reprogramed metabolism is one of the main characteristics of TME leading to higher adaptability of tumor cells with diverse mechanisms. The activation of autophagy has expanded our understanding on the interaction between tumor metabolism and TME. The aim of this review is to report recent advances on the metabolic cross-talk between stromal cells and solid tumor cells induced by autophagy in TME and revealed potential therapeutic targets.
RESUMEN
Background: TNBC, whose clinical prognosis is poorer than other subgroups of breast cancer, is a malignant tumor characterized by lack of estrogen receptors, progesterone hormone receptors, and HER2 overexpression. Due to the lack of specific targeted drugs, it is crucial to identify critical factors involved in regulating the progression of TNBC. Methods: We analyzed the expression profiles of TNBC in TCGA and the prognoses values of GLDC. Correlations of GLDC and tumor immune infiltration were also identified. CCK8 and BrdU incorporation assays were utilized to determine cell proliferation. The mRNA and protein levels were examined by using Real-time PCR and Western blot analysis. Results: In the present study, we analyzed the mRNA expression profiles of TNBC in TCGA and found that GLDC, a key enzyme in glycine cleavage system, was significantly up-regulated in TNBC tissues and higher expression of GLDC was correlated with a worse prognosis in TNBC. Moreover, the expression of GLDC was negatively correlated with macrophage and monocyte and positively correlated with activated CD4 T cell and type 2 T helper cell in TNBC. Overexpression of GLDC facilitated the proliferation of TNBC cells, whereas GLDC knockdown had the opposite effects. Additionally, miR-30e acts as a functional upstream regulator of GLDC and the inhibitory effects of miR-30e on cell proliferation were mitigated by the reintroduction of GLDC. Conclusions: These results imply that miR-30e-depressed GLDC acts as a tumor suppressive pathway in TNBC and provides potential targets for the treatment of TNBC.
Asunto(s)
MicroARNs , Neoplasias de la Mama Triple Negativas , Humanos , Neoplasias de la Mama Triple Negativas/metabolismo , Regulación Neoplásica de la Expresión Génica , MicroARNs/genética , MicroARNs/metabolismo , Receptores de Progesterona/metabolismo , Bromodesoxiuridina , Línea Celular Tumoral , Proliferación Celular/genética , ARN Mensajero , EstrógenosRESUMEN
Objective: To identify trastuzumab-resistant genes predicting drug response and poor prognosis in human epidermal growth factor receptor 2 positive (HER2+) breast cancer. Methods: Gene expression profiles from the GEO (Gene Expression Omnibus) database were obtained and analyzed. Differentially expressed genes (DEGs) between the pathological complete response (pCR) group and non-pCR group in a trastuzumab neoadjuvant therapy cohort and DEGs between Herceptin-resistant and wild-type cell lines were detected and evaluated. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways analyses were performed to select the functional hub genes. The hub genes' prognostic power was validated by another trastuzumab adjuvant treatment cohort. Results: Fifty upregulated overlapping DEGs were identified by analyzing two trastuzumab resistance-related GEO databases. Functional analysis picked out ten hub genes enriched in mitochondrial function and metabolism pathways: ASCL1, CPT2, DLD, ELVOL7, GAMT, NQO1, SLC23A1, SPR, UQCRB, and UQCRQ. These hub genes could distinguish patients with trastuzumab resistance from the sensitive ones. Further survival analysis of hub genes showed that DLD overexpression was significantly associated with an unfavorable prognosis in HER2+ breast cancer patients. Conclusion: Ten novel trastuzumab resistance-related genes were discovered, of which DLD could be used for trastuzumab response prediction and prognostic prediction in HER2+ breast cancer.
Asunto(s)
Neoplasias de la Mama , Neoplasias de la Mama/tratamiento farmacológico , Neoplasias de la Mama/genética , Neoplasias de la Mama/metabolismo , Femenino , Perfilación de la Expresión Génica , Regulación Neoplásica de la Expresión Génica , Humanos , Receptor ErbB-2 , Trastuzumab/farmacología , Trastuzumab/uso terapéuticoRESUMEN
PURPOSE: Despite accumulating evidence on dual blockade of HER2 for locally advanced HER2-positive breast cancer, no robust evidence supports the addition of pyrotinib to trastuzumab in the neoadjuvant setting. The NeoATP trial aimed to evaluate the efficacy and safety of pyrotinib with neoadjuvant trastuzumab and chemotherapy. PATIENTS AND METHODS: The phase II NeoATP trial included female patients with histologically confirmed stage IIA to IIIC and HER2-positive primary invasive breast cancer. Eligible patients received pyrotinib and trastuzumab with weekly paclitaxel-cisplatin neoadjuvant chemotherapy for four cycles. The primary endpoint was pathologic complete response (pCR; ypT0 ypN0) rate. Key secondary endpoints included locoregional pCR (ypT0/is ypN0) rate, biomarker analysis, and safety. RESULTS: Among 53 enrolled patients (median age, 47 years; 73.58% stage III), 52 completed the study treatment and surgery. Overall, 37 patients (69.81%) achieved pCR. For women with hormone receptor-negative and -positive tumors, the pCR rates were 85.71% and 59.38% (P = 0.041), while the corresponding rates were 69.23% and 70.00%, respectively, for those with and without PIK3CA mutation (P = 0.958). The most frequently reported Grade 3 to 4 adverse events were diarrhea (45.28%), leukopenia (39.62%), and neutropenia (32.08%). No deaths occurred, and no left ventricular ejection fraction <50% or >10 points drop from baseline to before surgery was reported. CONCLUSIONS: The addition of pyrotinib to trastuzumab plus chemotherapy is an efficacious and safe regimen for patients with HER2-positive locally advanced breast cancer in the neoadjuvant setting. The randomized controlled clinical trial is warranted to validate our results.
Asunto(s)
Neoplasias de la Mama , Terapia Neoadyuvante , Acrilamidas , Aminoquinolinas , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Neoplasias de la Mama/tratamiento farmacológico , Neoplasias de la Mama/genética , Neoplasias de la Mama/patología , Femenino , Humanos , Persona de Mediana Edad , Terapia Neoadyuvante/métodos , Receptor ErbB-2/genética , Receptor ErbB-2/uso terapéutico , Trastuzumab , Resultado del TratamientoRESUMEN
As our understanding of the microbiome has expanded, so has the recognition of its critical role in human health and disease, thereby emphasizing the importance of testing whether microbes are associated with environmental factors or clinical outcomes. However, many of the fundamental challenges that concern microbiome surveys arise from statistical and experimental design issues, such as the sparse and overdispersed nature of microbiome count data and the complex correlation structure among samples. For example, in the human microbiome project (HMP) dataset, the repeated observations across time points (level 1) are nested within body sites (level 2), which are further nested within subjects (level 3). Therefore, there is a great need for the development of specialized and sophisticated statistical tests. In this paper, we propose multilevel zero-inflated negative-binomial models for association analysis in microbiome surveys. We develop a variational approximation method for maximum likelihood estimation and inference. It uses optimization, rather than sampling, to approximate the log-likelihood and compute parameter estimates, provides a robust estimate of the covariance of parameter estimates and constructs a Wald-type test statistic for association testing. We evaluate and demonstrate the performance of our method using extensive simulation studies and an application to the HMP dataset. We have developed an R package MZINBVA to implement the proposed method, which is available from the GitHub repository https://github.com/liudoubletian/MZINBVA.
Asunto(s)
Microbiota , Simulación por Computador , Humanos , Modelos Estadísticos , Proyectos de InvestigaciónRESUMEN
Hypoxia-induced chemotherapy resistance is the main hindrance for solid tumor treatment. Hypoxia inducible factor-1α (HIF1α), an adaptive gene of hypoxia condition, played an important role in affecting chemotherapy sensitivity for many cancer types and various therapeutic regimens. This study focused on the impact of HIF1α on predicting response and survival of taxane-based neoadjuvant therapy (NAT) for breast cancer (BC) patients and the concrete mechanism that HIF1α mediated paclitaxel chemo-insensitivity. We evaluated HIF1α expression immunohistochemically from biopsies of 108 BC patients receiving paclitaxel-cisplatin NAT. Univariate and multivariate logistic regression analysis revealed that high HIF1α expression led to lower rate of pathological complete response (pCR) and worse prognosis. Analysis of GEO datasets also indicated negative association between HIF1α expression and response of taxane-based NAT in BC patients. The Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment of differential expression genes (DEGs) in different HIF1α expression groups from TCGA database showed that HIF1α participated in interleukin 17 (IL-17) signaling pathway. Correlation analysis suggested that HIF1α was positively related to the IL-17 pathway. CXC motif chemokine ligand 10 (CXCL10) was the only DEG in the IL-17 pathway inversely relating to NAT response. Experiments in vitro verified that HIF1α/IL-17 pathway influences paclitaxel sensitivity to BC cells. Correlation analysis between HIF1α/IL-17A/CXCL10 and infiltration of immune cells in BC uncovered that high expression of all the above three genes were positively correlated to neutrophil infiltration in BC. Collectively, our findings shed novel insight into the mechanism of chemotherapy resistance and implied that HIF1α inhibitor may be a promising drug combined with traditional chemotherapeutic drug to increase the chemotherapy efficacy.
RESUMEN
BACKGROUND: Triple negative breast cancer (TNBC) is a subtype of breast cancer with poor prognosis and lack of effective treatment target. Here we screened differentially expressed lncRNAs through bioinformatics analysis and identified CARMN as a downregulated lncRNA which is lowest expressed in TNBC. We aimed to identify the potential role and molecular mechanisms of CARMN in TNBC. METHODS: Predictive value of CARMN was explored in breast cancer cohorts. TNBC cell lines with CARMN overexpression or CARMN silence and were used for in vitro and in vivo experiments. RNA-seq of CARMN overexpressed cells was performed for exploring downstream of CARMN. RESULTS: CARMN is downregulated at different phase of malignant transformation of breast tissue. CARMN can predict both better prognosis and higher response rate of cisplatin-based neoadjuvant chemotherapy in breast cancer. A nomogram is built to predict cisplatin-based chemotherapy response in breast cancer. Through in vitro and in vivo studies, we confirmed CARMN can also inhibit tumorigenesis and enhance sensitivity to cisplatin in TNBC cells. RNA-seq and further experiments revealed CARMN can inhibit DNA replication. MCM5, an important DNA replication initiation factor, is the most downregulated gene in DNA replication pathway following CARMN overexpression. We confirmed CARMN can produce miR143-3p from its exon5 which is DROSHA and DICER dependent, resulting binding and decrease of MCM5. Moreover, suppressing miR143-3p can weaken function of CARMN in suppressing tumorigenesis and promoting chemosensitivity. CONCLUSIONS: Our results indicated lncRNA CARMN is a predictive biomarker of better prognosis and enhanced cisplatin sensitivity in TNBC. CARMN is the host gene of miR143-3p which downregulates MCM5, causing inhibited DNA replication.
Asunto(s)
Proteínas de Ciclo Celular/genética , Regulación hacia Abajo , MicroARNs/genética , ARN Largo no Codificante/genética , Neoplasias de la Mama Triple Negativas/patología , Adulto , Animales , Línea Celular Tumoral , Proliferación Celular/efectos de los fármacos , Supervivencia Celular/efectos de los fármacos , Cisplatino/farmacología , Ensayos Clínicos Fase III como Asunto , Femenino , Perfilación de la Expresión Génica , Regulación Neoplásica de la Expresión Génica , Humanos , Ratones , Persona de Mediana Edad , Nomogramas , Pronóstico , Neoplasias de la Mama Triple Negativas/tratamiento farmacológico , Neoplasias de la Mama Triple Negativas/genéticaRESUMEN
Three-dimension (3D) porous carbon-sheet microspheres (PCSMs) are prepared through coating coal tar pitch on basic zinc carbonate microspheres followed by in situ ZnO template carbonization and KOH activation. The as-prepared PCSMs show microsphere morphology composed of petal-like carbon nanosheets, which have large specific area (1359.88-2059.43 m2 g-1) and multiscale pores (mainly micropores and mesopores). As the supercapacitor electrodes, the 3D PCSMs present a good electrochemical performance with a large specific capacitance of 313 F g-1 at 1 A g-1 and high rate capability of 81.9% capacitance retention when increasing the current density up to 50 A g-1 in a three-electrode system. In addition, the energy density can reach up to 18.79 Wh kg-1 at a high power density of 878.4 W kg-1 for PCSMs-0.2a symmetrical supercapcitor in 1 M Na2SO4 electrolyte.
RESUMEN
Our work sheds light on using the O 2p-band center as a useful electronic descriptor for understanding the variations in catalytic reducibility of transition metal oxides (TMOs) and the promotional effect of MnO2 during catalytic benzene combustion. The "volcano"-type activity plot, in conjunction with the reduction characteristic of the TMOs, ultimately reflects the Sabatier principle, which states that a good catalyst (i.e., MnO2) balances the capability of oxygen abstraction and uptake in the case of benzene combustion.
RESUMEN
Recently, Mo-based metal catalysts are widely applied in the electrocatalytic nitrogen reduction reaction (NRR) due to the lower binding energy between the Mo atom and N atom. The design of a Mo-based catalyst@carbon heterostructure and the introduction of anion vacancies are effective measures to improve their NRR performance. In this research, the cross-linked Vo-MoO2@C (Vo means oxygen vacancies) heterostructure nanoparticles with rich oxygen vacancies are first synthesized via pectin assisted hydrothermal reaction followed by calcination and treating with NaBH4 solution. Vo-MoO2@C exhibits good electrocatalytic NRR performance with an ammonia yield rate of 9.75 µg h-1 mg-1 at -0.5 V (RHE) and a Faraday efficiency (FE) of 3.24% at -0.3 V (RHE) under ambient conditions.
RESUMEN
BACKGROUND: Treatment for locally recurrent rectal cancer after surgery is still a challenge. With the physical and biological advantages, carbon-ion radiotherapy (CIRT) could be a choice for these patients. The purpose of this study was to investigate the efficacy and safety of CIRT for unresectable locally recurrent rectal cancer in Chinese patients. METHODS: Date from 25 patients with unresectable locally recurrent rectal cancer treated by CIRT from July 2015 to April 2019 were analyzed retrospectively. The endpoints of this study were overall survival (OS), local control (LC) and acute and late toxicity. RESULTS: With the median follow-up of 19.6 (range 5.1-52.5) months, data of all 25 patients were collected. Median prescribed dose for tumor was 72Gy (relative biologic efficacy (RBE)) (range 48-75.6Gy (RBE)). The LC rates at 1 and 2 years were 90.4 and 71.8%. Overall LC at 1- and 2-year were 76.2 and 30.5% for 9 patients whose prescribed tumor doses of CIRT< 66 Gy (RBE), 100 and 100% for 16 patients whose prescribed doses of CIRT≥66 Gy (RBE). Patients received ≥66 Gy (RBE) had obviously better LC rates than those received < 66 Gy (RBE) (P = 0.001). The OS rates at 1 and 2 years were 82.9 and 65.1%, respectively. No acute toxicity over grade 2 was observed, grade 3 late toxicity were observed in 3 patients: gastrointestinal toxicity (n = 1), neuropathy (n = 1), pelvic infection (n = 1). No Grade 4 or higher toxicity was observed. CONCLUSION: Our study shows that CIRT is effective for unresectable locally recurrent rectal cancer patients with acceptable toxicity.
Asunto(s)
Radioterapia de Iones Pesados/métodos , Recurrencia Local de Neoplasia/radioterapia , Neoplasias del Recto/radioterapia , Adulto , Anciano , Femenino , Radioterapia de Iones Pesados/efectos adversos , Humanos , Masculino , Persona de Mediana Edad , Recurrencia Local de Neoplasia/mortalidad , Dosificación Radioterapéutica , Radioterapia de Intensidad Modulada , Neoplasias del Recto/mortalidad , Efectividad Biológica RelativaRESUMEN
Background: We aimed to explore whether the expression of serum miR-222-3p might contribute to early prediction of therapeutic response, clinical outcomes, and adverse events for HER2-positive breast cancer patients receiving neoadjuvant therapy (NAT). Methods: A total of 65 HER2-positive breast cancer patients receiving NAT were analyzed. The concentration of serum miR-222-3p was detected by quantitative real-time PCR. Logistic regression analysis was used to identify the association of serum miR-222-3p with pathological complete response (pCR). The relationship of serum miR-222-3p with disease-free survival (DFS) and overall survival (OS) was examined via log-rank test and Cox proportional hazards analysis. The ordered logistic regression was applied to evaluate the association between serum miR-222-3p and adverse events. Results: The miR-222-3p low group was more likely to achieve pCR [odds ratio (OR) = 0.258, P = 0.043]. The interaction between miR-222-3p and presenting Ki67 level was also detected for pCR (OR = 49.230, P interaction = 0.025). The miR-222-3p low group was correlated with superior DFS (P = 0.029) and OS (P = 0.0037). The expression of serum miR-222-3p was the independent protective factor for trastuzumab-induced cardiotoxicity (P < 0.05) and anemia (P = 0.013). Conclusions: Serum miR-222-3p is the potential factor to predict pCR, survival benefit and trastuzumab-induced cardiotoxicity for HER2-positive breast cancer patients receiving NAT.
RESUMEN
The commercially available V2O5/WO3-TiO2 is a well-known catalyst for selective catalytic reduction (SCR) of NO with NH3. When alkali ions are present in the exhaust (e.g., as impurities such as dust) of a reactor containing commercial V2O5/WO3-TiO2, alkali poisoning occurs, deactivating the catalyst. Consequently, there is substantial interest in the development of better-performing and more durable NH3-SCR catalysts with an improved resistance to alkali deactivation. For the present study, the protonated (H+) form of zeolite Y, HY, was used as a support and acted as buffer zone, leading to trapping (sticking) of foreign alkali poisons in the zeolite pore structure, preventing alkali poisoning of the Fe2O3/HY catalyst. Catalytic tests showed that the Fe2O3/HY retained 100% of its original catalytic reactivity for NH3-SCR reaction even after 1000 µmol Na+ g-1 poisoning. 1000 µmol Na+ g-1 treatment indicates a 26â¯000-h exposure under an alkaline dust-containing condition. In contrast, upon 1000 µmol Na+ g-1 treatment, severe alkali deactivation occurred for a commercial V2O5/WO3-TiO2. The catalyst activity of Fe2O3/HY remained unchanged because of the intercalation of Na+ in the internal HY zeolite pores that impedes the blocking of Na+ poison to the external active sites of Fe2O3. The findings in this work suggest that the zeolite HY may be revealed as an attractive building block for designing an alkali poisoning-resistant catalyst.
Asunto(s)
Zeolitas , Álcalis , Amoníaco , Catálisis , Titanio , Emisiones de VehículosRESUMEN
The exhaust gas contains harmful products, including fuel-additive elements such as compounds of sodium, which cause dramatic catalyst deactivation of catalysts during selective catalytic reduction (SCR) of NO with NH3. There is an increasing demand to synthesize alkali-poisoning-resistant catalysts for industrial NH3-SCR applications. In this study, the as-synthesized Fe2O3/MoO3/TiO2 exhibits a high degree of resistance toward Na2SO4 poisoning during the NH3-SCR reaction. With 500 µmol g-1 Na+ poisoning, Fe2O3/MoO3/TiO2 showed approximately 95% (or more) of its original activity throughout the entire temperature rage. Even with 700 µmol g-1 Na+ poisoning, Fe2O3/MoO3/TiO2 still performed well. The 500 and 700 µmol g-1 Na+ loadings dictate that, on average, SCR catalysts could be exposed to alkali-rich and highly dusty environments for more than 14â¯000 and 20â¯000 h, respectively. The layered MoO3 building block is used as a binding buffer and sandwiched between the active phase and TiO2 support to provide sufficiently stable binding sites for Na2SO4 poison and to present alkali blocking of the surface active phase. Our findings provide useful information regarding the use of MoO3 as a safety buffer for developing functional NH3-SCR catalysts with enhanced alkali-poisoning-resistant performance and long lifetimes.
Asunto(s)
Álcalis , Amoníaco , Catálisis , Dominio Catalítico , TitanioRESUMEN
Adrenergic receptors (ARs) have gained attention for their involvement in breast cancer (BC) progression. Dexmedetomidine, a selective α2 -AR agonist, has been reported to increase the malignancy of BC cells in vitro or stimulate tumor growth in mice. However, clinical evidence is lacking. Clinical research in this area is important as dexmedetomidine is widely used in BC surgery patients. Here we allocated 24 women with primary BC to the dexmedetomidine group (who received a total dose of 2 µg kg-1 dexmedetomidine perioperatively) or to the control group (who received the same volume of normal saline). Venous blood was obtained from all patients immediately upon entering the operating room and 24 hours postoperatively. Serum was then exposed to MCF-7 cells at a concentration of 10% for 24 hours. Cell proliferation, migration, and invasion were analyzed using EdU, Transwell, and Matrigel methods, respectively. We found that postoperative serum from those who received dexmedetomidine was associated with significantly increased cell proliferation, migration, and invasion compared with preoperative serum when used to culture MCF-7 cells. The mean percentage change from post to preoperative values in these cell functions was significantly larger in the dexmedetomidine group than in the control group (proliferation, 30.44% vs 8.45%, P = .0024; migration, 15.90% vs 3.25%, P = .0015; invasion, 8.17% vs 2.13%, P = .04). In conclusion, these findings suggest that in patients undergoing surgery for primary BC, perioperative administration of dexmedetomidine might influence the serum milieu in a way that favors the malignancy of MCF-7 cells. Clinical trial registration: NCT03108937.
Asunto(s)
Agonistas de Receptores Adrenérgicos alfa 2/farmacología , Analgésicos no Narcóticos/farmacología , Neoplasias de la Mama/sangre , Dexmedetomidina/farmacología , Periodo Perioperatorio , Agonistas de Receptores Adrenérgicos alfa 2/administración & dosificación , Agonistas de Receptores Adrenérgicos alfa 2/farmacocinética , Adulto , Analgésicos no Narcóticos/administración & dosificación , Analgésicos no Narcóticos/farmacocinética , Biomarcadores de Tumor , Neoplasias de la Mama/diagnóstico , Neoplasias de la Mama/tratamiento farmacológico , Neoplasias de la Mama/cirugía , Línea Celular Tumoral , Movimiento Celular/efectos de los fármacos , Proliferación Celular/efectos de los fármacos , Terapia Combinada , Dexmedetomidina/administración & dosificación , Dexmedetomidina/farmacocinética , Femenino , Humanos , Persona de Mediana Edad , Estadificación de NeoplasiasRESUMEN
A systematic investigation is performed on the electronic transport properties of armchair-graphene nanoribbon (AGNR) heterojunctions using spin-polarized density functional theory calculations in combination with the non-equilibrium Green's function formalism. 9-AGNR and 5-AGNR structures are used to form a single-well configuration by sandwiching a 5-AGNR between two 9-AGNRs. At the same time, these 9-AGNRs are matched at the left and right to electrodes, 9 and 5 being the number of carbon dimers as width. This heterojunction mimics an electronic device with two potential barriers (9-AGNR) and one quantum well (5-AGNR) where quasi-bound states are confined. First, we study the ground state properties, and then we calculate the electron transport properties of this device as a function of the well width. We show the presence of electronic tunnelling resonances between the barriers by delocalized electron density inside the well's structure. This is corroborated by transmission curves, localized densities of states (LDOS), current-vs.-bias voltage results, and the trend of the resonances as a function of the well width. This work shows that carbon AGNRs may be used as resonant-tunnelling devices for applications in nanoelectronics.
RESUMEN
BACKGROUND: Germline genetic polymorphisms in certain genes are associated with response to anthracycline- and taxane-based neoadjuvant chemotherapy in breast cancer (BC). Recent evidence has indicated that microRNA (miRNA) let-7 expression is associated with response to chemotherapeutics. This study aims to evaluate the potential role of let-7 miRNA-related single nucleotide polymorphisms (mirSNPs) in the prediction of pathologic complete response to taxane- and platinum-based neoadjuvant chemotherapy in locally advanced breast cancer (LABC). METHODS: We genotyped the SNPs that reside in and around miRNA let-7 binding sites of two target genes: hypoxia-inducible factor 1 subunit alpha inhibitor (HIF1AN) and claudin 12 (CLDN12). The distribution frequencies of the SNPs were genotyped in LABC patients who received taxane- and platinum-based neoadjuvant chemotherapy. Associations among tumour-relevant biomarkers, genotype and pathological complete response (pCR) were evaluated using Student's t-test for continuous variables and the chi-square or Fisher's exact tests for non-categorical variables. The modified odds ratios (ORs) with their 95% confidence intervals (CIs) were calculated by a multivariate logistic regression analysis to explore the association of genotype with pCR. RESULTS: For rs11292, which is located in the 3'-untranslated region (UTR) of HIF1AN, significant differences were detected in codominant, dominant and overdominant models between the patients who achieved pCR and those who did not (non-pCR) (P<0.05) in a multivariate analysis. For rs1017105, which is located in the 3'-UTR of CLDN12, significant differences were observed in the recessive model between the pCR and non-pCR patients with luminal-type BC. CONCLUSIONS: Let-7-related mirSNPs could predict pathologic complete response to taxane- and platinum-based neoadjuvant chemotherapy in LABC, which suggests the potential role of variants of miRNA let-7-related gene networks as predictive markers in a clinical setting.
RESUMEN
BACKGROUND: Let-7 is a microRNA (miRNA) that targets the ß2 adrenergic receptor (ADRB2), hypoxia inducible factor 1 subunit alpha inhibitor (HIF1AN), and claudin 12 (CLDN12) genes. Single nucleotide polymorphisms (SNPs) in the structural or regulatory regions of these miRNA let-7-related genes may be associated with breast cancer carcinogenesis and prognosis. Low let-7 expression may increase breast cancer risk. We investigated the effects of let-7-related gene SNP (mirSNPs) on breast cancer risk and clinical outcomes. METHODS: The distribution frequencies of the three SNPs were genotyped in patients with breast cancer and controls. Multivariate logistic regression analysis was used to evaluate the association between the SNPs and susceptibility to breast cancer. We investigated the effects of these mirSNPs prospectively on disease-free survival (DFS) using the Kaplan-Meier method and the extended multivariate Cox model. RESULTS: We found that rs1042713 in the ADRB2 gene and rs11292 in the 3'-UTR of the HIF1AN gene were associated with breast cancer susceptibility (P<0.05). The CLDN12 rs1017105 genotype was associated with estrogen receptor (P=0.031) and progesterone receptor status (P=0.007). The number of risk alleles was associated with estrogen receptor (P=0.034) status in breast cancer patients. In the survival analysis, the extended Cox model demonstrated that rs1042713 (P=0.000) and rs1017105 (P=0.004) were independent predictors of DFS. The number of risk alleles of the ADRB2, HIF1AN, and CLDN12 genes was an independent predictor of DFS (P<0.001). CONCLUSION: Let-7-related mirSNPs might be associated with carcinogenesis and clinical outcome in breast cancer, suggesting that variants of miRNA let-7-related gene networks coregulate breast cancer characteristics.
RESUMEN
Surface restructuring is a useful approach to modulating the properties of nanoparticles. A low-dimensional atomic-thickness active species may exhibit remarkably enhanced activity, in contrast to the inert nature of its bulk counterparts. Here, we report a procedure for growing in situ a low-dimensional monolayer-thick MoO3 entity from its bulk precursor. Traditional analysis of NO abatement catalyzed by vanadium-based materials implicates vanadium as the active site enhanced by the promoter element W or Mo. However, we report here that the atomic-thickness MoO3 film can function alone as an efficient NO abatement catalyst by itself; to achieve comparable performance with the industrial catalysts, it is not necessary to add vanadium oxide, which often has serious toxicity issues associated with it. We find that submonolayer MoO3 is responsible for the observed high activity. Electron microscopy and Raman spectroscopy reveal that the monolayer-thick MoO3 surface phase is directly attached to the anatase TiO2 support. The ab initio quantum calculations predict that the bidimensional MoO3 surface phase would provide more electron back-donation to the antibonding orbital of reactants and thus more efficient reactant activation. The spectral evolution of in situ DRIFTS indicates that the redox mechanism over the low-dimensional MoO3/TiO2 involves both Brønsted and Lewis acid sites during the reaction cycle.