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BACKGROUND: Treatment efficacy may differ among patients with nasopharyngeal carcinoma (NPC) at similar tumor-node-metastasis stages. Moreover, end-of-treatment tumor regression is a reliable indicator of treatment sensitivity. This study aimed to investigate whether quantitative dual-energy computed tomography (DECT) parameters could predict sensitivity to neck-lymph node radiotherapy in patients with NPC. METHODS: Overall, 388 lymph nodes were collected from 98 patients with NPC who underwent pretreatment DECT. The patients were divided into complete response (CR) and partial response (PR) groups. Clinical characteristics and quantitative DECT parameters were compared between the groups, and the optimal predictive ability of each parameter was determined using receiver operating characteristic (ROC) analysis. A nomogram prediction model was constructed and validated using univariate and binary logistic regression. RESULTS: DECT parameters were higher in the CR group than in the PR group. The iodine concentration (IC), normalized IC, Mix-0.6, spectral Hounsfield unit curve slope, effective atomic number, and virtual monoenergetic images were significantly different between the groups. The area under the ROC curve of the DECT parameters was 0.73-0.77. Based on the binary logistic regression, a column chart was constructed using 10 predictive factors, including age, sex, N stage, maximum lymph node diameter, arterial phase NIC, venous phase NIC, λHU and spectral Hounsfield units at 70 keV. The area under the ROC curve value of the constructed model was 0.813, with a sensitivity and specificity of 85.6% and 81.3%, respectively. CONCLUSION: Quantitative DECT parameters could effectively predict the sensitivity of NPC to radiotherapy. Therefore, DECT parameters and NPC clinical features can be combined to construct a nomogram with high predictive power and used as a clinical analytical tool.
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Linfonodos , Carcinoma Nasofaríngeo , Neoplasias Nasofaríngeas , Tomografia Computadorizada por Raios X , Humanos , Masculino , Feminino , Pessoa de Meia-Idade , Carcinoma Nasofaríngeo/radioterapia , Carcinoma Nasofaríngeo/patologia , Carcinoma Nasofaríngeo/diagnóstico por imagem , Neoplasias Nasofaríngeas/radioterapia , Neoplasias Nasofaríngeas/diagnóstico por imagem , Neoplasias Nasofaríngeas/patologia , Tomografia Computadorizada por Raios X/métodos , Linfonodos/patologia , Linfonodos/diagnóstico por imagem , Linfonodos/efeitos da radiação , Adulto , Nomogramas , Idoso , Metástase Linfática , Pescoço/diagnóstico por imagem , Estudos Retrospectivos , Prognóstico , Curva ROC , Adulto Jovem , Imagem Radiográfica a Partir de Emissão de Duplo Fóton/métodosRESUMO
BACKGROUND AND PURPOSE: To investigate the effect of combining Endostar with concurrent chemoradiotherapy (ECCRT) compared to concurrent chemoradiotherapy (CCRT) on the regression rate of retropharyngeal lymph nodes (RLNs) and the relationship between regression rate of RLNs and prognosis of patients with locally advanced nasopharyngeal carcinoma (LANPC). METHODS: A total of 122 LANPC patients with RLNs metastasis were included. Metastatic RLNs were delineated both before and after treatment slice by slice on the magnetic resonance images cross-section. The regression rate of RLNs, adverse effects (AE) were evaluated. The median regression rate of RLNs was taken as the cut-off value, and the patients were furtherly divided into high regression rate (HRR) group and low regression rate (LRR) group, then survival times were evaluated. RESULTS: The median regression rates of RLNs in the ECCRT and CCRT groups were 81% and 50%, respectively (P < 0.001). There was no statistically significant difference in the incidence of grade 3/4 AEs between the two groups, except for oral mucositis (ECCRT 26.23% vs. CCRT 44.26%, P = 0.037). The 3-year overall survival (OS), progression-free survival (PFS), distant metastasis-free survival (DMFS) and locoregional failure-free survival (LRFFS) rates in the HRR and LRR groups were 85.48% and 86.67% (P = 0.983), 80.65% and 68.33% (P = 0.037), 83.87% and 85% (P = 0.704), 93.55% and 81.67% (P = 0.033), respectively. CONCLUSIONS: Patients in the ECCRT group had higher regression rates of RLNs and lower incidence of severe oral mucositis. Furthermore, patients in the HRR group had a better 3-year PFS and LRFFS rate than those in the LRR group.
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Quimiorradioterapia , Metástase Linfática , Carcinoma Nasofaríngeo , Neoplasias Nasofaríngeas , Proteínas Recombinantes , Humanos , Masculino , Quimiorradioterapia/efeitos adversos , Quimiorradioterapia/métodos , Feminino , Carcinoma Nasofaríngeo/patologia , Carcinoma Nasofaríngeo/terapia , Carcinoma Nasofaríngeo/mortalidade , Pessoa de Meia-Idade , Estudos Retrospectivos , Prognóstico , Adulto , Neoplasias Nasofaríngeas/patologia , Neoplasias Nasofaríngeas/terapia , Neoplasias Nasofaríngeas/mortalidade , Neoplasias Nasofaríngeas/tratamento farmacológico , Linfonodos/patologia , Linfonodos/diagnóstico por imagem , Endostatinas/administração & dosagem , Idoso , Adulto JovemRESUMO
The clinical significance of the combination of neutrophil-lymphocyte ratio (NLR) and platelet-lymphocyte ratio (PLR) is unclear. This study investigated the predictive value of pretreatment NLR (pre-NLR) combined with pretreatment PLR (pre-PLR) for the survival and prognosis of nasopharyngeal carcinoma (NPC). A total of 765 patients with non-metastatic NPC from two hospitals were retrospectively analyzed. The pre-NLR-PLR groups were as follows: HRG, high pre-NLR and high pre-PLR. MRG, high pre-NLR and low pre-PLR or low pre-NLR and high pre-PLR. LRG, neither high pre-NLR nor high pre-PLR. Receiver operating characteristic (ROC) curves were used to identify the cutoff-value and discriminant performance of the model. We compared survival rates and factors affecting the prognosis among different groups. The 5-year overall survival (OS), local regional recurrence-free survival (LRRFS) and distant metastasis-free survival (DMFS) of NPC patients in HRG were significantly poorer than those in MRG and LRG. The pre-NLR-PLR score was positively correlated with T stage, clinical stage, ECOG, and pathological classification. Multivariate cox regression analysis showed that pre-NLR-PLR scoring system, ECOG, pre-ALB, pre-CRP and pre-LMR were independent risk factors affecting 5-year OS, LRRFS and DMFS. The ROC curve showed that area under the curve (AUC) values of pre-NLR-PLR of 5-year OS, LRRFS and DMFS were higher than those of pre-NLR and pre-PLR. pre-NLR-PLR is an independent risk factor for the prognosis of NPC. The pre-NLR-PLR scoring system can be used as an individualized clinical assessment tool to predict the prognosis of patients with non-metastatic NPC more accurately and easily.
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Plaquetas , Linfócitos , Carcinoma Nasofaríngeo , Neoplasias Nasofaríngeas , Neutrófilos , Humanos , Masculino , Feminino , Neutrófilos/patologia , Estudos Retrospectivos , Pessoa de Meia-Idade , Prognóstico , Carcinoma Nasofaríngeo/mortalidade , Carcinoma Nasofaríngeo/sangue , Carcinoma Nasofaríngeo/patologia , Neoplasias Nasofaríngeas/patologia , Neoplasias Nasofaríngeas/mortalidade , Neoplasias Nasofaríngeas/sangue , Linfócitos/patologia , Plaquetas/patologia , Adulto , Idoso , Curva ROC , Contagem de Plaquetas , Contagem de Linfócitos , Carcinoma/sangue , Carcinoma/mortalidade , Carcinoma/patologia , Adulto JovemRESUMO
Patients with gastroesophageal reflux disease (GERD) are more likely to develop esophageal cancer (EC). However, a causal relationship between the 2 has been difficult to determine. Therefore, this study aimed to evaluate the impact of GERD on EC using the Mendelian randomization (MR) method. The causal association between GERD and EC was analyzed based on 2 publicly available genetic summary datasets for the GERD cohort (129,080 cases vs 473,524 controls) and the EC cohort (740 cases vs 372,016 controls). The causal inference was mainly evaluated by the inverse variance weighted MR. The MR-Egger regression, MR Pleiotropy Residual Sum and Outlier test, and leave-one-out test were used to confirm the sensitivity of the MR results. Possible interfering factors were excluded by multivariate MR (MVMR) analysis. We used 73 single nucleotide polymorphisms as instrumental variables. GERD was associated with increasing EC risk (odds ratio [OR], 1.001; 95% confidence interval, 1.001-1.002; Pâ <â .001), which was identified using the inverse variance weighted method. The sensitivity analysis also demonstrated similar results with the causal explanation, and major bias in genetic pleiotropy was not identified (intercept, 0.001; standard error, 0.001; Pâ =â .418). The multivariate MR analysis demonstrated the effect of GERD on EC even after excluding possible mediating factors (OR, 1.003; 95% confidence interval, 1.001-1.005; Pâ =â .012). This study confirmed that GERD has a causal effect on EC. Therefore, interventional measures are recommended to prevent EC.
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Neoplasias Esofágicas , Refluxo Gastroesofágico , Humanos , Causalidade , Neoplasias Esofágicas/genética , Refluxo Gastroesofágico/complicações , Refluxo Gastroesofágico/genética , Estudo de Associação Genômica Ampla , Análise da Randomização Mendeliana , NonoxinolRESUMO
Aflatoxin B1 (AFB1), a hepatotoxic and carcinogenic food contaminant, is commonly found in agricultural food. Herein, Au NPs anchored ZIF-8-derived porous carbon-ZnO (Au NPs/PCZIF-8-ZnO) was firstly synthesized to act as the sensing substrate. Then, a ratiometric electrochemical (EC) and "off-on" photoelectrochemical (PEC) dual-mode paper-based aptasensor was presented for AFB1 detection based on a distance-modulation sensing strategy. The independent signal transduction mechanisms and output mode not only broaden the dynamic detection range but also provide a self-verification to assay results, improving the sensitivity and reliability. The wide detection ranges of 0.1 pg/mL-100 ng/mL (EC mode) and 0.02 pg/mL-100 ng/mL (PEC mode) were obtained using dual-mode aptasensor, with detection limits of 36.7 and 9.3 fg/mL, respectively. The fabricated aptasensor exhibited excellent selectivity, reproducibility and stability. Furthermore, it exhibited good practicability for AFB1 assays in real samples, demonstrating great potential applications for food safety evaluation.
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Aptâmeros de Nucleotídeos , Técnicas Biossensoriais , Nanopartículas Metálicas , Óxido de Zinco , Aflatoxina B1/análise , Reprodutibilidade dos Testes , Técnicas Biossensoriais/métodos , Técnicas Eletroquímicas/métodos , Limite de Detecção , OuroRESUMO
PURPOSE: Analyzing the prognostic value of Epstein-Barr virus (EBV) DNA load and platelet-to-lymphocyte ratio (PLR) in non-metastatic nasopharyngeal carcinoma (NPC) patients, thereby developing a reliable and effective marker. METHODS: We compared survival rates among different groups using the Kaplan-Meier method and the Log-rank test. The factors affecting the prognosis of NPC patients were determined using univariate and multivariate cox regression analysis. Receiver operating characteristic (ROC) curves were used to identify the cutoff-value and discriminant performance of the model. RESULTS: The ROC curve indicated a cut-off value of 775 copies/ml for EBV DNA and 203.3 for PLR. Kaplan-Meier and Log-rank tests showed that 3-year overall survival (OS), local recurrence-free survival (LRFS) and distant metastasis-free survival (DMFS) of NPC patients in high risk group (HRG) were significantly poorer than those in medium risk group (MRG) and low risk group (LRG). The 3-year OS of NPC patients was significantly correlated with age, N stage and EBV DNA-PLR. The 3-year LRFS were significantly correlated with sex, N stage, histology type, and EBV DNA-PLR. The 3-year DMFS were correlated with histology type. The ROC curve showed that area under the curve (AUC) values of EBV DNA-PLR of 3-year OS, LRFS and DMFS in NPC were higher than those of PLR and EBV DNA. CONCLUSION: EBV DNA-PLR is an independent risk factor for the prognosis of NPC. Compared with PLR or EBV DNA alone, the combination of EBV DNA and PLR may be more accurate in predicting the prognosis of NPC patients.
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Infecções por Vírus Epstein-Barr , Neoplasias Nasofaríngeas , Humanos , Prognóstico , Carcinoma Nasofaríngeo/patologia , Herpesvirus Humano 4/genética , Estudos Retrospectivos , Neoplasias Nasofaríngeas/patologia , Estadiamento de Neoplasias , DNA Viral , Linfócitos/patologiaRESUMO
Objective: To establish and validate a nomogram to predict the overall survival (OS) and cancer-specific survival (CSS) in patients with nasopharyngeal carcinoma (NPC) receiving radiotherapy by integrating multiple independent prognostic factors. Materials and Methods: Data from 5663 patients with NPC who received definite radiotherapy between 2004 and 2018 were included and divided into training and validation cohorts. Univariate and multivariate Cox regression analyses were performed to determine the independent prognostic factors of patients with NPC after radiotherapy. Thereafter, the predictive accuracy of the nomogram model was evaluated. Results: Age, race, marital status, pathological type, tumor size, T stage, N stage, M stage, American Joint Committee on Cancer stage, and chemotherapy were independent factors affecting the prognosis of patients with NPC receiving radiotherapy. Nomograms with a concordance index of 0.726 (95% confidence interval (CI): 0.675-0.777) and 0.732 (95% CI: 0.680-0.785) were able to predict OS and CSS, respectively. The area under the curve showed excellent predictive performance. Additionally, the calibration curve indicated that the predicted survival rate was consistent with the actual survival rate, and the decision curve indicated its clinical value. The established risk stratification system was able to accurately stratify patients receiving radiotherapy for NPC into three risk subgroups with significant differences in prognosis (P < 0.05). Conclusions: The constructed nomogram had good prognostic performance and could be used as an effective tool to evaluate the prognosis of patients with NPC after radiotherapy. This nomogram could be further used to guide clinical decisions and personalized treatment plans.
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Neoplasias Nasofaríngeas , Nomogramas , Humanos , Carcinoma Nasofaríngeo/patologia , Estadiamento de Neoplasias , Prognóstico , Programa de SEER , Neoplasias Nasofaríngeas/patologiaRESUMO
To create genistein particles, a brand-new antisolvent recrystallization technique was employed. The response surface approach was utilized to optimize the single factor test findings, which were acquired via the preliminary tests. The ideal liquid-to-liquid ratio was 9, the solution concentration was 21 mg/mL, the nozzle diameter was 700 µm, the feed rate was 39.65 mL/min, and the homogenization rate was 1500 rpm. The smallest mean particle size measured was 202.782 nm. SEM was used to study the powder's morphology, while thermal analysis and infrared imaging were used to evaluate its characteristics. The homogeneous antisolvent recrystallization method-prepared GMP has a better dissolving rate and stronger antioxidant activity when compared to genistein powder. The antisolvent recrystallization approach used in this study, which uses low-speed homogenizing instead of conventional grinding and homogenizing, can successfully reduce particle size, improve bioavailability, and use less energy. This topic may thus be made popular because it has real-world applications.
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Antioxidantes , Genisteína , Solventes/química , Pós , Tamanho da Partícula , SolubilidadeRESUMO
BACKGROUND: In recent years, pegylated liposomal doxorubicin (PLD) has been widely used to improve the survival of patients with ovarian cancer; however, it is unclear whether the combinational use of PLD with other drugs is more effective. Therefore, this meta-analysis aimed to confirm the efficacy and safety of trabectedin, combined with PLD, in the treatment of recurrent ovarian cancer. METHODS: Data corresponding to all eligible clinical trials as of May 15, 2022, was retrieved using several electronic retrieval databases including PubMed, Medical Literature Analysis and Retrieval System Online (MEDLINE), ClinicalTrials.gov, Excerpta Medica Database (EMBASE) and Cochrane Library clinical controlled trials (CENTRAL). Comprehensive hazard ratios (HRs), risk ratios (RRs), and 95% confidence intervals (CIs) were calculated using the Review Manager software 5.4 (RevMan 5.4). RESULTS: From two phase III randomized controlled trials, 1248 patients with recurrent ovarian cancer were included in this meta-analysis. Results of meta-analysis revealed that trabectedin, combined with PLD chemotherapy, significantly improved overall survival (OS) in patients with BReast CAncer gene (BRCA)-associated recurrence (HR, 0.49; 95% CI, [0.33-0.73]; P = 0.0004) and platinum-sensitive recurrence whose platinum-free interval (PFI) was 6-12 months (HR, 0.66; 95% CI, [0.52-0.84]; P = 0.0005). In addition, compared with PLD alone, combination therapy significantly improved the progression-free survival (PFS) in patients with recurrent ovarian cancer (HR, 0.86; 95% CI, [0.74-0.99]; P = 0.03). Combination therapy also significantly improved PFS in patients with BRCA-associated recurrence (HR, 0.58; 95% CI, [0.40-0.58]; P = 0.004), and platinum-sensitive recurrence (HR, 0.73; 95% CI, [0.56-0.95]; P = 0.02). Trabectedin combined with PLD was more prone to grade 3-4 toxic side effects than PLD alone (P < 0.05); however, fatal adverse events related to non-toxic side effects occurred. CONCLUSION: Trabectedin combined with PLD significantly improves OS and PFS in patients with BRCA-associated and platinum-sensitive recurrent ovarian cancers. The potential use of trabectedin combined with PLD should be selected according to the PFI and BRCA mutation status of patients.
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BACKGROUND: To retrospectively analyze the efficacy and safety of concurrent chemoradiotherapy (CCRT) plus recombinant human endostatin (Endostar, CCRT + E) versus CCRT alone in locally advanced nasopharyngeal carcinoma (LANPC). METHODS: A retrospective analysis of patients initially treated for LANPC from November 2016 to March 2019 was performed: trial group received CCRT + E and control group received CCRT. Prognoses and adverse effects were evaluated. RESULTS: Eighty-eight patients were included: 43 received CCRT + E and 45 received CCRT. The median follow-up time was 54.0 (range: 8.0-64.0) months. The survival data of the CCRT + E and CCRT groups were as follows: 3-year progression-free survival (PFS) rates, 81.4% and 63.6% (hazard ratio [HR] 0.418, 95%CI 0.181-0.963, P = 0.034); 3-year distant metastasis-free survival (DMFS) rates, 88.3% and 77.3% (HR 0.370, 95%CI 0.132-1.039, P = 0.049); 3-year overall survival rates, 88.2% and 81.9% (HR 0.437, 95%CI 0.151-1.260, P = 0.114); and 3-year locoregional failure-free survival rates, 87.8% and 86.9% (HR 0.795, 95%CI 0.242-2.616, P = 0.705). Three months after radiotherapy, the complete response (CR) rates of cervical lymph node regression were 97.7% and 82.2% for the CCRT + E and CCRT groups (P = 0.041). The corresponding CR rates were 100% and 80.0% for lymph node necrosis (P = 0.001) and 100% and 85.2% for extranodal extension (P = 0.041). The CCRT + E group had higher incidence of grade 3/4 leukopenia (32.6% vs. 13.3%, P = 0.031), with similar results for late toxicity. CONCLUSIONS: CCRT + E significantly prolonged 3-year PFS and DMFS in LANPC, and patients had better lymph node regression.
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Carcinoma , Neoplasias Nasofaríngeas , Protocolos de Quimioterapia Combinada Antineoplásica , Carcinoma/terapia , Quimiorradioterapia/métodos , Cisplatino , Endostatinas/uso terapêutico , Humanos , Carcinoma Nasofaríngeo/patologia , Carcinoma Nasofaríngeo/terapia , Neoplasias Nasofaríngeas/patologia , Proteínas Recombinantes , Estudos RetrospectivosRESUMO
By replacing one Al or N atom of aluminum nitride nanocage Al12N12 with an alkaline-earth metal atom, two series of compounds, namely, M@Al12N11 and M@Al11N12 (M = Be, Mg, and Ca), were constructed and investigated in theory. The substituted effect of alkaline-earth metal on the geometric structure and electronic properties of Al12N12 is studied in detail by density functional theory (DFT) methods. The calculated binding energies, HOMO-LUMO gaps, and VIE values of these compounds reveal that they possess high stability, though the NBO and HOMO analyses show that they are also excess electron compounds. Due to the existence of diffuse excess electrons, these alkaline-earth metal-substituted compounds exhibit larger first hyperpolarizabilities (ß 0) than pure Al12N12 nanocage. In particular, these considered compounds exhibit satisfactory infrared (IR) (>1800 nm) and ultraviolet (UV) (Ë 250 nm) transparency. Therefore, these proposed excess electron compounds with high stability may be regarded as potential candidates for new UV and IR NLO molecules.
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Objective: Nasopharyngeal carcinoma is particularly prevalent in Guangdong and Guangxi (southern China); the economic burden of nasopharyngeal cancer patients is heavy in China. This study is aimed at retrospectively analyzing the basic features and economic burden of newly diagnosed nasopharyngeal carcinoma patients admitted to the First Affiliated Hospital of Guangxi Medical University and at providing a scientific basis for nasopharyngeal carcinoma prevention and control strategies. Methods: The data of 3,727 nasopharyngeal carcinoma inpatients diagnosed from January 2012 to December 2020 were extracted from the Guangxi Nasopharyngeal Carcinoma Healthcare Big Data Management Information Platform. Basic demographic characteristics, duration of hospital stay, and hospitalization cost of nasopharyngeal carcinoma patients were collected and analyzed statistically. Results: The incidence period of nasopharyngeal carcinoma was primarily from 30 to 69 years of age, with the 40-49-year age group comprising the largest proportion of nasopharyngeal carcinoma patients, accounting for 34.18% of the patients with newly diagnosed nasopharyngeal carcinoma in the hospital. The male-to-female ratio was 2.87 : 1. There were 2,223 cases from rural areas, 2,153 from the Han ethnic group, and 1,460 from the Zhuang ethnic group, accounting for 59.65%, 55.77%, and 39.17% of the total number of cases, respectively. The average duration of hospitalization decreased whereas the average hospitalization cost increased annually. Multivariate analysis of hospitalization cost showed that the duration of hospital stay, rural/urban, and ethnicity was the main influencing factors: the longer the duration of hospital stay, the higher the hospitalization cost; patients from rural incurred lower costs than from urban; ethnic Zhuang patients incurred significantly lower costs than patients from other ethnicities. Conclusion: Early diagnosis and treatment should be actively carried out to reduce the incidence of nasopharyngeal carcinoma, especially for rural, ethnic Zhuang, and males in the 40-49-year age group patients. The future research on nasopharyngeal carcinoma will focus on exploring the pathogenesis of nasopharyngeal carcinoma, improving the screening system, and reducing the burden on patients, in order to further improve the survival rate and quality of life of patients with nasopharyngeal carcinoma.
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Pacientes Internados , Neoplasias Nasofaríngeas , China/epidemiologia , Etnicidade , Feminino , Estresse Financeiro , Hospitalização , Humanos , Masculino , Carcinoma Nasofaríngeo/epidemiologia , Neoplasias Nasofaríngeas/epidemiologia , Qualidade de Vida , Estudos RetrospectivosRESUMO
BACKGROUND: Cisplatin-based concurrent chemoradiotherapy has been identified as the primary and standard treatment for locally advanced nasopharyngeal carcinoma (NPC). However, the side effects of cisplatin affect the compliance to therapy. Thus, the search for a platinum-based substitute for NPC has always been a research focus. However, there is a variability in the efficacy of different platinum-based chemotherapies in the treatment of NPC. We performed a meta-analysis to compare the efficacy and safety of cisplatin-based regimens and other platinum-based derivatives (carboplatin, nedaplatin, and lobaplatin) for locally advanced NPC. METHODS: PubMed, EMBASE, Cochrane Library, Web of Science, and ClinicalTrials.gov were systematically searched for all potentially eligible clinical trials as of February 15, 2022. The pooled hazard ratios, risk ratio, and 95% confidence interval were calculated using Review Manager Software version 5.4. RESULTS: A total of 1,907 patients with locally advanced NPC were eligible from the 1,265 retrieved records. This systematic review included eight articles, six of which were randomized controlled clinical trials. There was no significant difference in the 3- and 5-year overall survival, progression-free survival, distant metastasis-free survival, and locoregional relapse-free survival between cisplatin-based chemotherapy and other platinum-based chemotherapy. Severe acute hematological side effects (≥ grade 3) during treatment, such as neutropenia, leukopenia, and thrombocytopenia, were equivalent in both groups. However, the incidence of anemia was higher in patients receiving other platinum-based chemotherapies. The risk of nausea, vomiting and weight loss was higher in the cisplatin group; however, there was no significant difference in the other non-hematological and late side effects between the two groups. CONCLUSIONS: Other types of platinum-based chemotherapies are as effective as cisplatin-based chemotherapy in the treatment of locally advanced NPC, thus acting as potential alternatives to cisplatin. Further studies providing high-level evidence are needed.
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Leucopenia , Neoplasias Nasofaríngeas , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Quimiorradioterapia , Cisplatino/efeitos adversos , Humanos , Quimioterapia de Indução , Leucopenia/induzido quimicamente , Carcinoma Nasofaríngeo/patologia , Neoplasias Nasofaríngeas/patologia , Recidiva Local de Neoplasia/tratamento farmacológico , Platina/uso terapêuticoRESUMO
The thinnest beryllium nanowires with high strength and uniformity are theoretically constructed of connected Be6 octahedron units. Based on this, Ca- and Mg-doped beryllium nanowires are successfully constructed and researched. They are unusual all-metal charge transfer salts Ca2+(Be6)n4-Mg2+ (n = 1-7), and they surprisingly display considerable second-order nonlinear optical (NLO) responses (ß0e = 1.05 × 104-1.12 × 105 au). This is because the effect of doping Ca and Mg atoms brings great increase in ß0e. In addition, more notably, the effect of the nanowire length on ß0e revealed that the ß0e value gradually and rapidly increases with the increase in the number of Be6 octahedron units (n). Thus, these doped beryllium nanowires are a new class of NLO nanowires. Fortunately, these NLO nanowires possess working wavebands in the infrared (IR, >2800 nm) and ultraviolet (UV, <200 nm) regions. Then, these doped beryllium NLO nanowires could also be used as new hot IR and UV NLO materials. Considering the dispersion effect, the frequency-dependent value of the electro-optical Pockels effect (EOPE) ße(-ω; ω, 0) at ω = 0.005 au is slightly larger than the corresponding value of ß0e. Significantly, the effect of the nanowire length on ße(-ω; ω, 0) is also displayed. Obviously, a new design strategy of enhancing NLO responses by increasing n was obtained. Noticeably, the nanowires display Janus electronic properties of both stronger electron-donating and electron-withdrawing behaviors. This work predicts that novel metal nanowires may be applied in new hot IR and UV NLO materials as well as molecular electronic devices.
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BACKGROUND: During infection by intracellular pathogens, a highly complex interplay occurs between the infected cell trying to degrade the invader and the pathogen which actively manipulates the host cell to enable survival and proliferation. Many intracellular pathogens pose important threats to human health and major efforts have been undertaken to better understand the host-pathogen interactions that eventually determine the outcome of the infection. Over the last decades, the unicellular eukaryote Dictyostelium discoideum has become an established infection model, serving as a surrogate macrophage that can be infected with a wide range of intracellular pathogens. In this study, we use high-throughput RNA-sequencing to analyze the transcriptional response of D. discoideum when infected with Mycobacterium marinum and Legionella pneumophila. The results were compared to available data from human macrophages. RESULTS: The majority of the transcriptional regulation triggered by the two pathogens was found to be unique for each bacterial challenge. Hallmark transcriptional signatures were identified for each infection, e.g. induction of endosomal sorting complexes required for transport (ESCRT) and autophagy genes in response to M. marinum and inhibition of genes associated with the translation machinery and energy metabolism in response to L. pneumophila. However, a common response to the pathogenic bacteria was also identified, which was not induced by non-pathogenic food bacteria. Finally, comparison with available data sets of regulation in human monocyte derived macrophages shows that the elicited response in D. discoideum is in many aspects similar to what has been observed in human immune cells in response to Mycobacterium tuberculosis and L. pneumophila. CONCLUSIONS: Our study presents high-throughput characterization of D. discoideum transcriptional response to intracellular pathogens using RNA-seq. We demonstrate that the transcriptional response is in essence distinct to each pathogen and that in many cases, the corresponding regulation is recapitulated in human macrophages after infection by mycobacteria and L. pneumophila. This indicates that host-pathogen interactions are evolutionary conserved, derived from the early interactions between free-living phagocytic cells and bacteria. Taken together, our results strengthen the use of D. discoideum as a general infection model.
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Infecções Bacterianas/microbiologia , Dictyostelium/microbiologia , Modelos Biológicos , Proteínas de Protozoários/genética , Células Cultivadas , Citoplasma/microbiologia , Perfilação da Expressão Gênica , Regulação da Expressão Gênica , Interações Hospedeiro-Patógeno/genética , Humanos , Legionella pneumophila/fisiologia , Macrófagos/microbiologia , Mycobacterium marinum/fisiologia , Proteínas de Protozoários/metabolismo , Especificidade da Espécie , Transcrição GênicaRESUMO
The interaction between the aluminum trimer and representative (super)halogens X (X = F, LiF2, BeF3, BF4) and (super)alkalis M (M = Li, FLi2, OLi3, NLi4) has been theoretically investigated at the MP2/6-311+(3df) level. Various geometrical structures were obtained for the resulting Al3-X and Al3-M superatom compounds, respectively. Natural bond orbital analysis reveals that the Al3 moiety exists in a cationic state in Al3-X while in an anionic state in Al3-M compounds. And the charge transfer between Al3 and (super)atoms is found to be enhanced in either polar or nonpolar solvent. The studied superatom compounds feature large bond energies, binding energies, and HOMO-LUMO gaps, which not only reflect their stability but indicate strong interactions between Al3 and (super)atoms. Although the solvent effect is not significant for the stability of Al3-X, the Al3-superalkali compounds can be better stabilized in the presence of solvent molecules. In addition, these superatom compounds exhibit aromaticity both in the gas phase and in solution.
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Glycolytic interconversion of phosphoglycerate isomers is catalysed in numerous pathogenic microorganisms by a cofactor-independent mutase (iPGM) structurally distinct from the mammalian cofactor-dependent (dPGM) isozyme. The iPGM active site dynamically assembles through substrate-triggered movement of phosphatase and transferase domains creating a solvent inaccessible cavity. Here we identify alternate ligand binding regions using nematode iPGM to select and enrich lariat-like ligands from an mRNA-display macrocyclic peptide library containing >1012 members. Functional analysis of the ligands, named ipglycermides, demonstrates sub-nanomolar inhibition of iPGM with complete selectivity over dPGM. The crystal structure of an iPGM macrocyclic peptide complex illuminated an allosteric, locked-open inhibition mechanism placing the cyclic peptide at the bi-domain interface. This binding mode aligns the pendant lariat cysteine thiolate for coordination with the iPGM transition metal ion cluster. The extended charged, hydrophilic binding surface interaction rationalizes the persistent challenges these enzymes have presented to small-molecule screening efforts highlighting the important roles of macrocyclic peptides in expanding chemical diversity for ligand discovery.
Assuntos
Bactérias/enzimologia , Inibidores Enzimáticos/farmacologia , Compostos Macrocíclicos/farmacologia , Peptídeos/farmacologia , Fosfoglicerato Mutase/antagonistas & inibidores , Sequência de Aminoácidos , Animais , Biocatálise/efeitos dos fármacos , Caenorhabditis elegans/enzimologia , Coenzimas/metabolismo , Cristalografia por Raios X , Cisteína/metabolismo , Compostos Macrocíclicos/química , Modelos Moleculares , Peptídeos/síntese química , Peptídeos/química , Fosfoglicerato Mutase/química , Fosfoglicerato Mutase/metabolismo , Filogenia , Conformação Proteica , Relação Estrutura-Atividade , Compostos de Sulfidrila/metabolismoRESUMO
Myristoylation is a lipid modification involving the addition of a 14-carbon unsaturated fatty acid, myristic acid, to the N-terminal glycine of a subset of proteins, a modification that promotes their binding to cell membranes for varied biological functions. The process is catalyzed by myristoyl-CoA:protein N-myristoyltransferase (NMT), an enzyme which has been validated as a drug target in human cancers, and for infectious diseases caused by fungi, viruses and protozoan parasites. We purified Caenorhabditis elegans and Brugia malayi NMTs as active recombinant proteins and carried out kinetic analyses with their essential fatty acid donor, myristoyl-CoA and peptide substrates. Biochemical and structural analyses both revealed that the nematode enzymes are canonical NMTs, sharing a high degree of conservation with protozoan NMT enzymes. Inhibitory compounds that target NMT in protozoan species inhibited the nematode NMTs with IC50 values of 2.5-10 nM, and were active against B. malayi microfilariae and adult worms at 12.5 µM and 50 µM respectively, and C. elegans (25 µM) in culture. RNA interference and gene deletion in C. elegans further showed that NMT is essential for nematode viability. The effects observed are likely due to disruption of the function of several downstream target proteins. Potential substrates of NMT in B. malayi are predicted using bioinformatic analysis. Our genetic and chemical studies highlight the importance of myristoylation in the synthesis of functional proteins in nematodes and have shown for the first time that NMT is required for viability in parasitic nematodes. These results suggest that targeting NMT could be a valid approach for the development of chemotherapeutic agents against nematode diseases including filariasis.
Assuntos
Aciltransferases/química , Brugia Malayi/enzimologia , Caenorhabditis elegans/enzimologia , Aciltransferases/antagonistas & inibidores , Aciltransferases/isolamento & purificação , Animais , Biologia Computacional , Sistemas de Liberação de Medicamentos , Terapia de Alvo MolecularRESUMO
How to generate a non-zero first hyperpolarizability for a centrosymmetric molecule is a challenging question. In this paper, an external (pump) electric field is used to make a centrosymmetric benzene molecule generate a non-zero value of the electric field induced first hyperpolarizability (ß (F) ). This comes from the centrosymmetry breaking of electron cloud. Two interesting rules are exhibited. (1) ß (F) is anisotropic for different directional fields (F i, i = X, Y, Z). (2) The field dependence of ß (F) is a non-monotonic function, and an optimum external electric field causes the maximum value of ß (F) . The largest first hyperpolarizability ß (F) reaches the considerable level of 3.9 × 10(5) a.u. under F Y = 330 × 10(-4) a.u. for benzene. The external electric field effects on non-centrosymmetric edge-modified graphene ribbon H2N-(3,3)ZGNR-NO2 was also studied in this work. The first hyperpolarizability reaches as much as 2.1 × 10(7) a.u. under F X = 600 × 10(-4) a.u. for H2N-(3,3)ZGNR-NO2. We show that the external electric field can not only create a non-zero first hyperpolarizability for centrosymmetric molecule, but also remarkably enhance the first hyperpolarizability for a non-centrosymmetric molecule.
RESUMO
The lowest-energy structures of the Al(n)Be (n = 1-13) clusters are obtained and compared with the corresponding Al(n+1) and Al(n+1)(+) (n = 2-13) as well as Al(n)Mg clusters at the B3LYP/aug-cc-pVDZ level. The configurations of Al(n)Be show strong resemblances to those of pure Al(n+1) clusters, and the first three-dimensional ground state in the Al(n)Be clusters occurs for Al(3)Be. Various properties of the Al(n)Be clusters are systematically investigated using the CCSD(T) method and their thermodynamic properties are also compared with those of corresponding Al(n+1)(+) clusters. The evolution of the energetic and electronic properties with the size of the clusters shows the unique stability of the 20-valence electron systems Al(6)Be and Al(7)(+), which can be understood from the spherical jellium model (SJM). However, different from Al(7)(+) with 1s(2)1p(6)1d(10)2s(2) shell occupation, the electronic-shell structure of 1s(2)1p(6)1d(6)2s(2)1d(4) for the Al(6)Be cluster demonstrates that the impurity atom makes the molecular orbital distribution of doped clusters much more complex than that of pure metal clusters.