Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 112
Filtrar
1.
Front Pharmacol ; 12: 627935, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34512316

RESUMO

Background: Despite the development of such multiple therapeutic approaches, approximately 20% patients experience recurrence. Identification of molecular markers for stratifying the different risks of tumour recurrence and progression is considered imperative. Methods: We used a RayBio Human Cytokine Antibody Array that simultaneously detected the levels of 297 proteins and profiled the conditioned medium of HONE1 cells and the radioresistant NPC cells HONE1-IR. We found Angiogenin(ANG) expression to be significantly increased in HONE1-IR and HONE1-IR cells exposed to 4-Gy X-ray radiation. Results: We investigated the expression of ANG in NPC tissues and explored its prognostic significance in patients with NPC. We found that ANG expression was increased in recurrent NPC tissues. Elevated expression of ANG induced radio-resistance in NPC cells, in addition to being significantly associated with shorter PFS, OS, and LRFS in patients with NPC. Multivariate analysis results revealed that ANG was an independent prognostic factor that predicted PFS, OS, and LRFS. Furthermore, a nomogram model was generated to predict OS in terms of ANG expression. Conclusion: Our results found the radioresistant function of ANG and proved the clinical prognostic significance of ANG, and the results could help predict radio-sensitivity and stratify high-risk patients or tumour recurrence.

2.
Radiother Oncol ; 163: 185-191, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34453953

RESUMO

BACKGROUND: Unsatisfactory tumor response to induction chemotherapy (IC) is an adverse prognostic factor of locoregionally advanced nasopharyngeal carcinoma (LANPC). A re-induction strategy which applies additional cycles of an alternative IC regimen prior to radiotherapy (RT) has been adopted. METHODS: A total of 419 LANPC patients who attained suboptimal response (stable disease or disease progression) according to the Response Evaluation in Solid Tumors (RECIST) guideline after initial IC were retrospectively included. They were divided into those who received additional cycles of re-induction regimen prior to RT (re-induction group, n = 87) and those who had no additional chemotherapy (direct to RT group, n = 332). Propensity score matching (PSM) was used to adjust for potential confounders. Tumor response and long-term survival were compared between two groups. RESULTS: After receiving a second IC regimen, 39.1% of the patients in re-induction group attained partial response; however, the tumor control of subsequent RT was not significantly improved when compared with direct to RT group (patients attaining complete response after RT 55.2% vs. 52.5%, P = 0.757). Patients who received re-induction therapy showed worse locoregional relapse-free survival (LRFS) and progression-free survival (PFS) than those proceeded directly to RT (3-year LRFS 75.7% vs. 83.1%, P = 0.005; 3-year PFS 62.4% vs. 68.3%, P = 0.037). The increased hematological toxicities were observed in re-induction group that included grade 3-4 anemia, thrombocytopenia and liver enzyme increase. CONCLUSION: Re-induction therapy decreased LRFS and PFS and increased toxicities among patients who attain suboptimal response to initial IC regimen, as compared with direct to RT strategy.

3.
Mol Cell Biochem ; 476(11): 4153-4159, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34313895

RESUMO

ATG4D, a member of autophagy-related protein 4 (ATG4) family, plays an interplay role between autophagy and apoptosis in cancers. However, the role of ATG4D in hepatocellular carcinoma (HCC) has not been defined. Herein, this study aimed to investigate the role and the underlying mechanism of ATG4D in regulating HCC cell apoptosis. ATG4D was silenced in MHCC-97L HCC cells, and then cell proliferation and apoptosis were examined. ATG4D expression was significantly upregulated in HCC tissues when compared with paired non-tumor tissues. In vitro assays revealed that silencing of ATG4D significantly suppressed cell proliferation, promoted cell apoptosis, and enhanced sensitivity to cisplatin of MHCC-97L cells. Furthermore, silencing of ATG4D decreased the phosphorylation of Akt and increased the protein level of caspase-3. Taken together, ATG4D may play an oncogenic role in HCC progression. These findings suggest that ATG4D may serve as a therapeutic target for HCC therapy.

4.
Ann Transl Med ; 9(7): 532, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33987230

RESUMO

Background: Nutritional status is a key factor influencing the prognosis of patients with cancer. The Geriatric Nutritional Risk Index (GNRI) has been used to predict mortality risk and long-term outcomes. In this study, we aimed to evaluate the predictive value of pretreatment GNRI in patients with nasopharyngeal carcinoma (NPC). Methods: A total of 1,065 patients with biopsy-proven non-disseminated nasopharyngeal carcinoma were included. Based on a cutoff value of pretreatment GNRI, patients were divided into two groups (low ≤107.7 and high >107.7). Combining GNRI and baseline Epstein-Barr virus (EBV) DNA, all patients were further stratified into three risk groups, namely, high-risk (high EBV DNA and low GNRI), low-risk (low EBV DNA and high GNRI), and medium-risk (except the above) groups. Multivariate analyses were performed using the Cox proportional hazards model to assess the predictive value of the GNRI. Results: Among the 1,065 patients, 527 (49.5%) and 538 (50.5%) were divided into low and high GNRI groups, respectively. Within a median follow-up of 83 months, patients with a high GNRI score exhibited significantly higher overall survival (OS), progression-free survival (PFS), and distant metastasis-free survival (DMFS) compared to those with low GNRI scores (P<0.05). Multivariate analyses revealed that high GNRI is an independent prognostic factor for OS and PFS (hazard ratio, HR, 0.471, 95% CI, 0.270-0.822, P=0.008; HR 0.638, 95% CI, 0.433-0.941, P=0.023, respectively). Using a combination of baseline GNRI and EBV DNA, a satisfying separation of survival curves between different risk groups for OS, PFS, DMFS was observed. The survival rates of patients in the high-risk group were significantly lower than those in the low- and medium-risk groups (all P<0.001). The combined classification was demonstrated to be an independent prognostic factor for OS and PFS after adjustment using multivariate analysis. Conclusions: Pretreatment GNRI is an independent prognostic factor for NPC patients. The combination of baseline GNRI score and EBV DNA level improved the prognostic stratification of NPC patients.

5.
Radiother Oncol ; 160: 9-17, 2021 07.
Artigo em Inglês | MEDLINE | ID: mdl-33839205

RESUMO

PURPOSE: Curative radiotherapy for nasopharyngeal carcinoma (NPC) can lead to acquired nasal cavity stenosis and atresia (ANCSA). As the first study to investigate risk factors of ANCSA in a large cohort of NPC patients, this article aims to develop and validate a multivariate normal tissue complication probability (NTCP) model to predict the development of ANCSA and to establish a nomogram for clinical use. METHODS AND MATERIALS: The retrospective cohort was comprised of 548 NPC patients treated with radical radiotherapy. The cohort was randomly divided into training and validation groups. Least absolute shrinkage and selection operator regression was performed for variable selection from the clinical and dosimetric characteristics in the training group. A multivariate NTCP model and a nomogram were established for the prediction of ANCSA development. Discrimination and calibration were tested using receiver operating characteristic (ROC) curves and calibration tests, respectively, for both groups. RESULTS: ANCSA was observed in 132 (24.1%) of 548 patients with NPC who underwent radical radiotherapy. The median time to ANCSA detection after treatment was 2.8 months (range, 0.0-57.7 months). Five potential predictors, including choanal invasion, low white blood cell count, high C-reactive protein level, high serum amyloid A level, and high V70Gy of the nasal cavity, were selected to develop the NTCP model based on 365 patients in the training group. The model had a fairly good discriminative power according to the ROC analysis in both the training (area under ROC curve = 0.79, 95%CI: 0.73-0.84) and validation (0.73, 0.64-0.82) groups. The calibration power was tested using the calibration test in the training (E-max = 0.069, E-avg = 0.015, p = 0.977) and validation (E-max = 0.057, E-avg = 0.032, p = 0.747) groups. CONCLUSIONS: We developed and successfully validated an NTCP model for early prediction of ANCSA in patients with NPC after radical radiotherapy. This could help clinicians assess the risk of ANCSA before the initiation of follow-ups and ensure appropriate and timely management of this complication.


Assuntos
Cavidade Nasal , Neoplasias Nasofaríngeas , Constrição Patológica , Humanos , Carcinoma Nasofaríngeo/radioterapia , Neoplasias Nasofaríngeas/radioterapia , Nomogramas , Estudos Retrospectivos , Fatores de Risco
6.
Dalton Trans ; 50(17): 5770-5775, 2021 May 07.
Artigo em Inglês | MEDLINE | ID: mdl-33876147

RESUMO

Herein, we have demonstrated synergistic zinc doping and defect engineering toward MoS2 nanosheet arrays assembled on carbon cloth (CC) by a one-pot hydrothermal approach for the first time, which are employed directly as a cathode for the hydrogen evolution reaction (HER). In our strategy, simultaneously doping sufficient Zn atoms and introducing a defect-rich structure into a MoS2 nanosheet can synergistically increase active sites. Additionally, the assembly of such nanosheets on CC can achieve lower charge-transfer resistance for the highly efficient HER.

7.
Radiother Oncol ; 162: 202-211, 2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-33839207

RESUMO

PURPOSE: This study aimed to establish an effective prognostic nomogram to predict the risk of early metastasis (EM) in nasopharyngeal carcinoma (NPC) patients, as a guide for intensive treatment. MATERIALS AND METHODS: A total of 9021 patients with biopsy-confirmed NPC at our institute were enrolled in this study between December 2006 to December 2016. We randomized these patients using a proportion of 2/3 and 1/3 and selected 6044 and 2977 patients as the training and validation cohorts, respectively. All patients received radiotherapy with or without chemotherapy. Univariate and multivariate logistical regressions were used to identify independent risk factors. The nomogram's predictive value was evaluated by concordance indexes (C-indexes), calibration curves, probability density functions (PDFs), and clinical utility curves (CUCs). ROC analysis using Delong test was used to compare efficiency between the nomogram and other risk factors. RESULTS: In total, 174 (2.9%) and 81 (2.7%) patients in training and validation cohorts, respectively, had EM. Pretreatment plasma EBV DNA, N stage, LDH, ALP, BMI, and sex were independent predictive factors of EM. The C-indexes of nomogram were 0.756 (95% CI = 0.719-0.793) and 0.766 (95% CI = 0.720-0.813), in the training and validation cohorts, respectively. The C-index of the nomogram was significantly superior to any one of independent factors. According to the PDFs and CUCs and considering the balance of the true positive EM patients and true positive non-EM patients, we chose 5.0% as a threshold probability for clinical decision-making, which could distinguish about 85% and 48% of non-EM and EM patients, respectively. CONCLUSION: Our nomogram had good accuracy in predicting EM incidence, and a 5.0% threshold was appropriate for clinical decision-making.


Assuntos
Neoplasias Nasofaríngeas , Nomogramas , Humanos , Carcinoma Nasofaríngeo/patologia , Carcinoma Nasofaríngeo/radioterapia , Neoplasias Nasofaríngeas/patologia , Neoplasias Nasofaríngeas/radioterapia , Estadiamento de Neoplasias , Prognóstico
8.
Laryngoscope ; 131(8): 1798-1804, 2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-33616259

RESUMO

OBJECTIVES/HYPOTHESIS: The routine practices of examining submucosal lesions are not suitable for deep lesions. Therefore, we evaluated the efficacy of non-real-time image-guided transnasal endoscopic fine-needle aspiration biopsy (FNAB) in diagnosing nasopharyngeal carcinoma (NPC) with submucosal lesions. STUDY DESIGN: The effectiveness evaluation of diagnostic methods. METHODS: Fifty suspected NPC patients who failed in conventional biopsies were enrolled in this study. The efficacy, maneuverability, and safety of FNAB in diagnosing these intractable cases were evaluated. RESULTS: The definitive diagnostic results of these 50 patients were NPC (34/50, 68.0%), nasopharyngeal necrosis (1/50, 2.0%), nasopharyngeal mucositis (12/50, 24.0%), and other cancers (3/50, 6.0%), respectively. The results of the diagnostic efficacy of FNAB were sensitivity, 89.2%; specificity, 100.0%; positive predictive value, 100.0%; negative predictive value, 76.5%; and accuracy, 92.0%, respectively. The area under the receiver operating characteristic curves was 0.946 (95% confidence interval = 0.884-1.00, P < .001). No severe complications occurred after FNAB. CONCLUSIONS: FNAB can improve the diagnostic efficiency of NPC occurring in the submucosal space. It can be an additional option for routine nasopharyngeal biopsy and is worthy of clinical application. LEVEL OF EVIDENCE: 4 Laryngoscope, 131:1798-1804, 2021.


Assuntos
Biópsia por Agulha Fina/métodos , Endoscopia/métodos , Biópsia Guiada por Imagem/métodos , Carcinoma Nasofaríngeo/diagnóstico , Neoplasias Nasofaríngeas/diagnóstico , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Mucosa Nasal/patologia , Mucosa Nasal/cirurgia , Nasofaringe/patologia , Nasofaringe/cirurgia , Valor Preditivo dos Testes , Curva ROC , Adulto Jovem
9.
Eur J Nucl Med Mol Imaging ; 48(8): 2586-2598, 2021 07.
Artigo em Inglês | MEDLINE | ID: mdl-33420610

RESUMO

PURPOSE: This study aimed to establish an effective nomogram to predict primary distant metastasis (DM) in patients with nasopharyngeal carcinoma (NPC) to guide the application of PET/CT. METHODS: In total, 3591 patients with pathologically confirmed NPC were consecutively enrolled. The nomogram was constructed based on 1922 patients treated between 2007 and 2014. Multivariate logistical regression was applied to identify the independent risk factors of DM. The predictive value of the nomogram was evaluated using the concordance index (C-index), calibration curve, probability density functions (PDFs), and clinical utility curve (CUC). The results were validated in 1669 patients enrolled from 2015 to 2016. Net reclassification improvement (NRI) was applied to compare performances of the nomogram with other clinical factors. The best cut-off value of the nomogram chosen for clinical application was analyzed. RESULTS: A total of 355 patients showed primary DM among 3591 patients, yielding an incidence rate of 9.9%. Sex, N stage, EBV DNA level, lactate dehydrogenase level, and hemoglobin level were independent predictive factors for primary DM. C-indices in the training and validation cohort were 0.796 (95% CI, 0.76-0.83) and 0.779 (95% CI, 0.74-0.81), respectively. The NRI indices demonstrated that this model had better predictive performance than plasma EBV DNA level and N stage. We advocate for a threshold probability of 3.5% for guiding the application of PET/CT depending on the clinical utility analyses. CONCLUSION: This nomogram is a useful tool to predict primary DM of NPC and guide the clinical application of PET/CT individually at the initial staging.


Assuntos
Neoplasias Nasofaríngeas , Nomogramas , Fluordesoxiglucose F18 , Humanos , Carcinoma Nasofaríngeo/diagnóstico por imagem , Neoplasias Nasofaríngeas/diagnóstico por imagem , Estadiamento de Neoplasias , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Prognóstico
10.
Luminescence ; 36(4): 894-903, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-33440065

RESUMO

Graphene quantum dots (GQDs) could be regarded as graphene with a lateral dimension less than 100 nm. Compared with graphene, GQDs not only possess the excellent properties of graphene but also have been proven to have low toxicity, high fluorescence stability, strong water solubility, as well as better biocompatibility. In this work, an amide bond-based, N-doped graphene quantum dot was synthesized using a simple hydrothermal method. When the reaction time was 4 h and the temperature was 180°C, fluorescence excitation and emission peaks of the product were 340 nm and 450 nm, respectively. Its interaction with human serum albumin (HSA) was investigated using spectroscopy, gel electrophoresis, and molecular simulation. Gel electrophoresis showed that the product did not cause complete scission of the peptide chain in HSA, indicating good biocompatibility. The results of molecular docking showed that the product tended to bind to site III of HSA. This paper provides a meaningful reference for design and development in nanomedicine.


Assuntos
Grafite , Pontos Quânticos , Glicina , Humanos , Simulação de Acoplamento Molecular , Nitrogênio , Albumina Sérica Humana
11.
World J Gastroenterol ; 27(1): 80-91, 2021 Jan 07.
Artigo em Inglês | MEDLINE | ID: mdl-33505152

RESUMO

BACKGROUND: Hepatic steatosis commonly occurs in some chronic liver diseases and may affect disease progression. AIM: To investigate the performance of controlled attenuation parameter (CAP) for the diagnosis of hepatic steatosis in patients with autoimmune liver diseases (AILDs). METHODS: Patients who were suspected of having AILDs and underwent liver biopsy were consistently enrolled. Liver stiffness measurement (LSM) and CAP were performed by transient elastography. The area under the receiver operating characteristic (AUROC) curve was used to evaluate the performance of CAP for diagnosing hepatic steatosis compared with biopsy. RESULTS: Among 190 patients with biopsy-proven hepatic steatosis, 69 were diagnosed with autoimmune hepatitis (AIH), 18 with primary biliary cholangitis (PBC), and 27 with AIH-PBC overlap syndrome. The AUROCs of CAP for the diagnosis of steatosis in AILDS were 0.878 (0.791-0.965) for S1, 0.764 (0.676-0.853) for S2, and 0.821 (0.716-0.926) for S3. The CAP value was significantly related to hepatic steatosis grade (P < 0.001). Among 69 patients with AIH, the median CAP score was 205.63 ± 47.36 dB/m for S0, 258.41 ± 42.83 dB/m for S1, 293.00 ± 37.18 dB/m for S2, and 313.60 ± 27.89 dB/m for S3. Compared with patients with nonalcoholic fatty liver disease (NAFLD) presenting with autoimmune markers, patients with AIH concomitant with NAFLD were much older and had higher serum IgG levels and LSM values. CONCLUSION: CAP can be used as a noninvasive diagnostic method to evaluate hepatic steatosis in patients with AILDs. Determination of LSM combined with CAP may help to identify patients with AIH concomitant with NAFLD from those with NAFLD with autoimmune phenomena.


Assuntos
Técnicas de Imagem por Elasticidade , Hepatopatia Gordurosa não Alcoólica , Área Sob a Curva , Biópsia , Humanos , Fígado/diagnóstico por imagem , Hepatopatia Gordurosa não Alcoólica/complicações , Hepatopatia Gordurosa não Alcoólica/diagnóstico por imagem , Curva ROC
12.
Eur Radiol ; 31(7): 5222-5233, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-33416977

RESUMO

OBJECTIVES: The value of using PET/CT for staging of stage I-II NPC remains unclear. Hence, we aimed to investigate the survival benefit of PET/CT for staging of early-stage NPC before radical therapy. METHODS: A total of 1003 patients with pathologically confirmed NPC of stages I-II were consecutively enrolled. Among them, 218 patients underwent both PET/CT and conventional workup ([CWU], head-and-neck MRI, chest radiograph, liver ultrasound, bone scintigraphy) before treatment. The remaining 785 patients only underwent CWU. The standard of truth (SOT) for lymph node metastasis was defined by the change of size according to follow-up MRI. The diagnostic efficacies were compared in 218 patients who underwent both PET/CT and CWU. After covariate adjustment using propensity scoring, a cohort of 872 patients (218 with and 654 without pre-treatment PET/CT) was included. The primary outcome was overall survival based on intention to treat. RESULTS: Retropharyngeal lymph nodes were metastatic based on follow-up MRI in 79 cases. PET/CT was significantly less sensitive than MRI in detecting retropharyngeal lymph node lesions (72.2% [62.3-82.1] vs. 91.1% [84.8-97.4], p = 0.004). Neck lymph nodes were metastatic in 89 cases and PET/CT was more sensitive than MRI (96.6% [92.8-100.0] vs. 76.4% [67.6-85.2], p < 0.001). In the survival analyses, there was no association between pre-treatment PET/CT use and improved overall survival, progression-free survival, local relapse-free survival, regional relapse-free survival, and distant metastasis-free survival. CONCLUSIONS: This study showed PET/CT is of little value for staging of stage I-II NPC patients at initial imaging. KEY POINTS: • PET/CT was more sensitive than MRI in detecting neck lymph node lesions whereas it was significantly less sensitive than MRI in detecting retropharyngeal lymph node lesions. • No association existed between pre-treatment PET/CT use and improved survival in stage I-II NPC patients.


Assuntos
Neoplasias Nasofaríngeas , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Estudos de Casos e Controles , Fluordesoxiglucose F18 , Humanos , Linfonodos/patologia , Carcinoma Nasofaríngeo/diagnóstico por imagem , Neoplasias Nasofaríngeas/diagnóstico por imagem , Neoplasias Nasofaríngeas/patologia , Recidiva Local de Neoplasia , Estadiamento de Neoplasias , Tomografia por Emissão de Pósitrons , Compostos Radiofarmacêuticos , Tomografia Computadorizada por Raios X
13.
J Physiol Biochem ; 77(1): 35-45, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-33188625

RESUMO

Development of liver fibrosis is associated with activation of quiescent hepatic stellate cells (HSCs) into myofibroblasts (activated HSCs), which produce excessive extracellular matrix. Peroxisome proliferator-activated receptor-gamma (PPAR-γ) exerts protective effects on hepatic inflammation and fibrosis. The current study was to explore the function of PPAR-γ on HSC activation and progression of nonalcoholic steatohepatitis (NASH). Our study found that HSCs were gradually activated during the progression of methionine-choline-deficient (MCD) diet-induced NASH, accompanied by decreased PPAR-γ expression and activated TGF-ß1/Smad signaling pathway in the liver. PPAR-γ agonist was found to inhibit primary HSCs and NIH/3T3 fibroblast activation and reverted their phenotypical morphology induced by TGF-ß1 in vitro. In addition to this, PPAR-γ agonist decreased expression of TGF-ß1 and phosphorylation of Smad2/3 while increased expression of Smad7. In vivo, rosiglitazone, a PPAR-γ agonist, inhibited HSC activation and alleviated liver fibrosis and inflammation similarly via inhibiting the activation of TGF-ß1/Smad signaling pathway. In parallel, rosiglitazone alleviated hepatic lipid accumulation and peroxidation, beneficial to reverse of NASH. From these findings, it can be concluded that the gradual activation of HSCs is crucial to the progression of NASH and modulating PPAR-γ expression can affect HSC activation via TGF-ß1/Smad signaling pathway and thereby influence hepatic fibrogenesis.


Assuntos
Cirrose Hepática/metabolismo , Hepatopatia Gordurosa não Alcoólica/metabolismo , PPAR gama/fisiologia , Fator de Crescimento Transformador beta1/metabolismo , Animais , Células Estreladas do Fígado , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Células NIH 3T3 , Transdução de Sinais , Proteína Smad2/metabolismo , Proteína Smad3/metabolismo
14.
J Am Chem Soc ; 143(2): 964-972, 2021 01 20.
Artigo em Inglês | MEDLINE | ID: mdl-33373207

RESUMO

2,4,5,6-Tetrakis(3,6-di-tert-butyl-9H-carbazol-9-yl)isophthalonitrile (4CzIPN-tBu) was developed as a photocatalyst for the phosphorus-radical-initiated cascade cyclization reaction of isocyanides. By using 4CzIPN-tBu as catalyst, we developed a visible-light-induced proton-coupled electron transfer strategy for the generation of phosphorus-centered radicals, via which a wide range of phosphorylated phenanthridines, quinolines, and benzothiazoles were successfully constructed.


Assuntos
Compostos Heterocíclicos/síntese química , Hidrocarbonetos Aromáticos/síntese química , Prótons , Catálise , Transporte de Elétrons , Compostos Heterocíclicos/química , Hidrocarbonetos Aromáticos/química , Estrutura Molecular , Fosforilação
15.
J Org Chem ; 85(22): 14744-14752, 2020 11 20.
Artigo em Inglês | MEDLINE | ID: mdl-33136392

RESUMO

A metal-free and base-free procedure for the phosphorylation of imidazo[1,2-a]pyridines with phosphine oxides under the irradiation of visible light at room temperature in green solvent was reported, featuring mild and sustainable conditions, convenient operation, as well as good functional group compatibility.

16.
Ther Adv Med Oncol ; 12: 1758835920928214, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32536983

RESUMO

Background: This study aimed to investigate the efficiency and toxicities of concurrent chemoradiotherapy (CCRT) and induction chemotherapy (IC) followed by radiotherapy (RT) in different risk locoregionally advanced nasopharyngeal carcinoma (NPC). Methods: A total of 1814 eligible patients with stage II-IVB disease treated with CCRT or IC plus RT were included. The overall survival (OS), progression-free survival (PFS) and distant metastasis-free survival (DMFS) were calculated using the Kaplan-Meier method, and the differences were compared using the log-rank test. Results: Nomograms were developed to predict OS, PFS and DMFS (C-index: 0.71, 0.70 and 0.71, respectively). Patients were then divided into three different risk groups based on the scores calculated by the nomogram for OS. In the low and intermediate-risk group, no significant survival differences were observed between patients treated with IC plus RT alone and CCRT (5-year OS, 97.3% versus 95.6%, p = 0.642 and 87.6% versus 89.7%, p = 0.381, respectively; PFS, 95.9% versus 95.6%, p = 0.325 and 87.6% versus 89.0%, p = 0.160, respectively; DMFS, 97.2% versus 94.8%, p = 0.339 and 87.2% versus 89.3%, p = 0.628, respectively). However, in the high-risk group, IC plus RT displayed an unfavorable 5-year OS (71.0% versus 77.2%, p = 0.022) and PFS (69.4.0% versus 75.4%, p = 0.019) compared with CCRT. A significantly higher incidence of grade 3 and 4 adverse events was documented in patients treated with CCRT than in those treated with IC plus RT in all risk groups (p = 0.040). Conclusion: IC followed by RT represents an alternative treatment strategy to CCRT for patients with low and intermediate-risk NPC, but it is not recommended for patients with high-risk NPC.

17.
J Immunother Cancer ; 8(1)2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-32303611

RESUMO

BACKGROUND: The tumor immune microenvironment has clinicopathological significance in predicting prognosis and therapeutic efficacy. We aimed to develop an immune signature to predict distant metastasis in patients with nasopharyngeal carcinoma (NPC). METHODS: Using multiplexed quantitative fluorescence, we detected 17 immune biomarkers in a primary screening cohort of 54 NPC tissues presenting with/without distant metastasis following radical therapy. The LASSO (least absolute shrinkage and selection operator) logistic regression model used statistically significant survival markers in the training cohort (n=194) to build an immune signature. The prognostic and predictive accuracy of it was validated in an external independent group of 304 patients. RESULTS: Eight statistically significant markers were identified in the screening cohort. The immune signature consisting of four immune markers (PD-L1+ CD163+, CXCR5, CD117) in intratumor was adopted to classify patients into high and low risk in the training cohort and it showed a high level of reproducibility between different batches of samples (r=0.988 for intratumor; p<0.0001). High-risk patients had shorter distant metastasis-free survival (HR 5.608, 95% CI 2.619 to 12.006; p<0.0001) and progression-free survival (HR 2.798, 95% CI 1.498 to 5.266; p=0·001). The C-indexes which reflected the predictive capacity in training and validation cohort were 0.703 and 0.636, respectively. Low-risk patients benefited from induction chemotherapy plus concurrent chemoradiotherapy (IC+CCRT) (HR 0.355, 95% CI 0.147 to 0.857; p=0·021), while high-risk patients did not (HR 1.329, 95% CI 0.543 to 3.253; p=0·533). To predict the individual risk of distant metastasis, nomograms with the integration of both immune signature and clinicopathological risk factors were developed. CONCLUSIONS: The immune signature provided a reliable estimate of distant metastasis risk in patients with NPC and might be applied to identify the cohort which benefit from IC+CCRT.


Assuntos
Carcinoma Nasofaríngeo/imunologia , Adolescente , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Metástase Neoplásica , Reprodutibilidade dos Testes , Microambiente Tumoral , Adulto Jovem
18.
Front Oncol ; 10: 378, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32266152

RESUMO

Objective: To compare the survival outcomes brought by different radiation dose schedules to bone lesions and different chemotherapy regimens in bone metastatic nasopharyngeal carcinoma (NPC). Background: The current treatment strategy for bone metastatic NPC patients was empirically given and poorly studied before. It is of necessity to optimize the treatment for bone metastasis to enhance the therapeutic effect and increase the proportion of long-term survived patients. Methods: Three hundred patients who received chemoradiotherapy from 2002 to 2018 were involved in the study. Demographics, laboratory results, and detailed treatment plans were recorded. Radiotherapy plans were classified into three categories based on the intensity, and the survival analysis was performed using log-rank test. Multivariable analysis was made by the Cox proportional regression model. Results: Patients who received 60-75 Gy/30-35 fractions of radiation to the metastatic bones had significantly longer bone relapse-free survival (BRFS) (HR, 0.53, 95% CI, 0.37-0.78, P = 0.003), overall survival (OS) (HR, 0.63, 95% CI, 0.46-0.84, P = 0.007), and progression-free survival (PFS) (HR, 0.80, 95% CI, 0.67-0.95, P = 0.041). The administration of paclitaxel, cisplatin and 5-fluorouracil regimen was also associated with better BRFS (HR, 0.27, 95% CI, 0.10-0.75, P = 0.007), PFS (HR, 0.60, 95% CI, 0.42-0.87, P = 0.007), and OS with borderline significance (HR, 0.54, 95% CI, 0.29-1.03, P = 0.058). In multivariable analysis, the post-treatment EBV DNA level and radical radiation dose were proved as independent prognostic factors for both BRFS and OS. Conclusions: Radiotherapy to metastatic bones with palliative dose prescription should not be considered in bone metastatic NPC patients. TPF chemotherapy regimen might help to improve the survivals in NPC patients but failed to be an independent protective factor.

19.
J Gastroenterol Hepatol ; 35(11): 1998-2008, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-32128893

RESUMO

BACKGROUND AND AIM: Chronic inflammation links closely to insulin resistance and lipid metabolism in nonalcoholic fatty liver disease (NAFLD). Macrophage M1 activation plays an important role in the initiation and continuing of pro-inflammatory response of NAFLD. Our study was to investigate whether macrophage M1/M2 polarization switching would affect hepatic inflammation and lipid metabolism through modulation of peroxisome proliferator-activated receptor-gamma (PPAR-γ) activity in vivo and in vitro. METHODS: RAW264.7 macrophages were treated with different fatty acids, and cell culture supernatants were collected to prepare conditioned media (CM). Different co-culture systems between primary hepatocytes and CM from macrophages were established. A PPAR-γ agonist or antagonist was administered to regulate PPAR-γ activity and macrophage polarization. M1/M2 phenotype markers, inflammatory signaling pathway, and lipid-related genes expression were determined. Wild-type C57BL/6 mice were fed a high-fat diet to induce NAFLD and given rosiglitazone to regulate PPAR-γ activity in vivo. RESULTS: Saturated fatty acids induced M1-polarized macrophages while polyunsaturated fatty acids induced M2-polarized macrophages. M1-polarized macrophages significantly promoted lipid synthesis and accumulation in primary hepatocytes through upregulation of a toll-like receptor 4 (TLR4)/NF-κB signaling pathway. The PPAR-γ agonist made lipid-induced M1-polarized macrophages switch to an M2-predominant phenotype, while PPAR-γ antagonist had the opposite effect. Macrophage polarization shifting subsequently affected lipid metabolism in primary hepatocytes. Administration of rosiglitazone improved high-fat diet induced hepatic steatosis and lipid metabolism through reducing hepatic TLR4/NF-κB expression and M1-polarized Kupffer cells. CONCLUSIONS: Lipid-induced macrophage M1 polarization promoted hepatic lipid metabolism. Modulation of PPAR-γ activity could shift macrophage polarization and subsequently affect lipid metabolism. Upregulation of the TLR4/NF-κB signaling pathway is closely linked to dysregulated lipid metabolism in NAFLD.


Assuntos
Metabolismo dos Lipídeos/genética , Fígado/metabolismo , Macrófagos/fisiologia , NF-kappa B/metabolismo , Hepatopatia Gordurosa não Alcoólica/metabolismo , PPAR gama/metabolismo , Transdução de Sinais/fisiologia , Receptor 4 Toll-Like/metabolismo , Animais , Polaridade Celular , Dieta Hiperlipídica/efeitos adversos , Hepatócitos/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , Hepatopatia Gordurosa não Alcoólica/etiologia , Células RAW 264.7 , Regulação para Cima
20.
Cancer Commun (Lond) ; 40(1): 32-42, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-32112522

RESUMO

BACKGROUND: Capecitabine was previously used as a second-line or salvage therapy for metastatic nasopharyngeal carcinoma (NPC) and has shown satisfactory curative effect as maintenance therapy in other metastatic cancers. This study aimed to explore the role of capecitabine as maintenance therapy in de novo metastatic NPC patients with different plasma Epstein-Barr virus (EBV) DNA levels before treatment. METHODS: We selected de novo metastatic NPC patients treated with locoregional radiotherapy (LRRT) for this retrospective study. The propensity score matching (PSM) was applied to balance potential confounders between patients who underwent capecitabine maintenance therapy and those who did not with a ratio of 1:3. Overall survival (OS) was the primary endpoint. The association between capecitabine maintenance therapy and survival was assessed using the log-rank test and a Cox proportional hazard model. RESULTS: Among all patients eligible for this study, 64 received capecitabine maintenance therapy after LRRT. After PSM, 192 patients were identified in the non-maintenance group. In the matched cohort, patients treated with capecitabine achieved a higher 3-year OS rate compared with patients in the non-maintenance group (68.5% vs. 61.8%, P = 0.037). Multivariate analysis demonstrated that capecitabine maintenance therapy was an independent prognostic factor. In subgroup analysis, 3-year OS rate was comparable between the maintenance and non-maintenance groups in patients with high pretreatment EBV DNA levels (˃30,000 copies/mL) (54.8% vs. 45.8%, P = 0.835), whereas patients with low pretreatment EBV DNA levels (≤30,000 copies/mL) could benefit from capecitabine maintenance therapy in OS (90.0% vs. 68.1%, P = 0.003). CONCLUSION: Capecitabine maintenance therapy may be superior to non-maintenance therapy in prolonging OS for de novo metastatic NPC patients with pretreatment EBV DNA ≤ 30,000 copies/mL.


Assuntos
Antimetabólitos Antineoplásicos/administração & dosagem , Capecitabina/administração & dosagem , Infecções por Vírus Epstein-Barr/virologia , Carcinoma Nasofaríngeo/tratamento farmacológico , Carcinoma Nasofaríngeo/virologia , Neoplasias Nasofaríngeas/tratamento farmacológico , Neoplasias Nasofaríngeas/virologia , Adolescente , Adulto , Idoso , Infecções por Vírus Epstein-Barr/tratamento farmacológico , Infecções por Vírus Epstein-Barr/patologia , Feminino , Herpesvirus Humano 4/genética , Herpesvirus Humano 4/isolamento & purificação , Humanos , Masculino , Pessoa de Meia-Idade , Carcinoma Nasofaríngeo/patologia , Neoplasias Nasofaríngeas/patologia , Metástase Neoplásica , Estadiamento de Neoplasias , Pontuação de Propensão , Estudos Retrospectivos , Taxa de Sobrevida , Adulto Jovem
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...