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1.
JAMA Oncol ; 2022 Mar 24.
Artigo em Inglês | MEDLINE | ID: mdl-35323856

RESUMO

Importance: Induction chemotherapy added to concurrent chemoradiotherapy significantly improves survival for patients with locoregionally advanced nasopharyngeal carcinoma, but the optimal induction regimen remains unclear. Objective: To determine whether induction chemotherapy with paclitaxel, cisplatin, and capecitabine (TPC) improves survival vs cisplatin and fluorouracil (PF) prior to chemoradiotherapy for patients with stage IVA to IVB nasopharyngeal carcinoma. Design, Setting, and Participants: This randomized, open-label, phase 3 clinical trial recruited 238 patients at 4 hospitals in China from October 20, 2016, to August 29, 2019. Patients were 18 to 65 years of age with treatment-naive, nonkeratinizing stage IVA to IVB nasopharyngeal carcinoma and an Eastern Cooperative Oncology Group performance status of 0 to 1. Interventions: Patients were randomly assigned (1:1) to receive induction chemotherapy with two 21-day cycles of TPC (intravenous paclitaxel [150 mg/m2, day 1], intravenous cisplatin [60 mg/m2, day 1], and oral capecitabine [1000 mg/m2 orally twice daily, days 1-14]) or PF (intravenous cisplatin [100 mg/m2, day 1] and fluorouracil [800 mg/m2 daily, days 1-5]), followed by chemoradiotherapy. Main Outcomes and Measures: The primary end point was failure-free survival in the intention-to-treat population. Secondary end points included distant metastasis-free survival, locoregional relapse-free survival, overall survival, tumor response, and safety. Results: Overall, 238 eligible patients (187 men [78.6%]; median age, 45 years [range, 18-65 years]) were randomly assigned to receive TPC (n = 118) or PF (n = 120). The median follow-up duration was 48.4 months (IQR, 39.6-53.3 months). Failure-free survival at 3 years was 83.5% (95% CI, 77.0%-90.6%) in the TPC group and 68.9% (95% CI, 61.1%-77.8%) in the PF group (stratified hazard ratio [HR] for recurrence or death, 0.47; 95% CI, 0.28-0.79; P = .004). Induction with the TPC regimen resulted in a significant reduction in the risk of distant metastases (stratified HR, 0.49 [95% CI, 0.24-0.98]; P = .04) and locoregional recurrence (stratified HR, 0.40 [95% CI, 0.18-0.93]; P = .03) compared with the PF regimen. However, there was no effect on early overall survival (stratified HR, 0.45 [95% CI, 0.17-1.18]; P = .10). The incidences of grade 3 to 4 acute adverse events and late-onset toxicities were 57.6% (n = 68) and 13.6% (16 of 118), respectively, in the TPC group and 65.8% (n = 79) and 17.9% (21 of 117), respectively, in the PF group. One treatment-related death occurred in the PF group. Conclusions and Relevance: This randomized clinical trial found that induction chemotherapy with 2 cycles of TPC for patients with stage IVA to IVB nasopharyngeal carcinoma improved failure-free survival compared with 2 cycles of PF, with no increase in the toxicity profile. Trial Registration: ClinicalTrials.gov Identifier: NCT02940925.

2.
PeerJ ; 10: e12919, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35251779

RESUMO

Avians have evolved many different modes of flying as well as various types of feathers for adapting to varied environments. However, the protein content and ratio of protein secondary structures (PSSs) in mature flight feathers are less understood. Further research is needed to understand the proportions of PSSs in feather shafts adapted to various flight modes in different avian species. Flight feathers were analyzed in chicken, mallard, sacred ibis, crested goshawk, collared scops owl, budgie, and zebra finch to investigate the PSSs that have evolved in the feather cortex and medulla by using nondestructive attenuated total reflection Fourier transform infrared spectroscopy (ATR-FTIR). In addition, synchrotron radiation-based, Fourier transform infrared microspectroscopy (SR-FTIRM) was utilized to measure and analyze cross-sections of the feather shafts of seven bird species at a high lateral resolution to resolve the composition of proteins distributed within the sampled area of interest. In this study, significant amounts of α-keratin and collagen components were observed in flight feather shafts, suggesting that these proteins play significant roles in the mechanical strength of flight feathers. This investigation increases our understanding of adaptations to flight by elucidating the structural and mechanistic basis of the feather composition.

3.
Small ; 18(5): e2104401, 2022 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-34825486

RESUMO

2D van der Waals (vdW) semiconductors hold great potentials for more-than-Moore field-effect transistors (FETs), and the efficient utilization of their theoretical performance requires compatible high-k dielectrics to guarantee the high gate coupling efficiency. The deposition of traditional high-k dielectric oxide films on 2D materials usually generates interface concerns, thereby causing the carrier scattering and degeneration of device performance. Here, utilizing a space-confined epitaxy growth approach, the authors successfully obtained air-stable ultrathin indium phosphorus sulfide (In2 P3 S9 ) nanosheets, the thickness of which can be scaled down to monolayer limit (≈0.69 nm) due to its layered structure. 2D In2 P3 S9 exhibits excellent insulating properties, with a high dielectric constant (≈24) and large breakdown voltage (≈8.1 MV cm-1 ) at room temperature. Serving as gate insulator, ultrathin In2 P3 S9 nanosheet can be integrated into MoS2 FETs with high-quality dielectric/semiconductor interface, thus providing a competitive electrical performance of device with subthreshold swings (SS) down to 88 mV dec-1 and a high ON/OFF ratio of 105 . This study proves an important strategy to prepare 2D vdW high-k dielectrics, and greatly facilitates the ongoing research of 2D materials for functional electronics.

4.
Otolaryngol Head Neck Surg ; 166(3): 490-497, 2022 03.
Artigo em Inglês | MEDLINE | ID: mdl-34182810

RESUMO

OBJECTIVE: Salvage endoscopic nasopharyngectomy (ENPG) is a reasonable choice for resectable recurrent nasopharyngeal carcinoma (rNPC). However, in past decades, complete removal of the tumor was not feasible when the recurrent lesion was adjacent to the internal carotid artery (ICA). The present article introduces innovative strategies to ensure sufficient surgical margins while avoiding accidental injury to the ICA. STUDY DESIGN: Retrospective study. SETTING: Tertiary care center. METHODS: We retrospectively reviewed rT2-3 rNPC patients with tumor lesions adjacent to the ICA (<5 mm) who underwent ENPG at the Sun Yat-sen University Cancer Center between January 2015 and June 2020. Thirty-seven patients were selected for this study. Seventeen patients underwent ENPG using direct dissection, 10 patients underwent endoscopic-assisted transcervical protection of the parapharyngeal ICA combined with ENPG, and 10 patients underwent ICA embolization followed by ENPG. RESULTS: With a median follow-up duration of 31 months (range, 5 to 53 months), the 2-year overall survival, progression-free survival, locoregional recurrence-free survival, and distant metastasis-free survival rates of salvage ENPG for rNPC adjacent to the ICA were 88.7%, 72.0%, 72.0%, and 97.3%, respectively. The incidences of grade 1-2 and grade 3-5 postoperative complications were 16.2% and 13.5%, respectively. Two patients experienced ICA rupture during direct dissection but were out of danger after vascular embolization therapy. One patient had a positive margin. Two patients had severe nasopharyngeal wound infections with mucosal flap necrosis. CONCLUSION: ENPG combined with ICA pretreatment allows the feasible and effective resection of rNPC lesions adjacent to the ICA.


Assuntos
Artéria Carótida Interna , Neoplasias Nasofaríngeas , Artéria Carótida Interna/patologia , Artéria Carótida Interna/cirurgia , Doença Crônica , Humanos , Carcinoma Nasofaríngeo/patologia , Neoplasias Nasofaríngeas/patologia , Recidiva Local de Neoplasia/patologia , Estudos Retrospectivos
5.
Clin Transl Radiat Oncol ; 32: 59-68, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-34935776

RESUMO

PURPOSE: Chemotherapy, when added to radiotherapy, improves survival in locally advanced nasopharyngeal carcinoma (NPC). This article presents the second update of the Meta-Analysis of Chemotherapy in NPC. METHODS: Published or unpublished randomized trials assessing radiotherapy (±a second chemotherapy timing) with/without chemotherapy in non-metastatic NPC patients were identified. Updated data were sought for studies included in the previous rounds of the meta-analysis. The primary endpoint was overall survival. All trials were analyzed following the intent-to-treat principle using a fixed-effects model. Treatments were classified in five subsets according to chemotherapy timing. The statistical analysis plan was pre-specified. RESULTS: Eighteen new trials were identified. Individual patient data were available for seven. In total, the meta-analysis now included 26 trials and 7,080 patients. The addition of chemotherapy reduced the risk of death, with a hazard ratio (HR) of 0.79 (95% confidence interval (CI) [0.73; 0.85]), and an absolute survival increase at 5 and 10 years of 6.1% [+3.9; +8.3] and + 8.4% [+5.7; +11.1], respectively. The largest effect was observed for concomitant + adjuvant, induction (with concomitant in both arms) and concomitant chemotherapy, with respective HR [95%CI] of 0.68 [0.59; 0.79] (absolute survival increase at 5 years: 12.3% (7.0%;17.6%)), 0.73 [0.63; 0.86] (6.0% (2.5%;9.5%)) and 0.81 [0.70; 0.92] (5.2% (0.8%;9.6%)). The benefit of chemotherapy was also demonstrated by improvement in progression-free survival, cancer mortality, locoregional control and distant control. There was a significant interaction between patient age and chemotherapy effect. CONCLUSION: This updated meta-analysis confirms the benefit of concomitant chemotherapy and concomitant + adjuvant chemotherapy, and suggests that addition of induction or adjuvant chemotherapy to concomitant chemotherapy improves tumor control and survival. The benefit of chemotherapy decreases with increasing patient age.

6.
Sci Rep ; 11(1): 18773, 2021 09 21.
Artigo em Inglês | MEDLINE | ID: mdl-34548502

RESUMO

Extensive loss of natural wetlands caused by changes in land use largely diminishes the food resources essential for the survival of migratory waterbirds. Globally, the decline in waterbird populations in East Asia is the most serious, with 64% of these populations showing a decreasing trend. In this study, we applied DNA metabarcoding to examine the spatiotemporal variations and diversities in the dietary compositions of migratory waterbirds in a natural/artificial wetland complex in Asia. By investigating 110 fecal samples from the endangered black-faced spoonbill (Platalea minor) wintering in the wetland, our results show that P. minor had a broad dietary spectrum. The birds fed on at least 26 species in the classes Actinopterygii and Malacostraca, with Mugiliformes, Cichliformes, and Gobiiformes being the main taxa in their diets. Our results also demonstrated clear patterns of the spatiotemporal variations between the roosting groups and intraspecific variations between the individuals, which potentially reflect some of their feeding habits, and the probable usage of different habitat types in the wetland complex. Using high-throughput sequencing, we were able to elucidate the food resources that are critical to P. minor non-invasively, this method can also be used to provide invaluable information for the conservation of many other waterbird species.


Assuntos
Aves/genética , Aves/fisiologia , Código de Barras de DNA Taxonômico , Dieta , Espécies em Perigo de Extinção , Animais , Fezes/química , Ensaios de Triagem em Larga Escala , Áreas Alagadas
7.
J Phys Condens Matter ; 33(49)2021 Sep 23.
Artigo em Inglês | MEDLINE | ID: mdl-34479213

RESUMO

Two-dimensional (2D) materials have attracted broad interests and been extensively exploited for a variety of functional applications. Moreover, one-dimensional (1D) atomic crystals can also be integrated into 2D templates to create mixed-dimensional heterostructures, and the versatility of combinations provides 2D-1D heterostructures plenty of intriguing physical properties, making them promising candidate to construct novel electronic and optoelectronic nanodevices. In this review, we first briefly present an introduction of relevant fabrication methods and structural configurations for 2D-1D heterostructures integration. We then discuss the emerged intriguing physics, including high optical absorption, efficient carrier separation, fast charge transfer and plasmon-exciton interconversion. Their potential applications such as electronic/optoelectronic devices, photonic devices, spintronic devices and gas sensors, are also discussed. Finally, we provide a brief perspective for the future opportunities and challenges in this emerging field.

8.
Oral Oncol ; 121: 105494, 2021 10.
Artigo em Inglês | MEDLINE | ID: mdl-34425533

RESUMO

BACKGROUND: Our previous trial confirmed that induction chemotherapy (IC) improved long-term survival outcomes in patients with locoregionally advanced nasopharyngeal carcinoma (NPC). In this study, we investigated the impact of IC on long-term quality of life (QoL) in this cohort. METHODS: Our trial was a randomised, open-label phase 3 trial comparing IC followed by concurrent chemoradiotherapy (CCRT) versus CCRT alone in patients with stage III-IVB (except T3N0-1) NPC. All participants completed two self-administered questionnaires, the European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire C30 (QLQ-C30) and the EORTC QLQ Head and Neck Cancer-Specific Module (H&N35). As per protocol, the questionnaires had to be completed before knowledge of treatment allocation by the patient (baseline). Patients were then approached to enroll at the time of the present study period. RESULTS: Ultimately, QoL data from 228 patients were included in the analysis. Most scales were both statistically and clinically decreased in both groups between baseline and the latest follow-up. The IC followed by CCRT group had significantly better outcome in role functioning, cognitive functioning, social functioning, fatigue, pain, and constipation in QLQ-C30 scales at the last follow-up. Similarly, in H&N35 scales, a significantly better result was observed in pain, sexuality, sticky saliva, pain killers use, nutritional supplements, and weight loss, but a poorer result in senses problems, for those treated by IC followed by CCRT. CONCLUSION: IC followed by CCRT seemed to have better long-term QoL outcomes compared with CCRT alone in patients with locoregionally advanced NPC.


Assuntos
Carcinoma Nasofaríngeo , Neoplasias Nasofaríngeas , Qualidade de Vida , Protocolos de Quimioterapia Combinada Antineoplásica , Quimiorradioterapia , Humanos , Quimioterapia de Indução , Carcinoma Nasofaríngeo/tratamento farmacológico , Carcinoma Nasofaríngeo/radioterapia , Neoplasias Nasofaríngeas/tratamento farmacológico , Neoplasias Nasofaríngeas/radioterapia , Dor
9.
BMC Cancer ; 21(1): 934, 2021 Aug 19.
Artigo em Inglês | MEDLINE | ID: mdl-34412621

RESUMO

The human microbiome is defined as the microorganisms that reside in or on the human body, such as bacteria, viruses, fungi, and protozoa, and their genomes. The human microbiome participates in the modulation of human metabolism by influencing several intricate pathways. The association between specific bacteria or viruses and the efficacy of cancer treatments and the occurrence of treatment-related toxicity in cancer patients has been reported. However, the understanding of the interaction between the host microbiome and the cancer treatment response is limited, and the microbiome potentially plays a greater role in the treatment of cancer than reported to date. Here, we provide a thorough review of the potential role of the gut and locally resident bacterial microbiota in modulating responses to different cancer therapeutics to demonstrate the association between the gut or locally resident bacterial microbiota and cancer therapy. Probable mechanisms, such as metabolism, the immune response and the translocation of microbiome constituents, are discussed to promote future research into the association between the microbiome and other types of cancer. We conclude that the interaction between the host immune system and the microbiome may be the basis of the role of the microbiome in cancer therapies. Future research on the association between host immunity and the microbiome may improve the efficacy of several cancer treatments and provide insights into the cause of treatment-related side effects.


Assuntos
Bactérias/imunologia , Microbioma Gastrointestinal , Sistema Imunitário/imunologia , Imunoterapia/métodos , Neoplasias/terapia , Probióticos/uso terapêutico , Animais , Humanos , Neoplasias/imunologia , Neoplasias/microbiologia
10.
Clin Cancer Res ; 27(15): 4186-4194, 2021 08 01.
Artigo em Inglês | MEDLINE | ID: mdl-34083231

RESUMO

PURPOSE: Previous studies suggest that a cumulative cisplatin dose of 200 mg/m2 might be adequate in the intensity-modulated radiation therapy (IMRT) era for locoregionally advanced nasopharyngeal carcinoma (LANPC). However, two cycles of once-every-3-weeks cisplatin at 100 mg/m2 has never been prospectively compared with standard once-a-week cisplatin regimen. PATIENTS AND METHODS: This trial was conducted at three hospitals from 2011 to 2016. Patients who met the eligibility criteria were recruited (ChiCTR-TRC-12001979) and randomly assigned (1:1) via a computer-generated sequence to receive once-every-3-weeks cisplatin at 100 mg/m2 for two cycles or once-a-week cisplatin at 40 mg/m2 for six cycles concurrently with IMRT. Primary endpoint was failure-free survival and between-group absolute difference of 10% as the noninferiority margin. RESULTS: A total of 510 patients were enrolled. Median follow-up time was 58.3 months with 85.4% of 3-year failure-free survival in the once-every-3-weeks group and 85.6% in the once-a-week group. An absolute difference of -0.2% (95% confidence interval, -6.3 to 5.9; P noninferiority = 0.0016). Acute toxicities of grade 3 or higher occurred in 55.8% in the once-every-3-weeks group and 66.3% in the once-a-week group (P = 0.015). The most common acute toxicities were hematologic abnormalities, including leukopenia (16% vs. 27%; P = 0.0022) and thrombocytopenia (1% vs. 5%; P = 0.015). The late grade 3-4 auditory loss rate was significantly lower in the once-every-3-weeks group than the once-a-week group (6% vs. 13%; P = 0.0039). CONCLUSIONS: Once-every-3-weeks cisplatin as concurrent chemoradiotherapy is noninferior to once-a-week cisplatin in the treatment efficacy in the LANPC. Although both regimens are well tolerated, severe acute toxicities and late-onset auditory loss are higher in the once-a-week group.


Assuntos
Antineoplásicos/administração & dosagem , Cisplatino/administração & dosagem , Carcinoma Nasofaríngeo/tratamento farmacológico , Neoplasias Nasofaríngeas/tratamento farmacológico , Adulto , Idoso , Esquema de Medicação , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Carcinoma Nasofaríngeo/patologia , Neoplasias Nasofaríngeas/patologia , Estadiamento de Neoplasias , Adulto Jovem
11.
J Cancer ; 12(14): 4424-4432, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34093843

RESUMO

Introduction: Biopsy is essential for some patients with suspected distant metastasis, so we aim to figure out whether biopsy of distant metastasis is associated with impaired survival in NPC. Methods: A total of 743 synchronous metastatic NPC patients from 2004 to 2016 were analyzed from the population-based Surveillance, Epidemiology, and End Results program. Propensity score matching was used to control confounders and create a well-balanced cohort. Five-year survival rate estimates and Kaplan-Meier survival curves were calculated. Cox proportional hazard ratios (HRs) were used to identify independent prognostic factors for survival. Results: Of 743 eligible patients, 194 (26.11%) underwent biopsy of distant metastasis. After control for demographic and clinicopathologic characteristics, patients with biopsy of distant metastasis achieved comparable 5-year overall survival (OS) (20.3% vs 24.7%; P = 0.41) and 5-year cancer specific survival (CSS) (31.0% vs 33.6%; P = 0.35) with patients without biopsies. Multivariate analysis further confirmed that biopsy of distant metastasis was not associated with impaired OS (HR = 1.03, 95% CI = 0.84-1.25; P = 0.80) or CSS (HR = 1.07, 95% CI = 0.86-1.34; P = 0.54). Conclusions: Biopsy of distant metastasis was not associated with impaired survival outcomes for synchronous metastatic NPC patients. Biopsy of distant metastasis could be another diagnosed choice for patients with suspected distant metastasis.

12.
J Pept Sci ; 27(9): e3333, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34114290

RESUMO

Interactions between charged amino acids significantly influence the structure and function of proteins. The encoded charged amino acids Asp, Glu, Arg, and Lys have different number of hydrophobic methylenes linking the backbone to the charged functionality. It remains to be fully understood how does this difference in the number of methylenes affect protein structure stability. Protein secondary structures are the fundamental three-dimensional building blocks of protein structures. ß-Sheet structures are particularly interesting, because these structures have been associated with a number of protein misfolding diseases. Herein, we report the effect of charged amino acid side chain length at two ß-strand positions individually on the stability of a ß-hairpin. The charged amino acids include side chains with a carboxylate, an ammonium, or a guanidinium group. The experimental peptides, fully folded reference peptides, and fully unfolded reference peptides were synthesized by solid phase peptide synthesis and analyzed by 2D NMR methods including TOCSY, DQF-COSY, and ROESY. Sequence specific assignments were performed for all peptides. The chemical shift data were used to derive the fraction folded population and the folding free energy for the experimental peptides. Results showed that the fraction folded population increased with increasing charged amino acid side chain length. These results should be useful for developing functional peptides that adopt the ß-conformation.


Assuntos
Aminoácidos , Peptídeos , Conformação Proteica em Folha beta , Dobramento de Proteína , Estrutura Secundária de Proteína , Termodinâmica
13.
Theranostics ; 11(13): 6427-6444, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33995666

RESUMO

Background: Reportedly, nasopharyngeal carcinoma (NPC) patients with MHC I Class aberration are prone to poor survival outcomes, which indicates that the deficiency of tumor neoantigens might represent a mechanism of immune surveillance escape in NPC. Methods: To clearly delineate the landscape of neoantigens in NPC, we performed DNA and RNA sequencing on paired primary tumor, regional lymph node metastasis and distant metastasis samples from 26 patients. Neoantigens were predicted using pVACseq pipeline. Subtype prediction model was built using random forest algorithm. Results: Portraying the landscape of neoantigens in NPC for the first time, we found that the neoantigen load of NPC was above average compared to that of other cancers in The Cancer Genome Atlas program. While the quantity and quality of neoantigens were similar among primary tumor, regional lymph node metastasis and distant metastasis samples, neoantigen depletion was more severe in metastatic sites than in primary tumors. Upon tracking the clonality change of neoantigens, we found that neoantigen reduction occurred during metastasis. Building a subtype prediction model based on reported data, we observed that subtype I lacked T cells and suffered from severe neoantigen depletion, subtype II highly expressed immune checkpoint molecules and suffered from the least neoantigen depletion, and subtype III was heterogenous. Conclusions: These results indicate that neoantigens are conducive to the guidance of clinical treatment, and personalized therapeutic vaccines for NPC deserve deeper basic and clinical investigations to make them feasible in the future.


Assuntos
Antígenos de Neoplasias/imunologia , Carcinoma Nasofaríngeo/secundário , Neoplasias Nasofaríngeas/imunologia , Adulto , Antígenos de Neoplasias/genética , DNA de Neoplasias/genética , DNA Viral/análise , DNA Viral/genética , Feminino , Antígenos HLA/genética , Antígenos HLA/imunologia , Herpesvirus Humano 4/genética , Humanos , Mutação INDEL , Inibidores de Checkpoint Imunológico/uso terapêutico , Estimativa de Kaplan-Meier , Metástase Linfática/imunologia , Masculino , Pessoa de Meia-Idade , Carcinoma Nasofaríngeo/imunologia , Carcinoma Nasofaríngeo/terapia , Carcinoma Nasofaríngeo/virologia , Neoplasias Nasofaríngeas/genética , Neoplasias Nasofaríngeas/terapia , Neoplasias Nasofaríngeas/virologia , Polimorfismo de Nucleotídeo Único , Intervalo Livre de Progressão , RNA Neoplásico/genética , Receptores de Antígenos de Linfócitos T/imunologia , Evasão Tumoral , Microambiente Tumoral/imunologia , Infecções Tumorais por Vírus/virologia
14.
Oral Oncol ; 115: 105200, 2021 04.
Artigo em Inglês | MEDLINE | ID: mdl-33610003

RESUMO

INTRODUCTION: The current metastatic category (M) of nasopharyngeal carcinoma (NPC) is a "catch-all" category, we previously successfully established a M1 subdivision system based on prognostic metastatic characteristics in epidemic areas. We aimed to figure out metastatic characteristics associated with survival outcomes of NPC in non-epidemic areas. METHODS: A total of 428 newly diagnosed de novo metastatic NPC patients from 2010 to 2016 were analyzed from the population-based Surveillance, Epidemiology, and End Results program. Cox proportional hazard ratios (HRs) were used to identify independent prognostic factors for survival. RESULTS: The most frequently involved metastatic locations were the bones (53.04%), the lungs (36.68%), the livers (29.21%) and the distant lymph nodes (24.07%). Univariate analysis indicated that bone involvement (HR = 1.39, 95% CI = 1.09-1.77), liver involvement (HR = 1.44, 95% CI = 1.12-1.85) and multiple metastatic locations (HR = 1.32, 95% CI = 1.04-1.67) were negative prognostic factors of overall survival (OS) for patients with synchronous metastasis. We established a new M1 subdivision system based on metastatic characteristics: M1a, without bone and liver involvement; M1b, single bone or liver involvement; M1c, multiple metastatic locations including bone and/or liver. Multivariate analysis confirmed that our new subcategories were associated with significantly different OS (M1b vs M1a: HR = 1.54, 95% CI = 1.11-2.16; M1c vs M1a: HR = 2.03, 95% CI = 1.47-2.78). CONCLUSIONS: Synchronous metastatic NPC patients with multiple metastatic locations involved bone and/or liver were prone to suffer from dismal OS and might need more attentions for selection of treatment modality.


Assuntos
Carcinoma Nasofaríngeo/mortalidade , Adulto , Idoso , Idoso de 80 Anos ou mais , Estudos de Coortes , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Metástase Neoplásica , Projetos Piloto , Prognóstico , Estudos Retrospectivos , Análise de Sobrevida , Adulto Jovem
15.
Nanomaterials (Basel) ; 11(2)2021 Jan 27.
Artigo em Inglês | MEDLINE | ID: mdl-33513990

RESUMO

In this study, a methodology utilizing peptide conformational imprints (PCIs) as a tool to specifically immobilize porcine pancreatic alpha-trypsin (PPT) at a targeted position is demonstrated. Owing to the fabrication of segment-mediated PCIs on the magnetic particles (PCIMPs), elegant cavities complementary to the PPT structure are constructed. Based on the sequence on targeted PPT, the individual region of the enzyme is trapped with different template-derived PCIMPs to show certain types of inhibition. Upon hydrolysis, N-benzoyl-L-arginine ethyl ester (BAEE) is employed to assess the hydrolytic activity of PCIMPs bound to the trypsin using high-performance liquid chromatography (HPLC) analysis. Further, the kinetic data of four different PCIMPs are compared. As a result, the PCIMPs presented non-competitive inhibition toward trypsin, according to the Lineweaver-Burk plot. Further, the kinetic analysis confirmed that the best parameters of PPT/PCIMPs 233-245+G were Vmax = 1.47 × 10-3 mM s-1, Km = 0.42 mM, kcat = 1.16 s-1, and kcat/Km = 2.79 mM-1 s-1. As PPT is bound tightly to the correct position, its catalytic activities could be sustained. Additionally, our findings stated that the immobilized PPT could maintain stable activity even after four successive cycles.

16.
Head Neck ; 43(1): 98-107, 2021 01.
Artigo em Inglês | MEDLINE | ID: mdl-32985734

RESUMO

BACKGROUND: Surgical access for retropharyngeal lymph node (RPLN) dissection is difficult. We aimed to examine the efficacy of transcervical endoscopic RPLN dissection (TSE-RPLND) for recurrent RPLN in nasopharyngeal carcinoma (NPC). METHODS: From April 2013 to February 2019, a total of 31 patients with NPC diagnosed with RPLN recurrence underwent TSE-RPLND. The clinical characteristics, complications, and survival outcomes were retrospectively analyzed. RESULTS: The mean duration of surgery, quantity of bleeding and postoperative hospitalization stay were 347.9 minutes, 107.7 mL, and 8.7 days, respectively. After a median follow-up of 31.0 months, the 2-year locoregional relapse-free survival, distant metastasis-free survival, progression-free survival, and overall survival rates were 63.9%, 95.2%, 59.9%, and 83.3%, respectively. The long-term incidences of swallowing problems, permanent nutrient tube, tongue atrophy, and shoulder problems were 6 (19.4%), 3 (9.7%), 3 (9.7%), and 3 (9.7%), respectively. CONCLUSIONS: TSE-RPLND is an effective method to treat RPLN recurrence in NPC, but nerve injury-related complications should not be ignored.


Assuntos
Neoplasias Nasofaríngeas , Recidiva Local de Neoplasia , Dissecação , Humanos , Excisão de Linfonodo , Linfonodos/cirurgia , Metástase Linfática , Carcinoma Nasofaríngeo/cirurgia , Neoplasias Nasofaríngeas/cirurgia , Estudos Retrospectivos
17.
Front Oncol ; 11: 814881, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34976847

RESUMO

OBJECTIVE: Anti-EGFR Targeted agents were found to be capable of modulating the antitumor immunity in head and neck cancer and become more and more frequently used in the treatment of nasopharyngeal carcinoma(NPC). We aimed to explore whether adding concurrent chemotherapy influences the survival outcome of patients with stage II-IVb NPC treated with concurrent anti-EGFR agents and intensity-modulated radiation therapy (IMRT) and explore other prognostic factors for the patients. MATERIALS AND METHODS: A total of 656 stage II-IVb NPC patients treated with concurrent anti-EGFR agents plus IMRT between January 2011 and November 2015 were enrolled. Firstly, from these patients, a well-balanced cohort of 302 patients who received concurrent chemotherapy was created by matching potential prognostic factors. Furthermore, for all 656 stage II-IVb NPC patients, univariate and multivariate analyses of overall survival (OS), progression-free survival (PFS), locoregional recurrence-free survival (LRRFS) and distant metastasis-free survival (DMFS) were conducted to identify prognostic factors and to confirm the findings from the matching cohort. RESULTS: Compared with concurrent anti-EGFR agents alone, combining concurrent cisplatin and anti-EGFR agents significantly improved the OS (5-year 94.7% versus 84.3%, P=0.012) and PFS (5-year 82.0% versus 71.7%, P=0.039) of NPC patients with more severe hematologic toxicity and mucositis. The independent prognostic factors identified by multivariate analysis of OS and PFS included concurrent chemotherapy, epstein-barr virus(EBV) status and clinical stage. Patients treated without induction chemotherapy (IC) may achieve more benefits from the addition of concurrent chemotherapy to concurrent anti-EGFR agents. CONCLUSIONS: For stage II-IVb NPC patients treated with concurrent anti-EGFR agents, the addition of concurrent chemotherapy can significantly improve the survival outcome.

18.
Biochim Biophys Acta Proteins Proteom ; 1868(12): 140528, 2020 12.
Artigo em Inglês | MEDLINE | ID: mdl-32853773

RESUMO

Mnemiopsin 2 from a luminous ctenophore with two functional EF-hand motifs is a calcium-regulated photoprotein that is responsible for emitting a bright blue bioluminescence upon reacting with coelenterazine and calcium ions in Mnemiopsis leidyi. Synchrotron radiation-based Fourier-transform infrared (SR-FTIR) spectroscopy was applied to analyze the distribution of secondary structures, the conformational changes resulting from calcium binding and the structural stabilities in wild-type mnemiopsin 2, as well as its mutant type that possesses three EF-hand motifs. The distribution of secondary structures of these proteins indicates that mutant apo-mnemiopsin 2 has a more stable secondary structure than the wild-type. Analyses of the SR-FTIR spectra revealed that the conformational changes at the secondary structures of both mnemiopsin 2 depend on the calcium concentrations, such that the most noticeable changes in structures of wild-type and mutant mnemiopsin 2 occur at optimum concentrations 6 and 2 mM of calcium chloride, respectively. The addition of calcium to both proteins increases the proportions of their secondary structures in the amide I and II regions. The major amide I bands in the IR spectra of both mnemiopsin­calcium complexes shift towards smaller wavenumbers, whereas their main amide II bands are identified at larger wavenumbers.


Assuntos
Cálcio/química , Proteínas Luminescentes/química , Estrutura Secundária de Proteína , Espectroscopia de Infravermelho com Transformada de Fourier , Concentração de Íons de Hidrogênio , Proteínas Luminescentes/genética , Proteínas Mutantes , Ligação Proteica , Conformação Proteica , Domínios e Motivos de Interação entre Proteínas , Soluções , Relação Estrutura-Atividade
19.
JAMA Oncol ; 6(9): 1345-1352, 2020 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-32701129

RESUMO

Importance: The role of locoregional radiotherapy in patients with de novo metastatic nasopharyngeal carcinoma (mNPC) is unclear. Objective: To investigate the efficacy and safety of locoregional radiotherapy in de novo mNPC. Design, Setting, and Participants: Patients with biopsy-proven mNPC, who demonstrated complete or partial response (RECIST v1.1) following 3 cycles of cisplatin and fluorouracil chemotherapy, were enrolled. Eligible patients were randomly assigned (1:1) to receive either chemotherapy plus radiotherapy or chemotherapy alone. Overall, 126 of 173 patients screened were eligible to the study, and randomized to chemotherapy plus radiotherapy (n = 63) or chemotherapy alone (n = 63). Median (IQR) follow-up duration was 26.7 (17.2-33.5) months. Interventions: The chemotherapy regimens were fluorouracil continuous intravenous infusion at 5 g/m2 over 120 hours and 100 mg/m2 intravenous cisplatin on day 1, administered every 3 weeks for 6 cycles. Patients assigned to the chemotherapy plus radiotherapy group received intensity-modulated radiotherapy (IMRT) after chemotherapy. Main Outcomes and Measures: The primary end point of the study was overall survival (OS). The secondary end point was progression-free survival (PFS) and safety. Results: Overall, 126 patients were enrolled (105 men [83.3%] and 21 women [16.7%]; median [IQR] age, 46 [39-52] years). The 24-month OS was 76.4% (95% CI, 64.4%-88.4%) in the chemotherapy plus radiotherapy group, compared with 54.5% (95% CI, 41.0%-68.0%) in the chemotherapy-alone group. The study met its primary end point of improved OS (stratified hazard ratio [HR], 0.42; 95% CI, 0.23-0.77; P = .004) in favor of chemotherapy plus radiotherapy. Progression-free survival was also improved in the chemotherapy plus radiotherapy group compared with the chemotherapy-alone group (stratified HR, 0.36; 95% CI, 0.23-0.57). No significant differences in acute hematological or gastrointestinal toxic effects were observed between the treatment arms. The frequency of acute grade 3 or higher dermatitis, mucositis, and xerostomia was 8.1%, 33.9%, and 6.5%, respectively, in the chemotherapy plus radiotherapy group. The frequency of late severe grade 3 or higher hearing loss and trismus was 5.2% and 3.4%, respectively, in the chemotherapy plus radiotherapy group. Conclusions and Relevance: In this randomized clinical trial, radiotherapy added to chemotherapy significantly improved OS in chemotherapy-sensitive patients with mNPC. Trial Registration: ClinicalTrials.gov Identifier: NCT02111460.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Carcinoma Nasofaríngeo/tratamento farmacológico , Carcinoma Nasofaríngeo/radioterapia , Radioterapia de Intensidade Modulada , Adulto , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Cisplatino/administração & dosagem , Cisplatino/efeitos adversos , Feminino , Fluoruracila/administração & dosagem , Fluoruracila/efeitos adversos , Humanos , Masculino , Pessoa de Meia-Idade , Carcinoma Nasofaríngeo/patologia , Metástase Neoplásica , Intervalo Livre de Progressão
20.
Sci Rep ; 10(1): 937, 2020 01 22.
Artigo em Inglês | MEDLINE | ID: mdl-31969674

RESUMO

Hypoxemic respiratory failure is usually accompanied with a certain extent of consolidation and alveolar derecruitment, which may still be present even after the patients have achieved the status of readiness to extubate. Functional residual capacity (FRC) is an indicator of lung aeration. This study aimed to evaluate whether pre-extubation FRC is associated with the risk of extubation failure in patients with hypoxemic respiratory failure. We prospectively included 92 patients intubated for hypoxemic respiratory failure. We used a technique based on a nitrogen multiple breath washout method to measure FRC before the planned extubation. The median FRC before extubation was 25 mL/kg (Interquartile range, 20-32 mL/Kg) per predicted body weight (pBW). After extubation, 20 patients (21.7%) were reintubated within 48 hours. The median FRC was higher in the extubation success group than in the extubation failure group (27 versus 21 mL/Kg, p < 0.001). Reduced FRC was associated with higher risk of extubation failure (odds ratio, 1.14 per each decreased of 1 mL/Kg of FRC/pBW, 95% CI, 1.05-1.23, p = 0.002). In conclusion, pre-extubation FRC is associated with the risk of extubation failure. Reduced FRC may be incorporated into the traditional risk factors to identify patients at high risk for extubation failure.


Assuntos
Capacidade Residual Funcional , Hipóxia/fisiopatologia , Intubação Intratraqueal , Insuficiência Respiratória/fisiopatologia , Desmame do Respirador/efeitos adversos , Idoso , Idoso de 80 Anos ou mais , Estudos de Coortes , Feminino , Humanos , Hipóxia/diagnóstico , Hipóxia/etiologia , Intubação Intratraqueal/efeitos adversos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Insuficiência Respiratória/diagnóstico , Insuficiência Respiratória/etiologia , Risco , Fatores de Risco , Desmame do Respirador/métodos
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