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1.
BMC Cancer ; 23(1): 28, 2023 Jan 07.
Artigo em Inglês | MEDLINE | ID: mdl-36611139

RESUMO

OBJECTIVE: Targeting deubiquitinases (DUBs) has emerged as a promising avenue for anticancer drug development. However, the effect and mechanism of pan-DUB inhibitor EOAI on non-small cell lung cancer (NSCLC) remains to be studied. MATERIALS AND METHODS: The expression of ubiquitin-specific peptidase 5 (USP5) in NSCLC was evaluated by immunohistochemistry. The effect of the USP5 inhibitor, EOAI, on NSCLC cell growth and cell cycle was evaluated by CCK-8 and PI staining. Apoptosis was detected by Annexin V-FITC/PI double staining. Autophagy was examined by LC3 immunofluorescence. Comet assay and γ-H2AX immunofluorescence staining were used to detect DNA damage, and Western blotting was used to detect the expression of apoptosis, cycle, autophagy and DNA damage-related proteins. In vivo experiments demonstrated the effect of EOAI on NSCLC. RESULTS: We also found that USP5 was significantly upregulated in NSCLC tissues in this study. In addition, we show that EOAI can cause DNA damage in NSCLC cells while modulating the transcriptional activity of P53, thereby inducing cell cycle arrest in NSCLC cells, autophagy and apoptosis. In vivo experiments have shown that EOAI can inhibit tumors and synergistically enhance the anti-tumor effect of cisplatin. CONCLUSION: USP5-mediated epigenetic regulation of oncogenes promotes the occurrence of NSCLC, which provides ideas for developing potential targeted therapy.


Assuntos
Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Humanos , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/genética , Carcinoma Pulmonar de Células não Pequenas/patologia , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patologia , Epigênese Genética , Linhagem Celular Tumoral , Dano ao DNA , Proteases Específicas de Ubiquitina/metabolismo , Apoptose , Autofagia , Proliferação de Células
2.
World J Surg Oncol ; 21(1): 30, 2023 Jan 31.
Artigo em Inglês | MEDLINE | ID: mdl-36721264

RESUMO

OBJECTIVE: According to the different characteristics of patients and cervical lymph node metastasis of oral and oropharyngeal cancer, the marginal mandibular branches of facial nerves were treated by different surgical procedures, and the safety and protective effects of different surgical procedures were investigated. METHODS: One hundred ninety-seven patients with oral and oropharyngeal cancer satisfying the inclusion criteria were selected. According to the different characteristics of patients and cervical metastatic lymph nodes, three different surgical procedures were used to treat the marginal mandibular branches of the facial nerve: finding and exposing the marginal mandibular branches of the facial nerves at the mandibular angles of the platysma flaps, finding and exposing the marginal mandibular branches of facial nerves at the intersections of the distal ends of facial arteries and veins with the mandible, and not exposing the marginal mandibular branches of the facial nerves. The anatomical position, injury, and complications of the marginal mandibular branches of the facial nerves were observed. RESULTS: The marginal mandibular branches of the facial nerves were found and exposed at the mandibular angles of the platysma flaps in 102 patients; the marginal mandibular branches of facial nerves were found and exposed at the intersections of the distal ends of the facial arteries and veins with the mandibles in 64 patients; the marginal mandibular branches of facial nerves were not exposed in 31 patients; among them, four patients had permanent injury of the marginal mandibular branches of the facial nerves, and temporary injury occurred in seven patients. There were statistically significant differences in the protection of the mandibular marginal branch of the facial nerve among the three different surgical methods (P = 0.0184). The best protective effect was to find and expose the mandibular marginal branch of the facial nerve at the mandibular angle of the platysma muscle flap, and the injury rate was only 2.94%. CONCLUSION: The three different surgical procedures were all safe and effective in treating the marginal mandibular branches of the facial nerves, the best protective effect was to find and expose the mandibular marginal branch of the facial nerve at the mandibular angle of the platysma muscle flap.


Assuntos
Nervo Facial , Neoplasias Orofaríngeas , Humanos , Excisão de Linfonodo , Neoplasias Orofaríngeas/cirurgia , Linfonodos/cirurgia , Metástase Linfática
3.
BMC Surg ; 23(1): 297, 2023 Sep 30.
Artigo em Inglês | MEDLINE | ID: mdl-37775750

RESUMO

OBJECTIVE: This study aimed to assess the effects of surgical timing and approach on operative duration, postoperative suture removal time, and postoperative recurrence rate in the management of preauricular fistula. A 12-year single-center clinical observation was conducted to analyze the potential effects of different surgical strategies on these critical outcomes. METHODS: The clinical data from 576 (782 ears) patients who underwent surgical resection for preauricular fistulas were examined in this retrospective study. The patients were classified into various groups based on differences in operative duration, surgical techniques and the use of intraoperative magnifying equipment. Furthermore, the specific data on operative duration, postoperative suture removal time, and postoperative recurrence rate were also recorded. RESULTS: The average operative duration for 782 ears and the average time required for postoperative suture removal were determined to be (34.57 ± 4.25) min and (3.62 ± 0.76) days, respectively. Among the cases examined, recurrence occurred in 13 ears, but all of them were cured after a second surgery, resulting in a recurrence rate of 1.67% (13/782). Interestingly, the operative and postoperative suture removal time was prolonged during the infection period (P < 0.05). The postoperative recurrence rate was significantly higher in the absence of magnifying equipment, as compared to those with the use of a microscope with 2.5× magnification (P < 0.05). No statistically significant differences were noted in the recurrence rate when comparing different anesthesia methods and types of surgical incisions, as well as the intraoperative use of methylene blue, and partial removal of cartilage of the pedicle (P > 0.05). CONCLUSION: The use of methylene blue, partial removal of the cartilage of the pedicle, and surgical incision during preauricular fistula resection did not affect the operative duration, postoperative suture removal time, and postoperative recurrence rate. Therefore, surgeons can select their preferred approaches based on their individual practices and patient-specific situations. However, the use of magnifying equipment during surgery is associated with a reduced risk of recurrence.


Assuntos
Fístula , Azul de Metileno , Humanos , Estudos Retrospectivos , Resultado do Tratamento , Orelha Externa/cirurgia , Recidiva
4.
Molecules ; 27(20)2022 Oct 13.
Artigo em Inglês | MEDLINE | ID: mdl-36296465

RESUMO

A new metal-organic framework (MOF), [Co2(L)2(azpy)]n (compound 1, H2L = 5-(pyridin-4-ylmethoxy)-isophthalic acid, azpy = 4,4'-azopyridine), was synthesized by a solvothermal method and further characterized by elemental analysis, IR spectra, thermogravimetric analysis, single-crystal and powder X-ray diffraction. The X-ray single-crystal diffraction analysis for compound 1 indicated that two cis L22- ligands connected to two cobalt atoms resulted in a macrocycle structure. Through a series of adsorption tests, we found that compound 1 exhibited a high capacity of CO2, and the adsorption capacity could reach 30.04 cm3/g. More interestingly, under 273 K conditions, the adsorption of CO2 was 41.33 cm3/g. In addition, when the Co-MOF was irradiated by a 730 nm laser, rapid temperature increases for compound 1 were observed (temperature variation in 169 s: 26.6 °C), showing an obvious photothermal conversion performance. The photothermal conversion efficiency reached 20.3%, which might be due to the fact that the parallel arrangement of azo units inhibited non-radiative transition and promoted photothermal conversion. The study provides an efficient strategy for designing MOFs for the adsorption of CO2 and with good photothermal conversion performance.

7.
Am J Hum Genet ; 96(4): 597-611, 2015 Apr 02.
Artigo em Inglês | MEDLINE | ID: mdl-25839328

RESUMO

Esophageal squamous cell carcinoma (ESCC) is one of the most common cancers worldwide and the fourth most lethal cancer in China. However, although genomic studies have identified some mutations associated with ESCC, we know little of the mutational processes responsible. To identify genome-wide mutational signatures, we performed either whole-genome sequencing (WGS) or whole-exome sequencing (WES) on 104 ESCC individuals and combined our data with those of 88 previously reported samples. An APOBEC-mediated mutational signature in 47% of 192 tumors suggests that APOBEC-catalyzed deamination provides a source of DNA damage in ESCC. Moreover, PIK3CA hotspot mutations (c.1624G>A [p.Glu542Lys] and c.1633G>A [p.Glu545Lys]) were enriched in APOBEC-signature tumors, and no smoking-associated signature was observed in ESCC. In the samples analyzed by WGS, we identified focal (<100 kb) amplifications of CBX4 and CBX8. In our combined cohort, we identified frequent inactivating mutations in AJUBA, ZNF750, and PTCH1 and the chromatin-remodeling genes CREBBP and BAP1, in addition to known mutations. Functional analyses suggest roles for several genes (CBX4, CBX8, AJUBA, and ZNF750) in ESCC. Notably, high activity of hedgehog signaling and the PI3K pathway in approximately 60% of 104 ESCC tumors indicates that therapies targeting these pathways might be particularly promising strategies for ESCC. Collectively, our data provide comprehensive insights into the mutational signatures of ESCC and identify markers for early diagnosis and potential therapeutic targets.


Assuntos
Carcinoma de Células Escamosas/genética , Citidina Desaminase/genética , Neoplasias Esofágicas/genética , Predisposição Genética para Doença/genética , Genoma Humano/genética , Mutação/genética , Fosfatidilinositol 3-Quinases/genética , Transdução de Sinais/genética , Desaminase APOBEC-1 , Análise de Variância , Sequência de Bases , Proteína de Ligação a CREB/genética , Linhagem Celular Tumoral , China , Classe I de Fosfatidilinositol 3-Quinases , Variações do Número de Cópias de DNA/genética , Carcinoma de Células Escamosas do Esôfago , Técnicas de Silenciamento de Genes , Humanos , Immunoblotting , Imuno-Histoquímica , Hibridização in Situ Fluorescente , Proteínas com Domínio LIM/genética , Ligases , Dados de Sequência Molecular , Receptores Patched , Receptor Patched-1 , Complexo Repressor Polycomb 1/genética , Proteínas do Grupo Polycomb/genética , Reação em Cadeia da Polimerase em Tempo Real , Receptores de Superfície Celular/genética , Análise de Sequência de DNA , Sais de Tetrazólio , Tiazóis , Fatores de Transcrição/genética , Proteínas Supressoras de Tumor/genética , Ubiquitina Tiolesterase/genética , Ubiquitina-Proteína Ligases/genética
8.
Anal Chem ; 90(19): 11203-11209, 2018 10 02.
Artigo em Inglês | MEDLINE | ID: mdl-30156405

RESUMO

A T790M secondary mutation in epidermal-growth-factor receptor (EGFR) is the most well-established EGFR-tyrosine-kinase-inhibitor (TKI) resistance marker in non-small-cell lung cancer (NSCLC). The current methods to rapidly and accurately detect T790M in clinical practice are not satisfactory because of several obstacles, including the unavailability of tumor-tissue rebiopsies and the low DNA copy number of T790M in circulating tumor DNA (ctDNA). Here, we develop library-aliquot-based droplet digital PCR (LAB-ddPCR) to increase detection sensitivity without affecting accuracy. This new LAB-ddPCR method is performed using aliquots of the ctDNA precapture next-generation-sequencing (NGS) library, in which the isolated ctDNA was amplified and enriched. We show that the LAB-ddPCR can precisely distinguish between T790M wild-type and mutation alleles without introducing extra false-positive signals. In a cohort of 70 post-TKI NSCLC patients, the LAB-ddPCR identified 41 T790M-positive cases (sensitivity 58.57%), but ddPCR only detected T790M in 27 cases (sensitivity 38.57%). Taking the ARMS-PCR result from matched tumor rebiopsies into consideration, the LAB-ddPCR method is better than ddPCR. In conclusion, the LAB-ddPCR ctDNA test offers a feasible and flexible option for the rapid and accurate detection of the T790M secondary mutation, which is helpful in dynamically monitoring drug response and disease progression throughout the therapeutic regimen.


Assuntos
Carcinoma Pulmonar de Células não Pequenas/genética , DNA Tumoral Circulante/genética , Análise Mutacional de DNA/métodos , Neoplasias Pulmonares/genética , Mutação , Reação em Cadeia da Polimerase/métodos , Carcinoma Pulmonar de Células não Pequenas/sangue , Receptores ErbB/genética , Biblioteca Gênica , Humanos , Limite de Detecção , Neoplasias Pulmonares/sangue
9.
BMC Cancer ; 14: 834, 2014 Nov 18.
Artigo em Inglês | MEDLINE | ID: mdl-25407901

RESUMO

BACKGROUND: The translocations of the anaplastic lymphoma kinase (ALK) gene with the echinoderm microtubule-associated protein-like 4 (EML4) gene on chromosome 2p have been identified in non-small-cell lung cancers (NSCLCs) as oncogenic driver mutations. It has been suggested that EML4-ALK fusion is associated with the resistance in NSCLCs to epidermal growth factor receptor tyrosine kinase inhibitors (EGFR TKIs), such as gefitinib and erlotinib. In contrast, ALK tyrosine kinase inhibitor (ALK TKI) crizotinib has shown superior effects in combating NSCLCs with EML4-ALK. Thus, characterization of EML4-ALK fusion genes and clinical features of resulting carcinomas would be a great benefit to disease diagnosis and designing customized treatment plans. Studies have suggested that EML4-ALK translocation occurs more frequently in never-smokers with NSCLC, especially in female patients. However, it is not clear whether this is the case in male patients, too. In this study, we have determined the frequency of EML4-ALK translocation in male never-smokers with NSCLC in a cohort of Chinese patients. The clinical features associated with EML4-ALK translocation were also investigated. METHODS: A cohort of 95 Chinese male never-smokers with NSCLC was enrolled in this study. EML4-ALK fusion genes were detected using one-step real time RT-PCR and DNA sequencing. We further determined the expression levels of ALK mRNA by RT-PCR and ALK protein by immunohistochemistry in these specimens. The clinical features of EML4-ALK-positive carcinomas were also determined. RESULTS: We have identified EML4-ALK fusion genes in 8 out of 95 carcinoma cases, accounting for 8.42% in Chinese male never-smokers with NSCLC. It is significantly higher than that in all Chinese male patients (3.44%) regardless smoking habit. It is also significantly higher than that in all Chinese smokers (8/356 or 2.25%) or in smokers worldwide (2.9%) by comparing to published data. Interestingly, EML4-ALK fusion genes are more frequently found in younger patients and associated with less-differentiated carcinomas. CONCLUSIONS: The frequency of EML4-ALK translocation is strongly associated with smoking habits in Chinese male patients with higher frequency in male never-smokers. EML4-ALK translocation is associated with early-onset and less-differentiated carcinomas.


Assuntos
Carcinoma Pulmonar de Células não Pequenas/genética , Neoplasias Pulmonares/genética , Proteínas de Fusão Oncogênica/genética , Receptores Proteína Tirosina Quinases/análise , Adulto , Fatores Etários , Idoso , Quinase do Linfoma Anaplásico , Carcinoma Pulmonar de Células não Pequenas/química , China , Humanos , Neoplasias Pulmonares/química , Masculino , Pessoa de Meia-Idade , RNA Mensageiro/análise , Receptores Proteína Tirosina Quinases/genética , Fumar , Translocação Genética
10.
Adv Mater ; : e2406147, 2024 Jun 26.
Artigo em Inglês | MEDLINE | ID: mdl-38925142

RESUMO

High-brightness laser lighting is confronted with crucial challenges in developing laser-excitable color converting materials with effective heat dissipation and super optical performance. Herein, a novel composite of phosphor-in-glass film on transparent diamond (PiGF@diamond) is designed and fabricated via a facile low-temperature co-sintering strategy. The as-prepared La3Si6N11:Ce3+ (LSN:Ce) PiGF@diamond with well-retained optical properties of raw phosphor shows a record thermal conductivity of ≈599 W m-1 K-1, which is about 60 times higher than that of currently well-used PiGF@sapphire (≈10 W m-1 K-1). As a consequence, this color converter can bear laser power density up to 40.24 W mm-2 and a maximum luminance flux of 5602 lm without luminescence saturation due to efficient inhibition of laser-induced heat accumulation. By further supplementing red spectral component of CaAlSiN3:Eu2+ (CASN:Eu), the PiGF@diamond based white laser diode is successfully constructed, which can yield warm white light with a high color rendering index of 89.3 and find practical LD-driven applications. The findings will pave the way for realizing the commercial application of PiGF composite in laser lighting and display.

11.
Ecotoxicology ; 22(6): 1033-42, 2013 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-23771790

RESUMO

The effect of citric acid (CA) and ethylene diamine tetraacetic acid (EDTA) on the growth, anatomical structure, physiological responses and lead (Pb) accumulation of Iris lactea var. chinensis seedling growing in Pb mine tailings for 30 days were studied. Results showed that the dry weights (DW) of roots decreased significantly under both levels of CA. The DWs of leaves and roots treated with 2 mmol/kg EDTA decreased significantly and were 23 and 54 %, respectively, lower than those of the control. The tolerant indexes of I. lactea var. chinensis under all treatments of organic acids were lower than control. The root tip anatomical structure was little affected under the treatments of 2 mmol/kg CA and 2 mmol/kg EDTA compared with control. However, the formation of photosynthesizing cells was inhibited by the treatment of 2 mmol/kg EDTA. The concentrations of chlorophyll a, chlorophyll b and total carotenoids in the leaves treated with 2 mmol/kg EDTA significantly decreased. Higher CA level and lower EDTA level could trigger the synthesis of ascorbic acid and higher level of EDTA could trigger the synthesis of glutathione. CA and EDTA could promote Pb accumulation of I. lactea var. chinensis and Pb concentration in the leaves and roots at 2 mmol/kg EDTA treatment increased significantly and reached to 160.44 and 936.08 µg/g DW, respectively, and 1.8 and 1.6 times higher than those of the control. The results indicated that I. lactea var. chinensis could be used to remediate Pb tailing and the role of EDTA in promoting Pb accumulation was better than CA did.


Assuntos
Ácido Cítrico/farmacologia , Ácido Edético/farmacologia , Gênero Iris/efeitos dos fármacos , Chumbo/toxicidade , Metais Pesados/toxicidade , Plântula/efeitos dos fármacos , Clorofila/análogos & derivados , Clorofila/análise , Clorofila A , Gênero Iris/crescimento & desenvolvimento , Mineração , Folhas de Planta/efeitos dos fármacos , Folhas de Planta/crescimento & desenvolvimento , Raízes de Plantas/efeitos dos fármacos , Raízes de Plantas/crescimento & desenvolvimento , Plântula/crescimento & desenvolvimento , Poluentes do Solo/toxicidade
12.
JCO Precis Oncol ; 7: e2200482, 2023 02.
Artigo em Inglês | MEDLINE | ID: mdl-36848606

RESUMO

PURPOSE: MET exon 14 (METex14) skipping is an actionable biomarker in non-small-cell lung cancer. However, MET variants are highly complex and diverse, and not all variants lead to exon 14 skipping. Assessing the skipping effect of unknown variants is still a key issue in molecular diagnosis. MATERIALS AND METHODS: We retrospectively collected MET variants around exon 14 from 4,233 patients with non-small-cell lung cancer who underwent next-generation sequencing testing using DNA, as well as two published data sets. RESULTS: Among the 4,233 patients, 44 unique variants including 29 novel variants (65.9%) were discovered from 53 patients. Notably, 31 samples (58.5%) failed RNA verification. Using RNA verification, nine novel skipping variants and five nonskipping variants were confirmed. We further used SpliceAI with the delta score cutoff of 0.315 to aid the classification of novel variants (sensitivity = 98.88% and specificity = 100%). When applied to the reported variants, we also found three wrongly classified nonskipping variants. Finally, an optimized knowledge-based interpretation procedure for clinical routine was built according to the mutation type and location, and five more skipping mutations from the 13 unknown variants were determined, which improved the population determination rate to 0.92%. CONCLUSION: This study discovered more METex14 skipping variants and optimized an innovative approach that could be adapted for the interpretation of infrequent or novel METex14 variants timely without experimental validation.


Assuntos
Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Humanos , Carcinoma Pulmonar de Células não Pequenas/diagnóstico , Carcinoma Pulmonar de Células não Pequenas/genética , Éxons/genética , Neoplasias Pulmonares/diagnóstico , Neoplasias Pulmonares/genética , Mutação/genética , Estudos Retrospectivos , RNA
13.
Artigo em Chinês | MEDLINE | ID: mdl-37828891

RESUMO

Adenoid cystic carcinoma usually occurs in the salivary glands of the head and neck. It is a malignant tumor with a high degree of malignancy, resistance to radiotherapy and chemotherapy and poor prognosis. The clinical course of adenoid cystic carcinoma is slow and easy to be misdiagnosed. The main diagnosis and treatment means are individualized and precise treatment under the multi-disciplinary consultation mode, that is, surgical treatment and radiotherapy and chemotherapy. Adenoid cystic carcinoma is prone to relapse and hematologic metastasis, and the traditional radiotherapy and chemotherapy based therapies have not achieved satisfactory efficacy in the past three decades. How to detect, diagnose and treat early is an urgent task faced by clinicians.


Assuntos
Carcinoma Adenoide Cístico , Humanos , Carcinoma Adenoide Cístico/diagnóstico , Carcinoma Adenoide Cístico/terapia , Carcinoma Adenoide Cístico/patologia , Recidiva Local de Neoplasia , Pescoço/patologia , Orofaringe/patologia , Erros de Diagnóstico
14.
Natl Sci Rev ; 10(2): nwac261, 2023 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-36817840

RESUMO

The immiscible alloy Ti-Co-Gd is solidified in space by using the Electrostatic Levitation Device on board the Chinese Space Station. A sample with in-situ composite structure is obtained. The microstructure formation and gravity effect are discussed.

15.
Adv Mater ; 35(31): e2300185, 2023 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-37089030

RESUMO

A single-electron emitter, based on a single quantized energy level, can potentially achieve ultimate temporal and spatial coherence with a large emission current, which is desirable for atomic-resolution electron probes. This is first developed by constructing a nano-object on a metal tip to form a quantized double barrier structure. However, the single-electron-emission current can only achieve a picoampere level due to the low electron tunneling rate of the heterojunction with large barrier width, which limits the practical applications. In this study, carbon nanotubes (CNTs) serve as a single-electron emitter and a current up to 1.5 nA is demonstrated. The double barrier structure formed on the CNT tip enables a high tunneling rate (≈1012  s-1 ) due to the smaller barrier width. The emitter also shows high temporal coherence (energy dispersion of ≈10 meV) and spatial coherence (effective source radius of ≈0.85 nm). This work represents a highly coherent electron source to simplify the electron optics system of atomic-resolution electron microscopy and sub-10 nm electron beam lithography.

16.
Nanomaterials (Basel) ; 13(11)2023 Jun 05.
Artigo em Inglês | MEDLINE | ID: mdl-37299707

RESUMO

3D printing technology has been used to directly produce various actual products, ranging from engines and medicines to toys, especially due to its advantage in producing items of complicated, porous structures, which are inherently difficult to clean. Here, we apply micro-/nano-bubble technology to the removal of oil contaminants from 3D-printed polymeric products. Micro-/nano-bubbles show promise in the enhancement of cleaning performance with or without ultrasound, which is attributed to their large specific surface area enhancing the adhesion sites of contaminants, and their high Zeta potential which attracts contaminant particles. Additionally, bubbles produce tiny jets and shock waves at their rupture, driven by coupled ultrasound, which can remove sticky contaminants from 3D-printed products. As an effective, efficient, and environmentally friendly cleaning method, micro-/nano-bubbles can be used in a range of applications.

17.
Medicine (Baltimore) ; 102(52): e36667, 2023 Dec 29.
Artigo em Inglês | MEDLINE | ID: mdl-38206746

RESUMO

RATIONALE: Many studies have shown that first- and second-generation epidermal growth factor receptor tyrosine kinase inhibitors are less effective in patients with epidermal growth factor receptor (EGFR) exon 20 insertion (ex20ins) mutations. The efficacy of third-generation epidermal growth factor receptor tyrosine kinase inhibitors is still under investigation. Although new targeted tyrosine kinase inhibitors and monoclonal antibody-based agents have made significant advances in the treatment of epidermal growth factor receptor exon 20 insertion (EGFR ex20ins) mutation, the efficacy of these novel agents is not quite satisfactory. Platinum- and pemetrexed-based chemotherapy remains the standard first-line treatment for patients harboring EGFR ex20ins mutation. PATIENT CONCERNS: We report for the first time 2 Chinese patients diagnosed with advanced lung adenocarcinoma with EGFR ex20ins mutations after analysis of the αC-helix sequence by next-generation sequencing. Both patients were treated with furmonertinib as the first-line therapy. INTERVENTIONS: The first case included a 38-year-old female who had an EGFR ex20ins mutation (p.S768_D770dupSVD). After 1 month of treatment with furmonertinib, her symptoms of pain and cough were significantly alleviated. She achieved a partial response according to response evaluation criteria in solid tumors.[1] The final progression-free survival was 8.13 months. The second case included a 40-year-old male who had an EGFR ex20ins mutation (p.N771_P772insVal). He had a good response to furmonertinib and exhibited stable disease according to response evaluation criteria in solid tumors with a progression-free survival of 10.90 months. OUTCOMES: Both patients experienced significant improvement in symptoms and prolonged survival after furmonertinib was used as first-line treatment. Side effects were limited but manageable. CONCLUSION: The present study indicates that furmonertinib may be a first-line treatment option for patients with non-small cell lung cancer harboring EGFR ex20ins mutation.


Assuntos
Adenocarcinoma de Pulmão , Carcinoma Pulmonar de Células não Pequenas , Indóis , Neoplasias Pulmonares , Piridinas , Pirimidinas , Humanos , Masculino , Feminino , Adulto , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patologia , Mutagênese Insercional , Inibidores de Proteínas Quinases/uso terapêutico , Inibidores de Proteínas Quinases/farmacologia , Adenocarcinoma de Pulmão/tratamento farmacológico , Adenocarcinoma de Pulmão/genética , Receptores ErbB , Mutação , Éxons
18.
Clin Chim Acta ; 540: 117224, 2023 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-36627008

RESUMO

The rapid development of next-generation sequencing (NGS) technology has promoted its wide clinical application in precision medicine for oncology. However, laborious and time-consuming manual operations, highly skilled personnel requirements, and cross-contamination are major challenges for the clinical implementation of NGS technology-based tests. The Automated NGS Diagnostic Solutions (ANDiS) 500 system is a fully enclosed cassette-dependent automated NGS library preparation system. This platform could produce qualified targeted amplicon library in three steps with only 15 min of hands-on time. Rigorous cross-contamination test using simulated contaminant plasmids confirmed that the design of disposable cassette guarantees zero sample cross-contamination. The BRCA1 and BRCA2 mutation detection panel and gastrointestinal cancer-related gene analysis panel for the ANDiS 500 platform showed 100% accuracy and precision in detecting germ-line mutations and somatic mutations respectively. Furthermore, those panels showed 100% concordance with verified methods in a prospective cohort study enrolling 363 patients and a cohort of 45 pan-cancer samples. In conclusion, the ANDiS 500 automated platform could overcome major challenges for implementing NGS assays clinically and is eligible for routine clinical tests.


Assuntos
Genes BRCA2 , Neoplasias , Humanos , Estudos Prospectivos , Sequenciamento de Nucleotídeos em Larga Escala/métodos , Mutação
19.
Ecotoxicology ; 21(3): 759-67, 2012 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-22161020

RESUMO

The physiological responses and Cu accumulation of Paulownia fortunei (Seem) Hemsl. were studied under 15.7-157 µmol L(-1) Cu treatments in liquid culture for 14 days; the impacts of Cu concentration in the seedlings were evaluated under Cu mine tailing culture with acetic acid and EDTA treatment for 60 days. Results showed that the concentrations of Chl-a, Chl-b and Carotenoids significantly increased (p < 0.05) at 15.7-78.7 µmol L(-1)Cu treatment and significantly decreased at 157 µmol L(-1) treatment after 14 days of Cu exposure. The activities of superoxide dismutase (SOD) and catalase (CAT) significantly increased as Cu levels were enhanced and the activities of both SOD and CAT under 157 µmol L(-1) Cu stress were 2.9 and 1.9 times higher than that of control, respectively. The concentrations of proline and soluble sugars in the leaves of P. fortunei significantly increased as the Cu concentrations were elevated. Cu concentrations in roots, stems and leaves of P. fortunei increased significantly as Cu levels increased and reached 1911, 101 and 93 µg g(-1) dry weights (DW) at 157 µmol L(-1) Cu treatment, respectively. The seedlings of P. fortunei cultivated in Cu tailing experienced unsuccessful growth and loss of leaves in all treatments due to poor nutrition of the Cu tailing. The dry weight of P. fortunei increased under all the treatments of acetic acid after 60 days exposure. However, dry weight significantly decreased under both levels of EDTA. The Cu concentrations increased significantly in roots and decreased in leaves when each was treated with both concentrations of acetic acid. The Cu concentrations in the roots, stems and leaves increased significantly, and the concentrations of Cu in the stems and leaves under the treatment of 2 µmol L(-1) EDTA reached 189.5 and 763.1 µg g(-1) DW, respectively. The result indicated that SOD, CAT, proline and soluble sugars played an important role in coping with the oxidative stress of copper. Acetic acid could promote growth and EDTA at the experimental levels, which could also enhance Cu absorption and translocation into the stems and leaves of P. fortune. Furthermore, acetic acid and EDTA could be rationally utilized in Cu-contaminated soil.


Assuntos
Cobre/toxicidade , Poluentes Ambientais/toxicidade , Mineração , Scrophulariaceae/efeitos dos fármacos , Ácido Acético/farmacologia , Biodegradação Ambiental , Quelantes/farmacologia , Cobre/metabolismo , Ácido Edético/farmacologia , Poluentes Ambientais/metabolismo , Resíduos Industriais , Estresse Oxidativo/efeitos dos fármacos , Oxirredutases/metabolismo , Estruturas Vegetais/efeitos dos fármacos , Estruturas Vegetais/crescimento & desenvolvimento , Estruturas Vegetais/metabolismo , Eliminação de Resíduos , Scrophulariaceae/crescimento & desenvolvimento , Scrophulariaceae/metabolismo
20.
Micromachines (Basel) ; 13(6)2022 Jun 17.
Artigo em Inglês | MEDLINE | ID: mdl-35744572

RESUMO

The die-bonding layer between chips and substrate determinates the heat conduction efficiency of high-power LED. Sn-based solder, AuSn20 eutectic, and nano-Ag paste were widely applied to LED interconnection. In this paper, the optical-thermal performances and high-temperature reliability of LED with these bonding materials have systematically compared and studied. The thermal conductivity, electrical resistivity, and mechanical property of these bonding materials were characterized. The LED module packaged with nano-Ag has a minimum working temperature of 21.5 °C. The total thermal resistance of LED packaged with nano-Ag, Au80Sn20, and SAC305 is 4.82, 7.84, and 8.75 K/W, respectively, which is 4.72, 6.14, and 7.84 K/W higher after aging for 500 h. Meanwhile, the junction temperature change of these LEDs increases from 2.33, 3.76, and 4.25 °C to 4.34, 4.81, and 6.41 °C after aging, respectively. The thermal resistance of the nano-Ag, Au80Sn20 and SAC305 layer after aging is 1.5%, 65.7%, and 151.5% higher than before aging, respectively. After aging, the LED bonded with nano-Ag has the better optical performances in spectral intensity and light output power, which indicates its excellent heat dissipation can improve the light efficiency. These results demonstrate the nano-Ag bonding material could enhance the optical-thermal performances and high-temperature reliability of high-power LED.

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