Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 67
Filtrar
1.
Opt Express ; 32(7): 11613-11628, 2024 Mar 25.
Artículo en Inglés | MEDLINE | ID: mdl-38571004

RESUMEN

The increasing use of transparent ceramics in laser systems presents a challenge; their low damage threshold has become a significant impediment to the development of powerful laser systems. Consequently, it is imperative to undertake research into the damage sustained by these materials. Micropores, the most common structural defects in transparent ceramics, inevitably remain within the material during its preparation process. However, the relationship between the density and size of these micropores and their impact on nanosecond laser damage threshold and damage evolution remains unclear. In this study, we utilize the annealing process to effectively manage the density and size of micropores, establishing a correlation between micropores in relation to damage thresholds. This study confirms for the first time that micropores significantly contribute to laser damage, comparing and analyzing the damage morphology characteristics of both front and rear surfaces of transparent ceramics. It also presents, potential mechanisms that may contribute to these differences in damage. This paper offers guidance for controlling micropores during the preparation and processing of transparent ceramics with high laser damage thresholds. The findings are expected to further improve the anti-nanosecond laser damage capabilities of transparent ceramics.

2.
Nat Commun ; 15(1): 897, 2024 Feb 05.
Artículo en Inglés | MEDLINE | ID: mdl-38316783

RESUMEN

Descriptive data are rapidly expanding in biomedical research. Instead, functional validation methods with sufficient complexity remain underdeveloped. Transcriptional reporters allow experimental characterization and manipulation of developmental and disease cell states, but their design lacks flexibility. Here, we report logical design of synthetic cis-regulatory DNA (LSD), a computational framework leveraging phenotypic biomarkers and trans-regulatory networks as input to design reporters marking the activity of selected cellular states and pathways. LSD uses bulk or single-cell biomarkers and a reference genome or custom cis-regulatory DNA datasets with user-defined boundary regions. By benchmarking validated reporters, we integrate LSD with a computational ranking of phenotypic specificity of putative cis-regulatory DNA. Experimentally, LSD-designed reporters targeting a wide range of cell states are functional without minimal promoters. Applied to broadly expressed genes from human and mouse tissues, LSD generates functional housekeeper-like sLCRs compatible with size constraints of AAV vectors for gene therapy applications. A mesenchymal glioblastoma reporter designed by LSD outperforms previously validated ones and canonical cell surface markers. In genome-scale CRISPRa screens, LSD facilitates the discovery of known and novel bona fide cell-state drivers. Thus, LSD captures core principles of cis-regulation and is broadly applicable to studying complex cell states and mechanisms of transcriptional regulation.


Asunto(s)
ADN , Regulación de la Expresión Génica , Animales , Humanos , Ratones , Regiones Promotoras Genéticas/genética , Expresión Génica , Biomarcadores
3.
Environ Sci Pollut Res Int ; 31(3): 4290-4309, 2024 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-38097841

RESUMEN

In order to analyze what factors may affect the role of carbon trading pilot in promoting total factor productivity, this paper constructs DID model combining information of listed companies with city and industry characteristics. The moderating effect model is used to research the influence of firms' induced behavior. The results show that (1) the characteristics of a city can influence the impact of carbon trading pilot, which is associated with the city's dominant industry, resource endowment, and geographical location; (2) the effect of carbon trading pilot is heterogeneous, primarily indicating a stronger effect on high-emission industries, while having no significant impact on high-pollution industries; and (3) the induced behavior of businesses, such as increasing green innovation and environmental protection expenditure, potentially "crowding out" the effects of the carbon trading pilot.


Asunto(s)
Carbono , Comercio , Contaminación Ambiental , Gastos en Salud , Industrias , China
4.
Ann Nucl Med ; 38(3): 188-198, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-38145431

RESUMEN

OBJECTIVES: To elucidate the impact of [18F]FDG positron emission tomography/computed tomography (PET/CT) vs. CT workup on staging and prognostic evaluation of clinical stage (c) I-II NSCLC. METHODS: We retrospectively identified 659 cI-II NSCLC who underwent CT (267 patients) or preoperative CT followed by PET/CT (392 patients), followed by curative-intended complete resection in our hospital from January 2008 to December 2013. Differences were assessed between preoperative and postoperative stage. Five-year disease-free survival (DFS) and overall survival (OS) rates were calculated using the Kaplan-Meier approach and compared with log-rank test. Impact of preoperative PET/CT on survival was assessed by Cox regression analysis. RESULTS: The study included 659 patients [mean age, 59.5 years ± 10.8 (standard deviation); 379 men]. The PET/CT group was superior over CT group in DFS [12.6 vs. 6.9 years, HR 0.67 (95% CI 0.53-0.84), p < 0.001] and OS [13.9 vs. 10.5 years, HR 0.64 (95% CI 0.50-0.81), p < 0.001]. In CT group, more patients thought to have cN0 migrated to pN1/2 disease as compared with PET/CT group [26.4% (66/250) vs. 19.2% (67/349), p < 0.001], resulting in more stage cI cases being upstaged to pII-IV [24.7% (49/198) vs. 16.1% (47/292), p = 0.02], yet this was not found in cII NSCLC [27.5% (19/69) vs. 27.0% (27/100), p = 0.94]. Cox regression analysis identified preoperative PET/CT as an independent prognostic factor of OS and DFS (p = 0.002, HR = 0.69, 95% CI 0.54-0.88; p = 0.004, HR = 0.72, 95% CI 0.58-0.90). CONCLUSION: Addition of preoperative [18F]FDG PET/CT was associated with superior DFS and OS in resectable cI-II NSCLC, which may result from accurate staging and stage-appropriate therapy.


Asunto(s)
Carcinoma de Pulmón de Células no Pequeñas , Neoplasias Pulmonares , Masculino , Humanos , Persona de Mediana Edad , Carcinoma de Pulmón de Células no Pequeñas/diagnóstico por imagen , Carcinoma de Pulmón de Células no Pequeñas/cirugía , Tomografía Computarizada por Tomografía de Emisión de Positrones/métodos , Fluorodesoxiglucosa F18 , Estudios de Seguimiento , Neoplasias Pulmonares/diagnóstico por imagen , Neoplasias Pulmonares/cirugía , Estudios Retrospectivos , Pronóstico , Estadificación de Neoplasias , Radiofármacos
5.
Signal Transduct Target Ther ; 8(1): 442, 2023 12 06.
Artículo en Inglés | MEDLINE | ID: mdl-38057314

RESUMEN

This prospective multicenter phase II study evaluated the clinical efficacy of neoadjuvant nivolumab-exclusive (N) and nivolumab-chemotherapy (N/C) combinations based on PD-L1 expression. Eligible patients exhibited resectable clinical stage IIA-IIIB (AJCC 8th edition) NSCLC without EGFR/ALK alterations. Patients received either mono-nivolumab (N) or nivolumab + nab-paclitaxel+ carboplatin (N/C) for three cycles based on PD-L1 expression. The primary endpoint was the major pathological response (MPR). Key secondary endpoints included the pathologic complete response (pCR), objective response rate (ORR), and event-free survival (EFS). Baseline PD-L1 expression and perioperative circulating tumor DNA (ctDNA) status were correlated with pCR and EFS. Fifty-two patients were enrolled, with 46 undergoing surgeries. The MPR was 50.0% (26/52), with 25.0% (13/52) achieving pCR, and 16.7% and 66.7% for patients with PD-L1 ≥ 50% in N and N/C groups, respectively. Thirteen (25.0%) patients experienced grade 3 or higher immune-related adverse events during neoadjuvant treatment. Patients with post-neoadjuvant ctDNA negativity was more likely to have pCR (39.1%) compared with those remained positive (6.7%, odds ratio = 6.14, 95% CI 0.84-Inf, p = 0.077). With a median follow-up of 25.1 months, the 18-month EFS rate was 64.8% (95% CI 51.9-81.0%). For patients with ctDNA- vs. ctDNA + , the 18m-EFS rate was 93.8% vs 47.3% (HR, 0.15; 95% CI 0.04, 0.94; p = 0.005). Immunochemotherapy may serve as an optimal neoadjuvant treatment even for patients with PD-L1 expression ≥ 50%. ctDNA negativity following neoadjuvant treatment and surgery could help identify superior pathological and survival benefits, which requires further confirmation in a prospective clinical trial (NCT04015778).


Asunto(s)
Carcinoma de Pulmón de Células no Pequeñas , Neoplasias Pulmonares , Humanos , Nivolumab/uso terapéutico , Terapia Neoadyuvante/efectos adversos , Platino (Metal)/uso terapéutico , Antígeno B7-H1/genética , Estudios Prospectivos , Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Carcinoma de Pulmón de Células no Pequeñas/genética , Carcinoma de Pulmón de Células no Pequeñas/patología , Neoplasias Pulmonares/tratamiento farmacológico , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patología
6.
iScience ; 26(10): 107699, 2023 Oct 20.
Artículo en Inglés | MEDLINE | ID: mdl-37810252

RESUMEN

Pulmonary nodules with part-solid imaging features manifest during the progression from preinvasive to invasive lung adenocarcinoma. To define the spatial composition and evolutionary trajectories of early-stage lung adenocarcinoma, we combined spatial transcriptomics (ST) and pathological annotations from 20 part-solid nodules (PSNs), four of which were matched with single-cell RNA sequencing. Two malignant cell populations (MC1 and MC2) were identified, and a linear evolutionary relationship was observed. Compared to MC2, the pre-existing malignant MC1 exhibited a lower metastatic signature, corresponding to the preinvasive component (lepidic) on pathology and the ground glass component on PSN imaging. Higher immune infiltration was observed among MC1 regions in ST profiles, and further analysis revealed that macrophages may be involved in this process through the CD74 axis. This work provides deeper insights into the evolutionary process and spatial immune cell composition behind PSNs and highlights the mechanisms of immune escape behind this adenocarcinoma trajectory.

7.
Ying Yong Sheng Tai Xue Bao ; 34(6): 1601-1609, 2023 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-37694423

RESUMEN

Protected areas (PAs) are important barriers to ensure the ecological security of territory. Light pollution is a threat to PAs, which is particularly obvious in the urban agglomeration environment. We used multi-source big data (satellite remote sensing light data, land cover types and points of interest) to quantitatively analyze the temporal and spatial dynamics of nighttime light in the PAs of the Pearl River Delta (PRD) urban agglomeration from 2000 to 2018, the correlation between the night light environment within the PAs and human activity intensity outside, as well as the sensitive distance of the PAs to artificial light interference. The results showed that the total value of nighttime light data of PAs in the PRD increased from 71107 nanoW·cm-2·sr-1 to 127682 nanoW·cm-2·sr-1 from 2000 to 2018, the mean value per pixel increased from 15.3 nanoW·cm-2·sr-1 to 23.7 nanoW·cm-2·sr-1, and the lighted ratio increased from 73.3% to 86.4%, indicating that the nighttime light environment of PAs in the region were facing cumulative deterioration risks and serious challenges. The nighttime light intensity of the PAs in the core area of the PRD was much higher than that in the peripheral areas such as Zhaoqing and Huizhou, whereas the expansion degree of the PAs in the peripheral areas was higher than that in the core area. The nighttime light environment inside the PAs was positively correlated with the intensity of human activities around it. The most sensitive distance of the PAs to the artificial light interference around it was 10 km, and the interference degree tended to be stable after 30 km. We proposed that 0-10 km area outside the boundary of the PAs should be the light control core zone and 10-20 km area as the control buffer zone.


Asunto(s)
Macrodatos , Ríos , Humanos , China , Luz
8.
Sci Adv ; 9(25): eadf4975, 2023 06 23.
Artículo en Inglés | MEDLINE | ID: mdl-37343108

RESUMEN

Epithelial immune responses govern tissue homeostasis and offer drug targets against maladaptation. Here, we report a framework to generate drug discovery-ready reporters of cellular responses to viral infection. We reverse-engineered epithelial cell responses to SARS-CoV-2, the viral agent fueling the ongoing COVID-19 pandemic, and designed synthetic transcriptional reporters whose molecular logic comprises interferon-α/ß/γ and NF-κB pathways. Such regulatory potential reflected single-cell data from experimental models to severe COVID-19 patient epithelial cells infected by SARS-CoV-2. SARS-CoV-2, type I interferons, and RIG-I drive reporter activation. Live-cell image-based phenotypic drug screens identified JAK inhibitors and DNA damage inducers as antagonistic modulators of epithelial cell response to interferons, RIG-I stimulation, and SARS-CoV-2. Synergistic or antagonistic modulation of the reporter by drugs underscored their mechanism of action and convergence on endogenous transcriptional programs. Our study describes a tool for dissecting antiviral responses to infection and sterile cues and rapidly discovering rational drug combinations for emerging viruses of concern.


Asunto(s)
COVID-19 , Interferón Tipo I , Humanos , SARS-CoV-2 , Pandemias , Células Epiteliales
9.
Thorac Cancer ; 14(5): 462-469, 2023 02.
Artículo en Inglés | MEDLINE | ID: mdl-36511202

RESUMEN

BACKGROUND: Anatomical variations often pose challenges to pulmonary surgery. Previous studies have mainly described the frequencies of bronchovascular anatomical variations in pulmonary segments, but did not determine the differences between pulmonary segments and the regularity behind these anatomical variations. Here, we attempted to investigate the regularity of bronchovascular anatomical variations in different pulmonary segments. METHODS: Thin-slice enhanced computed tomography data of 800 cases from our center were included in this study. Digitalized three-dimensional virtual lung segmentation was done, the dominant and inferior lung segments of the right upper lobe were defined, and the regularity of anatomical variations was explored. RESULTS: The mean volume ratio of the anterior segment of the right upper lobe (39.6 ± 8.6%) was highest, and that of the posterior segment (28.6 ± 7.9%) was lowest. Therefore, the dominant-type segment (DS + SDS) was dominant in the anterior segment, accounting for 74.6% (597/800), and the inferior-type segment (SIS + IS) was dominant in the posterior segment of the right upper lobe, accounting for 71.5% of cases (573/800). During the transformation of dominant and inferior lung segments, the corresponding regularity of anatomical variations could be displayed. For example, with an increase in the volume of the anterior segment of the right upper lobe, the occurrence rate of the bifurcated type of bronchus (B1 + 2, B3), the "central vein type" and the involvement of the trunk inferior and ascending artery in the blood supply of anterior segment gradually increased. CONCLUSIONS: The existence of dominant segments will increase the diversity of anatomical variations and the complexity of pulmonary segmentectomy.


Asunto(s)
Procedimientos Quirúrgicos Pulmonares , Venas Pulmonares , Humanos , Pulmón/cirugía , Arteria Pulmonar , Bronquios/diagnóstico por imagen
10.
iScience ; 25(12): 105496, 2022 Dec 22.
Artículo en Inglés | MEDLINE | ID: mdl-36419852

RESUMEN

The interaction of water molecules with graphene oxide (GO) at the interface or surface will lead to the reversible deformation response of GO-based materials. However, the fabrication of structurally stable and highly sensitive GO-based humidity-responsive films remains a challenge. Since the stability and sensitivity of GO-based humidity-responsive devices are significantly limited by the deformation differences between different components. Herein, we demonstrate that polyamidoamine (PAMAM) bridge-enhanced carboxylated holey GO (hGC/PAMAM) films are sensitive to moisture and exhibit excellent stability in water. Experiments and molecular dynamics (MD) simulation show that the formation of N-C=O between PAMAM and GO sheets significantly increased the interlayer bonding force. Dynamic monitoring of the surface strain of the hGC/PAMAM films showed that the strains spread a gradient from the high-humidity to the low-humidity side, causing asymmetric expansion along the horizontal and vertical directions. This work will provide a better understanding of the mechanism of water molecule transport between layers.

11.
Front Oncol ; 12: 1002953, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-36313666

RESUMEN

Background: Estimating the growth of pulmonary sub-solid nodules (SSNs) is crucial to the successful management of them during follow-up periods. The purpose of this study is to (1) investigate the measurement sensitivity of diameter, volume, and mass of SSNs for identifying growth and (2) seek to establish a deep learning-based model to predict the growth of SSNs. Methods: A total of 2,523 patients underwent at least 2-year examination records retrospectively collected with sub-solid nodules. A total of 2,358 patients with 3,120 SSNs from the NLST dataset were randomly divided into training and validation sets. Patients from the Yibicom Health Management Center and Guangdong Provincial People's Hospital were collected as an external test set (165 patients with 213 SSN). Trained models based on LUNA16 and Lndb19 datasets were employed to automatically obtain the diameter, volume, and mass of SSNs. Then, the increase rate in measurements between cancer and non-cancer groups was studied to evaluate the most appropriate way to identify growth-associated lung cancer. Further, according to the selected measurement, all SSNs were classified into two groups: growth and non-growth. Based on the data, the deep learning-based model (SiamModel) and radiomics model were developed and verified. Results: The double time of diameter, volume, and mass were 711 vs. 963 days (P = 0.20), 552 vs. 621 days (P = 0.04) and 488 vs. 623 days (P< 0.001) in the cancer and non-cancer groups, respectively. Our proposed SiamModel performed better than the radiomics model in both the NLST validation set and external test set, with an AUC of 0.858 (95% CI 0.786-0.921) and 0.760 (95% CI 0.646-0.857) in the validation set and 0.862 (95% CI 0.789-0.927) and 0.681 (95% CI 0.506-0.841) in the external test set, respectively. Furthermore, our SiamModel could use the data from first-time CT to predict the growth of SSNs, with an AUC of 0.855 (95% CI 0.793-0.908) in the NLST validation set and 0.821 (95% CI 0.725-0.904) in the external test set. Conclusion: Mass increase rate can reflect more sensitively the growth of SSNs associated with lung cancer than diameter and volume increase rates. A deep learning-based model has a great potential to predict the growth of SSNs.

12.
NPJ Precis Oncol ; 6(1): 66, 2022 Sep 19.
Artículo en Inglés | MEDLINE | ID: mdl-36123526

RESUMEN

Despite limited efficacy of immunotherapy for advanced non-small-cell lung cancer (NSCLC) with driver mutations, whether neoadjuvant immunotherapy could be clinically valuable in those patients warrants further investigation. We utilized 40 oncogene-mutant NSCLC treated with induction immunotherapy from a large consecutive multicenter cohort. Overall response rate was 62.5% while 2 patients had disease progression. Of 39 patients that received surgery, R0 resection rate was 97.4%. The major pathological response (MPR) rate was 37.5% and the pathological complete response (pCR) rate was 12.5%. Pre-treatment PD-L1 expression was not a predictive biomarker in these patients. Median disease-free survival for all oncogenic mutation and EGFR mutation was 28.5 months. Indirect comparison through integrating CTONG1103 cohort showed neoadjuvant immunotherapy plus chemotherapy yielded the most superior efficacy among erlotinib and chemotherapy for resectable EGFR-mutant NSCLC. No MPR patients were identified with neoadjuvant immunotherapy plus chemotherapy for uncommon EGFR insertion or point mutations. Our results indicated the potential clinical feasibility of neoadjuvant immunotherapy for resectable localized oncogene-mutant NSCLC especially for EGFR-mutant NSCLC.

13.
Thorac Cancer ; 13(15): 2210-2222, 2022 08.
Artículo en Inglés | MEDLINE | ID: mdl-35818719

RESUMEN

OBJECTIVE: In recent years, the lung cancer incidence has grown and the population is younger. We intend to find out the true detection rate of pulmonary nodules and the incidence of lung cancer in the population and search for the risk factors. METHOD: Hospital employees ≥40 years old who underwent low-dose computed tomography (CT) lung cancer screening from January 2019 to March 2022 were selected to record CT-imaging characteristics, pathology, staging, and questionnaires to investigate past history, smoking history, diet, mental health, etc. PM2.5 and radiation intake in radiation-related occupation received monitoring in hospital. RESULT: The detection rate of suspicious pulmonary nodules was 9.1% (233/2552), and the incidence rate of lung cancer (including adenocarcinoma in situ) was 4.0% (103/2552). Morbidity among doctors, nurses, technicians, administers, and logistics was no difference (p = 0.184), but higher in women than in men (4.7% vs 2.4% p = 0.002). The invasiveness increased with age and CT density of nodules (p = 0.018). The relationship between lung cancer morbidity and PM2.5 was not clear (p = 0.543); and no lung cancer has been found in employees related ionizing radiation. CONCLUSION: The high screening rate has brought about a high incidence of lung cancer. At present, the risk factor analysis of lung cancer based on small samples cannot find the direct cause. Most of the ground glass opacity (GGO)s detected by LDCT screening are indolent, but there are also rapidly progressive lung cancer. A predictive model to identify active and indolent GGO is necessary.


Asunto(s)
Neoplasias Pulmonares , Nódulos Pulmonares Múltiples , Adulto , China/epidemiología , Detección Precoz del Cáncer/métodos , Femenino , Hospitales , Humanos , Incidencia , Neoplasias Pulmonares/diagnóstico por imagen , Neoplasias Pulmonares/epidemiología , Neoplasias Pulmonares/etiología , Masculino , Factores de Riesgo
14.
Thorac Cancer ; 13(17): 2524-2531, 2022 09.
Artículo en Inglés | MEDLINE | ID: mdl-35822254

RESUMEN

Major pathological response (MPR) is a potential surrogate for overall survival. We determined whether the dynamic changes in 18 F-labeled fluoro-2-deoxyglucose positron emission tomography/computed tomography (18 F-FDG PET/CT) were associated with MPR in patients receiving neoadjuvant immunotherapy. Forty-four patients with stage II-III non-small cell lung cancer (NSCLC) who received neoadjuvant immunotherapy and radical surgery were enrolled. Moreover, 18 F-FDG PET/CT scans were performed at baseline and within 1 week before surgery to evaluate the disease. All histological sections were reviewed to assess MPR. The detailed clinical features of the patients were analyzed. The reliability of the clinical variables was assessed in differentiating between MPR and non-MPR using logistic regression. Receiver-operating characteristic (ROC) curve analysis identified the SUVmax changes threshold most associated with MPR. Most of the patients were pathologically diagnosed with squamous cell carcinoma and received anti-PD-1 antibodies plus chemotherapy. The immunotherapy regimens included nivolumab, pembrolizumab, and camrelizumab. MPR was observed in more than half of lesions. Tumors with MPR had a higher decrease in the longest dimension on dynamic PET/CT than those without MPR. Furthermore, the decline in SUVmax was significantly different between MPR and non-MPR diseases, and MPR lesions had a prominent mean reduction in SUVmax. SUVmax reduction was independently associated with MPR in the multivariate regression. On ROC analysis, the threshold of SUVmax decrease in 60% was associated with MPR. Dynamic changes in SUVmax were associated with MPR. The tumors with MPR showed a greater PET/CT response than those without MPR. A SUVmax decrease of more than 60% is more likely to result in an MPR after receiving neoadjuvant immunotherapy.


Asunto(s)
Carcinoma de Pulmón de Células no Pequeñas , Neoplasias Pulmonares , Carcinoma de Pulmón de Células no Pequeñas/diagnóstico por imagen , Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Fluorodesoxiglucosa F18 , Humanos , Inmunoterapia , Neoplasias Pulmonares/diagnóstico por imagen , Neoplasias Pulmonares/tratamiento farmacológico , Terapia Neoadyuvante , Tomografía Computarizada por Tomografía de Emisión de Positrones/métodos , Tomografía de Emisión de Positrones , Reproducibilidad de los Resultados , Estudios Retrospectivos
15.
BMC Med ; 20(1): 197, 2022 05 30.
Artículo en Inglés | MEDLINE | ID: mdl-35644609

RESUMEN

BACKGROUND: Despite the reported efficacy of osimertinib, central nervous system (CNS) progression is still frequent in EGFR-mutated NSCLC. This study aimed to reveal site-specific resistant mechanisms to osimertinib and investigate subsequent treatments for leptomeningeal metastases (LM). METHODS: EGFR-mutated NSCLC with LM who progressed on osimertinib were included. Molecular analysis of cerebrospinal fluid (CSF) at osimertinib progression was performed. Subsequent treatments of LM were collected and analyzed. RESULTS: A total of 246 patients were identified. Only those with LM as a progression site on osimertinib were included (n=81). In 58 CSF-plasma pairs, more alterations were uniquely detected in CSF (77%) than in plasma (7%). These mechanisms led to 22 patients receiving matched targeted therapy. Among them, 16 (72.7%) had a clinical response. The median overall survival was 7.2 months. For non-matched therapy (n=59), the osimertinib combination had a longer median overall survival than the regimen switch in CNS-only progression (15.3 vs. 7 months, p=0.03). Finally, serial monitoring by CSF revealed the potential evolution of LM. CONCLUSIONS: Private resistant mechanisms in CSF might match osimertinib-resistant LM for targeted therapy. Besides, continuing osimertinib with intensification strategy might prolong survival, especially for those with CNS-only progression. Prospective  exploration is needed.


Asunto(s)
Carcinoma de Pulmón de Células no Pequeñas , Neoplasias Pulmonares , Acrilamidas , Compuestos de Anilina , Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Carcinoma de Pulmón de Células no Pequeñas/genética , Carcinoma de Pulmón de Células no Pequeñas/patología , Receptores ErbB/genética , Receptores ErbB/uso terapéutico , Humanos , Neoplasias Pulmonares/tratamiento farmacológico , Neoplasias Pulmonares/genética , Mutación , Estudios Prospectivos
16.
Cancer Discov ; 12(7): 1690-1701, 2022 07 06.
Artículo en Inglés | MEDLINE | ID: mdl-35543554

RESUMEN

The efficacy and potential limitations of molecular residual disease (MRD) detection urgently need to be fully elucidated in a larger population of non-small cell lung cancer (NSCLC). We enrolled 261 patients with stages I to III NSCLC who underwent definitive surgery, and 913 peripheral blood samples were successfully detected by MRD assay. Within the population, only six patients (3.2%) with longitudinal undetectable MRD recurred, resulting in a negative predictive value of 96.8%. Longitudinal undetectable MRD may define the patients who were cured. The peak risk of developing detectable MRD was approximately 18 months after landmark detection. Correspondingly, the positive predictive value of longitudinal detectable MRD was 89.1%, with a median lead time of 3.4 months. However, brain-only recurrence was less commonly detected by MRD (n = 1/5, 20%). Further subgroup analyses revealed that patients with undetectable MRD might not benefit from adjuvant therapy. Together, these results expound the value of MRD in NSCLC. SIGNIFICANCE: This study confirms the prognostic value of MRD detection in patients with NSCLC after definitive surgery, especially in those with longitudinal undetectable MRD, which might represent the potentially cured population regardless of stage and adjuvant therapy. Moreover, the risk of developing detectable MRD decreased stepwise after 18 months since landmark detection. This article is highlighted in the In This Issue feature, p. 1599.


Asunto(s)
Carcinoma de Pulmón de Células no Pequeñas , Neoplasias Pulmonares , Carcinoma de Pulmón de Células no Pequeñas/diagnóstico , Carcinoma de Pulmón de Células no Pequeñas/genética , Carcinoma de Pulmón de Células no Pequeñas/cirugía , Humanos , Neoplasias Pulmonares/diagnóstico , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/cirugía , Neoplasia Residual/diagnóstico , Pronóstico
17.
Clin Lung Cancer ; 23(2): 135-142, 2022 03.
Artículo en Inglés | MEDLINE | ID: mdl-34645582

RESUMEN

BACKGROUND: Pleural effusion (PE) has been one of the promising sources of liquid biopsy in advanced lung cancer patients. However, its clinical utility is not widely accepted due to the lack of full estimation of its potential versus routine clinical samples. METHOD: A total of 164 advanced lung cancer patients were enrolled with 164 matched tumor tissue and PE-cfDNA, 153 accompanied plasma and 63 1PE-sDNA. RESULT: PE-cfDNA displayed significantly higher median mutant allele frequency and an overall mutation concordance rate of 65% to tissue, which was higher than PE-sDNA (43%) and plasma-cfDNA (43%). The discrepancies between PE-cfDNA and tumor tissue were high in several genes, including SMARCA4, PIK3CA, ERBB2, KM T2A, ALK and NF1. For clinically actionable mutations, the concordance rate between PE-cfDNA and tumor tissue is 87%. Eleven patients were identified with actionable mutations in PE-cfDNA and four patients benefited from PE-cfDNA-guided targeted. Meanwhile, PE-cfDNA recapitulated mutations of diverse tissue origins and provided more mutational information under the circumstance that tumor tissue or tumor tissue of different origins were unavailable. The combination of tumor tissue and PE-cfDNA profiling increased positive detection rates of patients compared to tumor tissue alone. Our finding highlighted the importance of PE-cfDNA in the optimal selection of patients for targeted therapy. CONCLUSION: The PE-cfDNA-based liquid biopsy displays better performance in the characterization of gene alterations than PE-sDNA and plasma-cfDNA. PE-cfDNA together with tumor tissue profiling optimizes comprehensively genomic profiling of lung cancer patients, which might be important for selecting patients for better treatment management.


Asunto(s)
Carcinoma de Pulmón de Células no Pequeñas/genética , Ácidos Nucleicos Libres de Células/genética , ADN Tumoral Circulante/genética , Análisis Mutacional de ADN/métodos , Neoplasias Pulmonares/genética , Biomarcadores de Tumor , Carcinoma de Pulmón de Células no Pequeñas/patología , Estudios de Casos y Controles , Humanos , Biopsia Líquida , Neoplasias Pulmonares/patología , Derrame Pleural
20.
Eur J Cancer ; 150: 23-30, 2021 06.
Artículo en Inglés | MEDLINE | ID: mdl-33882375

RESUMEN

OBJECTIVE: Leptomeningeal metastases (LM) occur in up to 5% of non-small cell lung cancer (NSCLC) patients and often develop after previous systemic treatments. In this article, we explored whether immune checkpoint inhibitors (ICIs) enhanced the dismal survival of patients with LM. MATERIALS AND METHODS: Data on NSCLC patients with LM prescribed ICIs were collected at the Guangdong Lung Cancer Institute. Furthermore, relevant literature was reviewed. RESULTS: A total of 255 NSCLC patients diagnosed with LM were screened from January 2015 to March 2020 at our institute. Cases reported by literature were also included. Finally, 32 NSCLC patients received ICIs after LM diagnosis; their median age was 55 years. Druggable genes were detected in 37.5% of all patients. The ICI regimens included nivolumab (n = 21), pembrolizumab (n = 9), and atezolizumab (n = 2). Ultimately, 62.5% of patients evidenced neurological symptom controlled. Two patients exhibited both intracranial and extracranial complete tumour response; one patient showed both intracranial and extracranial partial response (PR), one patient indicated intracranial PR and a systemic PR, and one patient showed central nervous system PR without extracranial response reported. The median progression-free survival (PFS) in the single-agent subgroup was 2.1 months (95% confidence interval [CI]: 1.4-2.9 months), and the median overall survival (OS) was 4.0 months (95% CI: 0.1-13.3 months). In the combined subgroup, the median PFS and OS were 3.0 months (95% CI: 1.1-4.9 months) and 5.4 months (95% CI: 0.5-10.3 months), respectively. Three patients exhibited remarkable PFS of over 20 months: all patients had ICI single agent, received cranial radiotherapy before ICI prescription, and took ICIs as second-line therapy, and two patients were EGFR/ALK wild type. Multivariate analysis showed that a better Eastern Cooperative Oncology Group Performance Status (ECOG-PS) score was associated with prolonged PFS (P = 0.04). No difference in survival was seen between monotherapy and combination therapy groups. CONCLUSION: NSCLC patients with LM may benefit from ICIs of both monotherapy and combination with other therapies, especially those with good ECOG-PS scores. Further work in this regard is required.


Asunto(s)
Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Inhibidores de Puntos de Control Inmunológico/uso terapéutico , Neoplasias Pulmonares/tratamiento farmacológico , Carcinomatosis Meníngea/tratamiento farmacológico , Adulto , Anciano , Anciano de 80 o más Años , Carcinoma de Pulmón de Células no Pequeñas/inmunología , Carcinoma de Pulmón de Células no Pequeñas/mortalidad , Carcinoma de Pulmón de Células no Pequeñas/secundario , Progresión de la Enfermedad , Femenino , Humanos , Inhibidores de Puntos de Control Inmunológico/efectos adversos , Neoplasias Pulmonares/inmunología , Neoplasias Pulmonares/mortalidad , Neoplasias Pulmonares/patología , Masculino , Carcinomatosis Meníngea/inmunología , Carcinomatosis Meníngea/mortalidad , Carcinomatosis Meníngea/secundario , Persona de Mediana Edad , Supervivencia sin Progresión , Estudios Retrospectivos , Factores de Tiempo
SELECCIÓN DE REFERENCIAS
DETALLE DE LA BÚSQUEDA
...