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1.
Nano Lett ; 23(13): 5902-5910, 2023 Jul 12.
Artigo em Inglês | MEDLINE | ID: mdl-37326403

RESUMO

Resistive random access memory (RRAM) is an important technology for both data storage and neuromorphic computation, where the dynamics of nanoscale conductive filaments lies at the core of the technology. Here, we analyze the current noise of various silicon-based memristors that involves the creation of a percolation path at the intermediate phase of filament growth. Remarkably, we find that these atomic switching events follow scale-free avalanche dynamics with exponents satisfying the criteria for criticality. We further prove that the switching dynamics are universal and show little dependence on device sizes or material features. Utilizing criticality in memristors, we simulate the functionality of hair cells in auditory sensory systems by observing the frequency selectivity of input stimuli with tunable characteristic frequency. We further demonstrate a single-memristor-based sensing primitive for representation of input stimuli that exceeds the theoretical limits dictated by the Nyquist-Shannon theorem.

2.
Small ; 19(11): e2207044, 2023 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-36642802

RESUMO

Precise design of low-cost, efficient and definite electrocatalysts is the key to sustainable renewable energy. Herein, this work develops a targeted-anchored and subsequent spontaneous-redox strategy to synthesize nickel-iron layered double hydroxide (LDH) nanosheets anchored with monodispersed platinum (Pt) sites (Pt@LDH). Intermediate metal-organic frameworks (MOF)/LDH heterostructure not only provides numerous confine points to guarantee the stability of Pt sites, but also excites the spontaneous reduction for PtII . Electronic structure, charge transfer ability and reaction kinetics of Pt@LDH can be effectively facilitated by the monodispersed Pt moieties. As a result, the optimized Pt@LDH that with the 5% ultra-low content Pt exhibits the significant increment in electrochemical water splitting performance in alkaline media, which only afford low overpotentials of 58 mV at 10 mA cm-2 for hydrogen evolution reaction (HER) and 239 mV at 10 mA cm-2 for oxygen evolution reaction (OER), respectively. In a real device, Pt@LDH can drive an overall water-splitting at low cell voltage of 1.49 V at 10 mA cm-2 , which can be superior to most reported similar LDH-based catalysts. Moreover, the versatility of the method is extended to other MOF precursors and noble metals for the design of ultrathin LDH supported monodispersed noble metal electrocatalysts promoting research interest in material design.

3.
Ann Surg Oncol ; 30(12): 7481-7491, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-37535274

RESUMO

BACKGROUND: This study aimed to determine the prognostic factors for the long-term outcome of stage IB non-small cell lung cancer (NSCLC). METHODS: Surgically resected patients with stage IB NSCLC diagnosed (based on TNM 8th edition) between April 2008 and December 2013 were retrospectively reviewed. The prognosis and possible risk factors among the stage IB NSCLC patients were evaluated. RESULTS: Of the 349 patients identified for the study, 80 (22.9%) received post-surgery adjuvant chemotherapy (ACT). The median follow-up time after surgery was 123.3 months. The 10-year overall survival (OS) rate was 69.6%, and the 10-year recurrence-free survival (RFS) rate was 62.8%. The patients in this cohort were divided into three groups (T1 with visceral pleural invasion [VPI], T2a without VPI, and T2a with VPI), and no significant differences in OS or RFS were found among the groups. Furthermore, survival analysis indicated that the absence of ground-glass opacity (GGO) components portends an adverse long-term OS and RFS. In a subgroup of patients with solid nodules, age older than 65 years (hazard ratio [HR] 1.987; 95% confidence interval [CI] 1.312-3.010; p = 0.001) and ACT (HR 0.392; 95% CI 0.225-0.684; p < 0.001) were independent prognostic factors for OS, whereas lymphovascular invasion (HR 1.792; 95% CI 0.995-3.227; p = 0.052) should be considered as an independent unfavorable prognostic factor for RFS. CONCLUSIONS: As an upstaging factor, VPI did not further stratify prognosis for the stage IB patients in our cohort. The presence of GGO components had a notable impact on a favorable prognosis in stage IB NSCLCs.

4.
Opt Express ; 30(15): 26967-26974, 2022 Jul 18.
Artigo em Inglês | MEDLINE | ID: mdl-36236878

RESUMO

Stimulated Raman scattering is a particularly robust nonlinearity, occurring in virtually every material because its spectral linewidth and associated frequency shift do not typically depend on phases or directions (i.e. wavevectors) of the interacting light beams. In amorphous materials such as glass fibers, Raman bandwidths are large, enabling its use as a broadband gain element. This ubiquity makes it a versatile means for achieving optical amplification or realizing lasers over a large range of pulsewidths at user-defined colors. However, this ease of deploying the effect also presents itself as a stubborn source of noise in fiber-based quantum sources or parasitic emission in fiber lasers. Here, we show that orbital angular momentum carrying light beams experiencing spin-orbit interactions yield novel phase-matching criteria for Raman scattering. This enables tailoring its spectral shape (by over half the Raman shift in a given material) as well as strength (by ∼ 100×) simply by controlling light's topological charge - a capability of utility across the multitude of applications where modulating Raman scattering is desired.

5.
Opt Express ; 30(16): 29708-29721, 2022 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-36299139

RESUMO

The strength of stimulated Brillouin scattering (SBS) in optical fibers is largely governed by the spatial overlap between supported optical and acoustic modes, leading to a complicated amalgamation of photon-phonon interactions in multimode fibers. Here, we study SBS dynamics in ring-core fibers that support modes carrying orbital angular momentum (OAM), which result in distinctive characteristics. We find that the OAM SBS response, as well as modal content, strongly depends on the polarization state of the pump, as OAM modes in fiber have distinct propagation dynamics depending on whether the input is circularly or linearly polarized. This is in contrast to conventionally posited wisdom that SBS strength is independent of the pump's input polarization state in an isotropic material. This increased specificity can lead to interesting effects such as spatial phase conjugation even in the presence of stably transmitted, i.e. non-aberrated, spatial pump modes. More generally, we show that using OAM modes yields additional degrees of control over SBS interactions beyond more conventional parameters, such as effective area, acousto-optic spatial overlaps, and material composition.

6.
Small ; 17(6): e2006259, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-33470525

RESUMO

Development of highly stabilized and reversible cathode materials has become a great challenge for sodium-ion batteries. O'3-type layered Mn-based oxides have deserved much attention as one of largely reversible-capacity cathodes featured by the resource-rich and low-toxic elements. However, the fragile slabs structure of typical layered oxides, low Mn-ion migration barriers, and Jahn-Teller distortion of Mn3+ have easily resulted in the severe degradation of cyclability and rate performances. Herein, a new queue-ordered superstructure is built up in the O'3-NaMn0.6 Al0.4 O2 cathode material. Through the light-metal Al substitution in O'3-NaMnO2 , the MnO6 and AlO6 octahedrons display the queue-ordered arrangements in the transition metal (TM) slabs. Interestingly, the presence of this superstructure can strengthen the layered structure, reduce the influence from Jahn-Teller effect, and suppress the TM-ions migrations during long-terms cycles. These characteristics results in O'3-NaMn0.6 Al0.4 O2 cathode deliver a high capacity of 160 mAh g-1 , an enhanced rate capability and the excellent cycling performance. This research strategy can provide the broaden insight for future electrode materials with high-performance sodium-ions storage.

7.
Exp Mol Pathol ; 123: 104684, 2021 12.
Artigo em Inglês | MEDLINE | ID: mdl-34547302

RESUMO

The immunoproteasomes are specific proteasomes that clear oxidant-damaged proteins under inflammatory conditions in various diseases. Toxoplasma gondii (T. gondii) infects the central nervous system and causeencephalitis. However, the relationship between the immunoproteasomes and brain inflammation during T. gondii infection is not well characterized. In this study, we established an in vivo mouse model of T. gondii PLK strain infection via intraperitoneal injection and evaluated the expression of immunoproteasome subunits in the brains of infected mice. The results demonstrated that first, pathological changes in the brains of infected mice increase in severity over time. Second, following T. gondii infection, activated microglia and astrocytes undergo a series of functional alterations and morphological transformations, including proliferation and migration. Third, T. gondii infection induces expression of inflammatory cytokines, including IFN-γ, IL-1ß, TNF-α, and IL-6. Fourth, the immunoproteasome subunits low-molecular-weight polypeptide 2 (LMP2), LMP7, and LMP10 mRNA and protein levels are significantly upregulated in T. gondii-infected mouse brains, as shown by RT-qPCR and western blot analysis, compared with that in vehicle-treated brains, and their expression is localized in the microglia, astrocytes, and neurons of T. gondii-infected brains, as determined via immunofluorescence staining. Furthermore, the western blot mean gray value for the immunoproteasome subunits and the positive microglia and astrocyte immunohistochemical signals in the brains of T. gondii-infected mice were positively correlated, indicating that the observed relationships were highly significant. Therefore, it was concluded that the induction of the immunoproteasomes is a pathogenic mechanism underlying T. gondii infection-induced inflammation.


Assuntos
Inflamação/genética , Complexo de Endopeptidases do Proteassoma/genética , Toxoplasmose/genética , Animais , Astrócitos/metabolismo , Astrócitos/patologia , Encéfalo/metabolismo , Encéfalo/microbiologia , Encéfalo/patologia , Humanos , Inflamação/microbiologia , Inflamação/patologia , Interferon gama/genética , Interleucina-1beta/genética , Interleucina-6/genética , Camundongos , Microglia/metabolismo , Microglia/patologia , Neurônios/metabolismo , Neurônios/patologia , Toxoplasma/genética , Toxoplasma/patogenicidade , Toxoplasmose/microbiologia , Toxoplasmose/patologia , Fator de Necrose Tumoral alfa/genética
8.
Opt Express ; 27(7): 9829-9837, 2019 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-31045141

RESUMO

Single-pixel cameras reconstruct images from a stream of spatial projection measurements recorded with a single-element detector, which itself has no spatial resolution. This enables the creation of imaging systems that can take advantage of the ultra-fast response times of single-element detectors. Here we present a single-pixel camera with a temporal resolution of 200 ps in the visible and short-wave infrared wavelengths, used here to study the transit time of distinct spatial modes transmitted through few-mode and orbital angular momentum mode conserving optical fiber. Our technique represents a way to study the spatial and temporal characteristics of light propagation in multimode optical fibers, which may find use in optical fiber design and communications.

9.
J Pept Sci ; 23(5): 392-402, 2017 May.
Artigo em Inglês | MEDLINE | ID: mdl-28299840

RESUMO

The misuse and overuse of antibiotics result in the emergence of resistant bacteria and fungi, which make an urgent need of the new antimicrobial agents. Nowadays, antimicrobial peptides have attracted great attention of researchers. However, the low physiological stability in biological system limits the application of naturally occurring antimicrobial peptides as novel therapeutics. In the present study, we synthesized derivatives of protonectin by substituting all the amino acid residues or the cationic lysine residue with the corresponding D-amino acids. Both the D-enantiomer of protonectin (D-prt) and D-Lys-protonectin (D-Lys-prt) exhibited strong antimicrobial activity against bacteria and fungi. Moreover, D-prt showed strong stability against trypsin, chymotrypsin and the human serum, while D-Lys-prt only showed strong stability against trypsin. Circular dichroism analysis revealed that D-Lys-prt still kept typical α-helical structure in the membrane mimicking environment, while D-prt showed left hand α-helical structure. In addition, propidium iodide uptake assay and bacteria and fungi killing experiments indicated that all D-amino acid substitution or partially D-amino acid substitution analogs could disrupt the integrity of membrane and lead the cell death. In summary, these findings suggested that D-prt and D-Lys-prt might be promising candidate antibiotic agents for therapeutic application against resistant bacteria and fungi infection. Copyright © 2017 European Peptide Society and John Wiley & Sons, Ltd.


Assuntos
Anti-Infecciosos/síntese química , Peptídeos Catiônicos Antimicrobianos/síntese química , Bactérias/efeitos dos fármacos , Fungos/efeitos dos fármacos , Venenos de Vespas/química , Substituição de Aminoácidos , Anti-Infecciosos/química , Anti-Infecciosos/farmacologia , Peptídeos Catiônicos Antimicrobianos/química , Peptídeos Catiônicos Antimicrobianos/farmacologia , Permeabilidade da Membrana Celular/efeitos dos fármacos , Dicroísmo Circular , Desenho de Fármacos , Testes de Sensibilidade Microbiana , Modelos Moleculares , Estrutura Secundária de Proteína , Relação Estrutura-Atividade , Venenos de Vespas/genética
10.
Biochim Biophys Acta ; 1848(10 Pt A): 2365-73, 2015 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-26209560

RESUMO

Candidiasis is often observed in immunocompromised patients and is the 4th most common cause of bloodstream infections. However, antifungals are limited, so novel antifungal agents are urgently needed. Antimicrobial peptides (AMPs) are considered as potential alternatives of conventional antibiotics. In the present study, antimicrobial peptide protonectin was chemically synthesized and its antifungal activity and mode of action were studied. Our results showed that protonectin has potent antifungal activity and fungicidal activity against the tested fungi cells. Its action mode involved the disruption of the membrane integrity and the inducing of the production of cellular ROS. Furthermore, protonectin could inhibit the formation of biofilm and kill the adherent fungi cells. In conclusion, with the increase of fungal infection, protonectin may offer a new strategy and be considered as a potential therapeutic agent against fungal disease.


Assuntos
Candida/classificação , Candida/fisiologia , Permeabilidade da Membrana Celular/fisiologia , Fluidez de Membrana/efeitos dos fármacos , Oligopeptídeos/farmacologia , Espécies Reativas de Oxigênio/metabolismo , Venenos de Vespas/farmacologia , Antifúngicos/química , Antifúngicos/farmacologia , Peptídeos Catiônicos Antimicrobianos/síntese química , Peptídeos Catiônicos Antimicrobianos/farmacologia , Candida/efeitos dos fármacos , Permeabilidade da Membrana Celular/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Sobrevivência Celular/fisiologia , Oligopeptídeos/síntese química , Venenos de Vespas/síntese química
11.
J Pept Sci ; 22(1): 28-35, 2016 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-26680221

RESUMO

The incidence of life-threatening invasive fungal infections increased significantly in recent years. However, the antifungal therapeutic options are very limited. Antimicrobial peptides are a class of potential lead chemical for the development of novel antifungal agents. Antimicrobial peptide polybia-CP was purified from the venom of the social wasp Polybia paulista. In this study, we synthesized polybia-CP and determined its antifungal effects against a series of Candidian species. Our results showed that polybia-CP has potent antifungal activity and fungicidal activity against the tested fungal cells with a proposed membrane-active action mode. In addition, polybia-CP could induce the increase of cellular reactive oxygen species production, which would attribute to its antifungal activity. In conclusion, the present study suggests that polybia-CP has potential as an antifungal agent or may offer a new strategy for antifungal therapeutic option.


Assuntos
Antifúngicos/farmacologia , Peptídeos Catiônicos Antimicrobianos/farmacologia , Candida/efeitos dos fármacos , Proteínas de Insetos/farmacologia , Venenos de Vespas/química , Animais , Antifúngicos/síntese química , Antifúngicos/isolamento & purificação , Peptídeos Catiônicos Antimicrobianos/síntese química , Peptídeos Catiônicos Antimicrobianos/isolamento & purificação , Candida/crescimento & desenvolvimento , Candida/metabolismo , Candida/ultraestrutura , Membrana Celular/efeitos dos fármacos , Membrana Celular/metabolismo , Membrana Celular/ultraestrutura , Parede Celular/efeitos dos fármacos , Parede Celular/metabolismo , Parede Celular/ultraestrutura , Eritrócitos/efeitos dos fármacos , Hemólise/efeitos dos fármacos , Humanos , Proteínas de Insetos/síntese química , Proteínas de Insetos/isolamento & purificação , Testes de Sensibilidade Microbiana , Ligação Proteica , Espécies Reativas de Oxigênio/agonistas , Espécies Reativas de Oxigênio/metabolismo , Vespas
12.
Opt Express ; 23(4): 5014-26, 2015 Feb 23.
Artigo em Inglês | MEDLINE | ID: mdl-25836536

RESUMO

We study the propagation of orbital angular momentum (OAM) modes in rectangular multimode waveguides. Due to the multimode interference effect, an OAM mode input forms self-images at certain propagation distances. As OAM modes can be decomposed as the superposition of a pair of quarter-wave phase-shifted even and odd modes, their symmetry properties lead to two different self-imaging categories - forming the OAM-maintaining and the field-splitting self-images. We analyze these phenomena using multimode interference theory, and establish the rules governing the OAM-maintaining self-imaging, which allows the multi-mode interference waveguides to be used as OAM mode splitters and couplers.

13.
Transl Lung Cancer Res ; 13(6): 1201-1209, 2024 Jun 30.
Artigo em Inglês | MEDLINE | ID: mdl-38973943

RESUMO

Background: The Japan Clinical Oncology Group (JCOG) 1211 suggested that segmentectomy should be considered as standard treatment for clinical T1N0 (cT1N0) ground glass opacity (GGO). However, over half of patients in JCOG1211 had pre-/minimal invasive adenocarcinoma. This study aims to retrospectively investigate the long-term survival of GGO featured cT1N0 invasive lung adenocarcinoma undergoing segmentectomy or lobectomy. Methods: This study screened patients with primary cT1N0 lung adenocarcinoma who received segmentectomy or lobectomy from 2010-2020. Prior computed tomography (CT) scans before surgery of all patients were reviewed and the inclusion was confirmed according to tumor diameter and consolidation tumor ratio (CTR). GGO nodules between 2-3 cm with CTR ≤0.5 or ≤2 cm with CTR between 0.25-0.5 were finally included. Patients with pathologically diagnosed pre-/minimally invasive lung adenocarcinoma were excluded. Long-term survivals between segmentectomy group and lobectomy group were compared after propensity score matching (PSM). Recurrence and postoperative complication events were also analyzed. Results: In total, 617 patients were enrolled, 159 received segmentectomy and 458 received lobectomy. Clinicopathological characteristics were well distributed between two groups. With a median follow-up time of 61.1 months (IQR: 42.3-71.7 months), after PSM, the 5-year overall survival rate was 98.8% (97.9-99.6%) for lobectomy and 99.3% (98.2-99.8%) for segmentectomy (P=0.42), the 5-year relapse-free survival rate was 95.3% (92.2-97.6%) for lobectomy and 95.2% for segmentectomy (92.3-98.7%) (P=0.81). The proportion of recurrence was 4.1% for lobectomy and 4.4% for segmentectomy (P=0.89). The proportion of grade 2 and above early postoperative complications was 9.6% for lobectomy and 8.8% for segmentectomy (P=0.86). Conclusions: For cT1N0 GGO featured invasive lung adenocarcinoma (2 cm < tumor diameter ≤3 cm, CTR ≤0.5 or tumor diameter ≤2 cm, 0.25< CTR ≤0.5), postoperative outcomes between segmentectomy group and lobectomy group were comparable. Concerning minimally invasive surgical strategy, segmentectomy should be confirmed as the standard surgical approach.

14.
Eur J Cancer ; 202: 113985, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38452722

RESUMO

BACKGROUND: In light of the ongoing clinical development of KRAS G12D-specific inhibitors, we sought to investigate the clinicopathologic, co-occurring genomic features and outcomes of patients with KRAS G12D-mutant lung adenocarcinoma. METHODS: 3828 patients with completely resected primary lung adenocarcinomas were examined for KRAS mutations between 2008 and 2020. The association between KRAS G12D and clinicopathologic features, molecular profiles, and outcomes was investigated. RESULTS: 65 patients (1.7%) with KRAS G12D-mutant lung adenocarcinoma were identified. KRAS G12D mutation was more frequent in males, former/current smokers, radiologic solid tumors, and invasive mucinous adenocarcinoma. TP53 and STK11 were the two most frequent concomitant mutations in the KRAS G12D group. KRAS G12D mutation did not appear to be a prognostic factor in resected stage I-III lung adenocarcinomas, while KRAS non-G12D mutation was related to worse survival, especially in stage I tumors. KRAS G12D mutations were associated with positive but low (1-49%) PD-L1 expression compared to negative (<1%), while KRAS non-G12D mutation was associated with high PD-L1 expression (≥50%). TP53 co-mutation indicated higher PD-L1 expression, while STK11 co-mutation had a negligible impact on PD-L1 expression. Furthermore, data mining of MSK datasets from cBioPortal revealed that KRAS G12D and SKT11 co-mutation were associated with a diminished response to immunotherapy. CONCLUSIONS: KRAS G12D-mutant lung adenocarcinoma harbored unique clinicopathologic and genomic characteristics. Despite not being prognostic in resected lung adenocarcinoma, KRAS G12D might be a valuable biomarker in combination with certain co-mutations for identifying relevant subgroups of patients that could eventually influence treatment regimens.


Assuntos
Adenocarcinoma de Pulmão , Neoplasias Pulmonares , Proteínas Proto-Oncogênicas p21(ras) , Humanos , Masculino , Adenocarcinoma de Pulmão/genética , Adenocarcinoma de Pulmão/cirurgia , Antígeno B7-H1/metabolismo , Genômica , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/cirurgia , Neoplasias Pulmonares/tratamento farmacológico , Mutação , Prognóstico , Proteínas Proto-Oncogênicas p21(ras)/genética
15.
Artigo em Inglês | MEDLINE | ID: mdl-38527651

RESUMO

OBJECTIVE: KRAS G12V is one of the most common KRAS mutation variants in lung adenocarcinoma (LUAD), and yet its prognostic value is still unrevealed. In this study, we investigated the clinicopathologic characteristics and prognostic value of the KRAS G12V mutation in LUAD. METHODS: Data of 3829 patients who underwent LUAD resection between 2008 and 2020 were collected. Mutations were classified as wild-type, G12V, or non-G12V. The clinicopathologic characteristics, postoperative outcomes, and recurrence pattern were analyzed among groups. RESULTS: In total, 3554 patients were wild-type and 275 patients harbored a KRAS mutation: 60 patients with G12V (22.2%) and 215 patients with non-G12V (77.8%). The KRAS G12V mutation was more frequent in male patients, older patients (≥60 years), former/current smokers, those patients with radiologic solid nodules, and those with highly invasive histologic subtypes. Tumors carrying KRAS G12V mutation exhibited elevated programmed death-ligand 1 expression in comparison with wild-type tumors. KRAS G12V was more prevalent in older patients and had less lymphovascular invasion compared with other mutation types. FGF3, RET, and KDR co-mutations occurred more frequently in the KRAS G12V group. Multivariate analysis demonstrated that the KRAS G12V mutation was an independent prognostic factor in stage Ⅰ tumors, whereas the KRAS non-G12V mutation was not. KRAS G12V was associated with early recurrence and locoregional recurrence. CONCLUSIONS: The KRAS G12V mutation was associated with aggressive clinical-pathologic phenotype and early recurrence. To note, this mutation exhibited a significantly worse prognosis in patients with part-solid and stage Ⅰ lung adenocarcinoma. Meanwhile, the prognostic significance of KRAS G12C and G12V variants was comparable.

16.
Science ; 380(6642): 278-282, 2023 Apr 21.
Artigo em Inglês | MEDLINE | ID: mdl-37079683

RESUMO

Spatial mode-count scalability in optical fibers is of paramount importance for addressing the upcoming information-capacity crunch, reducing energy consumption per bit, and for enabling advanced quantum computing networks, but this scalability is severely limited by perturbative mode mixing. We show an alternative means of light guidance, in which light's orbital angular momentum creates a centrifugal barrier for itself, thereby enabling low-loss transmission of light in a conventionally forbidden regime wherein the mode mixing can be naturally curtailed. This enables kilometer-length-scale transmission of a record ~50 low-loss modes with cross-talk as low as -45 decibels/kilometer and mode areas of ~800 square micrometers over a 130-nanometer telecommunications spectral window. This distinctive light-guidance regime promises to substantially increase the information content per photon for quantum or classical networks.

17.
J Thorac Cardiovasc Surg ; 166(6): e479-e499, 2023 12.
Artigo em Inglês | MEDLINE | ID: mdl-37142051

RESUMO

OBJECTIVES: The role of KRAS G12C is of particular interest given the promising clinical activity of KRAS G12C-specific inhibitors. This study comprehensively investigated the clinicopathological characteristics and prognostic value of KRAS G12C mutation in patients with surgically resected lung adenocarcinoma. METHODS: Data were collected on 3828 patients with completely resected primary lung adenocarcinomas who underwent KRAS mutation analysis between 2008 and 2020. The association between KRAS G12C and clinicopathologic characteristics, molecular profiles, recurrence patterns, and postoperative outcome were explored. RESULTS: Two hundred seventy-five patients (7.2%) were confirmed to harbor a KRAS mutation, of whom 83 (30.2%) had the G12C subtype. KRAS G12C was more frequent in men, former/current smokers, radiologic solid nodules, invasive mucinous adenocarcinoma, and solid predominant tumors. KRAS G12C tumors had more lymphovascular invasion and higher programmed death-ligand 1 expression than KRAS wild-type tumors. TP53 (36.8%), STK11 (26.3%), and RET (18.4%) mutations were the 3 most frequent in the KRAS G12C group. Logistic regression analysis showed patients with KRAS G12C mutation were prone to experience early recurrence and locoregional recurrence. KRAS G12C mutation was found to be significantly associated with poor survival after propensity score matching. Stratified analysis showed that the KRAS G12C was an independent prognostic factor in stage I tumors and part-solid lesions, respectively. CONCLUSIONS: The KRAS G12C mutation had a significant prognostic value in stage I lung adenocarcinomas as well as in part-solid tumors. Furthermore, it exhibited a potentially aggressive phenotype associated with early and locoregional recurrence. These findings might be relevant as better KRAS treatments are developed for clinical application.


Assuntos
Adenocarcinoma de Pulmão , Neoplasias Pulmonares , Masculino , Humanos , Prognóstico , Proteínas Proto-Oncogênicas p21(ras)/genética , Neoplasias Pulmonares/diagnóstico por imagem , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/cirurgia , Recidiva Local de Neoplasia/genética , Adenocarcinoma de Pulmão/genética , Mutação
18.
J Cancer Res Clin Oncol ; 149(4): 1383-1389, 2023 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-35445333

RESUMO

PURPOSE: Owing to the popularity of low-dose computed tomography in lung cancer screening, young women spotted with ground-glass opacities (GGO) is a growing subgroup in clinical practice. We aim to investigate the influence of pregnancy on GGOs suspected for lung adenocarcinoma. METHODS: This retrospective study collected a series of female patients who were pregnant in follow-up of GGO lesions. The last CT images of GGO before pregnancy (CT1) and the first CT images after pregnancy (CT2) were reviewed to assess any radiologic change. Young female patients who were not pregnant in long-term (> 12 months) follow-up of GGO were enrolled as a comparison group. We also enrolled patients who gave birth within 2 years before surgical resection of GGOs. RESULTS: Four patients were enrolled according to the criteria. There was no significant change of the GGOs in all four patients with a median follow-up duration of 45.5 (range 17-86) months. Two patients were diagnosed pathologically to be minimally invasive adenocarcinoma, one was invasive adenocarcinoma and one did not underwent surgery. Six patients were enrolled in the comparison group and no significant change was witnessed in all the nodules. In those patients who gave birth within two years before surgical resection of GGOs, we found that the majority present as preinvasive lesions, and those with invasive adenocarcinomas were bigger in size and possess more solid component radiologically. CONCLUSION: Pregnancy seems to have little impact on GGOs suspected for lung adenocarcinoma. Therefore, pregnancy might be safely planned during the follow-up of GGOs.


Assuntos
Adenocarcinoma de Pulmão , Adenocarcinoma , Neoplasias Pulmonares , Humanos , Feminino , Gravidez , Neoplasias Pulmonares/diagnóstico por imagem , Neoplasias Pulmonares/cirurgia , Neoplasias Pulmonares/patologia , Estudos Retrospectivos , Detecção Precoce de Câncer , Adenocarcinoma de Pulmão/diagnóstico por imagem , Adenocarcinoma de Pulmão/patologia , Adenocarcinoma/diagnóstico por imagem , Adenocarcinoma/cirurgia , Adenocarcinoma/patologia
19.
Transl Lung Cancer Res ; 12(11): 2181-2192, 2023 Nov 30.
Artigo em Inglês | MEDLINE | ID: mdl-38090517

RESUMO

Background: The eighth T classification excluded lepidic and ground-glass opacity (GGO) components. Current studies demonstrated lepidic and GGO components showed independent prognostic significances. This study elucidated the correlations and prognostic impacts of pathological and radiological T descriptors in invasive lung adenocarcinoma. Methods: A total of 1,490 patients with invasive lung adenocarcinoma were retrospectively reviewed. Correlation between pathological invasive size (PIS) and radiological solid size (RSS), and lepidic ratio and GGO ratio were comprehensively evaluated. Impacts of these pathological and radiological T descriptors on recurrence-free survival (RFS) were comparatively analyzed. Results: Clinical (c)T-stage was more frequently downstaged than upstaged comparing with the pathological (p)T-stage (28.4% vs. 18.2%). The correlation between PIS and RSS in solid nodule was stronger than that in part-solid nodule (solid: R2=0.750 vs. part-solid: R2=0.355). Some pathological invasive components except solid component were featured as GGO. Among T1 patients, lepidic absent GGO showed better RFS than lepidic present solid nodule (pT1: P=0.001; cT1: P=0.021). Multivariable analysis revealed GGO ratio was an independent prognostic factor for RFS in T1 invasive lung adenocarcinoma, whereas lepidic ratio was not. Conclusions: Among T1 invasive lung adenocarcinoma, GGO ratio showed independent prognostic value for RFS, regardless of RSS. Meanwhile, lepidic ratio was not an independent RFS factor. GGO component rather than lepidic component should be considered as an additional T descriptor.

20.
J Thorac Dis ; 15(4): 1559-1571, 2023 Apr 28.
Artigo em Inglês | MEDLINE | ID: mdl-37197537

RESUMO

Background: Although subcentimeter nodules represent precursor or minimally invasive lung cancer in most cases, there are still a few that are subcentimeter invasive adenocarcinoma (IAC). The aim of this study was to investigate the prognostic effect of ground-glass opacity (GGO) and the optimal surgical procedure in this special group. Methods: Patients with subcentimeter IAC were enrolled and were categorized into pure GGO, part-solid, and solid nodules based on the radiological appearance. Cox proportional hazards model and the Kaplan-Meier method were used for survival analyses. Results: A total of 247 patients were enrolled. Among them, 66 (26.7%) were in the pure-GGO group, 107 (43.3%) were in the part-solid group, and 74 (30.0%) were in the solid group. Survival analysis demonstrated a significantly worse survival in the solid group. Cox multivariate analyses confirmed that the absence of GGO component was an independent risk factor for worse recurrence-free survival (RFS) and overall survival (OS). As for surgical procedures, lobectomy did not provide a significant better RFS or OS than sublobar resection in the whole cohort or in a subgroup of patients with solid nodules. Conclusions: The radiological appearance stratified the prognosis of IAC with size of smaller than or equal to 1 cm. Sublobar resection may be feasible for subcentimeter IAC, even for those appearing as solid nodules; however, caution should be taken when applying wedge resection.

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