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Human Neutrophil Elastase Activated Fluorescent Probe for Pulmonary Diseases Based on Fluorescence Resonance Energy Transfer Using CdSe/ZnS Quantum Dots
摘要： There is an increasing demand for effective noninvasive diagnosis against common pulmonary diseases which are rising sharply due to the serious air pollution. Human neutrophil elastase (HNE), a typical protease highly involved in pulmonary inflammatory diseases and lung cancer, is a potential predictor for disease progression. Currently, few of HNE-targeting probes is applicable In Vivo due to the limitation in sensitivity and biocompatibility. Herein we reported the achievement of In Vitro detection and In Vivo imaging of HNE, by incorporating the HNE-specific peptide substrate, quantum dots (QDs) and organic dyes into the fluorescence resonance energy transfer (FRET) system. The refined nanoprobe, termed as QDP, could specifically measure the HNE with excellent sensitivity of 7.15 pM at aqueous solution, and successfully image the endogenous and exogenous HNE in living cells. In addition, this nanoprobe enabled the HNE imaging in the mouse models of lung cancer and acute lung injury, and continuously monitored the HNE activity at high temporal and spatial resolution. Most importantly, QDP successfully discriminated the serums of patients with lung diseases from those of the healthy controls based on the HNE activity determination. Overall, this study demonstrates the advantages of FRET system-based nanoprobe in imaging performance and provides an applicable tool for In Vivo HNE detection and pulmonary diseases diagnosis.
关键词： human neutrophil elastase,quantum dots,pulmonary diseases,lung cancer,fluorescence resonance energy transfer
更新于2025-09-23 15:19:57
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Synthesis of novel small-molecule fluorescently labeled probes for the in vitro imaging of KCa3.1 channels
摘要： In order to facilitate the in vitro visualization of KCa3.1 channel-expressing cells, novel small-molecule imaging probes were designed and developed. Senicapoc showing high affinity and excellent selectivity towards the KCa3.1 channels was selected as targeting component. Different BODIPY dyes (15 - 20) were synthesized and connected by a Cu-catalyzed azide alkyne [3+2]cycloaddition with propargyl ether derivative 8 of senicapoc yielding fluorescently labeled ligands 21 - 26 targeting KCa3.1 channels. The novel dimethylpyrrole-based imaging probes 25 and 26 allow staining of KCa3.1 ion channels in NSCLC cells following a simple, fast and efficient protocol. The specificity was shown by removing the punctate staining pattern by pre-incubation with senicapoc. The density of KCa3.1 channels detected with fluorescent probe 25 and by immunostaining was identical. The punctate structure of the labeled channels could be observed in living cells as well. Molecular modeling studies showed binding of the senicapoc targeting component towards the binding site within the ion channel and orientation of the linker with the dye along the inner surface of the ion channel.
关键词： labeled ligands,KCa3.1 channel,fluorescent probes,non-small cell lung cancer cells,molecular modelling,imaging agents,cycloaddition
更新于2025-09-23 15:19:57
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A molecular ferroelectrics induced electroactive β-phase in solution processed PVDF films for flexible piezoelectric sensors
摘要： Background: Precise diagnosis of the tissue origin for metastatic cancer of unknown primary (CUP) is essential for deciding the treatment scheme to improve patients’ prognoses, since the treatment for the metastases is the same as their primary counterparts. The purpose of this study is to identify a robust gene signature that can predict the origin for CUPs. Methods: The within-sample relative gene expression orderings (REOs) of gene pairs within individual samples, which are insensitive to experimental batch effects and data normalizations, were exploited for identifying the prediction signature. Results: Using gene expression profiles of the lung-limited metastatic colorectal cancer (LmCRC), we firstly showed that the within-sample REOs in lung metastases of colorectal cancer (CRC) samples were concordant with the REOs in primary CRC samples rather than with the REOs in primary lung cancer. Based on this phenomenon, we selected five gene pairs with consistent REOs in 498 primary CRC and reversely consistent REOs in 509 lung cancer samples, which were used as a signature for predicting primary sites of metastatic CRC based on the majority voting rule. Applying the signature to 654 primary CRC and 204 primary lung cancer samples collected from multiple datasets, the prediction accuracy reached 99.36%. This signature was also applied to 24 LmCRC samples collected from three datasets produced by different laboratories and the accuracy reached 100%, suggesting that the within-sample REOs in the primary site could reveal the original tissue of metastatic cancers. Conclusions: The result demonstrated that the signature based on within-sample REOs of five gene pairs could exactly and robustly identify the primary sites of CUPs.
关键词： Lung cancer,Cancer of unknown primary,Colorectal cancer,Relative gene expression orderings,Metastasis
更新于2025-09-19 17:15:36
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Computed tomography criteria for the use of advanced localization techniques in minimally invasive thoracoscopic lung resection
摘要： Background: The significant improvement of patient outcomes from minimally invasive lung surgery has led to the development of advanced lung nodule localization techniques to help manage patients with small suspicious lung nodules or to help resect patients with small pulmonary metastases. However, there are no clear computed tomography (CT) criteria to guide the use of advanced localization techniques for this group of patients. Methods: We conducted a retrospective chart review of patients who had undergone initial wedge resection of single or multiple lung nodules. We collected demographics, surgical information and surgical outcomes as well as CT scan features. Multiple logistic regression was performed to determine which factors were most predictive of the need for advanced localization techniques. Results: A total of 45 patients (73%) were resected by direct identification alone while 17 patients (27%) required advanced localization techniques. Of those requiring advanced localization, 11 patients had cone beam CT, 3 patients had transbronchial localization using electromagnetic navigation and 3 patients had preoperative CT guided wire localization. Patients requiring advanced localization had significantly smaller lung nodules at 0.8 cm compared to 1.4 cm (P=0.01), nodules that were further away from the pleura at 1.3 cm compared 0.1 cm (P<0.001) and were more likely to have ground glass nodules (P=0.01) compared to patients who were resected by direct identification alone. Multiple logistic regression confirmed that nodule size, distance to pleura and ground glass attenuation were predictive factors for requiring advanced localizing techniques. Every patient was treated with minimally invasive lung resection. A 1.3-cm or greater solitary pulmonary nodule less than 5 mm from the pleura can be removed without advanced techniques with a 96% success rate. Conclusions: Overall, in patients undergoing resection of a suspicious primary or metastatic lung nodule, advanced localization techniques should be considered in those with small non-solid nodules, which are not near the pleural surface on CT scan.
关键词： computed tomography guided localization (CT guided localization),navigation bronchoscopy,cone beam computed tomography (cone beam CT),lung cancer,Lung nodule
更新于2025-09-19 17:15:36
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ALK positive lung cancer identification and targeted drugs evaluation using microscopic hyperspectral imaging technique
摘要： It is important to distinguish ALK positive lung cancer from ALK negative lung cancer and to monitor the efficacy of targeted drugs. This paper applies a microscopic hyperspectral imaging technique to identify ALK positive lung cancer cells and evaluate the therapeutic effect. The hyperspectral images of five groups of lung tissues are captured by the home-made microscopic hyperspectral imaging system. A preprocessing algorithm is proposed to reduce obvious banding noise and noise particles from original data. Then a segmentation algorithm, which assembles Supported Vector Machine (SVM) and Majority analysis together with the Clumping processing, is presented. The ALK positive and negative lung cancers can be distinguished by both the fluctuation of spectral curves and the relative proportion between cytoplasm and cell nucleus. In addition, the treatment efficacy can be surveyed in the same way. The experimental results show that the relative proportion of cytoplasm in Group ALK-neg is 77.3%, while that in Group ALK-pos is 40.6%. It is obvious that there exist differences in contents and spectra between Group ALK-neg and Group ALK-pos. Moreover, the experimental results of quantitative analysis and spectral curves analysis show that ALK positive lung cancer cells treated with the low concentration of targeted drugs will be developed towards the ALK negative lung cancer. This paper shows the potential of using hyperspectral images to detect the ALK positive lung cancer cells and evaluate the therapeutic effect of targeted drugs.
关键词： Spectral analysis,Therapeutic effect evaluation,Microscopic hyperspectral imaging,ALK positive lung cancer
更新于2025-09-19 17:15:36
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Preliminary result of definitive radiotherapy in patients with non-small cell lung cancer who have underlying idiopathic pulmonary fibrosis: comparison between X-ray and proton therapy
摘要： Background: Idiopathic pulmonary fibrosis (IPF) is associated with fatal complications after radiotherapy (RT) for lung cancer patients; however, the role of proton therapy to reduce the incidence of life-threatening complications is unclear. Herein, we present the preliminary results of early-stage lung cancer patients having IPF and treated with RT, with a focus on the comparison between X-ray and proton therapy. Methods: From January 2010 to October 2017, we retrospectively reviewed the medical records of 264 patients with stage I-II non-small cell lung cancer (NSCLC) treated with definitive RT alone. Ultimately, 30 patients (11.4%) who had underlying IPF were analyzed. Among these, X-ray and proton RT were delivered to 22 and 8 patients, respectively. Treatment-related complications and survival outcomes were compared between X-ray and proton therapy. Results: The median follow-up duration was 11 months (range, 2 to 51 months). All living patients were followed-up at least 9 months. Treatment-related death occurred in four patients (18.2%) treated with X-ray but none with proton therapy. Most patients died within one month after the onset of pulmonary symptoms in spite of aggressive treatment. In addition, the 1-year overall survival (OS) rate in patients treated with X-ray and proton was 46.4 and 66.7%, respectively, and patients treated with proton therapy showed a tendency of better survival compared to X-ray (p = 0.081). Especially, in GAP stage II and III subgroups, patients treated with proton therapy showed significantly increased survival outcomes compared to X-ray (1-year OS rate; 50.0% versus 26.4%, p = 0.036) in univariate analysis. Conclusions: RT is associated with serious treatment-related complications in patients with IPF. Proton therapy may be helpful to reduce these acute and fatal complications.
关键词： Non-small cell lung cancer,Radiotherapy,Complication,Proton therapy,Idiopathic pulmonary fibrosis
更新于2025-09-19 17:15:36
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Real-time molecular optical micro-imaging of EGFR mutations using a fluorescent erlotinib based tracer
摘要： Background: EGFR mutations are routinely explored in lung adenocarcinoma by sequencing tumoral DNA. The aim of this study was to evaluate a fluorescent-labelled erlotinib based theranostic agent for the molecular imaging of mutated EGFR tumours in vitro and ex vivo using a mice xenograft model and fibred confocal fluorescence microscopy (FCFM). Methods: The fluorescent tracer was synthesized in our laboratory by addition of fluorescein to an erlotinib molecule. Three human adenocarcinoma cell lines with mutated EGFR (HCC827, H1975 and H1650) and one with wild-type EGFR (A549) were xenografted on 35 Nude mice. MTT viability assay was performed after exposure to our tracer. In vitro imaging was performed at 1 μM tracer solution, and ex vivo imaging was performed on fresh tumours excised from mice and exposed to a 1 μM tracer solution in PBS for 1 h. Real-time molecular imaging was performed using FCFM and median fluorescence intensity (MFI) was recorded for each experiment. Results: MTT viability assay confirmed that addition of fluorescein to erlotinib did not suppress the cytotoxic of erlotinib on tumoral cells. In vitro FCFM imaging showed that our tracer was able to distinguish cell lines with mutated EGFR from those lines with wild-type EGFR (p < 0.001). Ex vivo FCFM imaging of xenografts with mutated EGFR had a significantly higher MFI than wild-type (p < 0.001). At a cut-off value of 354 Arbitrary Units, MFI of our tracer had a sensitivity of 100% and a specificity of 96.3% for identifying mutated EGFR tumours. Conclusion: Real time molecular imaging using fluorescent erlotinib is able to identify ex vivo tumours with EGFR mutations.
关键词： Lung cancer,Erlotinib,Theranostic,EGFR,Epidermal growth factor,Fibred confocal fluorescence microscopy,Molecular imaging
更新于2025-09-19 17:15:36
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Virtual fluoroscopy during transbronchial biopsy for locating ground-glass nodules not visible on X-ray fluoroscopy
摘要： Background: Virtual fluoroscopy (VF) is a novel guided technique that provides ray summation images of target lesions similar to X-ray fluoroscopy. Endobronchial ultrasound with a guide sheath (EBUS-GS) is a useful modality for imaging ground-glass nodules (GGNs) but is not ideal for GGNs that cannot be detected on X-ray fluoroscopy. We evaluated whether the addition of VF to EBUS-GS improved the diagnostic yield. Methods: Consecutive patients who had undergone diagnostic bronchoscopy for GGNs that were not detected on X-ray fluoroscopy between September 2012 and January 2016 were retrospectively enrolled. The patients were divided into two groups: a non-VF group [performed using conventional thin-section computed tomography (CT), X-ray fluoroscopy, EBUS-GS, and virtual bronchoscopy for reference], and a VF group (performed using additional VF to non-VF group). We then compared the diagnostic yields between the two groups and performed a multivariate analysis to identify factors associated with an increased diagnostic yield. Results: A total of 74 patients (VF, 35 patients; non-VF, 39 patients) were enrolled and were included in the analysis. The diagnostic yield was significantly higher in the VF group (77.1%) than in the non-VF group (51.2%, P=0.030). There were no clinically significant complications in either group. In the multivariate analysis, a positive bronchus sign [odds ratio (ORs), 5.41; 95% confidence interval (CI), 1.36–21.40] and the use of VF (odds ratio, 3.68; 95% confidence interval, 1.16–11.60) were significantly associated with successful bronchoscopic diagnosis. Conclusions: The addition of VF to EBUS-GS helped to identify GGNs that were not visible on X-ray fluoroscopy.
关键词： bronchoscopy,virtual bronchoscopy (VB),radial endobronchial ultrasound with a guide sheath (EBUS-GS),ground-glass nodule (GGN),Lung cancer,virtual fluoroscopy (VF)
更新于2025-09-19 17:15:36
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Diagnostic performance of fluorine-18 fluorodeoxyglucose positron emission tomography in the management of solitary pulmonary nodule: a meta-analysis
摘要： Background: In the setting of solitary pulmonary nodules (SPNs), fluorine-18 fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG-PET/CT) is considered a useful non-invasive diagnostic tool though false positive (FP) and false negative (FN) results affects accuracy due to different conditions, such as inflammatory diseases or low-uptake neoplasms. Aim of this study is to evaluate overall diagnostic performance of 18F-FDG-PET/CT for malignant pulmonary nodules. Methods: A computerized research, including published articles from 2012 and 2017, was carried out. 18F-FDG-PET/CT overall sensitivity (Se), specificity (Spe), positive likelihood ratio (PLR), negative likelihood ratio (NLR), positive predictive value (PPV), negative predictive value (NPV), diagnostic index and odds ratio were pooled. No selection-bias were found according to asymmetry test. Results: A total of twelve studies were included in the meta-analysis. The pooled Se, Spe, PLR, NLR, PPV, NPV and accuracy index (AI) with relative 95% confidence intervals (CI) were 0.819 (95% CI: 0.794–0.843), 0.624 (95% CI: 0.582–0.665), 2.190 (95% CI: 1.950–2.440), 0.290 (95% CI: 0.250–0.330), 0.802 (95% CI: 0.783–0.819), 0.652 (95% CI: 0.618–0.684) and 0.649 (95% CI: 0.625–0.673), respectively. The diagnostic odds ratio (DOR) was 7.049 with a relative 95% CI between 5.550 and 8.944. Conclusions: The results suggest 18F-FDG-PET/CT has good diagnostic accuracy in SPNs evaluation; but, it should not be considered as a discriminatory test rather than a method to be included in a clinical and diagnostic pathway.
关键词： Fluorine-18 fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG-PET/CT),solitary pulmonary nodules (SPNs),lung cancer
更新于2025-09-19 17:15:36
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Non-invasive prediction of lung cancer histological types through exhaled breath analysis by UV-irradiated electronic nose and GC/QTOF/MS
摘要： Lung cancer (LC) is one of the most lethal diseases from the last decades. Accurate diagnosis of LC histology could lead to the prescription of personalized medical treatment to the affected subjects, which could reduce the mortality rate. We present here an experimental study performed in the pulmonology units of three hospitals from Morocco to non-invasively detect LC and predict LC histology via the analysis of the volatile organic compounds (VOCs) emitted through breathing. Gas chromatography coupled to a quadrupole time-of-flight mass spectrometer (GC/QTOF/MS) employed to detect the breath VOCs, revealed 30 discriminative VOCs in the breath of healthy subjects and LC patients; among them, 4 unique of LC (non-small cell LC and small cell LC), as well as between two of the major subtypes of employed to characterize the overall composition of the collected breath samples, providing a non-small cell LC, namely squamous cell carcinoma (SCC) and adenocarcinoma (ADC). The satisfactory discrimination between the breath patterns of LC patients and healthy subjects. novel sensing technique in breath analysis, based on UV-irradiation of the gas sensors, was Importantly, the e-nose could further discriminate with high accuracy between the two types breath VOCs were found for the first time in the breath of LC patients, and could be used as new biomarkers for future LC diagnosis. Besides, an electronic nose (e-nose) system using a Keywords: Breath analysis, Lung cancer, Histology, GC/QTOF/MS, Electronic nose, UV- can provided an accurate mean for the non-invasive diagnosis of LC and LC histology. reported results prove that breath analysis with chemical gas sensors and analytical techniques irradiated WO3 sensors.
关键词： Lung cancer,Histology,UV-irradiated WO3 sensors,Electronic nose,Breath analysis,GC/QTOF/MS
更新于2025-09-19 17:13:59