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Optical nanogap antennas as plasmonic biosensors for the detection of miRNA biomarkers
摘要： Nanoplasmonic biosensors based on nanogap antennas structures usually demand complex and expensive fabrication processes in order to achieve a good performance and sensitive detection. We here report the fabrication of large-area nanoplasmonic sensor chips based on nanogap antennas by employing a customized, simple and low-cost colloidal lithography process. By precisely controlling the angle for tilted e-beam metal evaporation, an elliptical mask is produced, which defines the total length of the dipole antenna nanostructures while assuring that the plasmonic response is oriented in the same direction along the sensor chip. Large-area sensor chips of nanogap antennas formed by pairs of gold nanodisks separated by gaps with an average size of 11.6 ± 4.7 nm are obtained. The optical characterization of the nanogap antenna structures in an attenuated total reflection (ATR) configuration shows a bulk refractive index sensitivity of 422 nm/RIU, which is in agreement with FDTD numerical simulations. The biosensing potential of the cm2-sized nanostructured plasmonic sensor chips has been evaluated for the detection of miRNA-210, a relevant biomarker for lung cancer diagnosis, through a DNA/miRNA hybridization assay. A limit of detection (LOD) of 0.78?nM (5.1 ng mL-1) was achieved with no need of further amplification steps, demonstrating the high sensitivity of these plasmonic nanogap antennas for the direct and label-free detection of low molecular weight biomolecules as miRNAs.
关键词： nanoplasmonic biosensors,miRNA biomarkers,colloidal lithography,nanogap antennas,lung cancer diagnosis
更新于2025-09-19 17:13:59
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Bypassing pro-survival and resistance mechanisms of autophagy in EGFR-positive lung cancer cells by targeted delivery of 5FU using theranostic Ag <sub/>2</sub> S quantum dots
摘要： Targeted drug delivery systems that combine imaging and therapeutic functions in a single structure have become very popular in nanomedicine. Near-infrared (NIR) emitting Ag2S quantum dots (QDs) are excellent candidates for this task. Here, we have developed PEGylated Ag2S QDs functionalized with Cetuximab (Cet) antibody and loaded with an anticancer drug, 5-fluorouracil (5FU). These theranostic QDs were used for targeted NIR imaging and treatment of lung cancer using low (H1299) and high (A549) Epidermal Growth Factor Receptor (EGFR) overexpressing cell lines. The Cet conjugated QDs effectively and selectively delivered 5FU to A549 cells and provided significantly enhanced cell death associated with apoptosis. Interestingly, while treatment of cells with free 5FU activated autophagy, a cellular mechanism conferring resistance to cell death, these EGFR targeting multimodal QDs significantly overcame drug resistance compared to 5FU treatment alone. The improved therapeutic outcome of 5FU delivered to A549 cells by Cet conjugated Ag2S QDs is suggested as the synergistic outcome of enhanced receptor mediated uptake of nanoparticles, and hence the drug, coupled with suppressed autophagy even in the absence of addition of an autophagy suppressor.
关键词： lung cancer,EGFR,theranostic,Ag2S quantum dots,autophagy,targeted drug delivery,5-fluorouracil
更新于2025-09-16 10:30:52
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Evaluation of 64Cu radiolabeled anti-hPD-L1 Nb6 for positron emission tomography imaging in lung cancer tumor mice model
摘要： Recently, we selected a novel anti-hPD-L1-specific HCAb named Nb6 with high affinity (EC50= 0.65 ng/mL) for potential hPD-L1 targeted non-invasive PET imaging. In this research, Nb6 was conjugated with the bifunctional chelator NCS-Bz-NOTA ((2-[(4-Isothiocyanophenyl) methyl]-1,4,7-triazacy-clononane-1,4,7-triacetic acid)) and further labeled with radio-nuclide 64Cu. 64Cu-NOTA-Nb6 was prepared with over 95% labeling yield, over 99% radiochemical purity and 14~16 GBq/μmol specific activity after PD-10 column purification. It shows good stability in 0.01 M PBS and 5% HSA solutions. 64Cu-NOTA-Nb6 has a high binding affinity to 3.60 nM which was tested by human lung adenocarcinoma A549 cell lines. Tumor lesion can be clearly observed from 20 h to 38 h by Micro-PET equipment after 64Cu-NOTA-Nb6 administration. The study revealed that 64Cu-NOTA-Nb6 has good lesion detection ability, high ratios between tumor and non-tumor signal and can specifically target A549 xenografted tumor model. Taken together of good stability, high binding affinity, and tumor detection ability, 64Cu labeled Nb6 is a promising radio-tracer in diagnosing of hPD-L1 overexpression tumor, supposed to monitor PD-L1overexpression tumor progression and guide targeted therapy with PET molecular imaging.
关键词： Lung cancer,PET/CT imaging,64Cu-NOTA-Nb6,heavy chain-only antibody (HCAb),PD-L1
更新于2025-09-12 10:27:22
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Quantum‐Chemical Evaluation of Impact of Chlorination versus Fluorination on the Electronic Properties of Donors and Acceptors for Organic Solar Cells
摘要： Lung cancer is one of the most prevalent and fatal cancer worldwide. The traditional treatments including surgery, radiotherapy, chemotherapy and targeted therapy are not satisfactory because of severe side effects and/or relapse. Genetically engineered T-cell–based immunotherapy for malignant cancer shows promise in recent clinical trials. T-cell receptor (TCR)-engineered T cells targeting New York esophageal squamous cell carcinoma 1 (NY-ESO-1) have been employed in a number of clinical trials for late stage melanoma, synovial sarcoma, multiple myeloma and other malignancies. Owing to the significant efficacy and controllable side effect, NY-ESO-1 has been considered as one of the most ideal TCR-engineered T cell therapy (TCR-T) cell target for solid tumors, including nonsmall cell lung cancer (NSCLC). However, the incidence of NY-ESO-1 expression and its relationship with immunosuppressive microenvironment of NSCLC are largely unclear. In this study, we analyzed the expression of NY-ESO-1 and two key immune regulators, Forkhead box P3 (Foxp3) and indoleamine-2,3-dioxygenase (IDO), in 156 NSCLC specimens by immunohistochemistry. Our results showed that NY-ESO-1 positive rate is 28.1% (44/156) and significantly higher in distal metastasis (P = 0.012) and late stage (P = 0.019) NSCLC patients. In addition, we found that NY-ESO-1 expression was positively associated with Foxp3 level but not IDO. These findings implied the potential role of NY-ESO-1 in tumor immune escape of NSCLC and indicated the requirement to remove Treg cells in TCR-T cell therapy for NSCLC patients.
关键词： NY-ESO-1,Foxp3,nonsmall cell lung cancer,IDO,immunotherapy
更新于2025-09-11 14:15:04
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[IEEE 2017 21st National Biomedical Engineering Meeting (BIYOMUT) - Istanbul (2017.11.24-2017.12.26)] 2017 21st National Biomedical Engineering Meeting (BIYOMUT) - Detection of Candidate Nodules in Lung Tomography by Image Processing Techniques
摘要： In this project, the data set generated from the data of the National Cancer Institute (NCI) derived from DICOM-formatted lung cancer data has been converted to PNG format to make it suitable for the operation of image processing algorithms. The converted data is filtered by a second-order median filter to prevent noise. A laplacian filter was applied to clarify the boundaries of the candidate nodules. The threshold must be determined according to the histogram value of each view. To select a different threshold for each image was subjected to the determination threshold Otsu method. In Otsu threshold selection method determines the point at which the minimum-class variance and between-class variance is a maximum, and determines the the availability of candidate nodules, nodule diameter is intended for detection of the large nodules than 2 mm. To meet this requirement, the Otsu thresholding method was applied on the MATLAB platform to sieve nodules smaller than 2 mm in diameter and candidate nodules were detected. By determining the morphological characteristics of the identified candidate nodules in MATLAB platform, candidate nodule; Major features such as area, major axis length, minor axis length, and perimeters are extracted. The boundaries of the identified candidate nodules are bounded by the edge detection algorithm and numerically ordered.
关键词： Image Processing,Lung Cancer,Otsu Tresholding
更新于2025-09-10 09:29:36
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[IEEE 2018 IEEE 3rd International Conference on Image, Vision and Computing (ICIVC) - Chongqing (2018.6.27-2018.6.29)] 2018 IEEE 3rd International Conference on Image, Vision and Computing (ICIVC) - A New Strategy to Detect Lung Cancer on CT Images
摘要： Lung cancer has a very low cure rate in the advanced stages, with effective early detection, the survival rate of lung cancer could be highly raised. Detection of lung cancer in the early stages plays a vital role for human health. Computed tomography (CT) images, which provide electronic densities of tissues, are widely applied in radiotherapy planning. The proposed system based on CT technology consists of image acquisition, preprocessing, feature extraction, and classification. In the preprocessing stage, RGB images are converted to grayscale images, the median filter and the Wiener filter are used to uproot noises, Otsu thresholding method is applied to convert CT images, and REGIONPROPS function is used to exact body region from binary images. In the feature extraction stage, features, like Contrast, Correlation, Energy, Homogeneity, are extracted through statistic method Gray Level Co-occurrence Matrix (GLCM). In the final stage, extracted features, together with Support Vector Machine (SVM) and Back Propagation Neural Network (BPNN), are used to identify lung cancer from CT images. The performance of the proposed system shows satisfactory results of 96.32% accuracy on SVM and 83.07% accuracy on BPNN respectively.
关键词： BPNN,SVM,image processing,lung cancer detection,GLCM
更新于2025-09-10 09:29:36
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Automatic classification of label-free cells from small cell lung cancer and poorly differentiated lung adenocarcinoma with 2D light scattering static cytometry and machine learning
摘要： Small cell lung cancer (SCLC) needs to be classified from poorly differentiated lung adenocarcinoma (PDLAC) for appropriate treatment of lung cancer patients. Currently, the classification is achieved by experienced clinicians, radiologists and pathologists based on subjective and qualitative analysis of imaging, cytological and immunohistochemical (IHC) features. Label-free classification of lung cancer cell lines is developed here by using two-dimensional (2D) light scattering static cytometric technique. Measurements of scattered light at forward scattering (FSC) and side scattering (SSC) by using conventional cytometry show that SCLC cells are overlapped with PDLAC cells. However, our 2D light scattering static cytometer reveals remarkable differences between the 2D light scattering patterns of SCLC cell lines (H209 and H69) and PDLAC cell line (SK-LU-1). By adopting support vector machine (SVM) classifier with leave-one-out cross-validation (LOO-CV), SCLC and PDLAC cells are automatically classified with an accuracy of 99.87%. Our label-free 2D light scattering static cytometer may serve as a new, accurate, and easy-to-use method for the automatic classification of SCLC and PDLAC cells.
关键词： static cytometry,2D light scattering,label-free,lung cancer,machine learning
更新于2025-09-10 09:29:36
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Morphological analysis of blood vessels near lung tumors using 3-D quantitative CT
摘要： BACKGROUND: Improved visualization of lung cancer-associated vessels is vital. OBJECTIVE: To evaluate the ef?cacy of 3-D quantitative CT in lung cancer-associated pulmonary vessel assessment. METHODS: Vascular CT changes were assessed visually and using FACT-Digital lung TM software (n = 162 patients, 178 controls). The total number of pulmonary vessels (TNV) and mean lumen area of pulmonary vessels (MAV) vertical to cross-sections of ?fth/sixth-generation bronchioles were measured. RESULTS: Visual investigation revealed fewer ipsilateral pulmonary vascular abnormalities in lung cancer (151/162) than did quantitative CT (162/162), and required more time (3.2 ± 1.5 vs. 2.5 ± 1.3 min) (P < 0.05). CT measurements revealed that the TNV vertical to the ?fth-generation bronchial cross-section of the ipsilateral, contralateral, and control groups was 14.58 ± 4.75, 9.58 ± 3.74, and 10.22 ± 4.07 and the MAV in these groups was 99.70 ± 26.20, 58.76 ± 29.29, and 57.76 ± 18.32, respectively. The TNV vertical to the sixth-generation bronchial cross-section of the ipsilateral, contralateral, and control groups was 16.64 ± 5.14, 11.59 ± 4.06, and 11.75 ± 4.16 and the MAV was 110.22 ± 31.47, 67.62 ± 30.41, and 60.24 ± 16.18, respectively. The TNV and MAV in ipsilateral lung cancer tissues exceeded those in the contralateral side and control group tissues (P < 0.001). CONCLUSIONS: Automated 3-D quantitative CT could successfully characterize pulmonary vessels and their lung cancer-associated changes.
关键词： CT,total number of vessels,quantitative measurement,Lung cancer,mean lumen area of vessels
更新于2025-09-10 09:29:36
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Treatment of erlotinib induced acneiform eruption with chromophore?gel‐assisted?phototherapy
摘要： A 49-year-old female presented with an acneiform eruption induced by erlotinib. She had been diagnosed with Stage IV (T1N3M1) EGFR mutant adenocarcinoma of the lung and commenced on erlotinib 150mg daily. Within three days she developed an acneiform eruption prompting empiric treatment with topical hydrocortisone and systemic doxycycline 100mg daily. The acneiform eruption progressed with evolution to widespread pustules and papules with proud erythema involving the entire face with minor extension to the scalp, décolletage and back (Fig.1). Treatment was escalated to daily washes with benzoyl peroxide and transition to topical methylprednisolone aceponate and minocycline 100mg daily, met with modest response (Supplementary Fig 1). The patient was demonstrating a reduction in tumour burden on erlotinib but significant cutaneous toxicity recalcitrant to standard therapy. Given the significant burden on her quality of life (QOL), it was decided to continue erlotinib but trial adjuvant chromophore gel-assisted phototherapy (CGAP). The patient received twelve treatment sessions over six weeks involving application of a 2mm layer of the photoconverter chromophore gel (Kleresca? SKR-treatment) followed by irradiation with a multi-LED lamp (447nm) (Kleresca?, Balerup, Denmark). Within three weeks of treatment, the acneiform eruption was arrested and topical treatment was withdrawn one week after. The patient completed a further three weeks of CGAP as per standard protocol and maintained on minocycline 50mg daily thereafter. The severity of her acneiform eruption decreased from an Investigator’s Global Assessment (IGA) of 5 to 0. Scoring of the patient reported outcomes of the Acne Quality of Life Index decreased from 78 to 23 and increased on the Acne-specific Quality of Life Questionnaire (Acne-QOL) from 49 to 109 demonstrating marked improvement in quality of life.1, 2 She continues treatment with erlotinib maintaining tumour arrest without any active cutaneous toxicity; only post-inflammatory erythema, hyperpigmentation and ice-pick scarring as sequelae of the initial acneiform eruption (Fig.2).
关键词： Lung cancer,Epidermal growth factor receptor,Acne,Erlotinib,Phototherapy
更新于2025-09-09 09:28:46
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Multimodal Imaging in Lung Cancer: It Is Time to Change
摘要： The imaging techniques can be classified into two main groups: Structural/morphological imaging (SMI), which includes X rays (XR), computed tomography (CT), ultrasounds (US) as well as some varieties of magnetic resonance (MRI), and shows anatomic-morphological aspects, and molecular imaging (MI), which includes nuclear medicine (SPECT, PET), fMRI, optical and nanosystems techniques, and provides information about biochemistry/biological activity, often before structural changes. According to Society of Nuclear Medicine and Molecular Imaging, MI “is the visualization, characterization, and measurement of biological processes at the molecular and cellular levels in humans and other living systems”. MI procedures are noninvasive, safe and painless. Its sensitivity is greater than SMI, but it lacks anatomical detail, which has led to the development of multimodal imaging, combining structural and molecular techniques, widely used at present in daily practice. The pillars of MI are biochemistry/biology, instrumentation and software, and its cycle is the following: study of biology/biochemistry of a process, establishment/definition of specific targets, and development of tracers, preclinical imaging, histological validation and finally clinical imaging. This new concept led to the individualized diagnostic and treatment, being the patient the center of the medical activity. “As opposed to the doctor-centric, curative model of the past, the future is going to be patient-centric and proactive” said Dr. Zerhouni (NIH Medline Plus Winter 2007). The doctor must adapt to the needs of the own patient and this fact requires a true change of heart, because MI is intimately tied to the biology of the disease to analyzing. A new and strong interrelationship came into being: a bidirectional system biology-imaging that will allow to be much more effective in the daily practice, not only in relation to diagnosis (specific and early), but also with therapy (guide cancer treatment selection and evaluate early treatment response). There is an absolute necessity to lock the two together. Likewise, in the future the biology of a disease will indicate us what is the most adequate imaging technique and vice versa. In this regard, we know that in non-small cell lung cancer (NSCLC), ALK+ status is associated with distinct characteristics at CT imaging (CT radiogenomic characterization) [1], and that in lung adenocarcinomas 18F-FDG uptake values are related with expression levels of cellular Glucose Transporters and EGFR mutations. For this reason, different EGFR mutations correlate with different FDG uptake values.
关键词： Small Cell Lung Cancer,PET,Biomarkers,CT,MRI,Lung Cancer,Molecular Imaging,Multimodal Imaging,Non-Small Cell Lung Cancer,Structural/Morphological Imaging
更新于2025-09-04 15:30:14