Deep Visual Proteomics defines single-cell identity and heterogeneity

Nature Biotechnology, Journal Year: 2022, Volume and Issue: 40(8), P. 1231 - 1240

Published: May 19, 2022

Despite the availabilty of imaging-based and mass-spectrometry-based methods for spatial proteomics, a key challenge remains connecting images with single-cell-resolution protein abundance measurements. Here, we introduce Deep Visual Proteomics (DVP), which combines artificial-intelligence-driven image analysis cellular phenotypes automated single-cell or single-nucleus laser microdissection ultra-high-sensitivity mass spectrometry. DVP links to complex subcellular while preserving context. By individually excising nuclei from cell culture, classified distinct states proteomic profiles defined by known uncharacterized proteins. In an archived primary melanoma tissue, identified spatially resolved proteome changes as normal melanocytes transition fully invasive melanoma, revealing pathways that change in manner cancer progresses, such mRNA splicing dysregulation metastatic vertical growth coincides reduced interferon signaling antigen presentation. The ability retain precise information tissue context has implications molecular profiling clinical samples.

Language: Английский

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Molecular Landscape of LncRNAs in Prostate Cancer: A focus on pathways and therapeutic targets for intervention

Journal of Experimental & Clinical Cancer Research, Journal Year: 2022, Volume and Issue: 41(1)

Published: July 1, 2022

Abstract Background One of the most malignant tumors in men is prostate cancer that still incurable due to its heterogenous and progressive natures. Genetic epigenetic changes play significant roles development. The RNA molecules with more than 200 nucleotides length are known as lncRNAs these factors do not encode protein. They regulate gene expression at transcriptional, post-transcriptional levels. LncRNAs vital biological functions cells pathological events, hence their undergoes dysregulation. Aim review role alterations development emphasized here. Therefore, were chosen for this purpose level interaction other signaling networks progression examined. Key scientific concepts aberrant has been well-documented rate tumor regulated via affecting STAT3, NF-κB, Wnt, PI3K/Akt PTEN, among molecular pathways. Furthermore, radio-resistance chemo-resistance features cells. Overexpression tumor-promoting such HOXD-AS1 CCAT1 can result drug resistance. Besides, induce immune evasion upregulating PD-1. Pharmacological compounds quercetin curcumin have applied targeting lncRNAs. siRNA tool reduce thereby suppressing progression. Prognosis diagnosis clinical course be evaluated by exosomal lncRNA-p21 investigated serum patients a reliable biomarker.

Language: Английский

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Melanoma Management: From Epidemiology to Treatment and Latest Advances

Cancers, Journal Year: 2022, Volume and Issue: 14(19), P. 4652 - 4652

Published: Sept. 24, 2022

Melanoma is the deadliest skin cancer, whose morbidity and mortality indicators show an increasing trend worldwide. In addition to its great heterogeneity, melanoma has a high metastatic potential, resulting in very limited response therapies currently available, which were restricted surgery, radiotherapy chemotherapy for many years. Advances knowledge about pathophysiological mechanisms of disease have allowed development new therapeutic classes, such as immune checkpoint small molecule kinase inhibitors. However, despite incontestable progress quality life survival rates patients, effectiveness still far from desired. Some adverse side effects resistance are main barriers. Thus, search better options resulted clinical trials that now investigating drugs and/or combinations. The low water solubility drugs, stability rapid metabolism limit potential use some compounds. research nanotechnology-based strategies being explored basis broad application different types nanosystems treatment melanoma. Future focus on challenges understanding make these more effective.

Language: Английский

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SNC_Net: Skin Cancer Detection by Integrating Handcrafted and Deep Learning-Based Features Using Dermoscopy Images

Mathematics, Journal Year: 2024, Volume and Issue: 12(7), P. 1030 - 1030

Published: March 29, 2024

The medical sciences are facing a major problem with the auto-detection of disease due to fast growth in population density. Intelligent systems assist professionals early detection and also help provide consistent treatment that reduces mortality rate. Skin cancer is considered be deadliest most severe kind cancer. Medical utilize dermoscopy images make manual diagnosis skin This method labor-intensive time-consuming demands considerable level expertise. Automated methods necessary for occurrence hair air bubbles dermoscopic affects research aims classify eight different types cancer, namely actinic keratosis (AKs), dermatofibroma (DFa), melanoma (MELa), basal cell carcinoma (BCCa), squamous (SCCa), melanocytic nevus (MNi), vascular lesion (VASn), benign (BKs). In this study, we propose SNC_Net, which integrates features derived from through deep learning (DL) models handcrafted (HC) feature extraction aim improving performance classifier. A convolutional neural network (CNN) employed classification. Dermoscopy publicly accessible ISIC 2019 dataset utilized train validate model. proposed model compared four baseline models, EfficientNetB0 (B1), MobileNetV2 (B2), DenseNet-121 (B3), ResNet-101 (B4), six state-of-the-art (SOTA) classifiers. With an accuracy 97.81%, precision 98.31%, recall 97.89%, F1 score 98.10%, outperformed SOTA classifiers as well models. Moreover, Ablation study performed on its performance. therefore assists dermatologists other detection.

Language: Английский

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Integrated microfluidics-based construction of anti-BTN2A2 gel droplet cell preparations for non-invasive tumor-infiltrating lymphocyte therapy

Materials Today Bio, Journal Year: 2025, Volume and Issue: 31, P. 101545 - 101545

Published: Feb. 4, 2025

Tumor infiltrating lymphocyte therapy (TIL therapy) is one of the effective treatments for solid tumors. However, certain periods or sites tumors are not amenable to surgical resection. Meanwhile, abundant and dense extracellular matrix (ECM) regulatory cells (e.g., T (Tregs), myeloid-derived suppressor (MDSC)) in when infused back into treatment will prevent cell infiltration proliferation, thus inhibiting efficacy this approach. In study, a novel preparation was successfully developed by integrating microfluidic chip design with carbodiimide chemical modification. This surface modified BTN2A2 antibodies internally contained isolated from blood tumor hosts, along simulated collagen peptide CMP. Specifically, exerted its anti-tumor effects through multiple mechanisms: Firstly, effectively inhibited proliferation Tregs MDSCs within microenvironment; Secondly, leveraging antigen receptors (TCRs) present cells, which were similar those tumor-infiltrating lymphocytes, significantly enhanced their targeting cytotoxic capabilities; Furthermore, CMP component droplets promoted tissues. complex immunosuppressive microenvironment, synergistic action these components markedly clearance immune system. Experimental results demonstrated that cellular exhibited promising therapeutic both melanoma pancreatic cancer models. research provided platform cooperation various methods immunotherapy, holding broad application prospects.

Language: Английский

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Decoding Melanoma Development and Progression: Identification of Therapeutic Vulnerabilities

Frontiers in Oncology, Journal Year: 2021, Volume and Issue: 10

Published: Feb. 4, 2021

Melanoma, a cancer of the skin, arises from transformed melanocytes. Melanoma has highest mutational burden any partially attributed to UV induced DNA damage. Localized melanoma is “curable” by surgical resection and followed radiation therapy eliminate remaining cells. Targeted therapies against components MAPK signaling cascade immunotherapies which block immune checkpoints have shown remarkable clinical responses, however with onset resistance in most patients, and, disease relapse, these patients eventually become refractory treatments. Although great advances been made our understanding metastatic process cancers including melanoma, failure suggests that much remains be learned understood about multi-step tumor metastasis. In this review we provide an overview melanocytic transformation into malignant key molecular events occur during evolution. A better complex processes entailing cell dissemination will improve mechanistic driven design target specific steps involved metastasis response rates overall survival all patients.

Language: Английский

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Unraveling the Wide Spectrum of Melanoma Biomarkers

Diagnostics, Journal Year: 2021, Volume and Issue: 11(8), P. 1341 - 1341

Published: July 26, 2021

The use of biomarkers in medicine has become essential clinical practice order to help with diagnosis, prognostication and prediction treatment response. Since Alexander Breslow's original report on "melanoma prognostic values thickness", providing the first biomarker for melanoma, many promising new have followed. These include serum markers, such as lactate dehydrogenase S100 calcium-binding protein B. However, our understanding DNA mutational profile progresses, gene targets proteins been identified. point mutations, mutations BRAF tumour suppressor tP53. At present, only a small number available are being utilised, but this may soon change more studies published. aim article is provide comprehensive review melanoma their utility current and, potentially, future practice.

Language: Английский

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Nobiletin Induces Ferroptosis in Human Skin Melanoma Cells Through the GSK3β-Mediated Keap1/Nrf2/HO-1 Signalling Pathway

Frontiers in Genetics, Journal Year: 2022, Volume and Issue: 13

Published: March 8, 2022

Melanoma is an aggressive malignant skin tumour with increasing global incidence. However, current treatments have limitations owing to the acquired drug resistance. Ferroptosis a recently discovered form of programmed cell death characterised by iron accumulation and lipid peroxidation plays critical role in growth inhibition. Recently, ferroptosis inducers been regarded as promising therapeutic strategy overcome apoptosis resistance cells. In this study, we reported that nobiletin, natural product isolated from citrus peel, exhibited antitumour activity inducing melanoma Subsequently, further explored potential mechanism nobiletin-induced ferroptosis, found expression level glycogen synthase kinase 3β (GSK3β) tissue patients was significantly reduced compared normal tissue. Additionally, nobiletin increased GSK3β Moreover, Kelch-like Ech-associated protein-1 (Keap1) increased, while nuclear factor erythroid 2-related 2 (Nrf2), haem oxygenase-1 (HO-1) decreased nobiletin-treated cells, suggesting antioxidant defence system downregulated. Furthermore, knockdown upregulated Keap1/Nrf2/HO-1 signalling pathway, opposite observed cells overexpressing GSK3β. addition, molecular docking assay results indicated showed strong binding affinities for GSK3β, Keap1, Nrf2, HO-1. Taken together, our demonstrated could induce regulating GSK3β-mediated pathway human Hence, stands candidate treatment development prospects.

Language: Английский

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Phenotype Switching and the Melanoma Microenvironment; Impact on Immunotherapy and Drug Resistance

International Journal of Molecular Sciences, Journal Year: 2023, Volume and Issue: 24(2), P. 1601 - 1601

Published: Jan. 13, 2023

Melanoma, a highly heterogeneous tumor, is comprised of functionally diverse spectrum cell phenotypes and subpopulations, including stromal cells in the tumor microenvironment (TME). Melanoma has been shown to dynamically shift between different transcriptional states or phenotypes. This referred as phenotype switching melanoma, it involves quiescent proliferative cycle states, dramatic shifts invasiveness, well changes signaling pathways melanoma cells, immune composition TME. plasticity associated with altered gene expression cancer-associated fibroblasts, extracellular matrix, which drive metastatic cascade therapeutic resistance. Therefore, resistance therapy not only dependent on genetic evolution, but also suggested be driven by adaptive phenotypic plasticity. review discusses recent findings switching, immunotherapy resistance, balancing homeostatic TME subpopulations. We discuss future perspectives biology neural crest-like state(s) melanoma.

Language: Английский

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Deep learning-based scoring of tumour-infiltrating lymphocytes is prognostic in primary melanoma and predictive to PD-1 checkpoint inhibition in melanoma metastases

EBioMedicine, Journal Year: 2023, Volume and Issue: 93, P. 104644 - 104644

Published: June 8, 2023

Recent advances in digital pathology have enabled accurate and standardised enumeration of tumour-infiltrating lymphocytes (TILs). Here, we aim to evaluate TILs as a percentage electronic TIL score (eTILs) investigate its prognostic predictive relevance cutaneous melanoma.

Language: Английский

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