Volume electron microscopy

Nature Reviews Methods Primers, Journal Year: 2022, Volume and Issue: 2(1)

Published: July 7, 2022

Language: Английский

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Artificial intelligence assists precision medicine in cancer treatment

Frontiers in Oncology, Journal Year: 2023, Volume and Issue: 12

Published: Jan. 4, 2023

Cancer is a major medical problem worldwide. Due to its high heterogeneity, the use of same drugs or surgical methods in patients with tumor may have different curative effects, leading need for more accurate treatment tumors and personalized treatments patients. The precise essential, which renders obtaining an in-depth understanding changes that undergo urgent, including their genes, proteins cancer cell phenotypes, order develop targeted strategies Artificial intelligence (AI) based on big data can extract hidden patterns, important information, corresponding knowledge behind enormous amount data. For example, ML deep learning subsets AI be used mine deep-level information genomics, transcriptomics, proteomics, radiomics, digital pathological images, other data, make clinicians synthetically comprehensively understand tumors. In addition, find new biomarkers from assist screening, detection, diagnosis, prognosis prediction, so as providing best individual improving clinical outcomes.

Language: Английский

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Pan-cancer analysis of post-translational modifications reveals shared patterns of protein regulation

Cell, Journal Year: 2023, Volume and Issue: 186(18), P. 3945 - 3967.e26

Published: Aug. 1, 2023

Post-translational modifications (PTMs) play key roles in regulating cell signaling and physiology both normal cancer cells. Advances mass spectrometry enable high-throughput, accurate, sensitive measurement of PTM levels to better understand their role, prevalence, crosstalk. Here, we analyze the largest collection proteogenomics data from 1,110 patients with profiles across 11 types (10 National Cancer Institute's Clinical Proteomic Tumor Analysis Consortium [CPTAC]). Our study reveals pan-cancer patterns changes protein acetylation phosphorylation involved hallmark processes. These revealed subsets tumors, different types, including those dysregulated DNA repair driven by phosphorylation, altered metabolic regulation associated immune response acetylation, affected kinase specificity crosstalk between modified histone regulation. Overall, this resource highlights rich biology governed PTMs exposes potential new therapeutic avenues.

Language: Английский

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Real-world clinical multi-omics analyses reveal bifurcation of ER-independent and ER-dependent drug resistance to CDK4/6 inhibitors

Nature Communications, Journal Year: 2025, Volume and Issue: 16(1)

Published: Jan. 22, 2025

Language: Английский

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Molecular Characterization and Landscape of Breast cancer Models from a multi-omics Perspective

Journal of Mammary Gland Biology and Neoplasia, Journal Year: 2023, Volume and Issue: 28(1)

Published: June 3, 2023

Abstract Breast cancer is well-known to be a highly heterogenous disease. This facet of makes finding research model that mirrors the disparate intrinsic features challenging. With advances in multi-omics technologies, establishing parallels between various models and human tumors increasingly intricate. Here we review systems their relation primary breast using available omics data platforms. Among reviewed here, cell lines have least resemblance since they accumulated many mutations copy number alterations during long use. Moreover, individual proteomic metabolomic profiles do not overlap with molecular landscape cancer. Interestingly, analysis revealed initial subtype classification some was inappropriate. In major subtypes are all well represented share tumors. contrast, patient-derived xenografts (PDX) organoids (PDO) superior mirroring cancers at levels, making them suitable for drug screening analysis. While patient derived spread across luminal, basal- normal-like subtypes, PDX samples were initially largely basal but other been described. Murine offer tumor landscapes, inter intra-model heterogeneity, give rise different phenotypes histology. reduced mutational burden compared transcriptomic resemblance, representation can found among variety subtypes. To date, while mammospheres three- dimensional cultures lack comprehensive data, these excellent study stem cells, fate decision differentiation, also used screening. Therefore, this explores landscapes characterization by comparing recent published

Language: Английский

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Entinostat in combination with nivolumab in metastatic pancreatic ductal adenocarcinoma: a phase 2 clinical trial

Nature Communications, Journal Year: 2024, Volume and Issue: 15(1)

Published: Nov. 12, 2024

Abstract Pancreatic ductal adenocarcinoma (PDA) is characterized by low cytotoxic lymphocytes, abundant immune-suppressive cells, and resistance to immune checkpoint inhibitors (ICI). Preclinical PDA models showed the HDAC inhibitor entinostat reduced myeloid cell immunosuppression, sensitizing tumors ICI therapy. This phase II study combined with nivolumab (PD1 inhibitor) in patients advanced (NCT03250273). Patients received 5 mg orally once weekly for 14-day lead-in, followed nivolumab. The primary endpoint was objective response rate (ORR) RECIST v1.1. Secondary endpoints included safety, duration of response, progression free-survival overall survival. Between November 2017 2020, 27 evaluable were enrolled. Three partial responses (11% ORR, 95% CI, 2.4%-29.2%) a median 10.2 months. Median progression-free survival (PFS) (OS) were, respectively, 1.89 (95% 1.381-2.301) 2.729 1.841-5.622) Grade ≥3 treatment-related adverse events occurred 19 (63%), including decreased lymphocyte count, anemia, hypoalbuminemia, hyponatremia. As exploratory analysis, peripheral tumor profiles changes assessed using CyTOF, mIHC, RNA-seq. Entinostat increased dendritic activation maturation. Gene expression analysis revealed an enrichment inflammatory pathways combination treatment. Although not met, durable small subset patients. Myeloid immunomodulation supported preclinical hypothesis, providing basis future combinatorial therapies enhance clinical benefits PDA.

Language: Английский

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Longitudinal glioma monitoring via cerebrospinal fluid cell-free DNA: one patient at a time

medRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: Feb. 24, 2024

ABSTRACT IMPORTANCE Current methods for glioma treatment response assessment are limited. Intracranial cerebrospinal fluid (CSF) may provide a previously untapped source of longitudinal biomarkers, such as cell-free DNA (cfDNA), disease monitoring. OBJECTIVE To assess the feasibility obtaining intracranial CSF cfDNA from patients with gliomas during their course. DESIGN This case series was initiated in 2021, followed until last clinical follow-up (death or present time). SETTING single-center study conducted at large academic medical center. PARTICIPANTS Adults were recruited collection using 1) Ommaya reservoirs, which would be sampled on least two separate occasions, 2) other clinically indicated access devices, ventriculoperitoneal (VP) shunts. INTERVENTIONS collected reservoirs four and an existing VP shunt one patient. MAIN OUTCOMES AND MEASURES The aimed to collect biobanking biomarker discovery, hypothesis that could serve longitudinally acquirable biomarkers. RESULTS Five (2 females, 3 males; median: 40 years, range 32-64 years) underwent via (n=4/5 patients) (n=1/5). Three had glioblastoma astrocytoma, IDH-mutant, grade 4. In total, thirty-five samples obtained (median: 3.80 mL; 0.5-5 mL), 30 (85.7%) yielding sufficient Next-Generation Sequencing (n=28) Low-Pass Whole Genome sequencing (all samples). Tumor fraction found increase radiographic progression. Changes variant allelic frequencies (VAFs) seen within individual after resection chemoradiation. patients, changes tumor-specific IDH1 VAF correlated D-2-hydroxyglutarate levels, oncometabolite IDH mutant tumors. Copy number burden (CNB) decreased below limit quantification treatment. CONCLUSIONS RELEVANCE Longitudinal can feasibly devices Ongoing studies will evaluate hypotheses generated this regarding how utilized sensitively detect burden. Trial Registration NCT04692324 https://clinicaltrials.gov/study/NCT04692324 ; NCT04692337 https://clinicaltrials.gov/study/NCT04692337 QUESTION What is high-grade treatment? FINDING series, we find throughout devices. We tumor tumor-associated allele correlate trajectory, VAFs positively correlating candidate MEANING inform impact specific patient’s course, time through

Language: Английский

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Natural killer cells occupy unique spatial neighborhoods in HER2- and HER2+ human breast cancers

Breast Cancer Research, Journal Year: 2025, Volume and Issue: 27(1)

Published: Jan. 24, 2025

Tumor-infiltrating lymphocytes are considered clinically beneficial in breast cancer, but the significance of natural killer (NK) cells is less well characterized. As increasing evidence has demonstrated that spatial organization immune tumor microenvironments a significant parameter for impacting disease progression as therapeutic responses, an improved understanding tumor-infiltrating NK and their location within contextures needed to improve design effective cell-based therapies. In this study, we developed multiplex immunohistochemistry (mIHC) antibody panel designed quantitatively interrogate leukocyte lineages, focusing on phenotypes, two independent cancer patient cohorts (n = 26 n 30). Owing clinical supporting role HER2+ mediating responses Trastuzumab, further evaluated HER2- specimens separately. Consistent with literature, found CD3+ T were dominant subset across specimens. comparison, cells, identified by CD56 or NKp46 expression, scarce all low granzyme B expression indicating reduced cytotoxic functionality. Whereas cell density phenotype did not appear be influenced HER2 status, analysis revealed distinct phenotypes regarding proximity neoplastic associated status. Spatial cellular neighborhood multiple unique compositions surrounding where from tumors more frequently proximal whereas instead cells. This study establishes utility quantitative mIHC evaluate at single-cell proteomics level illustrates how characteristics neighborhoods vary context cancers.

Language: Английский

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Enhancing cell instance segmentation in scanning electron microscopy images via a deep contour closing operator

Computers in Biology and Medicine, Journal Year: 2025, Volume and Issue: 190, P. 109972 - 109972

Published: April 4, 2025

Accurately segmenting and individualizing cells in scanning electron microscopy (SEM) images is a highly promising technique for elucidating tissue architecture oncology. While current artificial intelligence (AI)-based methods are effective, errors persist, necessitating time-consuming manual corrections, particularly areas where the quality of cell contours image poor requires gap filling. This study presents novel AI-driven approach refining boundary delineation to improve instance-based segmentation SEM images, also reducing necessity residual correction. A convolutional neural network (CNN) Closing Operator (COp-Net) introduced address gaps contours, effectively filling regions with deficient or absent information. The takes as input contour probability maps potentially inadequate missing information outputs corrected delineations. lack training data was addressed by generating low integrity using tailored partial differential equation (PDE). To ensure reproducibility, COp-Net weights source code solving PDE publicly available at https://github.com/Florian-40/CellSegm. We showcase efficacy our augmenting precision both private from patient-derived xenograft (PDX) hepatoblastoma tissues accessible datasets. proposed closing operator exhibits notable improvement tested datasets, achieving respectively close 50% (private data) 10% (public increase accurately-delineated proportion compared state-of-the-art methods. Additionally, need corrections significantly reduced, therefore facilitating overall digitalization process. Our results demonstrate enhancement accuracy instance segmentation, challenging compromises boundaries, Therefore, work should ultimately facilitate tumour bioarchitecture onconanotomy field.

Language: Английский

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Integration of Organoids With CRISPR Screens: A Narrative Review

Biology of the Cell, Journal Year: 2025, Volume and Issue: 117(4)

Published: April 1, 2025

ABSTRACT Organoids represent a significant advancement in disease modeling, demonstrated by their capacity to mimic the physiological/pathological structure and functional characteristics of native tissue. Recently CRISPR/Cas9 technology has emerged as powerful tool combination with organoids for development novel therapies preclinical settings. This review explores current literature on applications pooled CRISPR screening emerging role these models understanding cancer. We highlight evolution genome‐wide gRNA library screens organoids, noting increasing adoption field over past decade. Noteworthy studies utilizing investigate oncogenic vulnerabilities developmental pathways various organoid systems are discussed. Despite promise hold, challenges such standardization, reproducibility, complexity data interpretation remain. The also addresses ideas assessing tumor (tumoroids) against established cancer hallmarks potential studying intercellular cooperation within models. Ultimately, we propose that particularly when personalized patient‐specific applications, could revolutionize drug therapeutic approaches, minimizing reliance traditional animal enhancing precision clinical interventions.

Language: Английский

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