Phytomedicine Plus, Journal Year: 2025, Volume and Issue: unknown, P. 100754 - 100754
Published: Jan. 1, 2025
Language: Английский
Citations
2Protein conformational ensembles in function: roles and mechanisms
RSC Chemical Biology, Journal Year: 2023, Volume and Issue: 4(11), P. 850 - 864
Published: Jan. 1, 2023
The
Language: Английский
Citations
36Small cells – big issues: biological implications and preclinical advancements in small cell lung cancer
Molecular Cancer, Journal Year: 2024, Volume and Issue: 23(1)
Published: Feb. 24, 2024
Abstract Current treatment guidelines refer to small cell lung cancer (SCLC), one of the deadliest human malignancies, as a homogeneous disease. Accordingly, SCLC therapy comprises chemoradiation with or without immunotherapy. Meanwhile, recent studies have made significant advances in subclassifying based on elevated expression transcription factors ASCL1, NEUROD1, and POU2F3, well certain inflammatory characteristics. The role regulator YAP1 defining unique subset remains be established. Although preclinical analyses described numerous subtype-specific characteristics vulnerabilities, so far non-existing clinical subtype distinction may contributor negative trial outcomes. This comprehensive review aims provide framework for development novel personalized therapeutic approaches by compiling most discoveries achieved research. We highlight challenges faced due limited access patient material accomplished implementing state-of-the-art models methodologies.
Language: Английский
Citations
13Development of a cancer metastasis-on-chip assay for high throughput drug screening
Frontiers in Oncology, Journal Year: 2024, Volume and Issue: 13
Published: Jan. 4, 2024
Metastasis is the cause of most triple-negative breast cancer deaths, yet anti-metastatic therapeutics remain limited. To develop new to prevent metastasis, pathophysiologically relevant assays that recapitulate tumor microenvironment essential for disease modeling and drug discovery. Here, we have developed a microfluidic metastasis-on-chip assay early stages metastasis integrated with cell line (MDA-MB-231), stromal fibroblasts perfused microvessel. High-content imaging automated quantification methods was optimized assess invasion intravasation within model. Cell were enhanced when co-cultured (MDA-MB-231). However, non-invasive line, MCF7, remained in our model, even presence fibroblasts. screening targeted anti-cancer therapy library conducted evaluate response sensitivity Through this screening, identified 30 compounds reduced by 60% compared controls. Multi-parametric phenotypic analysis applied combining data from metastasis-on-chip, proliferation 2D migration screens, revealing clustered into eight distinct groups similar responses. Notably, MEK inhibitors enriched cluster intravasation. In contrast, drugs molecular targets: ABL, KIT, PDGF, SRC, VEGFR clusters showing strong effect on less impact or proliferation, which, Imatinib, multi-kinase inhibitor targeting BCR-ABL/PDGFR/KIT. Further experimental showed Imatinib endothelial barrier stability as measured trans-endothelial electrical resistance significantly activity cells. Our findings demonstrate potential powerful tool studying biology, discovery aims, assessing responses, offering prospects personalized therapies patients.
Language: Английский
Citations
11Cancer drug sensitivity prediction from routine histology images
npj Precision Oncology, Journal Year: 2024, Volume and Issue: 8(1)
Published: Jan. 6, 2024
Abstract Drug sensitivity prediction models can aid in personalising cancer therapy, biomarker discovery, and drug design. Such require survival data from randomised controlled trials which be time consuming expensive. In this proof-of-concept study, we demonstrate for the first that deep learning link histological patterns whole slide images (WSIs) of Haematoxylin & Eosin (H&E) stained breast sections with sensitivities inferred cell lines. We employ patient-wise imputed gene expression-based mapping effects on lines to train a model predicts patients’ multiple drugs WSIs. show it is possible use routine WSIs predict profile patient number approved experimental drugs. also proposed approach identify cellular associated profiles patients.
Language: Английский
Citations
7Recent Advancement in Breast Cancer Research: Insights from Model Organisms—Mouse Models to Zebrafish
Cancers, Journal Year: 2023, Volume and Issue: 15(11), P. 2961 - 2961
Published: May 29, 2023
Animal models have been utilized for decades to investigate the causes of human diseases and provide platforms testing novel therapies. Indeed, breakthrough advances in genetically engineered mouse (GEM) xenograft transplantation technologies dramatically benefited elucidating mechanisms underlying pathogenesis multiple diseases, including cancer. The currently available GEM employed assess specific genetic changes that underlay many features carcinogenesis, variations tumor cell proliferation, apoptosis, invasion, metastasis, angiogenesis, drug resistance. In addition, mice render it easier locate biomarkers recognition, prognosis, surveillance cancer progression recurrence. Furthermore, patient-derived (PDX) model, which involves direct surgical transfer fresh samples immunodeficient mice, has contributed significantly advancing field discovery therapeutics. Here, we a synopsis zebrafish used research as well an interdisciplinary 'Team Medicine' approach not only accelerated our understanding varied aspects carcinogenesis but also instrumental developing therapeutic strategies.
Language: Английский
Citations
15Zebrafish Avatar-test forecasts clinical response to chemotherapy in patients with colorectal cancer
Nature Communications, Journal Year: 2024, Volume and Issue: 15(1)
Published: June 5, 2024
Abstract Cancer patients often undergo rounds of trial-and-error to find the most effective treatment because there is no test in clinical practice for predicting therapy response. Here, we conduct a study validate zebrafish patient-derived xenograft model (zAvatar) as fast predictive platform personalized colorectal cancer. zAvatars are generated with patient tumor cells, treated exactly same their corresponding and analyzed at single-cell resolution. By individually comparing responses 55 zAvatar-test, develop decision tree integrating stage, zAvatar-apoptosis, zAvatar-metastatic potential. This accurately forecasts progression 91% accuracy. Importantly, sensitive zAvatar-test exhibit longer progression-free survival compared those resistant test. We propose rapid approach guide decisions, optimizing options improving cancer patients.
Language: Английский
Citations
5Advancing Cancer Drug Delivery with Nanoparticles: Challenges and Prospects in Mathematical Modeling for In Vivo and In Vitro Systems
Cancers, Journal Year: 2025, Volume and Issue: 17(2), P. 198 - 198
Published: Jan. 9, 2025
Mathematical models are crucial for predicting the behavior of drug conjugate nanoparticles and optimizing delivery systems in cancer therapy. These simulate interactions among nanoparticle properties, tumor characteristics, physiological conditions, including resistance targeting specificity. However, they often rely on assumptions that may not accurately reflect vivo conditions. In vitro studies, while useful, fully capture complexities environment, leading to an overestimation nanoparticle-based therapy effectiveness. Advancements mathematical modeling, supported by preclinical data artificial intelligence, vital refining therapies improving their translation into effective clinical treatments.
Language: Английский
Citations
0A facile automated multiple‐well platform of immunized tumor organoid cultures in ECM‐mimicked hydrogels for chem‐immunotherapy evaluation
Deleted Journal, Journal Year: 2025, Volume and Issue: unknown
Published: Feb. 24, 2025
Abstract Breast cancer often develops drug resistance during chemotherapy, and immunotherapeutic agents always exhibit ineffectiveness when used as a single treatment; thus, it is necessary to develop chemo‐immunotherapy strategy in clinics. However, there still challenge evaluate the efficacy by conventional 2D cell culture animal models. In this study, we developed facile automated multiple‐well platform for fabricating tumor associated macrophages (TAMs)‐immunized breast organoids alginate hydrogels. An robotic microinjection system was building hydrogels situ seeding mixed suspensions of cells TAMs into form organoids. The induced epirubicin observed with TAMs, but could be inhibited targeted immunotherapy PLX3397. synergistic effects were also evaluated several co‐administration strategies PLX3397 combination epirubicin. RNA‐seq quantitative polymerase chain reaction further examine gene transcription levels find out three genes (IL6, CD37, GLS2) significant differences, which involved necrosis factor signaling, PI3K‐Akt signaling epidermal growth receptor tyrosine kinase inhibitor pathway. results demonstrated that showed potential replace bulk method evaluating therapeutic chem‐immunotherapy.
Language: Английский
Citations
0A Novel Mouse Cell Line Model Reveals the Tumor Intrinsic and Immune Characteristics of EGFR-Mutant Lung Cancer
Published: Jan. 1, 2025
Language: Английский
Citations
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