Improving tumor microenvironment assessment in chip systems through next-generation technology integration DOI Creative Commons

Daniela Gaebler,

Stephanie J. Hachey, Christopher C.W. Hughes

et al.

Frontiers in Bioengineering and Biotechnology, Journal Year: 2024, Volume and Issue: 12

Published: Sept. 25, 2024

The tumor microenvironment (TME) comprises a diverse array of cells, both cancerous and non-cancerous, including stromal cells immune cells. Complex interactions among these play central role in driving cancer progression, impacting critical aspects such as initiation, growth, invasion, response to therapy, the development drug resistance. While targeting TME has emerged promising therapeutic strategy, there is need for innovative approaches that accurately replicate its complex cellular non-cellular interactions; goal being develop targeted, personalized therapies can effectively elicit anti-cancer responses patients. Microfluidic systems present notable advantages over conventional

Language: Английский

A Novel DNA Repair‐Gene Model to Predict Responses to Immunotherapy and Prognosis in Patients With EGFR‐Mutant Non‐Small Cell Lung Cancer DOI Creative Commons
Fen Wang, Xue‐Wu Wei, Mingyi Yang

et al.

Thoracic Cancer, Journal Year: 2025, Volume and Issue: 16(4)

Published: Feb. 1, 2025

The epidermal growth factor receptor mutant (EGFRm) non-small cell lung cancer (NSCLC) has a unique "cold" immune profile. DNA damage repair (DDR) genes are closely related to tumorigenesis and the effectiveness of immunotherapy in many tumors. However, role mechanism DDR genesis progression EGFRm NSCLC remain unclear. This study included 101 samples from Cancer Genome Atlas (TCGA) dataset GSE31210 (external set) GEO database. Cluster analysis was used identify different subtypes based on expression genes. Univariate LASSO regression develop DDR-based predictive model. prognostic significance this model assessed using Cox regression, Kaplan-Meier, receiver operating characteristic (ROC) curve analyses. Bioinformatics performed investigate clinicopathological characteristics profiles associated with In vitro experiment testify NSCLC. We identified two NSCLC: DDR-activated DDR-suppressed. subtype showed more aggressive clinical behavior poorer prognosis responsive immunotherapy. A for constructed four genes: CAPS, FAM83A, IGLV8-61, SLC7A5. derived risk score could serve as an independent indicator. High- low-risk patients exhibited distinct characteristics, profiles, responses T-cell inflammation Tumor Immune Dysfunction Exclusion (TIDE) scores differed between high- subgroups, both showing enhanced subgroup. Targeted therapy such BI.2536, inhibitor polo-like kinase 1, be effective high-risk Meanwhile, detection approved response. demonstrated diversity developed these assist identifying potential candidates assessing personalized treatment

Language: Английский

Citations

0

Defeating lethal cancer: Interrupting the ecologic and evolutionary basis of death from malignancy DOI Open Access
Kenneth J. Pienta,

Patrick L. Goodin,

Sarah R. Amend

et al.

CA A Cancer Journal for Clinicians, Journal Year: 2025, Volume and Issue: unknown

Published: March 9, 2025

Despite the advances in cancer prevention, early detection, and treatments, all of which have led to improved survival, globally, there is an increased incidence cancer-related deaths. Although each patient tumor wholly unique, tipping point incurable disease common across patients: dual capacity for cancers metastasize resist systemic treatment. The discovery genetic mutations epigenetic variation that emerges during progression highlights evolutionary ecology principles can be used understand how evolves a lethal phenotype. By applying such eco-evolutionary framework, authors reinterpret our understanding metastatic process as one ecologic invasion define paths evolving therapy resistance. With this understanding, draw from successful strategies optimized strategic interventions with goal altering trajectory cancer. Ultimately, studying, treating using provides opportunity improve lives patients

Language: Английский

Citations

0

Methods for Processing and Analyzing Images of Vascularized Micro-Organ and Tumor Systems DOI Creative Commons
Stephanie J. Hachey, Christopher J. Hatch,

Daniela Gaebler

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2025, Volume and Issue: unknown

Published: March 14, 2025

Our group has developed and validated an advanced microfluidic platform to improve preclinical modeling of healthy disease states, enabling extended culture detailed analysis tissue-engineered miniaturized organ constructs, or "organs-on-chips." Within this system, diverse cell types self-organize into perfused microvascular networks under dynamic flow within tissue chambers, effectively mimicking the structure function native tissues. This setup facilitates physiological intravascular delivery nutrients, immune cells, therapeutic agents, creates a realistic microenvironment study cellular interactions responses. Known as vascularized micro-organ (VMO), adaptable can be customized represent various systems tumors, forming micro-tumor (VMT) for cancer studies. The VMO/VMT system closely simulates in vivo nutrient exchange drug 3D microenvironment, establishing high-fidelity model screening mechanistic studies vascular biology, cancer, organ-specific pathologies. Furthermore, optical transparency device supports high-resolution, real-time imaging fluorescently labeled cells molecules construct, providing key insights responses, interactions, processes such epithelial-mesenchymal transition. To manage extensive data generated, we created standardized, high-throughput workflows image analysis. manuscript presents our processing pipeline, utilizing suite tools Fiji/ImageJ streamline extraction from model, substantially reducing manual time. Additionally, demonstrate how these adapted analyzing traditional vitro models microphysiological by other researchers.

Language: Английский

Citations

0

Improving tumor microenvironment assessment in chip systems through next-generation technology integration DOI Creative Commons

Daniela Gaebler,

Stephanie J. Hachey, Christopher C.W. Hughes

et al.

Frontiers in Bioengineering and Biotechnology, Journal Year: 2024, Volume and Issue: 12

Published: Sept. 25, 2024

The tumor microenvironment (TME) comprises a diverse array of cells, both cancerous and non-cancerous, including stromal cells immune cells. Complex interactions among these play central role in driving cancer progression, impacting critical aspects such as initiation, growth, invasion, response to therapy, the development drug resistance. While targeting TME has emerged promising therapeutic strategy, there is need for innovative approaches that accurately replicate its complex cellular non-cellular interactions; goal being develop targeted, personalized therapies can effectively elicit anti-cancer responses patients. Microfluidic systems present notable advantages over conventional

Language: Английский

Citations

1