scholarly journals A three-dimensional in vitro ovarian cancer coculture model using a high-throughput cell patterning platform

2011 ◽  
Vol 6 (2) ◽  
pp. 204-212 ◽  
Author(s):  
Feng Xu ◽  
Jonathan Celli ◽  
Imran Rizvi ◽  
Sangjun Moon ◽  
Tayyaba Hasan ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
High Throughput ◽  
Three Dimensional ◽  
Cell Patterning ◽  
Coculture Model

scholarly journals Newly developed dual topoisomerase inhibitor P8-D6 is highly active in ovarian cancer

2021 ◽  
Vol 13 ◽  
pp. 175883592110598
Author(s):  
Inken Flörkemeier ◽  
Tamara N. Steinhauer ◽  
Nina Hedemann ◽  
Magnus Ölander ◽  
Per Artursson ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Topoisomerase I ◽  
Ex Vivo ◽  
Chemotherapy Resistance ◽  
Membrane Integrity ◽  
Three Dimensional ◽  
New Drugs ◽  
Highly Active ◽  
Gynaecologic Neoplasms

Background: Ovarian cancer (OvCa) constitutes a rare and highly aggressive malignancy and is one of the most lethal of all gynaecologic neoplasms. Due to chemotherapy resistance and treatment limitations because of side effects, OvCa is still not sufficiently treatable. Hence, new drugs for OvCa therapy such as P8-D6 with promising antitumour properties have a high clinical need. The benzo[ c]phenanthridine P8-D6 is an effective inductor of apoptosis by acting as a dual topoisomerase I/II inhibitor. Methods: In the present study, the effectiveness of P8-D6 on OvCa was investigated in vitro. In various OvCa cell lines and ex vivo primary cells, the apoptosis induction compared with standard therapeutic agents was determined in two-dimensional monolayers. Expanded by three-dimensional and co-culture, the P8-D6 treated cells were examined for changes in cytotoxicity, apoptosis rate and membrane integrity via scanning electron microscopy (SEM). Likewise, the effects of P8-D6 on non-cancer human ovarian surface epithelial cells and primary human hepatocytes were determined. Results: This study shows a significant P8-D6-induced increase in apoptosis and cytotoxicity in OvCa cells which surpasses the efficacy of well-established drugs like cisplatin or the topoisomerase inhibitors etoposide and topotecan. Non-cancer cells were affected only slightly by P8-D6. Moreover, no hepatotoxic effect in in vitro studies was detected. Conclusion: P8-D6 is a strong and rapid inductor of apoptosis and might be a novel treatment option for OvCa therapy.

An in vitro three-dimensional coculture model of cerebral microvascular angiogenesis and differentiation

1997 ◽  
Vol 33 (9) ◽  
pp. 684-691 ◽  
Author(s):  
Laura R. Ment ◽  
William B. Stewart ◽  
Dominick Scaramuzzino ◽  
Joseph A. Madri
Keyword(s):  
Three Dimensional ◽  
Coculture Model

scholarly journals Development of a Scalable, High-Throughput-Compatible Assay to Detect Tau Aggregates Using iPSC-Derived Cortical Neurons Maintained in a Three-Dimensional Culture Format

2016 ◽  
Vol 21 (8) ◽  
pp. 804-815 ◽  
Author(s):  
X. Medda ◽  
L. Mertens ◽  
S. Versweyveld ◽  
A. Diels ◽  
L. Barnham ◽  
...  
Keyword(s):  
High Throughput ◽  
Cortical Neurons ◽  
High Throughput Screening ◽  
Three Dimensional ◽  
Culture Conditions ◽  
Novel Treatments ◽  
Entry Points ◽  
Induced Pluripotent ◽  
Tau Aggregation

Tau aggregation is the pathological hallmark that best correlates with the progression of Alzheimer’s disease (AD). The presence of neurofibrillary tangles (NFTs), formed of hyperphosphorylated tau, leads to neuronal dysfunction and loss, and is directly associated with the cognitive decline observed in AD patients. The limited success in targeting β-amyloid pathologies has reinforced the hypothesis of blocking tau phosphorylation, aggregation, and/or spreading as alternative therapeutic entry points to treat AD. Identification of novel therapies requires disease-relevant and scalable assays capable of reproducing key features of the pathology in an in vitro setting. Here we use induced pluripotent stem cells (iPSCs) as a virtually unlimited source of human cortical neurons to develop a robust and scalable tau aggregation model compatible with high-throughput screening (HTS). We downscaled cell culture conditions to 384-well plate format and used Matrigel to introduce an extra physical protection against cell detachment that reduces shearing stress and better recapitulates pathological conditions. We complemented the assay with AlphaLISA technology for the detection of tau aggregates in a high-throughput-compatible format. The assay is reproducible across users and works with different commercially available iPSC lines, representing a highly translational tool for the identification of novel treatments against tauopathies, including AD.

scholarly journals Amyloid fibril-based hydrogels for high-throughput tumor spheroid modeling

2020 ◽  
Author(s):  
Namrata Singh ◽  
Komal Patel ◽  
Ambuja Navalkar ◽  
Pradeep Kadu ◽  
Debalina Datta ◽  
...  
Keyword(s):  
Drug Resistance ◽  
High Throughput ◽  
Three Dimensional ◽  
3D Cell Culture ◽  
Cancer Therapeutics ◽  
Cost Effective ◽  
Cell Types ◽  
Tumor Spheroid ◽  
Tumor Modeling

AbstractBiomaterials mimicking extracellular matrices (ECM) for three-dimensional (3D) cultures have gained immense interest in tumor modeling and in vitro organ development. Here, we introduce versatile, thixotropic amyloid hydrogels as a bio-mimetic ECM scaffold for 3D cell culture as well as high-throughput tumor spheroid formation using a drop cast method. The unique cross-β-sheet structure, sticky surface, and thixotropicity of amyloid hydrogels allow robust cell adhesion, survival, proliferation, and migration, which are essential for 3D tumor modeling with various cancer cell types. The spheroids formed show overexpression of the signature cancer biomarkers and confer higher drug resistance compared to two-dimensional (2D) monolayer cultures. Using breast tumor tissue from mouse xenograft, we showed that these hydrogels support the formation of tumor spheroids with a well-defined necrotic core, cancer-associated gene expression, higher drug resistance, and tumor heterogeneity reminiscent of the original tumor. Altogether, we have developed a rapid and cost-effective platform for generating in vitro cancer models for the screening of anti-cancer therapeutics and developing personalized medicines.

Modulation of In Vitro Angiogenesis in a Three-Dimensional Spheroidal Coculture Model for Bone Tissue Engineering

2004 ◽  
Vol 10 (9) ◽  
pp. 1536-1547 ◽  
Author(s):  
A. Wenger ◽  
A. Stahl ◽  
H. Weber ◽  
G. Finkenzeller ◽  
H.G. Augustin ◽  
...  
Keyword(s):  
Tissue Engineering ◽  
Bone Tissue Engineering ◽  
Bone Tissue ◽  
Three Dimensional ◽  
Coculture Model

Patient-derived organoids for personalized drug screening in intrahepatic cholangiocarcinoma.

2020 ◽  
Vol 38 (4_suppl) ◽  
pp. 581-581
Author(s):  
Ricardo J. Antonia ◽  
Kan Toriguchi ◽  
Eveliina Karelehto ◽  
Dania Annuar ◽  
Luika Timmerman ◽  
...  
Keyword(s):  
High Throughput ◽  
Drug Screening ◽  
Intrahepatic Cholangiocarcinoma ◽  
Three Dimensional ◽  
Small Samples ◽  
Patient Specific ◽  
Mtor Inhibition ◽  
Drug Responses

581 Background: Despite standard treatment with gemcitabine and cisplatin, median survival for unresectable Intrahepatic Cholangiocarcinoma (ICC) is < 1 year. Clearly, novel therapeutic strategies are urgently needed. The paucity of targetable mutations in ICC and the as yet unproven benefit of genetically targeted drugs led us to ask whether a reliable clinical benefit may be revealed by patient-specific therapeutic testing in novel models of ICC. Here we describe our ability to establish patient-derived three-dimensional organoid cultures (PDO) that enable individualized identification of active single agents or drug combinations in surrogate models of ICC. Methods: To model patient-specific drug responses, we used the freshly resected ICCs from small samples of single patient tumors to generate PDXs and PDOs, small spheroidal clusters of tumor cells grown in vitro. We have employed a high-throughput drug screening platform using AI-enhanced robotics (Yamaha Motor Corporation) to identify and distribute single, uniformly sized PDOs into 384-well ultra-low adherent plates. This is coupled with a TECAN D300e drug dispenser that rapidly delivers nanoliter volumes of a 34-drug panel, thereby facilitating rapid, reliable drug response analyses. Results: Our data show that PDOs retain characteristic genomic and histological features of the patients’ tumors. Drug responses were specific to each patient tumor, but PDOs from all patients responded to a greater or lesser degree to mTOR inhibition, suggesting that this pathway is important in ICC. The responses of PDO to the mTOR inhibitor Sapanisertib (INK128), was recapitulated in the same patient’s PDX. Further, INK128 was synergistic with gemcitabine in patient 970 PDOs as well as in vivo in PDX also from patient 970. Conclusions: As it is believed that PDX can predict patient responses to drugs, our results suggest that PDO may also predict patient drug responses. The establishment of PDO may allow economical patient-specific, high throughput drug screens that could ultimately inform clinical practice. [Table: see text]

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