Engineering high throughput screening platforms of cervical cancer.
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| Title: | Engineering high throughput screening platforms of cervical cancer. |
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| Authors: | Cadena, Ines A.1 (AUTHOR), Buchanan, Mina R.1 (AUTHOR), Harris, Conor G.1 (AUTHOR), Jenne, Molly A.1 (AUTHOR), Rochefort, Willie E.1 (AUTHOR), Nelson, Dylan2 (AUTHOR), Fogg, Kaitlin C.1 (AUTHOR) kaitlin.fogg@oregonstate.edu |
| Source: | Journal of Biomedical Materials Research, Part A. Jun2023, Vol. 111 Issue 6, p747-764. 18p. |
| Abstract: | Cervical cancer is the second leading cause of cancer‐related death in women under 40 and is one of the few cancers to have an increased incidence rate and decreased survival rate over the last 10 years. One in five patients will have recurrent and/or distant metastatic disease and these patients face a 5‐year survival rate of less than 17%. Thus, there is a pressing need to develop new anticancer therapeutics for this underserved patient population. However, the development of new anticancer drugs remains a challenge, as only 7% of novel anticancer drugs are approved for clinical use. To facilitate identification of novel and effective anticancer drugs for cervical cancer, we developed a multilayer multicellular platform of human cervical cancer cell lines and primary human microvascular endothelial cells that interfaces with high throughput drug screening methods to evaluate the anti‐metastatic and anti‐angiogenic drug efficacy simultaneously. Through the use of design of experiments statistical optimization, we identified the specific concentrations of collagen I, fibrinogen, fibronectin, GelMA, and PEGDA in each hydrogel layer that maximized both cervical cancer invasion and endothelial microvessel length. We then validated the optimized platform and assessed its viscoelastic properties. Finally, using this optimized platform, we conducted a targeted drug screen of four clinically relevant drugs on two cervical cancer cell lines. Overall, this work provides a valuable platform that can be used to screen large compound libraries for mechanistic studies, drug discovery, and precision oncology for cervical cancer patients. [ABSTRACT FROM AUTHOR] |
| Copyright of Journal of Biomedical Materials Research, Part A is the property of Wiley-Blackwell and its content may not be copied or emailed to multiple sites without the copyright holder's express written permission. Additionally, content may not be used with any artificial intelligence tools or machine learning technologies. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.) | |
| Database: | Engineering Source |
| FullText | Text: Availability: 0 |
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| Header | DbId: egs DbLabel: Engineering Source An: 163092255 AccessLevel: 6 PubType: Academic Journal PubTypeId: academicJournal PreciseRelevancyScore: 0 |
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| Items | – Name: Title Label: Title Group: Ti Data: Engineering high throughput screening platforms of cervical cancer. – Name: Author Label: Authors Group: Au Data: <searchLink fieldCode="AR" term="%22Cadena%2C+Ines+A%2E%22">Cadena, Ines A.</searchLink><relatesTo>1</relatesTo> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Buchanan%2C+Mina+R%2E%22">Buchanan, Mina R.</searchLink><relatesTo>1</relatesTo> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Harris%2C+Conor+G%2E%22">Harris, Conor G.</searchLink><relatesTo>1</relatesTo> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Jenne%2C+Molly+A%2E%22">Jenne, Molly A.</searchLink><relatesTo>1</relatesTo> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Rochefort%2C+Willie+E%2E%22">Rochefort, Willie E.</searchLink><relatesTo>1</relatesTo> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Nelson%2C+Dylan%22">Nelson, Dylan</searchLink><relatesTo>2</relatesTo> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Fogg%2C+Kaitlin+C%2E%22">Fogg, Kaitlin C.</searchLink><relatesTo>1</relatesTo> (AUTHOR)<i> kaitlin.fogg@oregonstate.edu</i> – Name: TitleSource Label: Source Group: Src Data: <searchLink fieldCode="JN" term="%22Journal+of+Biomedical+Materials+Research%2C+Part+A%22">Journal of Biomedical Materials Research, Part A</searchLink>. Jun2023, Vol. 111 Issue 6, p747-764. 18p. – Name: Abstract Label: Abstract Group: Ab Data: Cervical cancer is the second leading cause of cancer‐related death in women under 40 and is one of the few cancers to have an increased incidence rate and decreased survival rate over the last 10 years. One in five patients will have recurrent and/or distant metastatic disease and these patients face a 5‐year survival rate of less than 17%. Thus, there is a pressing need to develop new anticancer therapeutics for this underserved patient population. However, the development of new anticancer drugs remains a challenge, as only 7% of novel anticancer drugs are approved for clinical use. To facilitate identification of novel and effective anticancer drugs for cervical cancer, we developed a multilayer multicellular platform of human cervical cancer cell lines and primary human microvascular endothelial cells that interfaces with high throughput drug screening methods to evaluate the anti‐metastatic and anti‐angiogenic drug efficacy simultaneously. Through the use of design of experiments statistical optimization, we identified the specific concentrations of collagen I, fibrinogen, fibronectin, GelMA, and PEGDA in each hydrogel layer that maximized both cervical cancer invasion and endothelial microvessel length. We then validated the optimized platform and assessed its viscoelastic properties. Finally, using this optimized platform, we conducted a targeted drug screen of four clinically relevant drugs on two cervical cancer cell lines. Overall, this work provides a valuable platform that can be used to screen large compound libraries for mechanistic studies, drug discovery, and precision oncology for cervical cancer patients. [ABSTRACT FROM AUTHOR] – Name: AbstractSuppliedCopyright Label: Group: Ab Data: <i>Copyright of Journal of Biomedical Materials Research, Part A is the property of Wiley-Blackwell and its content may not be copied or emailed to multiple sites without the copyright holder's express written permission. Additionally, content may not be used with any artificial intelligence tools or machine learning technologies. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract.</i> (Copyright applies to all Abstracts.) |
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| RecordInfo | BibRecord: BibEntity: Identifiers: – Type: doi Value: 10.1002/jbm.a.37522 Languages: – Code: eng Text: English PhysicalDescription: Pagination: PageCount: 18 StartPage: 747 Titles: – TitleFull: Engineering high throughput screening platforms of cervical cancer. Type: main BibRelationships: HasContributorRelationships: – PersonEntity: Name: NameFull: Cadena, Ines A. – PersonEntity: Name: NameFull: Buchanan, Mina R. – PersonEntity: Name: NameFull: Harris, Conor G. – PersonEntity: Name: NameFull: Jenne, Molly A. – PersonEntity: Name: NameFull: Rochefort, Willie E. – PersonEntity: Name: NameFull: Nelson, Dylan – PersonEntity: Name: NameFull: Fogg, Kaitlin C. IsPartOfRelationships: – BibEntity: Dates: – D: 01 M: 06 Text: Jun2023 Type: published Y: 2023 Identifiers: – Type: issn-print Value: 15493296 Numbering: – Type: volume Value: 111 – Type: issue Value: 6 Titles: – TitleFull: Journal of Biomedical Materials Research, Part A Type: main |
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