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Your search keyword '"Gabriel Frampton"' showing total 11 results
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11 results on '"Gabriel Frampton"'

1. Generating Shigella that internalize into glioblastoma cells

Author

Austin Shipley, Gabriel Frampton, Bryan W. Davies, and Benjamin J. Umlauf

Subjects
Shigella, glioblastoma, drug delivery, microbial factories, myristoylation, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282
Abstract

IntroductionThe use of microorganisms as drug delivery systems to treat cancer has expanded recently, including FDA approval of certain viruses as oncolytics. Microorganisms have several unique benefits compared to traditional pharmacologic agents including dose independence, the ability to produce therapeutic proteins locally within the tumor, and simplicity of administration. However, current microbial delivery systems such as AAV9 and herpes virus have limited cassette sizes, minimal cancer cell selectivity, and low innate cytotoxicity. To address these issues, we sought to generate a strain of Shigella flexneri to selectively internalize into glioblastoma (GBM) brain tumor cells as an initial step to generating a bacterial-based drug delivery system.MethodsWe generated S. flexneri that selectively internalize into GBM cells using iterative co-cultured assays.ResultsAfter 50 rounds of co-culture, the new strain infected 95 percent of GBM cells in 2 hours. GBM-infecting Shigella demonstrate a 124-fold preference for internalizing in nine different GBM cell lines compared to Normal Astrocytes (NA) controls. Additionally, we developed an in-cell western to identify GBM-infecting Shigella clones that preferentially internalize in patient samples without iterative co-culture. Finally, we demonstrate internalization into GBM cells is mediated via a factor modified by myristoylation.DiscussionIn conclusion, here we present a novel bacterial platform that preferentially internalizes in brain tumor cells. This system provides numerous potential benefits over current interventions and other microbial strategies for treating brain tumors.

Published
2023
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2. Supplementary Table 1 from Serotonin Metabolism Is Dysregulated in Cholangiocarcinoma, which Has Implications for Tumor Growth

Author

Sharon DeMorrow, Antonio Benedetti, Marco Marzioni, Sum P. Lee, Domenico Alvaro, Gabriel Frampton, Monique Coufal, Antonio Franchitto, Paolo Onori, Francesca Bernuzzi, Shelley Kopriva, Julie Venter, Eugenio Gaudio, Pietro Invernizzi, and Gianfranco Alpini

Abstract

Supplementary Table 1 from Serotonin Metabolism Is Dysregulated in Cholangiocarcinoma, which Has Implications for Tumor Growth

Published
2023

3. Supplementary Figure 5 from Serotonin Metabolism Is Dysregulated in Cholangiocarcinoma, which Has Implications for Tumor Growth

Author

Sharon DeMorrow, Antonio Benedetti, Marco Marzioni, Sum P. Lee, Domenico Alvaro, Gabriel Frampton, Monique Coufal, Antonio Franchitto, Paolo Onori, Francesca Bernuzzi, Shelley Kopriva, Julie Venter, Eugenio Gaudio, Pietro Invernizzi, and Gianfranco Alpini

Abstract

Supplementary Figure 5 from Serotonin Metabolism Is Dysregulated in Cholangiocarcinoma, which Has Implications for Tumor Growth

Published
2023

4. Supplementary Figure 1 from Serotonin Metabolism Is Dysregulated in Cholangiocarcinoma, which Has Implications for Tumor Growth

Author

Sharon DeMorrow, Antonio Benedetti, Marco Marzioni, Sum P. Lee, Domenico Alvaro, Gabriel Frampton, Monique Coufal, Antonio Franchitto, Paolo Onori, Francesca Bernuzzi, Shelley Kopriva, Julie Venter, Eugenio Gaudio, Pietro Invernizzi, and Gianfranco Alpini

Abstract

Supplementary Figure 1 from Serotonin Metabolism Is Dysregulated in Cholangiocarcinoma, which Has Implications for Tumor Growth

Published
2023

5. Supplementary Figure 2 from Serotonin Metabolism Is Dysregulated in Cholangiocarcinoma, which Has Implications for Tumor Growth

Author

Sharon DeMorrow, Antonio Benedetti, Marco Marzioni, Sum P. Lee, Domenico Alvaro, Gabriel Frampton, Monique Coufal, Antonio Franchitto, Paolo Onori, Francesca Bernuzzi, Shelley Kopriva, Julie Venter, Eugenio Gaudio, Pietro Invernizzi, and Gianfranco Alpini

Abstract

Supplementary Figure 2 from Serotonin Metabolism Is Dysregulated in Cholangiocarcinoma, which Has Implications for Tumor Growth

Published
2023

6. Supplementary Figure Legends 1-5 from Serotonin Metabolism Is Dysregulated in Cholangiocarcinoma, which Has Implications for Tumor Growth

Author

Sharon DeMorrow, Antonio Benedetti, Marco Marzioni, Sum P. Lee, Domenico Alvaro, Gabriel Frampton, Monique Coufal, Antonio Franchitto, Paolo Onori, Francesca Bernuzzi, Shelley Kopriva, Julie Venter, Eugenio Gaudio, Pietro Invernizzi, and Gianfranco Alpini

Abstract

Supplementary Figure Legends 1-5 from Serotonin Metabolism Is Dysregulated in Cholangiocarcinoma, which Has Implications for Tumor Growth

Published
2023

7. Supplementary Figure 3 from Serotonin Metabolism Is Dysregulated in Cholangiocarcinoma, which Has Implications for Tumor Growth

Author

Sharon DeMorrow, Antonio Benedetti, Marco Marzioni, Sum P. Lee, Domenico Alvaro, Gabriel Frampton, Monique Coufal, Antonio Franchitto, Paolo Onori, Francesca Bernuzzi, Shelley Kopriva, Julie Venter, Eugenio Gaudio, Pietro Invernizzi, and Gianfranco Alpini

Abstract

Supplementary Figure 3 from Serotonin Metabolism Is Dysregulated in Cholangiocarcinoma, which Has Implications for Tumor Growth

Published
2023

8. Supplementary Figure 4 from Serotonin Metabolism Is Dysregulated in Cholangiocarcinoma, which Has Implications for Tumor Growth

Author

Sharon DeMorrow, Antonio Benedetti, Marco Marzioni, Sum P. Lee, Domenico Alvaro, Gabriel Frampton, Monique Coufal, Antonio Franchitto, Paolo Onori, Francesca Bernuzzi, Shelley Kopriva, Julie Venter, Eugenio Gaudio, Pietro Invernizzi, and Gianfranco Alpini

Abstract

Supplementary Figure 4 from Serotonin Metabolism Is Dysregulated in Cholangiocarcinoma, which Has Implications for Tumor Growth

Published
2023

9. Leptin Enhances Hepatic Fibrosis and Inflammation in a Mouse Model of Cholestasis

Author

Anca D. Petrescu, Stephanie Grant, Elaina Williams, Su Yeon An, Nikhil Seth, Mark Shell, Tyson Amundsen, Christopher Tan, Yusra Nadeem, Matthew Tjahja, Lancaster Weld, Christopher S. Chu, Julie Venter, Gabriel Frampton, Matthew McMillin, and Sharon DeMorrow

Subjects
Inflammation, Leptin, Liver Cirrhosis, Male, Mice, Knockout, Cholestasis, Hyperplasia, Regular Article, Antibodies, Neutralizing, Pathology and Forensic Medicine, Disease Models, Animal, Mice, Liver, Hepatic Stellate Cells, Animals, Cytokines, Receptors, Leptin, Female, Proto-Oncogene Proteins c-akt
Abstract

Leptin is an adipokine with roles in food intake and energy metabolism through its actions on neurons in the hypothalamus. The role of leptin in obesity and cardiovascular disorders is well documented. However, its influence on liver conditions such as cholestasis is poorly understood. The effects of exogenous leptin and leptin-neutralizing antibody on biliary hyperplasia, hepatic fibrosis, and inflammation in the multidrug resistance protein 2 knockout (Mdr2KO) mouse model of cholestasis were assessed by quantifying markers specific for cholangiocytes, activated hepatic stellate cells (HSCs), and cytokines. Serum and hepatic leptin were increased in Mdr2KO mice compared with FVB/NJ (FVBN) controls, and exogenous leptin enhanced biliary hyperplasia and liver fibrosis in Mdr2KO and FVBN mice. Leptin administration increased hepatic expression of C-C motif chemokine ligand 2 and IL-6 in Mdr2KO mice. In contrast, leptin-neutralizing antibody reduced intrahepatic bile duct mass and decreased HSC activation in Mdr2KO mice compared with FVBN controls. Sex-related differences were noted, with female Mdr2KO mice having more leptin than males. In cholangiocytes and LX2 cells in vitro, leptin increased phosphorylated Akt and stimulated cell proliferation. Leptin receptor siRNA and inhibitors of Akt phosphorylation impaired leptin-induced cell proliferation and proinflammatory cytokines. The current data suggest that leptin is abnormally increased in cholestatic mice, and excess leptin increases ductular reaction, hepatic fibrosis, and inflammation via leptin receptor–mediated phosphorylation of Akt in cholangiocytes and HSCs.

Published
2022

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