Ahuja, Avani
(2019)
Glioma cancer immunosuppressive microenvironment.
Master's Thesis, University of Pittsburgh.
(Unpublished)
Abstract
Glioblastoma (GBM) tumors, World Health Organization (WHO) grade IV tumor, are the most malignant tumors. Despite of aggressive standard treatment regimens including surgical resection, radiotherapy and chemotherapy temozolomide (TMZ), GBM patients have a high mortality rate and poor prognosis. A weak immunogenic and immunosuppressive tumor environment of GBM presents as a barrier for the newly developed immunotherapies. Na/H exchanger isoform 1 (NHE1) expressed in GBM drives H+ efflux in exchange for Na+ influx for maintaining an alkaline intracellular pH and acidic tumor microenvironment. Imbalance in the pH homeostasis, known as the Warburg effect, triggers cancer cells to rely on oxidative glycolysis instead of mitochondrial oxidative phosphorylation. In our study, we investigated roles of NHE1 in GBM bioenergetic metabolism and effects of pharmacological blockade of NHE1 on glycolysis and oxidative phosphorylation in glioma. Our results show that inhibiting NHE1 increases glioma cell oxidative phosphorylation, suggesting that NHE1 could be a therapeutic target for reversing the altered tumorigenic metabolism to treat GBM. Moreover, the emergence of blockade of NHE1 and TMZ combined treatment as cancer therapy would increase patient survival significantly and hence have a great public health relevance.
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Details
| Item Type: |
University of Pittsburgh ETD
|
| Status: |
Unpublished |
| Creators/Authors: |
|
| ETD Committee: |
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| Date: |
24 June 2019 |
| Date Type: |
Publication |
| Defense Date: |
18 April 2019 |
| Approval Date: |
24 June 2019 |
| Submission Date: |
4 April 2019 |
| Access Restriction: |
No restriction; Release the ETD for access worldwide immediately. |
| Number of Pages: |
42 |
| Institution: |
University of Pittsburgh |
| Schools and Programs: |
School of Public Health > Human Genetics |
| Degree: |
MS - Master of Science |
| Thesis Type: |
Master's Thesis |
| Refereed: |
Yes |
| Uncontrolled Keywords: |
Oncology, Glioma, Immunology, Cellular respiration, Tissue culture |
| Date Deposited: |
24 Jun 2019 13:44 |
| Last Modified: |
24 Jun 2019 13:44 |
| URI: |
http://d-scholarship.pitt.edu/id/eprint/36279 |
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