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Glioma cancer immunosuppressive microenvironment

Ahuja, Avani (2019) Glioma cancer immunosuppressive microenvironment. Master's Thesis, University of Pittsburgh. (Unpublished)

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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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Item Type: University of Pittsburgh ETD
Status: Unpublished
CreatorsEmailPitt UsernameORCID
Ahuja, Avaniava13@pitt.eduava13
ETD Committee:
TitleMemberEmail AddressPitt UsernameORCID
Committee ChairDandan,
Committee MemberPadiath,
Committee MemberKamboh,
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


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