Link to the University of Pittsburgh Homepage
Link to the University Library System Homepage Link to the Contact Us Form

Glioma cancer immunosuppressive microenvironment

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 (Unpublished)

[img]
Preview
PDF
Submitted Version

Download (1MB) | Preview

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.


Share

Citation/Export:
Social Networking:
Share |

Details

Item Type: University of Pittsburgh ETD
Status: Unpublished
Creators/Authors:
CreatorsEmailPitt UsernameORCID
Ahuja, Avaniava13@pitt.eduava13
ETD Committee:
TitleMemberEmail AddressPitt UsernameORCID
Committee ChairDandan, Sunsund@upmc.edu
Committee MemberPadiath, Quasarqpadiath@pitt.edu
Committee MemberKamboh, Ilyaskamboh@pitt.edu
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: Graduate 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

Metrics

Monthly Views for the past 3 years

Plum Analytics


Actions (login required)

View Item View Item