Date of Award

5-2024

Document Type

Campus Access Dissertation

Degree Name

Doctor of Philosophy (PhD)

Department

Integrative Biosciences

First Advisor

Jonathan Celli

Second Advisor

Chandra Yelleswarapu

Third Advisor

Changmeng Cai, Joanna Dahl, Mohammad Saad

Abstract

Head and neck cancer squamous cell carcinoma (HNSCC) is the sixth most commonly diagnosed cancer globally, with a five-year survival rate below 60%. New treatments are urgently needed especially in low and middle income countries (LMICs) in south Asia where disease is disproportionately prevalent. Photodynamic therapy (PDT) is a light-based treatment in which wavelength-specific activation of a photosensitizing molecule leads to site-directed tumor destruction. This thesis focuses on evaluation of PDT using 5-aminolevulinic acid (ALA) photosensitization, for treatment of oral squamous cell carcinoma (OSCC), emphasizing in particular requirements for clinical feasibility and efficacy in resource limited settings. Initial studies focus on pre-clinical testing of a portable PDT system which was later deployed in a clinical study. Further studies, motivated by feedback from clinical collaborators focused on determinants of ALA induced protophyrin IX photosensitization and strategies for overall PDT optimization. We observed that a drug-resistant cell line characterized by a notable increase in PpIX accumulation, and down regulated in genes expression of antioxidant defense system, exhibited an enhanced response to PDT. Additionally, using 3D cell culture models, we explored spatial heterogeneity in cytotoxic response within tumor nodules, uncovering correlations in localization-based cell death, photosensitizer, and treatment effectiveness. Moreover, we investigated differentiation-promoting agents as a strategy to enhance PDT response through the combination of ALA-based PDT and preconditioning with Vitamin D analogs. Combined with recent clinical data, the findings from this thesis could assist in shaping strategies to further optimize ALA-PDT as an effective treatment for oral cancers, including drug-resistant disease.

Comments

Free and open access to this Campus Access Thesis is made available to the UMass Boston community by ScholarWorks at UMass Boston. Those not on campus and those without a UMass Boston campus username and password may gain access to this thesis through resources like Proquest Dissertations & Theses Global (https://www.proquest.com/) or through Interlibrary Loan. If you have a UMass Boston campus username and password and would like to download this work from off-campus, click on the "Off-Campus UMass Boston Users

Download
Off-Campus UMass Boston Users

Share

COinS