Photodynamic Therapy As An Effective Therapeutic Approach In Mame Models Of Triple Negative And Inflammatory Breast Cancers

<p>Introduction: Photodynamic therapy (PDT) is a minimally invasive, FDA approved therapy for</p> <p>treatment of several indications including endobronchial and esophageal cancers that are</p> <p>accessible to light. Triple negative breast cancer (TNBC) and inflammatory breast cancer (IBC)</p> <p>are aggressive and lethal subtypes of breast cancer that spread to chest wall and dermal</p> <p>lymphatics, respectively, sites that would be accessible to light. Both TNBC and IBC patients</p> <p>have a relatively poor survival rate due to lack of targeted therapies. Use of PDT is</p> <p>underexplored for breast cancers but has been proposed for treatment of subtypes for which a</p> <p>targeted therapy is unavailable.</p> <p>Methods: We optimized and used a mammary architecture and microenvironment engineering</p> <p>(MAME) model of IBC to examine the effects of PDT using two treatment protocols. The first</p> <p>protocol used the benzoporphyrin derivative monoacid A (BPD) activated at doses ranging from</p> <p>45 mJ/cm2 to 540 mJ/cm2. The second PDT protocol used two photosensitizers: BPD and mono-</p> <p>L-aspartyl chlorin e6 (NPe6), which were sequentially activated. Effects of PDT were assessed</p> <p>by live-dead assays.</p> <p>89</p> <p>Results: Using a MAME model of TNBC and IBC, we demonstrate a significant dose-response</p> <p>in photokilling by BPD-PDT. We found that sequential activation of NPe6 followed by BPD is</p> <p>more effective in photokilling of tumor cells than is BPD alone. Sequential activation at a dose</p> <p>of 45 mJ/cm2 each resulted in >90% cell death, a response only achieved by BPD-PDT at a dose</p> <p>of 360 mJ/cm2. Furthermore, our data show that volumetric measurement of 3D MAME</p> <p>structures reflect efficacy of PDT treatment. We also show that the mechanism of cell death</p> <p>after sequential activation of NPe6 followed by BPD is apoptosis.</p> <p>Conclusion: Our study is the first to demonstrate the potential of PDT in treating MAME</p> <p>structures of TNBC and IBC.</p>

Name thesis:degree_name

Ph.D.

Level thesis:degree_level

Open Access Dissertation

Discipline thesis:degree_discipline

Physiology

Year dc:date.available

2015

Author dc:creator

• Aggarwal, Neha

Contributors dc:contributor

• Bonnie F. Sloane
• Douglas Yingst

• inflammatory breast cancer
• MAME cultures
• microscopy and imaging
• Photodynamic therapy
• three dimensional
• triple negative breast cancer
• Molecular Biology
• Oncology
• Pharmacology

Repository record dc:identifier

https://digitalcommons.wayne.edu/oa_dissertations/1328

OAI identifier oai:identifier

oai:digitalcommons.wayne.edu:oa_dissertations-2327