{"id":{"repo_id":"wayne-thes","oai_identifier":"oai:digitalcommons.wayne.edu:oa_dissertations-2327"},"canonical_url":"https://search.dev.ndltd.org/etd/wayne-thes/oai:digitalcommons.wayne.edu:oa_dissertations-2327","repository":{"repo_id":"wayne-thes","name":"Wayne State University","base_url":"https://digitalcommons.wayne.edu/do/oai/"},"display":{"title":"Photodynamic Therapy As An Effective Therapeutic Approach In Mame Models Of Triple Negative And Inflammatory Breast Cancers","abstract":"<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>","abstract_html":"&lt;p&gt;Introduction: Photodynamic therapy (PDT) is a minimally invasive, FDA approved therapy for&lt;/p&gt; &lt;p&gt;treatment of several indications including endobronchial and esophageal cancers that are&lt;/p&gt; &lt;p&gt;accessible to light. Triple negative breast cancer (TNBC) and inflammatory breast cancer (IBC)&lt;/p&gt; &lt;p&gt;are aggressive and lethal subtypes of breast cancer that spread to chest wall and dermal&lt;/p&gt; &lt;p&gt;lymphatics, respectively, sites that would be accessible to light. Both TNBC and IBC patients&lt;/p&gt; &lt;p&gt;have a relatively poor survival rate due to lack of targeted therapies. Use of PDT is&lt;/p&gt; &lt;p&gt;underexplored for breast cancers but has been proposed for treatment of subtypes for which a&lt;/p&gt; &lt;p&gt;targeted therapy is unavailable.&lt;/p&gt; &lt;p&gt;Methods: We optimized and used a mammary architecture and microenvironment engineering&lt;/p&gt; &lt;p&gt;(MAME) model of IBC to examine the effects of PDT using two treatment protocols. The first&lt;/p&gt; &lt;p&gt;protocol used the benzoporphyrin derivative monoacid A (BPD) activated at doses ranging from&lt;/p&gt; &lt;p&gt;45 mJ/cm2 to 540 mJ/cm2. The second PDT protocol used two photosensitizers: BPD and mono-&lt;/p&gt; &lt;p&gt;L-aspartyl chlorin e6 (NPe6), which were sequentially activated. Effects of PDT were assessed&lt;/p&gt; &lt;p&gt;by live-dead assays.&lt;/p&gt; &lt;p&gt;89&lt;/p&gt; &lt;p&gt;Results: Using a MAME model of TNBC and IBC, we demonstrate a significant dose-response&lt;/p&gt; &lt;p&gt;in photokilling by BPD-PDT. We found that sequential activation of NPe6 followed by BPD is&lt;/p&gt; &lt;p&gt;more effective in photokilling of tumor cells than is BPD alone. Sequential activation at a dose&lt;/p&gt; &lt;p&gt;of 45 mJ/cm2 each resulted in &gt;90% cell death, a response only achieved by BPD-PDT at a dose&lt;/p&gt; &lt;p&gt;of 360 mJ/cm2. Furthermore, our data show that volumetric measurement of 3D MAME&lt;/p&gt; &lt;p&gt;structures reflect efficacy of PDT treatment. We also show that the mechanism of cell death&lt;/p&gt; &lt;p&gt;after sequential activation of NPe6 followed by BPD is apoptosis.&lt;/p&gt; &lt;p&gt;Conclusion: Our study is the first to demonstrate the potential of PDT in treating MAME&lt;/p&gt; &lt;p&gt;structures of TNBC and IBC.&lt;/p&gt;","abstract_has_math":false,"creators":["Aggarwal, Neha"],"institution":null,"degree_name":"Ph.D.","degree_level":"Open Access Dissertation","degree_discipline":"Physiology","degree_department":null,"school":null,"contributors":["Bonnie F. Sloane","Douglas Yingst"],"advisors":[],"committee_chairs":[],"committee_members":[],"year":2015,"date_issued":"2015-01-01T08:00:00Z","date_published":"2015-01-01T08:00:00Z","updated_at":"2026-07-24T06:00:17Z","subjects":["inflammatory breast cancer","MAME cultures","microscopy and imaging","Photodynamic therapy","three dimensional","triple negative breast cancer","Molecular Biology","Oncology","Pharmacology"],"languages":[],"rights":[],"rights_urls":[],"identifier_entries":[]},"links":{"outbound_url":"https://digitalcommons.wayne.edu/oa_dissertations/1328","outbound_label":"Repository record","outbound_source":"dc:identifier"},"metadata_groups":[{"id":"people","label":"People","entries":[{"key":"dc:contributor","label":"Contributor","values":["Bonnie F. Sloane","Douglas Yingst"]},{"key":"dc:creator","label":"Author","values":["Aggarwal, Neha"]}]},{"id":"academic_context","label":"Academic Context","entries":[{"key":"dc:date.available","label":"Dc Date Available","values":["2015-01-01T08:00:00Z"]},{"key":"thesis:degree_discipline","label":"Discipline","values":["Physiology"]},{"key":"thesis:degree_level","label":"Degree Level","values":["Open Access Dissertation"]},{"key":"thesis:degree_name","label":"Degree Name","values":["Ph.D."]}]},{"id":"subjects_keywords","label":"Subjects and Keywords","entries":[{"key":"dc:subject","label":"Dc Subject","values":["inflammatory breast cancer","MAME cultures","microscopy and imaging","Photodynamic therapy","three dimensional","triple negative breast cancer","Molecular Biology","Oncology","Pharmacology"]}]},{"id":"identifiers","label":"Identifiers","entries":[{"key":"dc:identifier","label":"Identifier","values":["https://digitalcommons.wayne.edu/oa_dissertations/1328"]}]},{"id":"additional","label":"Additional Metadata","entries":[{"key":"dc:description.abstract","label":"Abstract","values":["<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>"]},{"key":"dc:title","label":"Title","values":["Photodynamic Therapy As An Effective Therapeutic Approach In Mame Models Of Triple Negative And Inflammatory Breast Cancers"]}]}],"canonical_facts":{"dc:contributor":["Bonnie F. Sloane","Douglas Yingst"],"dc:creator":["Aggarwal, Neha"],"dc:date.available":["2015-01-01T08:00:00Z"],"dc:description.abstract":["<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>"],"dc:identifier":["https://digitalcommons.wayne.edu/oa_dissertations/1328"],"dc:subject":["inflammatory breast cancer","MAME cultures","microscopy and imaging","Photodynamic therapy","three dimensional","triple negative breast cancer","Molecular Biology","Oncology","Pharmacology"],"dc:title":["Photodynamic Therapy As An Effective Therapeutic Approach In Mame Models Of Triple Negative And Inflammatory Breast Cancers"],"thesis:degree_discipline":["Physiology"],"thesis:degree_level":["Open Access Dissertation"],"thesis:degree_name":["Ph.D."]},"updated_at":"2026-07-24T06:00:17Z"}