@article{overchuk_ruhi_rickard_ligler_rizvi_2023, title={Development of a light emitting device for the treatment of peritoneal car- cinomatosis of ovarian origin by intracavitary photodynamic therapy}, volume={41}, ISSN={["1873-1597"]}, DOI={10.1016/j.pdpdt.2023.103406}, abstractNote={Peritoneal carcinomatosis of ovarian origin (PCO) is an evolution of ovarian cancer, which is the fourth leading cause of death by cancer in women in France. PCO is defined by dissemination of cancerous cells from ovarian cancer to the peritoneal cavity. Photodynamic therapy (PDT) has been proposed in complement to the standard of care, consisting of surgery and chemotherapy. However, litterature has highlighted the lack of selectivity of available photosensitizers (PS) leading to inconclusive results [1, 2]. In this context, PRODYNOV project, initiated by our research team INSERM U1189 ONCOTHAI, has enabled the development of a patented PS. The high selectivity of this PS makes possible to carry out relevant PDT for PCO provided that an adequate illumination device would exist. In this study, we developed and assessed such a device. First, a test bench aiming to evaluate quantity and homogeneity of the delivered illumination has been developed. It is composed of a fantom of peritoneal cavity in which seven optical probes connected to a power-meter were placed in strategic zones characterised by high recurrence risk. Then, three illumination devices were implemented and assessed. The first one consisted of six fixed light emitting fabrics (LEF), the second one was a moving luminous wand, and the last one, a hybrid one, combined a fixed luminous wand and six fixed LEF. Light doses received by the probes have been calculated by integrating measured powers over illumination time. Each of the seven optical probes received a mean light dose of 0.68 mJ with the first illumination device (minimum: 18.37 10−3 mJ, maximum: 2.66 mJ), 0.11 mJ with the second one (minimum: 5.25 10−3 mJ, maximum: 0.35 mJ) and 0.65 mJ with the third one (minimum: 48.19 10−3 mJ, maximum: 1.27 mJ). With a variation coefficient of 77.1% (versus 93.1% for the first device and 119.5% for the second one), the hybrid device enabled to homogeneously illuminate the largest part of the cavity. For these reasons, the hybrid method has been selected as illumination process for PDT of PCO. Illumination solutions for PDT of PCO have been proposed and tested. One of these solutions has been approved. The light dose necessary for an effective treatment remains to be determined and first feasability tests will be led on mini-pig by the end of the year.}, journal={PHOTODIAGNOSIS AND PHOTODYNAMIC THERAPY}, author={Overchuk, Marta and Ruhi, Mustafa Kemal and Rickard, Brittany and Ligler, Frances and Rizvi, Imran}, year={2023}, month={Mar} }
 @article{rickard_overchuk_tulino_tan_ligler_bae-jump_fenton_rizvi_2023, title={Exposure to select PFAS and PFAS mixtures alters response to platinum-based chemotherapy in endometrial cancer cell lines}, volume={22}, ISSN={["1476-069X"]}, DOI={10.1186/s12940-023-01034-2}, abstractNote={Abstract}, number={1}, journal={ENVIRONMENTAL HEALTH}, author={Rickard, Brittany P. and Overchuk, Marta and Tulino, Justin and Tan, Xianming and Ligler, Frances S. and Bae-Jump, Victoria L. and Fenton, Suzanne E. and Rizvi, Imran}, year={2023}, month={Dec} }
 @misc{rickard_overchuk_chappell_kemal ruhi_sinawang_nguyen hoang_akin_demirci_franco_fenton_et al._2023, title={Methods to Evaluate Changes in Mitochondrial Structure and Function in Cancer}, volume={15}, ISSN={["2072-6694"]}, url={https://doi.org/10.3390/cancers15092564}, DOI={10.3390/cancers15092564}, abstractNote={Mitochondria are regulators of key cellular processes, including energy production and redox homeostasis. Mitochondrial dysfunction is associated with various human diseases, including cancer. Importantly, both structural and functional changes can alter mitochondrial function. Morphologic and quantifiable changes in mitochondria can affect their function and contribute to disease. Structural mitochondrial changes include alterations in cristae morphology, mitochondrial DNA integrity and quantity, and dynamics, such as fission and fusion. Functional parameters related to mitochondrial biology include the production of reactive oxygen species, bioenergetic capacity, calcium retention, and membrane potential. Although these parameters can occur independently of one another, changes in mitochondrial structure and function are often interrelated. Thus, evaluating changes in both mitochondrial structure and function is crucial to understanding the molecular events involved in disease onset and progression. This review focuses on the relationship between alterations in mitochondrial structure and function and cancer, with a particular emphasis on gynecologic malignancies. Selecting methods with tractable parameters may be critical to identifying and targeting mitochondria-related therapeutic options. Methods to measure changes in mitochondrial structure and function, with the associated benefits and limitations, are summarized.}, number={9}, journal={CANCERS}, author={Rickard, Brittany P. P. and Overchuk, Marta and Chappell, Vesna A. A. and Kemal Ruhi, Mustafa and Sinawang, Prima Dewi and Nguyen Hoang, Tina Thuy and Akin, Demir and Demirci, Utkan and Franco, Walfre and Fenton, Suzanne E. E. and et al.}, year={2023}, month={Apr} }
 @article{overchuk_ruhi_rickard_ligler_rizvi_2023, title={Targeted PDT Combinations to Overcome Fluid Shear Stress-induced Plat- inum Resistance in Ovarian Cancer}, volume={41}, ISSN={["1873-1597"]}, DOI={10.1016/j.pdpdt.2023.103405}, abstractNote={Ovarian cancer is the deadliest gynecologic malignancy — in 2020 alone, ovarian cancer claimed lives of 13,940 patients in the United States and 29,000 in Europe [1]. Such high ovarian cancer mortality can be explained by the fact that most patients are diagnosed with advanced-stage disease and 70% of them develop resistance to platinum-based therapies within the first 5 years [1]. One of the potential contributing factors to treatment failure in ovarian cancer is malignant ascites, or excessive fluid buildup in the peritoneal cavity. Ascites creates a unique molecular and biophysical environment, providing cancer cells with a nutrient- and growth factor-rich media and exposing them to abnormal physical stress. Our research group has been studying the effects of fluid shear stress (FSS) on ovarian cancer cell phenotypes and treatment responsiveness [2]. It was found that FSS confers resistance to carboplatin, activates the epidermal growth factor receptor (EGFR) as well as the downstream signaling cascades, and promotes epithelial-mesenchymal transition. These findings revealed the need for strategies that would remain effective under flow conditions and aid the effectiveness of standard of care treatments. Photodynamic therapy (PDT), which utilizes photosensitizers and light to generate cytotoxic reactive molecular species, provides a mechanistically distinct way of targeting chemoresistant cell populations. It was demonstrated that low-dose PDT with EGFR-targeted benzoporphyrin derivative photoimmunoconjugates remains effective in a 3D perfusion model for ovarian cancer, under conditions that induce resistance to carboplatin and EGFR overexpression and activation [2]. Encouraged by these findings, we continue exploring benzoporphyrin derivative-enabled PDT as a stand-alone therapy or in combination with cisplatin under static and flow conditions. Overall, we believe that photodynamic therapy has a potential to become an indispensable tool in late-stage ovarian cancer treatment, effectively destroying and/or sensitizing chemoresistant cell populations, decreasing the required chemotherapy dose and expanding the therapeutic window.}, journal={PHOTODIAGNOSIS AND PHOTODYNAMIC THERAPY}, author={Overchuk, Marta and Ruhi, Mustafa Kemal and Rickard, Brittany and Ligler, Frances and Rizvi, Imran}, year={2023}, month={Mar} }
 @article{sorrin_zhou_may_liu_mcnaughton_rahman_liang_rizvi_roque_huang_2023, title={Transient fluid flow improves photoimmunoconjugate delivery and photoimmunotherapy efficacy}, volume={26}, ISSN={["2589-0042"]}, DOI={10.1016/j.isci.2023.107221}, abstractNote={Circulating drugs in the peritoneal cavity is an effective strategy for advanced ovarian cancer treatment. Photoimmunotherapy, an emerging modality with potential for the treatment of ovarian cancer, involves near-infrared light activation of antibody-photosensitizer conjugates (photoimmunoconjugates) to generate cytotoxic reactive oxygen species. Here, a microfluidic cell culture model is used to study how fluid flow-induced shear stress affects photoimmunoconjugate delivery to ovarian cancer cells. Photoimmunoconjugates are composed of the antibody, cetuximab, conjugated to the photosensitizer, and benzoporphyrin derivative. Longitudinal tracking of photoimmunoconjugate treatment under flow conditions reveals enhancements in subcellular photosensitizer accumulation. Compared to static conditions, fluid flow-induced shear stress at 0.5 and 1 dyn/cm2 doubled the cellular delivery of photoimmunoconjugates. Fluid flow-mediated treatment with three different photosensitizer formulations (benzoporphyrin derivative, photoimmunoconjugates, and photoimmunoconjugate-coated liposomes) led to enhanced phototoxicity compared to static conditions. This study confirms the fundamental role of fluid flow-induced shear stress in the anti-cancer effects of photoimmunotherapy.}, number={8}, journal={ISCIENCE}, author={Sorrin, Aaron J. and Zhou, Keri and May, Katherine and Liu, Cindy and McNaughton, Kathryn and Rahman, Idrisa and Liang, Barry J. and Rizvi, Imran and Roque, Dana M. and Huang, Huang-Chiao}, year={2023}, month={Aug} }
 @article{kessel_obaid_rizvi_2022, title={Critical PDT theory II: Current concepts and indications}, volume={39}, ISSN={["1873-1597"]}, DOI={10.1016/j.pdpdt.2022.102923}, abstractNote={While photodynamic therapy (PDT) is effective for the eradication of select neoplasia and certain other pathologic conditions, it has yet to achieve wide acceptance in clinical medicine. A variety of factors contribute to this situation including relations with the pharmaceutical industry that have often been problematic. Some current studies relating to photodynamic effects are 'phenomenological', i.e., they describe phenomena that only reiterate what is already known. The net result has been a tendency of granting agencies to become disillusioned with support for PDT research. This report is intended to provide some thoughts on current research efforts that improve clinical relevance and those that do not.}, journal={PHOTODIAGNOSIS AND PHOTODYNAMIC THERAPY}, author={Kessel, David and Obaid, Girgis and Rizvi, Imran}, year={2022}, month={Sep} }
 @article{rickard_rizvi_fenton_2022, title={Per- and poly-fluoroalkyl substances (PFAS) and female reproductive outcomes: PFAS elimination, endocrine-mediated effects, and disease}, volume={465}, ISSN={["0300-483X"]}, url={https://doi.org/10.1016/j.tox.2021.153031}, DOI={10.1016/j.tox.2021.153031}, abstractNote={Per- and poly-fluoroalkyl substances (PFAS) are widespread environmental contaminants frequently detected in drinking water supplies worldwide that have been linked to a variety of adverse reproductive health outcomes in women. Compared to men, reproductive health effects in women are generally understudied while global trends in female reproduction rates are declining. Many factors may contribute to the observed decline in female reproduction, one of which is environmental contaminant exposure. PFAS have been used in home, food storage, personal care and industrial products for decades. Despite the phase-out of some legacy PFAS due to their environmental persistence and adverse health effects, alternative, short-chain and legacy PFAS mixtures will continue to pollute water and air and adversely influence women's health. Studies have shown that both long- and short-chain PFAS disrupt normal reproductive function in women through altering hormone secretion, menstrual cyclicity, and fertility. Here, we summarize the role of a variety of PFAS and PFAS mixtures in female reproductive tract dysfunction and disease. Since these chemicals may affect reproductive tissues directly or indirectly through endocrine disruption, the role of PFAS in breast, thyroid, and hypothalamic-pituitary-gonadal axis function are also discussed as the interplay between these tissues may be critical in understanding the long-term reproductive health effects of PFAS in women. A major research gap is the need for mechanism of action data - the targets for PFAS in the female reproductive and endocrine systems are not evident, but the effects are many. Given the global decline in female fecundity and the ability of PFAS to negatively impact female reproductive health, further studies are needed to examine effects on endocrine target tissues involved in the onset of reproductive disorders of women.}, journal={TOXICOLOGY}, publisher={Elsevier BV}, author={Rickard, Brittany P. and Rizvi, Imran and Fenton, Suzanne E.}, year={2022}, month={Jan} }
 @article{rickard_overchuk_obaid_ruhi_demirci_fenton_santos_kessel_rizvi_2022, title={Photochemical Targeting of Mitochondria to Overcome Chemoresistance in Ovarian Cancer}, ISSN={["1751-1097"]}, DOI={10.1111/php.13723}, abstractNote={Abstract}, journal={PHOTOCHEMISTRY AND PHOTOBIOLOGY}, author={Rickard, Brittany P. and Overchuk, Marta and Obaid, Girgis and Ruhi, Mustafa Kemal and Demirci, Utkan and Fenton, Suzanne E. and Santos, Janine H. and Kessel, David and Rizvi, Imran}, year={2022}, month={Oct} }
 @article{karimnia_stanley_fitzgerald_rizvi_slack_celli_2022, title={Photodynamic Stromal Depletion Enhances Therapeutic Nanoparticle Delivery in 3D Pancreatic Ductal Adenocarcinoma Tumor Models}, ISSN={["1751-1097"]}, DOI={10.1111/php.13663}, abstractNote={ABSTRACT}, journal={PHOTOCHEMISTRY AND PHOTOBIOLOGY}, author={Karimnia, Vida and Stanley, M. Elizabeth and Fitzgerald, Christian T. and Rizvi, Imran and Slack, Frank J. and Celli, Jonathan P.}, year={2022}, month={Aug} }
 @article{rickard_tan_fenton_rizvi_2022, title={Select Per- and Polyfluoroalkyl Substances (PFAS) Induce Resistance to Carboplatin in Ovarian Cancer Cell Lines}, volume={23}, ISSN={["1422-0067"]}, url={https://www.mdpi.com/1422-0067/23/9/5176}, DOI={10.3390/ijms23095176}, abstractNote={Per- and polyfluoroalkyl substances (PFAS) are ubiquitous environmental contaminants associated with adverse reproductive outcomes including reproductive cancers in women. PFAS can alter normal ovarian function, but the effects of PFAS on ovarian cancer progression and therapy response remain understudied. Ovarian cancer is the most lethal gynecologic malignancy, and a major barrier to effective treatment is resistance to platinum-based chemotherapy. Platinum resistance may arise from exposure to external stimuli such as environmental contaminants. This study evaluated PFAS and PFAS mixture exposures to two human ovarian cancer cell lines to evaluate the ability of PFAS exposure to affect survival fraction following treatment with carboplatin. This is the first study to demonstrate that, at sub-cytotoxic concentrations, select PFAS and PFAS mixtures increased survival fraction in ovarian cancer cells following carboplatin treatment, indicative of platinum resistance. A concomitant increase in mitochondrial membrane potential, measured by the JC-1 fluorescent probe, was observed in PFAS-exposed and PFAS + carboplatin-treated cells, suggesting a potential role for altered mitochondrial function that requires further investigation.}, number={9}, journal={INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES}, publisher={MDPI AG}, author={Rickard, Brittany P. and Tan, Xianming and Fenton, Suzanne E. and Rizvi, Imran}, year={2022}, month={May} }
 @article{soto_guimaraes_reis_franco_rizvi_demirci_2021, title={Emerging biofabrication approaches for gastrointestinal organoids towards patient specific cancer models}, volume={504}, ISSN={["1872-7980"]}, DOI={10.1016/j.canlet.2021.01.023}, abstractNote={Tissue engineered organoids are simple biomodels that can emulate the structural and functional complexity of specific organs. Here, we review developments in three-dimensional (3D) artificial cell constructs to model gastrointestinal dynamics towards cancer diagnosis. We describe bottom-up approaches to fabricate close-packed cell aggregates, from the use of biochemical and physical cues to guide the self-assembly of organoids, to the use of engineering approaches, including 3D printing/additive manufacturing and external field-driven protocols. Finally, we outline the main challenges and possible risks regarding the potential translation of gastrointestinal organoids from laboratory settings to patient-specific models in clinical applications.}, journal={CANCER LETTERS}, author={Soto, Fernando and Guimaraes, Carlos F. and Reis, Rui L. and Franco, Walfre and Rizvi, Imran and Demirci, Utkan}, year={2021}, month={Apr}, pages={116–124} }
 @misc{rickard_conrad_sorrin_ruhi_reader_huang_franco_scarcelli_polacheck_roque_et al._2021, title={Malignant Ascites in Ovarian Cancer: Cellular, Acellular, and Biophysical Determinants of Molecular Characteristics and Therapy Response}, volume={13}, ISSN={["2072-6694"]}, DOI={10.3390/cancers13174318}, abstractNote={Ascites refers to the abnormal accumulation of fluid in the peritoneum resulting from an underlying pathology, such as metastatic cancer. Among all cancers, advanced-stage epithelial ovarian cancer is most frequently associated with the production of malignant ascites and is the leading cause of death from gynecologic malignancies. Despite decades of evidence showing that the accumulation of peritoneal fluid portends the poorest outcomes for cancer patients, the role of malignant ascites in promoting metastasis and therapy resistance remains poorly understood. This review summarizes the current understanding of malignant ascites, with a focus on ovarian cancer. The first section provides an overview of heterogeneity in ovarian cancer and the pathophysiology of malignant ascites. Next, analytical methods used to characterize the cellular and acellular components of malignant ascites, as well the role of these components in modulating cell biology, are discussed. The review then provides a perspective on the pressures and forces that tumors are subjected to in the presence of malignant ascites and the impact of physical stress on therapy resistance. Treatment options for malignant ascites, including surgical, pharmacological and photochemical interventions are then discussed to highlight challenges and opportunities at the interface of drug discovery, device development and physical sciences in oncology.}, number={17}, journal={CANCERS}, author={Rickard, Brittany P. and Conrad, Christina and Sorrin, Aaron J. and Ruhi, Mustafa Kemal and Reader, Jocelyn C. and Huang, Stephanie A. and Franco, Walfre and Scarcelli, Giuliano and Polacheck, William J. and Roque, Dana M. and et al.}, year={2021}, month={Sep} }
 @article{karimnia_rizvi_slack_celli_2021, title={Photodestruction of Stromal Fibroblasts Enhances Tumor Response to PDT in 3D Pancreatic Cancer Coculture Models}, volume={97}, ISSN={["1751-1097"]}, DOI={10.1111/php.13339}, abstractNote={Abstract}, number={2}, journal={PHOTOCHEMISTRY AND PHOTOBIOLOGY}, author={Karimnia, Vida and Rizvi, Imran and Slack, Frank J. and Celli, Jonathan P.}, year={2021}, month={Mar}, pages={416–426} }
 @article{anbil_pigula_huang_mallidi_broekgaarden_baglo_de silva_simeone_mino-kenudson_maytin_et al._2020, title={Vitamin D Receptor Activation and Photodynamic Priming Enables Durable Low-dose Chemotherapy}, volume={19}, ISSN={["1538-8514"]}, DOI={10.1158/1535-7163.MCT-19-0791}, abstractNote={Abstract}, number={6}, journal={MOLECULAR CANCER THERAPEUTICS}, author={Anbil, Sriram and Pigula, Michael and Huang, Huang-Chiao and Mallidi, Srivalleesha and Broekgaarden, Mans and Baglo, Yan and De Silva, Pushpamali and Simeone, Diane M. and Mino-Kenudson, Mari and Maytin, Edward V and et al.}, year={2020}, month={Jun}, pages={1308–1319} }
 @article{spring_lang_kercher_rizvi_wenham_conejo-garcia_hasan_gatenby_enderling_2019, title={Illuminating the Numbers: Integrating Mathematical Models to Optimize Photomedicine Dosimetry and Combination Therapies}, volume={7}, ISSN={["2296-424X"]}, DOI={10.3389/fphy.2019.00046}, abstractNote={Cancer photomedicine offers unique mechanisms for inducing local tumor damage with the potential to stimulate local and systemic anti-tumor immunity. Optically-active nanomedicine offers these features as well as spatiotemporal control of tumor-focused drug release to realize synergistic combination therapies. Achieving quantitative dosimetry is a major challenge, and dosimetry is fundamental to photomedicine for personalizing and tailoring therapeutic regimens to specific patients and anatomical locations. The challenge of dosimetry is perhaps greater for photomedicine than many standard therapies given the complexity of light delivery and light-tissue interactions as well as the resulting photochemistry responsible for tumor damage and drug-release, in addition to the usual intricacies of therapeutic agent delivery. An emerging multidisciplinary approach in oncology utilizes mathematical and computational models to iteratively and quantitively analyze complex dosimetry, and biological response parameters. These models are parameterized by preclinical and clinical observations and then tested against previously unseen data. Such calibrated and validated models can be deployed to simulate treatment doses, protocols, and combinations that have not yet been experimentally or clinically evaluated and can provide testable optimal treatment outcomes in a practical workflow. Here, we foresee the utility of these computational approaches to guide adaptive therapy, and how mathematical models might be further developed and integrated as a novel methodology to guide precision photomedicine.}, journal={FRONTIERS IN PHYSICS}, author={Spring, Bryan Q. and Lang, Ryan T. and Kercher, Eric M. and Rizvi, Imran and Wenham, Robert M. and Conejo-Garcia, Jose R. and Hasan, Tayyaba and Gatenby, Robert A. and Enderling, Heiko}, year={2019}, month={Apr} }
 @article{conrad_gray_stroka_rizvi_scarcelli_2019, title={Mechanical Characterization of 3D Ovarian Cancer Nodules Using Brillouin Confocal Microscopy}, volume={12}, ISSN={["1865-5033"]}, DOI={10.1007/s12195-019-00570-7}, abstractNote={The mechanical interaction between cells and their microenvironment is emerging as an important determinant of cancer progression and sensitivity to treatment, including in ovarian cancer (OvCa). However, current technologies limit mechanical analysis in 3D culture systems. Brillouin Confocal Microscopy is an optical non-contact method to assess the mechanical properties of biological materials. Here, we validate the ability of this technology to assess the mechanical properties of 3D tumor nodules.OvCa cells were cultured in 3D using two established methods: (1) overlay cultures on Matrigel; (2) spheroids in ultra-low attachment plates. To alter the mechanical state of these tumors, nodules were immersed in PBS with varying levels of sucrose to induce osmotic stress. Next, nodule mechanical properties were measured by Brillouin microscopy and validated with standard stress-strain tests: Atomic Force Microscopy (AFM) and a parallel plate compression device (Microsquisher). Finally, the nodules were treated with a chemotherapeutic commonly used to manage OvCa, carboplatin, to determine treatment-induced effects on tumor mechanical properties.Brillouin microscopy allows mechanical analysis with limited penetration depth (~ 92 µm for Matrigel method; ~ 54 µm for low attachment method). Brillouin microscopy metrics displayed the same trends as the corresponding "gold-standard" Young's moduli measured with stress-strain methods when the osmolality of the medium was increased. Nodules treated with carboplatin showed a decrease in Brillouin frequency shift.This validation study paves the way to evaluate the mechanics of 3D nodules, with micron-scale three-dimensional resolution and without contact, thus extending the experimental possibilities.}, number={3}, journal={CELLULAR AND MOLECULAR BIOENGINEERING}, author={Conrad, Christina and Gray, Kelsey M. and Stroka, Kimberly M. and Rizvi, Imran and Scarcelli, Giuliano}, year={2019}, month={Jun}, pages={215–226} }