Conectar
by Makiko Sasaki, Mamoru Tanaka, Akihiro Nomoto, Ryusei Yamasaki, Tomokazu Yoshimura, Shigenobu Yano, Yasunari Sasaki, Yuki Kojima, Taketo Suzuki, Hirotada Nishie, Keiji Ozeki, Takaya Shimura, Eiji Kubota, Hiromi Kataoka
Photodynamic therapy (PDT) is an anti-cancer therapy that employs a photosensitizer (PS) and an optimal wavelength of light, causing a photochemical reaction that releases reactive oxygen species, thereby inducing cancer cell death via oxidative stress. Because light irradiation is limited to the tumor site, PDT has minimal adverse effects. The cancer cell selectivity of the PS is important for reducing damage to the normal mucosa caused by scattered light. Antibody-drug conjugates (ADC) are novel anti-cancer therapies that combine a monoclonal tumor-surface-receptor-targeting antibody with a drug bonded through chemical linkers. ADCs enable the targeted delivery of a variety of drugs to cancer cells while minimizing their delivery to healthy tissues. One such tumor surface receptor is the human epidermal growth factor receptor 2 (HER2), which is of interest in the treatment of many cancers, including gastrointestinal cancer. To improve tumor selectivity and minimize damage to the mucosa surrounding the tumor in PDT, we established a novel PS glucose-linked chlorin e6-conjugated trastuzumab (G-Ce6-trastuzumab) that is conjugated to existing PS glucose-linked chlorin e6 (G-Ce6) and evaluated its anti-cancer effect compared to G-Ce6. The effect of PDT was evaluated using HER2-high-expression cells NCI-N87 and HER2-low-expression cells MKN-45. G-Ce6-trastuzumab is internalized by the intracellular organelles in cancer cells. Evaluation of cell death using the WST-8 assay also demonstrated a significantly higher cytotoxic effect of G-Ce6-trastuzumab in HER2-high-expression cells compared with conventional PS G-Ce6. Thereby, G-Ce6-trastuzumab may be an excellent novel PS for PDT because of its strong selectivity for HER2-high-expression cells.Despite the continued burden of opioid overdose in communities in the USA, effective treatments for opioid use disorder (OUD), such as medication for opioid use disorder (MOUD), remain underused. Motivational interviewing techniques and linkage to MOUD via digital health are innovative practices developed to overcome persistent barriers to accessing MOUD treatment. These practices are merged in a comprehensive digital health platform, RecoveryPad (developed by the Center for Progressive Recovery). Our study, ‘Using System Dynamics Modeling to Foster Real-time Connections to Care’ (NIH Award #: 1R61DA057675-01), is a pilot to assess the feasibility and behaviour change potential of RecoveryPad for our target audience of people experiencing OUD.
This study will recruit 40 participants in Connecticut and New York through online platforms, such as social media and digital advertising, and direct access via quick-response (QR) codes distributed by local community partners. Eligibility assessment and enrolment will be conducted virtually. Individuals reporting symptoms indicating moderate to severe OUD who are at least 18 years of age are eligible for the study, excluding those who are currently receiving MOUD, pregnant or incarcerated. Enrolled participants will interact with an automated chatbot, live recovery coaches and, if desired, be referred to a telehealth MOUD provider via the RecoveryPad platform. Participants will have access to the platform for 30 days and will be asked to complete brief surveys to assess MOUD engagement and secondary outcomes at 30 and 90 days. Additionally, system dynamics (SD) models will be developed at the individual level to simulate participant interactions with RecoveryPad, and at the community level to improve understanding of the systems affecting OUD and MOUD access.
This project received approval from the Yale University Human Investigation Committee in 2024 (HIC # 2000034414). All participants will complete an electronic consent form with detailed study information and release of information to obtain data related to MOUD appointment attendance. Findings and conclusions from this pilot will be disseminated via peer-reviewed publication, advisory board meetings and meetings with community partners.
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