ABSTRACT
Cell-based immunotherapy for glioblastoma (GBM) encounters major challenges due to the infiltration-resistant and immunosuppressive tumor microenvironment (TME). γδ T cells, unconventional T cells expressing the characteristic γδ T cell receptor, have demonstrated promise in overcoming these challenges, suggesting great immunotherapeutic potential. This review presents the role of γδ T cells in GBM and proposes several research avenues for future studies. Using the PubMed, ScienceDirect, and JSTOR databases, we performed a review of the literature studying the biology of γδ T cells and their role in GBM treatment. We identified 15 studies focused on γδ T cells in human GBM. Infiltrative γδ T cells can incite antitumor immune responses in certain TMEs, though rapid tumor progression and TME hypoxia may impact the extent of tumor suppression. In the studies, available findings have shown both the potential for robust antitumor activity and the risk of protumor activity. While γδ T cells have potential as a therapeutic agent against GBM, the technical challenges of extracting, isolating, and expanding γδ T cells, and the activation of antitumoral versus protumoral cascades, remain barriers to their application. Overcoming these limitations may transform γδ T cells into a promising immunotherapy in GBM.
ABSTRACT
Nearly 30% of Pancreatic ductal adenocarcinoma (PDAC)s exhibit a marked overexpression of Monocarboxylate Transporter 1 (MCT1) offering a unique opportunity for therapy. However, biochemical inhibitors of MCT1 have proven unsuccessful in clinical trials. In this study we present an alternative approach using 3-Bromopyruvate (3BP) to target MCT1 overexpressing PDACs. 3BP is a cytotoxic agent that is known to be transported into cells via MCT1, but its clinical usefulness has been hampered by difficulties in delivering the drug systemically. We describe here a novel microencapsulated formulation of 3BP (ME3BP-7), that is effective against a variety of PDAC cells in vitro and remains stable in serum. Furthermore, systemically administered ME3BP-7 significantly reduces pancreatic cancer growth and metastatic spread in multiple orthotopic models of pancreatic cancer with manageable toxicity. ME3BP-7 is, therefore, a prototype of a promising new drug, in which the targeting moiety and the cytotoxic moiety are both contained within the same single small molecule. One Sentence Summary: ME3BP-7 is a novel formulation of 3BP that resists serum degradation and rapidly kills pancreatic cancer cells expressing high levels of MCT1 with tolerable toxicity in mice.
ABSTRACT
The purpose of this paper is to evaluate the quality of information and guidance on dietary sodium reduction available on consumer-facing websites. Google Trends was used to identify the five most-used search terms related to dietary sodium reduction. For each term, websites on the first two pages were collected (n = 18-20). Of 93 websites collected, 24 were excluded due to defective links, duplicate websites, or not being consumer-focused. The remaining 69 websites were evaluated using a novel instrument, JHU-SALT, that includes 14 questions on topics related to salt reduction. The questions are grouped into three domains ("information," "guidance," and "accuracy"). For each question, websites were scored using a 3-step ordinal scale ("topic not addressed," "topic somewhat addressed," or "topic addressed adequately"). Only three of 14 JHU-SALT questions were addressed adequately by a majority of websites. Many websites provided information on the adverse health effects of a high sodium diet (74%, n = 51) or mentioned intake recommendations (64%, n = 44). Information on fundamental concepts was largely missing. The majority of websites (80%, n = 55) provided information on lifestyle strategies to reduce blood pressure, but most did not provide guidance to help implement those strategies. While missing information was common, misinformation was uncommon. The DISCERN questionnaire was utilized as well. Consumers seeking information and guidance on dietary sodium reduction will find that most available websites provide accurate but limited information, and insufficient guidance on how to lower sodium intake. Websites that provide both relevant information and guidance are needed to help consumers effectively reduce dietary sodium.
