{"title":"Novel Strategies for Improved Treatment of O6-Methylguanine-DNA Methyltransferase Promoter-Methylated Glioma.","authors":"Juan C Vasquez, Ranjit S Bindra, Susan E Gueble","doi":"10.18103/mra.v13i9.6944","DOIUrl":"10.18103/mra.v13i9.6944","url":null,"abstract":"<p><p>Adult diffuse gliomas are primary brain tumors notorious for leading to devastating neurologic consequences from both tumor progression and therapeutic interventions. The arsenal of current established treatments primarily includes surgery, radiotherapy, and DNA alkylating chemotherapy agents. Unfortunately, even with aggressive treatments, long-term cure is typically not attainable, except in certain cases of low-grade gliomas amenable to complete surgical resection. Grade 4 glioblastoma (GBM) represents the most aggressive and most common type of glioma in adults, is often resistant to current therapies, and is associated with a median survival of approximately 15 months. While biomarker-based therapies for gliomas are limited, O6-methylguanine-DNA methyltransferase (MGMT) is one well-established prognostic marker in GBM and is associated with improved response to the alkylating agent temozolomide (TMZ). Methylation of the MGMT promoter leading to loss of MGMT expression occurs in approximately half of GBMs and 70-80% of anaplastic and low-grade gliomas. While MGMT promoter-methylated gliomas are responsive to TMZ, a characteristic resistance mechanism of mismatch repair loss often emerges, resulting in recurrent drug-resistant disease. In prior work, we identified a new TMZ derivative \"KL-50\" which overcomes resistance to TMZ driven by loss of mismatch repair in preclinical glioma models. KL-50 functions via a novel DNA-modifying mechanism involving evolution of a primary alkyl lesion to a DNA interstrand crosslink specifically in the absence of MGMT. Research is ongoing to establish this new class of agents as a potential improved therapy in human gliomas. In this review, we provide an overview of the history and evolution of alkylator use in GBM, discuss the mechanisms and pitfalls of current therapies including toxicity or susceptibility to resistance mechanisms, and present the potential of a new wave of DNA modifiers to improve outcomes in gliomas.</p>","PeriodicalId":94137,"journal":{"name":"Medical research archives","volume":"13 9","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12571228/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145411051","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Association Between Trigger Surprisal and Tension-Type Headache Attacks.","authors":"Dana P Turner, Twinkle Patel, Timothy T Houle","doi":"10.18103/mra.v13i9.6969","DOIUrl":"10.18103/mra.v13i9.6969","url":null,"abstract":"<p><strong>Background: </strong>The causes of individual headache attacks are commonly sought, yet the multiple potential influences make this task difficult. Information theory provides a framework for addressing this challenge by quantifying how unexpected an exposure is through <i>surprisal</i>. Prior research has shown that higher surprisal scores predict migraine onset, but the extent to which this relationship generalizes to tension-type headache remains unknown.</p><p><strong>Aims: </strong>This study aimed to determine whether surprisal is associated with incident tension-type headache attacks among individuals with episodic migraine.</p><p><strong>Methods: </strong>This secondary analysis proceeded from a prospective daily diary study in which 109 participants with migraine recorded potential triggers, headache activity, and symptoms twice daily for up to 28 days. Surprisal values were computed from person-specific probability distributions of diary responses, aggregated to yield average surprisal scores per diary entry. Associations between current surprisal and the onset of headache attacks within 12- and 24-hour intervals were evaluated. Analyses were conducted for all headaches combined and separately for migraine-only and tension-type headache-only attack sets.</p><p><strong>Results: </strong>Headache attacks occurred in 1,345 of 4,530 (29.7%) of 12-hour and 2,122 of 4,947 (42.9%) of 24-hour windows. Stratified analyses showed a strong association for migraine attacks, OR: 2.18 (95%CI: 1.15 - 4.14) at 12 hours and OR: 2.88 (95%CI: 1.77 - 4.69) at 24 hours. In contrast, associations with tension-type headache were weak and nonsignificant, OR: 1.01 (95%CI: 0.45 - 2.23) at 12 hours and OR: 1.40 (95%CI: 0.69 -2.86) at 24 hours. Exploratory nonlinear and contextual analyses within the tension-type headache subset revealed no consistent gradients or effect modification by prior-day surprisal.</p><p><strong>Conclusions: </strong>Surprisal was associated with migraine but not tension-type headache attacks in this cohort. These findings suggest that migraine may be more sensitive to contextual unpredictability in the environment than tension-type headache. Future research should examine surprisal in populations with primary tension-type headache diagnoses to clarify whether the absence of association reflects true diagnostic differences or misclassification of attacks.</p>","PeriodicalId":94137,"journal":{"name":"Medical research archives","volume":"13 9","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12646078/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145644173","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Head Up Cardiopulmonary Resuscitation: Novel Physiological Discoveries and Latest Clinical Outcomes.","authors":"Pouria Pourzand, Anja Metzger, Keith Lurie","doi":"10.18103/mra.v13i8.6907","DOIUrl":"10.18103/mra.v13i8.6907","url":null,"abstract":"<p><p>Despite decades of research, survival rates following cardiac arrest remain dismal. The recent use of pressure-volume (PV) loop analysis has provided important insights into the underlying physiology of cardiopulmonary resuscitation (CPR). During conventional CPR (C-CPR), ventricular ejection is limited, contributing to poor circulatory effectiveness. In contrast, automated head-up CPR (AHUP-CPR)-which combines active compression-decompression (ACD) CPR, an impedance threshold device (ITD), and controlled head-thorax elevation-generates favorable negative intrathoracic pressure, promoting cerebral venous drainage and increases right heart preload, resulting in enhanced stroke volume, cardiac output, and end-tidal CO<sub>2</sub> (ETCO<sub>2</sub>) by improving ventricular-pulmonary-arterial circulation. This article summarizes recent advances related to AHUP-CPR with a focus on novel physiological findings derived from intraventricular conductance catheter recordings during ventricular fibrillation, C-CPR, and AHUP-CPR. The PV loop observations shed new light on the mechanisms through which AHUP-CPR improves circulatory efficiency and neurological outcomes.</p>","PeriodicalId":94137,"journal":{"name":"Medical research archives","volume":"13 8","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12872178/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146127926","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Gabriel P Bonvillain, Lauren D Pierce, Adria Abella Villafranca, Sam E Stephens, Luke E Ferguson, Hanna K Jensen, Joseph A Sanford, Jingxian Wu, Kevin Sexton, Morten Jensen
{"title":"The Importance of a Continuously Changing Heart Rate in Venous and Arterial Pressure Analysis.","authors":"Gabriel P Bonvillain, Lauren D Pierce, Adria Abella Villafranca, Sam E Stephens, Luke E Ferguson, Hanna K Jensen, Joseph A Sanford, Jingxian Wu, Kevin Sexton, Morten Jensen","doi":"10.18103/mra.v13i8.6824","DOIUrl":"10.18103/mra.v13i8.6824","url":null,"abstract":"<p><strong>Purpose: </strong>Previous studies have suggested that minimally invasive peripheral venous and arterial pressure waveforms provide a greater ability to detect acute changes in blood volume than traditional vital signs. Many of these studies are using Fast Fourier Transforms and power spectral densities to evaluate changes in the power at the heart rate frequency. Using the frequency domain requires a segment of the time domain to be converted into the frequency domain, which means that the heart rate derived from frequency domain analysis is an average of the segment used. However, in clinical settings the heart rate is changing continuously.</p><p><strong>Methods: </strong>This study evaluates the changing heart rate frequency power under varying time segments and compares the heart rate obtained from Fast Fourier Transform and power spectral density analysis with the instantaneous heart rate to gain a better insight into how a changing heart rate may influence the heart rate frequency power.</p><p><strong>Results: </strong>Spectral analysis revealed non-linear trends in heart rate frequency power, with changes that correspond to changes in the heart rate. We found the time segment chosen and the absolute difference between the instantaneous heart rate and the average heart rate obtained from power spectral density analysis influences the heart rate frequency power, such that as the instantaneous heart rate approaches the average heart rate, the heart rate frequency power increases.</p><p><strong>Conclusion: </strong>These results suggest that the time segment chosen for frequency domain analysis influences the power spectrum of the pressure waveforms. Furthermore, this study emphasizes the importance of utilizing a continuously changing heart rate in pressure waveform analysis.</p>","PeriodicalId":94137,"journal":{"name":"Medical research archives","volume":"13 8","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12574384/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145433364","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Characterizing Prescription Stimulant Use in Adults with Overdose Involving Psychostimulants.","authors":"Elizabeth Bolt, Wen-Jan Tuan","doi":"10.18103/mra.v13i7.6741","DOIUrl":"10.18103/mra.v13i7.6741","url":null,"abstract":"<p><p>The objective of this brief report is to characterize the use of prescription stimulants in adults with psychostimulant-related overdose in the United States amid the rising prevalence of stimulant prescriptions and stimulant-related overdose deaths. Using the International Classification of Diseases, Tenth Revision coding system, we identified adults with diagnoses related to overdose involving psychostimulants between 2010 and 2022 and used descriptive statistics to characterize these individuals. The analysis included 15,744 adults with stimulant-related overdoses (16.5% intentional, 83.5% unintentional). We found that 17.7% of adults with stimulant-related overdose events had a previous stimulant prescription. Nearly half of those with a stimulant-related overdose had a previously identified mental health disorder (49.9%) or substance use disorder (43.2%). The prevalence of overdose in high-risk adult populations highlights the need for additional safety interventions. Risk-benefit analysis and tailored guidelines for prescribing stimulants, especially in populations with mental health or substance use disorders, are warranted to mitigate overdose risk and enhance patient safety.</p>","PeriodicalId":94137,"journal":{"name":"Medical research archives","volume":"13 7","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13309182/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148348089","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Liliana Arida-Moody, Sarah Austin, Erika N Hanson, Emerson Delacroix, Erika Koeppe, John D Rice, Matthew Demerath, Shayna Weiner, Jennifer J Griggs, Kenneth Resnicow, Elena M Stoffel
{"title":"Predictors of Genetic Testing for Hereditary Cancer in Qualified Individuals.","authors":"Liliana Arida-Moody, Sarah Austin, Erika N Hanson, Emerson Delacroix, Erika Koeppe, John D Rice, Matthew Demerath, Shayna Weiner, Jennifer J Griggs, Kenneth Resnicow, Elena M Stoffel","doi":"10.18103/mra.v13i7.6661","DOIUrl":"10.18103/mra.v13i7.6661","url":null,"abstract":"<p><strong>Introduction and methods: </strong>We surveyed individuals in the United States whose personal and/or family history met clinical criteria for genetic testing for cancer susceptibility. Using univariate and multivariable logistic regression analyses, we examined demographic and clinical factors associated with self-reported receipt of clinical genetic testing.</p><p><strong>Results: </strong>Of the 1,269 respondents with personal and/or family history meeting clinical criteria for genetic testing, 48.1% reported having undergone clinical genetic testing. Testing uptake varied by cancer type (p<0.05) and was highest among individuals with personal diagnoses of breast (73.9%), ovarian (88.2%), and pancreatic (70.2%) cancers, as compared with prostate cancer (33.6%). Females were significantly more likely than males to have undergone genetic testing (odds ratio, OR, 1.67, CI: 1.17-2.37), and people 70 years or older were less likely to have had testing when compared with those age under 50 (OR 0.33, CI: 0.22-0.48). Individuals who were diagnosed with cancer 15 or more years ago were less likely to have had genetic testing than those with more recent cancer diagnoses (OR 0.47 CI: 0.30-0.74). Individuals who were eligible to receive genetic testing based on their family history of cancer alone were less likely to have had testing than those with a personal cancer diagnosis (OR 0.65, CI: 0.44-0.97).</p><p><strong>Conclusion: </strong>While clinical genetic testing is routinely offered to specific groups of patients at risk for hereditary cancer syndromes (especially those with a personal or family history of breast and/or ovarian cancers), uptake remains low among men and among individuals who qualify for genetic testing based on diagnoses of non-gynecologic cancers and/or family history alone. Patient- and clinician-facing interventions are needed to raise awareness of indications for clinical genetic testing for cancer susceptibility.</p>","PeriodicalId":94137,"journal":{"name":"Medical research archives","volume":"13 7","pages":"6661"},"PeriodicalIF":0.0,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13559554/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148932152","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Joshua D Gazzetta, Poster P Mutambo, Mutimba B Mpabalwani, Mwamba Jc Mulenga, Cyrus Phiri, Kelvin Shaba, Emmanuel M Makasa
{"title":"The Implementation of a Perioperative Registry in a Resource-Limited Setting: A Feasibility, Fidelity, and Acceptance Study.","authors":"Joshua D Gazzetta, Poster P Mutambo, Mutimba B Mpabalwani, Mwamba Jc Mulenga, Cyrus Phiri, Kelvin Shaba, Emmanuel M Makasa","doi":"10.18103/mra.v13i6.6574","DOIUrl":"10.18103/mra.v13i6.6574","url":null,"abstract":"<p><strong>Background: </strong>In low and middle-income countries, nine out of every ten persons is unable to access safe and timely surgery. The limited perioperative data in resource-limited settings compromises surgical and research capacity growth. By increasing data availability, surgical disparities may be addressed through research efforts and quality initiatives. This project aimed to implement and evaluate a perioperative registry in a tertiary care hospital in a low-income country.</p><p><strong>Methods: </strong>A prospective emergency laparotomy perioperative registry was implemented in Zambia's largest teaching and referral hospital. Over the first 6-months of implementation, 162 patients were included. Data was collected postoperatively, before discharge, and at 30 days. The registries feasibility was assessed by evaluating patient accrual, retention, and 30-day completion rates. The registries fidelity was measured by evaluating data missingness. A participant acceptance survey was retrospectively collected and analyzed for the first 25 consecutively enrolled patients.</p><p><strong>Results: </strong>The capture rate of the registry could not be calculated due to a destroyed theatre logbook. The participant accrual and retention rates were 99.4% and 95.1%, respectively. The participant completion rate at 30-days was 75.6%. The overall incidence of missing information in the registry was 3.5%. More than 75% of participant responses to the acceptance survey were positive in each category regarding the ethical conduct of research and the storing of personal data.</p><p><strong>Conclusion: </strong>The value of this study is the reporting and evaluation of a successful perioperative registry implementation with minimal external funding. This framework is being used to develop new data registries and may provide a roadmap for other hospitals with resource constraints.</p>","PeriodicalId":94137,"journal":{"name":"Medical research archives","volume":"13 6","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12360225/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144884687","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Inertia-Driven Mitral and Aortic Valves: The Isovolumic Myth.","authors":"Neil B Ingels, Matts Karlsson, Morten O Jensen","doi":"10.18103/mra.v13i6.6694","DOIUrl":"10.18103/mra.v13i6.6694","url":null,"abstract":"<p><strong>Background: </strong>For the past century, the Wiggers Diagram has been universally taught as defining the phases of the cardiac cycle. However, the concepts underlying this diagram have never been fully and directly tested on intact, beating hearts.</p><p><strong>Methods: </strong>In vivo datasets from sheep recorded left ventricular and aortic pressures and flows along with simultaneous 4-D coordinates of 30 miniature strategically placed radiopaque markers. This allowed hemodynamic synchronization with tracking of key anatomical landmarks every 16.7 msec to test Wiggers' concepts.</p><p><strong>Results: </strong>The Wiggers Diagram is not supported as there were no consistent isovolumic periods; the mitral valve closed anywhere during the rising phase of left ventricular pressure, and aortic valve closure and mitral valve opening were <i>simultaneous</i> at the end of the systolic pressure drop.</p><p><strong>Conclusions: </strong>The Wiggers Diagram describes valve opening and closing solely in terms of pressure differences which can be transmitted almost instantaneously through incompressible blood in the ventricle. However, pressure differences do not open and close the valves; <i>it is inertial flow through the valves.</i> The present study redefines the description of the interaction between the left ventricle and its valves and shows that the periods of isovolumic contraction and relaxation are mythical concepts.</p>","PeriodicalId":94137,"journal":{"name":"Medical research archives","volume":"13 6","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12721858/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145822633","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Kameron Suire, Brian Helsel, April Bowling, Amanda E Staiano, Joseph Sherman, Annie Rice, Lauren Ptomey
{"title":"The Adoption of the GameSquad Exergaming Intervention for Young Adults with Down Syndrome: A Qualitative Analysis.","authors":"Kameron Suire, Brian Helsel, April Bowling, Amanda E Staiano, Joseph Sherman, Annie Rice, Lauren Ptomey","doi":"10.18103/mra.v13i6.6608","DOIUrl":"10.18103/mra.v13i6.6608","url":null,"abstract":"<p><strong>Introduction: </strong>Adults with Down syndrome face persistent barriers to physical activity, including mobility limitations, lack of accessible programming, and low self-efficacy. Exergaming represents a potentially scalable, home-based approach to increasing physical activity in this population.</p><p><strong>Purpose: </strong>This qualitative study explored the experiences, preferences, and perceived barriers of young adults with Down syndrome and their live-in caregivers who participated in a 12-week exergaming intervention. The program paired the narrative-based game <i>Ring Fit Adventure</i> <sup>™</sup> (Nintendo Switch<sup>™</sup>) with weekly 15-minute virtual health coaching sessions designed to review weekly progress, reinforce the importance of moderate-to-vigorous physical activity address any technical issues (e.g., related to the game, system, or Fitbit), and provide social support and encouragement.</p><p><strong>Methods: </strong>Twenty adults with Down syndrome (<i>M</i> age= 23.2 ± 3.9, 85% non-Hispanic white, 65% female) enrolled and 19 completed the trial. One participant ceased communication with the research team after completing pre-testing. Semi-structured exit interviews were conducted with participants and their caregivers. Interviews were transcribed verbatim and analyzed using reflexive thematic analysis. Themes were developed iteratively using a six-step framework.</p><p><strong>Results: </strong>Through analysis, we identified five distinct themes that reflect shared and unique experiences related to 1) engagement, 2) autonomy, 3) physical challenge, 4) technology, and 5) long-term value. Participants were motivated by the immersive game design and reported a preference for playing independently. Caregivers described their roles in supporting routine formation and providing occasional technical assistance.</p><p><strong>Conclusion: </strong>Exergaming, supported by light-touch health coaching, was perceived as an engaging, accessible, and sustainable strategy to increase physical activity among young adults with Down syndrome. These findings support the design of home-based interventions that promote autonomy and long-term adherence for individuals with intellectual disabilities.</p>","PeriodicalId":94137,"journal":{"name":"Medical research archives","volume":"13 6","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13038042/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147597135","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Novel Protein Adjuvant Activating Innate IFN-γ and IL-18 Expression and Inducing Rejection of Implanted Colorectal Cancer Following Immunotherapy Using This Adjuvant in Mice.","authors":"Rajesh Mani, B Mark Evers, Yasuhiro Suzuki","doi":"10.18103/mra.v13i6.6615","DOIUrl":"10.18103/mra.v13i6.6615","url":null,"abstract":"<p><p>Our recent study demonstrated that immunizations with nonreplicable MC38 colorectal cancer cells plus a novel recombinant protein adjuvant, the amino-terminus region of dense granule protein 6 (rGRA6Nt) of <i>Toxoplasma gondii</i> (a protozoan parasite), effectively activate the cancer cell-specific CD8<sup>+</sup> T cytotoxic cells and inhibit the growth of implanted tumors of the identical cancer cells after its challenge implantation. In the present study, we first examined whether rGRA6Nt activates mRNA expression for IFN-γ, IL-12, IL-15, and IL-18, which are known to assist an activation of the CD8<sup>+</sup> T cells, in innate immune cells. Following an intraperitoneal injection of rGRA6Nt (40 μg) into SCID mice deficient in both T and B cells, markedly increased levels of mRNA for only IFN-γ and IL-18 were detected in their peritoneal exudate innate immune cells. When C57BL/6 mice were immunized with nonreplicable MC38 colorectal cancer cells plus rGRA6Nt adjuvant twice and challenged with replication-capable cancer cells of the identical colorectal cancer, more than one fifth (22.2%, 6/27) of the immunized mice rejected the growth of the implanted tumors, whereas none (0/27, <i>P</i><0.05) of unimmunized control mice rejected the implanted tumors. These results indicate that rGRA6Nt protein adjuvant has a unique capability to selectively activate expression of IFN-γ and IL-18 in innate immune cells, and that immunizations with nonreplicable cancer cells in combination with this protein adjuvant can induce a protection to reject the growth of the identical tumor cells after its challenge implantation in a significant portion of the immunized mice.</p>","PeriodicalId":94137,"journal":{"name":"Medical research archives","volume":"13 6","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12360206/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144884686","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}