Tag: pubmed

Cell Biochem Biophys. 2025 Apr 28. doi: 10.1007/s12013-025-01764-9. Online ahead of print.

ABSTRACT

Triple-negative breast cancer (TNBC) is an aggressive subtype lacking hormonal and HER2 receptors, making it highly resistant to treatment. Apo2L/TRAIL, a tumor necrosis factor-related ligand, induces apoptosis in cancer cells via the death receptor DR4. However, TNBC often develops resistance to TRAIL-mediated apoptosis, limiting its therapeutic potential. This study investigates whether arsenic trioxide (ATO) can overcome TRAIL resistance by modulating the Apo2L/TRAIL pathway and enhancing the effects of carboplatin (CP) and cyclophosphamide (CY). TNBC cell lines BT-20 and MDA-MB-231 were treated with ATO, CP, CY, and their combinations. Cell viability was measured using the MTT assay, while real-time PCR and Western blot analysis assessed Apo2L/TRAIL and DR4 expression. Statistical analysis was performed using ANOVA with Dunnett’s post hoc test. ATO induced dose-dependent cytotoxicity in TNBC cells, which was significantly enhanced in combination treatments. The highest reductions in cell viability were observed with 3 µM ATO plus 5000 µM CP or 500 µM CY (p < 0.0001). ATO markedly upregulated Apo2L/TRAIL and DR4 at both mRNA and protein levels, with the most pronounced effects seen in ATO-CY combinations. These findings indicate that ATO sensitizes TNBC cells to TRAIL-mediated apoptosis by upregulating DR4 and Apo2L/TRAIL, while also exhibiting strong synergistic cytotoxicity with CP and CY. This highlights ATO’s potential as an adjuvant therapy to improve TNBC treatment efficacy and overcome chemoresistance, warranting further clinical exploration.

PMID:40293700 | DOI:10.1007/s12013-025-01764-9

J Racial Ethn Health Disparities. 2025 Apr 28. doi: 10.1007/s40615-025-02455-0. Online ahead of print.

ABSTRACT

INTRODUCTION: Black patients have the worst survival outcomes from colorectal cancer (CRC) in the US. In addition, disparities and differences in mortality outcomes among Black and NHW patients across the four US census regions (Northeast [NE], South, West, Midwest [MW]) remain unexplored. We hypothesized that survival outcomes for Black patients would differ across the US census regions and might correlate with socioeconomic factors.

METHODS: Black and Non-Hispanic White (NHW) patients ≥ 45 years of age with a diagnosis of colon or rectal adenocarcinoma between 2010 and 2018 were identified in the National Cancer Database for survival analysis. Survival differences were further validated using the Surveillance, Epidemiology, and End Results (SEER) database to investigate 5-year cause-specific survival (CSS).

RESULTS: For colon adenocarcinoma, the largest difference in median overall survival (OS) between NHW and Black patients was in the MW (67 months Black vs. 74 months NHW, P < 0.001). For rectal cancer, the largest difference was in the West (60 months Black vs. 84 months NHW, P < 0.001). Black patients receiving care in the MW had the lowest median OS for CRC, while those in the NE had the highest (colon: 67 months MW vs. 100 months NE; rectum: 55 months MW vs. 79 months NE). In multivariable analyses of the Black patient cohort, cancer care in the NE was associated with decreased mortality risk compared to other regions.

CONCLUSION: Geographic region of care appears to correlate with survival differences for CRC. Exploring these differences may facilitate improved understanding of systemic and structural drivers of health inequities and aid improved resource allocation.

PMID:40293690 | DOI:10.1007/s40615-025-02455-0

Pharmacoeconomics. 2025 Apr 28. doi: 10.1007/s40273-025-01491-2. Online ahead of print.

ABSTRACT

OBJECTIVE: In this study we aimed to identify possible changes over time in validation efforts and the way in which they are reported for model-based health economic (HE) evaluations, given the introduction of several new validation tools and methods in the past decade.

METHODS: A systematic review was conducted using PubMed and Embase on published HE models for early breast cancer (EBC) for the period 2016 to 2024. AdViSHE-consisting of four validation categories that cover the main HE model aspects-was utilized to systematically evaluate the reported evaluation efforts. The percentage of studies reporting validation per category was compared with the review by de Boer et al. that covers the years 2008 to 2015.

RESULTS: Of the 2199 records, 78 studies fulfilled the eligibility criteria. Reported validation efforts did not significantly improve compared with the previous period, except for the validation of input data by experts. Reporting on the validation of the conceptual model remained low with around 10% of the studies providing validation. Validation of the computerized model and validation against outcomes using alternative input data were the most underreported validation categories with < 4% of the studies. The validation of model outcomes, specifically cross validity and the comparison with empirical data, remained the most reported categories in this review also, with 52% and 36%, respectively. When validation efforts were reported, this was done in a non-systematic manner, and the tests and results were rarely detailed.

CONCLUSION: Overall reporting of validation efforts for model-based HE evaluations in the past decade did not significantly change compared with the previous decade.

PMID:40293688 | DOI:10.1007/s40273-025-01491-2

J Neurooncol. 2025 Apr 28. doi: 10.1007/s11060-025-05047-4. Online ahead of print.

ABSTRACT

BACKGROUND: This study aimed to investigate the feasibility of introducing additional Mixed Reality (MR) visualisation of patient-specific imaging during the neurosurgical consultation to improve patients’ understanding, as well as the potential benefits from a patient’s perspective to the consultation process.

METHODS: An IDEAL Stage 2a feasibility randomised controlled trial was conducted involving patients with radiologically suspected brain tumours at a large, tertiary UK neurosurgery institution. Patients were randomised into two groups: standard 2D monitor versus additional MR visualisation. Primary feasibility outcomes included recruitment rates, MR intervention adherence, fidelity, and acceptability. Secondary outcomes included patient-reported experiences. Quantitative and qualitative analyses were performed via validated questionnaires.

RESULTS: A total of 36 patients were randomised over 12 months, 17 to a Mixed Reality (MR) Group and 19 to a standard 2D monitor-only group, with no significant baseline differences. MR intervention was deemed feasible for further clinical evaluation with high fidelity and user acceptability. Patients in the MR group reported statistically higher satisfaction with information received, an improved patient-doctor relationship, greater confidence in decision-making, and a better understanding of their condition compared to the standard 2D monitor-only group. No major technological issues were encountered. No adverse effects were reported or observed (including cybersickness). Patients found the MR technology easy to use.

CONCLUSIONS: Our findings suggest that incorporating MR visualisation into routine neurosurgical consultations is feasible and offers potential benefits for patients. With minor modifications to the intervention and assessments, we aim to perform a larger-scale, multi-centre randomised feasibility trial, which will also address implementation challenges for widespread adoption and provide more indication of efficacy.

PMID:40293673 | DOI:10.1007/s11060-025-05047-4

J Neurooncol. 2025 Apr 28. doi: 10.1007/s11060-025-05031-y. Online ahead of print.

ABSTRACT

PURPOSE: High-Mobility Group A1 (HMGA1) is a chromatin-associated protein involved in regulating key cellular processes, including DNA transcription, replication, recombination, and repair. It is highly expressed during embryogenesis and reactivated in various cancers, where it contributes to tumor progression and metastasis. We investigated the prognostic significance of HMGA1 gene expression in gliomas by comparing its expression in normal brain tissue and different glioma grades.

METHODS: Real-time quantitative PCR (qPCR) was performed on 75 glioma samples obtained from Aga Khan University Hospital (Pakistan), along with 10 Normal Adjacent Tissue (NAT) samples. The correlation between HMGA1 expression and prognosis was evaluated using Kaplan-Meier (KM) plotter in glioma patients. Statistical analyses were conducted using the R platform and further validated through the online database Chinese Glioma Genome Atlas (CGGA) using online tools.

RESULTS: HMGA1 expression was significantly upregulated in gliomas compared to NAT (p < 0.001) and increased with tumor grade (p = 0.015). High HMGA1 expression correlated with Ki-67 levels and was associated with worse survival (p = 0.0014). Patients with elevated HMGA1 had a 3.5-fold higher mortality risk (95% CI: 1.5-7.9, p = 0.003). ROC analysis yielded an AUC of 0.752, indicating its potential prognostic value.

CONCLUSION: HMGA1 overexpression is associated with poor prognosis in gliomas, suggesting its potential as a prognostic marker. However, further validation is needed to confirm its clinical utility.

PMID:40293672 | DOI:10.1007/s11060-025-05031-y

Int J Clin Pharm. 2025 Apr 28. doi: 10.1007/s11096-025-01924-0. Online ahead of print.

ABSTRACT

BACKGROUND: The effect of sodium-glucose cotransporter 2 (SGLT2) inhibitors on cancer incidence compared to other hypoglycemic drugs remains unclear.

AIM: This systematic review and meta-analysis was designed to investigate the association of SGLT2 inhibitors with cancer compared to active comparators.

METHOD: A systematic search was conducted up to March 11, 2024 across Web of Science, PubMed, and ClinicalTrials.gov, and included trials with a follow-up period of at least 52 weeks. The Mantel-Haenszel statistical method was utilized, applying risk ratio (RR) and 95% confidence intervals (CI) for binary variables.

RESULTS: Twenty trials covering 16,399 type 2 diabetes mellitus patients were included. Median follow-up duration was 1.0 (1.0) years. The effect of SGLT2 inhibitors on the overall risk of cancer was neutral compared to active comparators (RR 1.00; 95%CI 0.71-1.40; p = 0.99; moderate certainty of evidence). SGLT2 inhibitors did not have a significant impact on breast cancer, endometrial/uterine cancer, gastrointestinal cancer, prostate cancer, renal cancer, or respiratory cancer. Subgroup analysis indicated a significant reduction in the risk of gastrointestinal cancer with SGLT2 inhibitors compared to metformin (RR 0.23; 95%CI 0.06-0.95; p = 0.04). SGLT2 inhibitors potentially increased gastrointestinal cancer risk relative to sulfonylureas (RR 3.52; 95%CI 0.91-13.64; p = 0.07).

CONCLUSION: SGLT2 inhibitors showed neutral cancer risk in T2DM patients but may reduce gastrointestinal cancer versus metformin, guiding tailored therapy based on patient risk profiles.

PMID:40293640 | DOI:10.1007/s11096-025-01924-0

Biochem Genet. 2025 Apr 28. doi: 10.1007/s10528-025-11119-x. Online ahead of print.

ABSTRACT

Mitochondrial sirtuin 3 (SIRT3) is a gene involved in key functions like acetylation, DNA repair, stress response, and tumorigenesis. Several studies have been published that showed the role of SIRT3 in various cancers. Still, few studies have been reported on the genetic and expression variation of the SIRT3 gene in gastric carcinogenesis. This study was designed to explore the involvement of the SIRT3 gene in gastric cancer. In this study, we used two study cohorts, cohort 1 contained 510 gastric cancer (GC) patients and an equal number of age and gender-matched controls. Cohort 2 included 220 GC tissue samples along with adjacent control tissues. Tetra Arms PCR was used to measure the frequency of three selected SNPs of the SIRT3 gene (rs28365927, rs11246029, and rs3817629) in cohort 1. Quantitative PCR and immunohistochemistry were performed to analyze the SIRT3 expression variation in cohort 2 GC patients. The superoxide dismutase (SOD), and 8-hydroxydeoxyguanosine (8-OHdG) levels were measured using ELISA, and DNA damage was measured using the LORD-Q assay. Statistical analysis showed the significant increased frequency of mutant allele of selected SNPs (rs28365927 (p < 0.0001); rs11246029 (p < 0.0001); and rs3817629 (p < 0.0001) in GC patients compared to controls. Expression analysis results showed significant downregulation of the SIRT3 gene at mRNA level (P < 0.001) and protein level (P < 0.001) in gastric tumor section vs control tissues. Multivariant Cox regression analysis showed that downregulated SIRT3 expression (p < 0.000001), H. pylori status (p < 0.0001), T-stage (p < 0.008), and N-stage (p < 0.001) act as prognostic markers in GC patients. ROC curve analysis showed the 90% and 100% specificity of the SIRT3 gene as a diagnostic marker in GC at the mRNA level and protein level, respectively. Significant increased oxidative stress (antioxidant enzyme level p < 0.0001; 8-OHdG level p < 0.0001) and lesion frequency/10 kb (p < 0.03) were indicated in the gastric tumor tissue sections vs controls. The result showed the tumor suppressor role of the SIRT3 gene in GC and was found linked with the surge in oxidative stress and damage in GC patients.

PMID:40293630 | DOI:10.1007/s10528-025-11119-x

Environ Sci Process Impacts. 2025 Apr 28. doi: 10.1039/d4em00804a. Online ahead of print.

ABSTRACT

Volatile chemical products (VCPs) in urban environments account for a significant portion of the volatile organic compounds (VOCs), enhancing the production of tropospheric ozone and secondary organic aerosols. Residential areas are an important source of VCPs in the urban environment, though few studies have examined the emission of VCPs in metropolitan areas from subtropical regions. To bridge the knowledge gap, this study aims to analyze the concentration and emission of D5-siloxane, a compound typically served as a tracer to characterize VCP emission from residential areas. The Texas A&M mobile laboratory, equipped with a Vocus 2R Chemical Ionization Mass Spectrometer (CIMS), and other gas and particle analyzers, continuously sampled the ambient gas phase concentration of D5-siloxane during a field deployment in a residential neighborhood near Houston, TX. A 0-D box model combining Planetary Boundary Layer Height (PBL) height, hourly D5-siloxane concentration, gas deposition velocities, and D5-siloxane reaction rate with hydroxyl radicals was constructed to represent emissions during our sampling period to derive the emission intensities of D5-siloxane. Monte Carlo statistical analysis was performed to gain insights into the emission profile of D5-siloxane, showing higher emission rates compared with other cities in North America but comparable to emissions of European cities. This study presents time-series concentrations and emissions of D5-siloxane in a subtropical residential area during the wintertime. The findings illustrate the temporal profile of D5-siloxane in a typical residential neighborhood in the Southeast United States and provide valuable data to enhance model parameterizations.

PMID:40289910 | DOI:10.1039/d4em00804a

Arthritis Care Res (Hoboken). 2025 Apr 28. doi: 10.1002/acr.25562. Online ahead of print.

ABSTRACT

OBJECTIVES: This study aimed to improve contraception and reproductive planning documentation within rheumatology providers’ notes at a single academic center.

METHODS: Female patients aged 18-45 years old with autoimmune inflammatory rheumatic diseases were identified and chart review was performed for documentation of contraception and pregnancy planning. Baseline data were collected from 148 charts between May 2022 and March 2023. In June 2023, a reproductive health assessment questionnaire was integrated into the electronic health record and sent to patients for completion prior to their visits. Post intervention data was collected from 176 charts between July 2023 and December 2023. Demographics of patients (race, ethnicity, gender) and provider gender were collected. Telehealth and face to face visits were assessed separately.

RESULTS: A statistically significant increase (p<0.0001) was seen in provider documentation of both contraception (44.6% to 70.5%) and pregnancy planning (15.5% to 60.2%) after implementation of the pre-visit questionnaire. When patients prescribed teratogenic medications were analyzed separately, there was statistically significant (p<0.0001) better documentation of pregnancy planning after the intervention. Secondary analyses found that patient age, race/ethnicity, encounter type, or provider gender had no significant impact on documentation rates.

CONCLUSIONS: By integrating an electronic, pre-visit questionnaire into the patient portal, documentation was significantly improved for contraception and pregnancy planning. The results were sustained for 6 months. Further studies are needed to see if improved documentation translates into more effective reproductive health care discussions, referrals to gynecology, and subsequent improvement in reproductive health outcomes.

PMID:40289896 | DOI:10.1002/acr.25562

Arthritis Rheumatol. 2025 Apr 28. doi: 10.1002/art.43199. Online ahead of print.

ABSTRACT

OBJECTIVES: Tapering of tumor necrosis factor inhibitor (TNFi) treatment in rheumatoid arthritis (RA) remission is debated. We assessed the effect of tapering TNFi to withdrawal versus continued stable TNFi on flare-free survival and joint damage progression over three years.

METHODS: ARCTIC REWIND was a multicenter, open-label, non-inferiority trial including patients with RA in remission for ≥12 months on stable TNFi therapy. Patients were randomized 1:1 to taper TNFi to withdrawal or continue stable treatment. The primary endpoints of the current study were flare-free survival and radiographic progression over three years. Flare-free survival was analyzed by Kaplan-Meier methods, flare rates by Cox regression, and radiographic progression by logistic mixed effects models.

RESULTS: Of 99 randomized patients, 92 received the allocated therapy, 80 completed 3-year follow-up. Mean baseline DAS based on 44 joint count was 0.8, csDMARD co-medication was used by 90%. After 3 years, 25% (95%CI: 13-38%) remained flare-free in the tapering TNFi group compared to 85% (70-93%) in the stable group, corresponding hazard ratio for flare 9.4 (3.9-22.8), p<0.0001. In the tapering group 6/41 (15%) experienced radiographic progression, compared with 3/38 (8%) in the stable group, risk difference 6.7% (-7.1%-20.5%, p=0.3). Adverse events occurred in 81% of the patients in the tapering group, and 89% of the patients in the stable group.

CONCLUSION: In contrast to those receiving stable TNFi treatment, a minority of RA patients in remission tapering TNFi to withdrawal remained flare-free over three years. There was no statistically significant difference in radiographic progression between the groups.

PMID:40289847 | DOI:10.1002/art.43199