Arctigenin (Arc), a novel anti-inflammatory lignan derived primarily from Arctium lappa, has demonstrated promising anticancer activity in multiple cancer types. This study was designed to evaluate the anticancer efficacy of Arc across distinct molecular subtypes of breast cancer in vitro and in vivo and to gain mechanistic insights into its mode of action. In vitro evaluation was conducted in estrogen-receptor-positive MCF-7, human epidermal growth factor receptor 2 (HER2)-positive SKBR3, and triple-negative MDA-MB-231 breast cancer cell lines. In vivo efficacy and safety were evaluated using female severe combined immunodeficient (SCID) mice (5-7 weeks old) bearing MCF-7 or MDA-MB-231 xenografts. Mice received daily oral gavage of Arc at 50 mg/kg body weight for 8 weeks. In vitro, Arc inhibited cell proliferation across all three breast cancer subtypes in a dose-dependent manner. PCR-array analysis of gene expression revealed that Arc targets multiple signaling molecules involved in cell proliferation, cell cycle regulation, apoptosis, migration/invasion, and drug transport, demonstrating a subtype-specific target profile. Arc induced cell-cycle arrest at the G2/M phase in MCF-7 cells and at G0/G1 in MDA-MB-231 cells, accompanied by significant induction of apoptosis in both cell lines. Migration assays further demonstrated marked inhibition of wound closure in Arc-treated cells. In vivo, Arc treatment significantly inhibited tumor growth in both xenograft models, decreased Ki67 expression, and produced no overt toxicity. In summary, Arc exhibits potent anticancer activity against distinct breast cancer subtypes through multi-targeting mechanisms. Given the heterogeneity of breast cancer, Arc appears to be a promising candidate for further preclinical investigation.
Background/Objectives: Tissue factor (TF)-expressing cancer cells and their extracellular vesicles (CaCe-dEVs) are key drivers of cancer-associated hypercoagulability and vascular dysfunction. While low-molecular-weight heparins (LMWHs) and direct FXa inhibitors are standard therapies for cancer-associated thrombosis, their direct effects on cancer cell procoagulant potential and endothelial responses remain incompletely defined. This study compared the impact of LMWHs (enoxaparin, tinzaparin), apixaban, and quercetin on cancer cell viability, thrombin generation, and CaCe-dEVs-induced endothelial injury. Methods: Pancreatic (BXPC3) and breast (MCF7) cancer cells and their vesicles were analyzed for TF expression and thrombin generation. Human umbilical vein endothelial cells (HUVECs) were pretreated with each agent prior to vesicle exposure. Cell viability, thrombin generation, and endothelial morphology were assessed using standard assays and microscopy. Results: Tinzaparin and quercetin significantly reduced cancer cell viability, whereas enoxaparin and apixaban showed no cytotoxicity. None of the agents affected HUVEC viability. All suppressed TF-mediated thrombin generation induced by cancer cells, with tinzaparin being most effective in BXPC3 cells. Quercetin exhibited a partial and limited protective effect on endothelial cells against CaCe-dEVs-induced dysfunction, while LMWHs and apixaban did not prevent endothelial damage. Conclusions: These findings suggest that LMWHs, apixaban, and quercetin modulate cancer-cell-driven hypercoagulability beyond anticoagulation, with quercetin and tinzaparin showing additional cytotoxic potential. Such dual effects may reduce thrombosis risk while impacting tumor progression, meriting further investigation.
Breast conserving surgery (BCS) aims to excise breast tumors whilst preserving breast-related quality of life, but is complicated by the challenge of accurately identifying the margin between healthy and cancerous tissue. Raman spectroscopy (RS) has been shown to distinguish between normal breast tissue and breast cancer. Thus, this study aimed to further evaluate the diagnostic performance of RS in ex vivo breast tissue subtype classification via investigation of signals from healthy tissues and three breast cancer subtypes (invasive ductal carcinoma, IDC; invasive lobular carcinoma, ILC; and ductal carcinoma in situ, DCIS). A total of 80 tissue samples (46 normal and 34 cancerous) from 71 individuals were measured using a confocal Raman microscope. Spectral signatures were investigated, and supervised classification was performed for both two-class (healthy vs. cancer) and four-class (healthy vs. IDC vs. ILC vs. DCIS) classification tasks. RS successfully differentiated cancerous from normal breast tissue (97.84% sensitivity, 97.18% specificity). For four-class classification, RS achieved in-class sensitivity ranging from 83 to 96% and specificity from 93 to 99%. These findings demonstrate that RS can accurately distinguish normal from cancerous tissue and capture clinically relevant differences among histological subtypes, including invasive and pre-invasive disease, supporting its promise for intraoperative tissue characterization during BCS.
Diagnostic delays contribute to poorer outcomes in cancer care. Because most symptomatic patients enter the healthcare system through general practice, educational interventions for primary care teams could lead to earlier investigation, referral, and follow-up. We mapped educational interventions in primary care designed to reduce diagnostic delays for cancer and described their formats, targeted behaviours, outcomes, and gaps. We undertook a scoping review using the PRISMA-ScR checklist. PubMed, Embase, Scopus, and Web of Science were searched from January 2000 to January 2026. We included studies (and protocols) describing or evaluating educational interventions for primary care clinicians and teams intended to improve the timeliness of symptomatic cancer diagnosis (for example, safety-netting, diagnostic activity, referral quality, or time-based outcomes). Data were charted and synthesised descriptively and thematically. Sixteen publications representing ten distinct intervention programmes were included. Interventions ranged from brief clinician teaching and educational outreach to simulation-based mastery learning, national or regional continuing medical education programmes, whole-practice workshops, and education bundled with electronic decision support or electronic safety-netting tools. Most evaluations reported improvements in clinician competence, confidence, or process proxies (for example, documentation quality or diagnostic activity). Only a small number of studies assessed time-based outcomes such as primary care interval or total diagnostic interval, and effects were mixed or null; several digital interventions were further constrained by workflow misfit and low uptake. Educational interventions in primary care can improve behaviours relevant to earlier cancer diagnosis, but evidence for reductions in diagnostic delays remains limited. Future work should integrate education with practice systems, use standardised interval definitions, and evaluate timeliness and equity outcomes. This review synthesises evidence to inform curriculum design and continuing professional development for primary care teams, focusing on teachable behaviours (diagnostic reasoning under uncertainty, safety-netting, and appropriate thresholding for investigation/referral) that can shorten diagnostic intervals for cancer.
Cancer remains a major global health challenge, with rising incidence and persistent therapy resistance highlighting the need for new multi-targeted therapeutic agents. Pinocembrin (5,7-dihydroxyflavanone), a naturally occurring flavanone found in honey, propolis, and several medicinal plants, has gained increasing attention for its broad-spectrum anticancer potential. Recent studies demonstrate that pinocembrin modulates multiple hallmarks of cancer by regulating the PI3K/Akt/mTOR, STAT3, and NF-κB pathways, resulting in antiproliferative, pro-apoptotic, anti-metastatic, and anti-inflammatory effects. Evidence from diverse cancer models-including breast, prostate, colon, lung, ovarian, and melanoma-shows that pinocembrin induces cell-cycle arrest, activates intrinsic and extrinsic apoptotic pathways, inhibits angiogenesis, and suppresses epithelial-mesenchymal transition. Structure-activity relationship (SAR) analyses further reveal that modifications such as hydroxylation, esterification, and glycosylation enhance its bioavailability and anticancer activity. Despite its therapeutic promise, the clinical utility of pinocembrin is limited by poor solubility and rapid metabolic clearance. Recent nanotechnology-based formulations, including polymeric micelles, liposomes, nanoparticles, and nanoemulsions, have significantly improved their stability, bioavailability, and tumor-targeted delivery. Pinocembrin also exhibits synergistic effects with conventional chemotherapeutics while maintaining low toxicity toward normal cells, underscoring its suitability for combination therapy and chemoprevention. Preliminary clinical data indicate a favorable safety profile, although long-term toxicity, optimal dosing, and pharmacokinetic parameters require further investigation. This review synthesizes current knowledge on the anticancer mechanisms, SAR-driven insights, nanotechnology-enhanced delivery, synergistic actions, and safety considerations of pinocembrin. By integrating recent findings and highlighting research gaps, it provides a comprehensive foundation for advancing pinocembrin toward future preclinical and clinical applications in oncology.
Circulating tumor cells (CTCs) are frequently detected in patients with breast cancer, but key studies investigating their clinical significance in early-stage disease rely on less-sensitive methods for CTC detection. To evaluate the prevalence and prognostic implications of CTCs in patients undergoing NAC for early-stage breast cancer. This was a single-center prospective cohort study. Patients with early-stage breast cancer who were planned to receive NAC were enrolled. CTCs were measured before NAC and again at least 4 weeks following definitive surgery using the Epic Sciences platform. Clinical, pathological, and treatment data were abstracted from electronic medical records and summarized. A total of 40 patients comprised the analyzable study population. The median age at diagnosis was 53 years. Breast cancer subtypes included HER2+ (38%), hormone receptor-positive/HER2-negative (HR+/HER2-, 32%), and triple-negative breast cancer (TNBC, 25%). After a median follow-up of 39.8 months, only 5 patients (12%) had experienced disease recurrence. CTCs were detected in 82% of patients before treatment and 45% of patients after treatment (P = .001). All subgroups of patients had numerically lower rates of CTC prevalence post-treatment compared to pretreatment; subgroups in whom this difference was statistically significant included patients with TNBC (90% vs. 30%, P = .006), premenopausal patients (79% vs. 29%, P = .008), and patients who did not experience disease recurrence (80% vs. 43%, P = .001). CTCs are more prevalent both before and after NAC than had previously been reported. The clinical significance of their persistence warrants further investigation.
Given the known therapeutic properties of gold compounds such as auranofin, this study aimed to evaluate the anticancer potential of a newly synthesized gold(III) Schiff base complex. We hypothesized that this complex could selectively induce apoptosis in cancer cells while minimizing inflammatory responses in normal cells. A gold(III) complex bearing a tetradentate Schiff base ligand was synthesized, and its cytotoxicity was assessed using MTT assay and sulforhodamine B staining. KYSE-30 esophageal cancer cells and NIH/3T3 normal fibroblasts were treated with the complex and compared to cisplatin. Gene expression analysis was performed to evaluate apoptotic and inflammatory genes. The gold(III) Schiff base complex significantly inhibited KYSE-30 cell proliferation more effectively than cisplatin after 48 hours. Unlike cisplatin, it did not induce cytotoxicity in NIH/3T3 cells. The complex elevated the BAK1/Bcl-xL ratio by 2.22-fold, suggesting activation of the intrinsic mitochondrial apoptotic pathway, which was not observed with cisplatin. It also downregulated the anti-apoptotic Bcl-xL gene (0.662-fold) and the resistance-associated AKT1 gene (0.0544-fold). Both the gold(III) Schiff base complex and cisplatin activated the extrinsic apoptotic pathway via Caspase-3. Importantly, neither compound induced TNF-α expression, indicating no inflammatory response in normal cells. These findings demonstrate that the gold(III) Schiff base complex selectively targets esophageal cancer cells through dual apoptotic pathways while sparing normal cells from cytotoxicity and inflammation. Its ability to suppress resistance-related genes further highlights its therapeutic promise. The gold(III) Schiff base complex represents a compelling alternative to cisplatin, offering enhanced anticancer efficacy, reduced toxicity to normal cells, and minimal inflammatory activation. Further investigation into its clinical potential is warranted.
Estrogen receptor-positive (ER+) breast cancer is the most prevalent breast cancer subtype, and doxorubicin is a key systemic therapeutic drug. However, its use is limited by toxicity and mechanisms of drug resistance. Steryl glucosides are bioactive glycolipids with potential anticancer and immunomodulatory properties, but their role as chemotherapy-sensitizing agents remains undefined. Here, we investigated whether a soybean-derived steryl glucoside preparation (SG) enhances doxorubicin activity primarily in the MCF-7 ER+ breast cancer model. SG co-treatment increased doxorubicin-associated cytotoxicity and reduced cell viability of MCF-7. Dose-response matrix analysis and exploratory Bliss independence modeling identified concentration-dependent regions of greater-than-expected combined activity, supporting pharmacological potentiation but not definitive synergy. SG co-treatment also increased γ-H2AX-positive nuclei, consistent with enhanced doxorubicin-associated DNA damage signaling. Fluorescence-based extraction analysis showed increased doxorubicin-associated intracellular fluorescence in SG co-treated cells, while ABCB1 qRT-PCR revealed concentration-dependent transcriptional changes. These findings suggest altered intracellular drug exposure or transport-associated responses, although functional efflux activity was not directly assessed. In an ovariectomized, estradiol-supplemented MCF-7 xenograft model, the SG-doxorubicin group showed the lowest mean tumor-growth trajectory, reduced cumulative tumor burden, lower terminal tumor weight, reduced Ki-67 staining, and increased tumor necrosis. However, the longitudinal tumor-volume analysis did not establish unequivocal superiority over doxorubicin monotherapy. Exploratory T47D data indicated weaker responsiveness, suggesting that the effect may be model-dependent. This study provides proof-of-concept evidence that SG can enhance doxorubicin-associated antitumor activity mainly in the MCF-7 model. Further studies are required to define functional transport mechanisms, model generalizability, toxicity, and formal dose-sparing potential. This study provides proof-of-concept evidence that a soybean-derived steryl glucoside preparation can enhance doxorubicin-associated cytotoxicity, DNA damage signaling, and antitumor activity primarily in the MCF-7 estrogen receptor-positive breast cancer model. The findings support further investigation of SG as a candidate chemotherapy-sensitizing adjuvant, while highlighting the need for functional transport assays, broader model validation, comprehensive toxicity assessment, and formal dose-sparing studies before translational conclusions can be drawn.
Cancer Waiting Times (CWT) targets are a central instrument of cancer policy in England, yet conventional performance indicators often obscure changes in service throughput. The COVID-19 pandemic exposed limitations in existing monitoring approaches, particularly for assessing disruption and recovery across cancer pathways. A novel case throughput metric (CTM) was developed by extracting National Health Service (NHS) England CWT data spanning 2017-23, covering 334 trusts and an average of 300 000 patients annually. The metric defines service throughput as the ratio of patient volumes meeting waiting time standards during defined periods of investigation normalized to a pre-pandemic baseline, enabling meaningful comparison across trusts while accounting for variation in trust sizes and pre-existing differences in service provision. The metric revealed substantial heterogeneity in both disruption and recovery across cancer pathways, with diagnostic and referral routes experiencing greater and more persistent throughput loss than treatment pathways. Recovery trajectories also varied markedly between regions, with exploratory analyses suggesting associations with sociodemographic factors. The CTM provides a policy-relevant complement to existing CWT indicators by making changes in service throughput explicit. It offers a practical tool for monitoring cancer system resilience and informing recovery planning during and beyond major system shocks.
This novel biology-guided radiotherapy system (BgRT), the RefleXion X1 SCINTIX™ system, uses annihilation photons produced from a PET-avid tumor to plan and then subsequently guide the delivery of beamlets of radiation to the tumor, tracking the dose delivered in real time. The current BgRT system is cleared by the U.S. Food and Drug Administration (FDA) to treat tumors in the lung or bone characterized by periodic or non-periodic motion, respectively. In this work, we assessed the robustness and adaptability of the dose tracking capability under tumor motion perturbation. We designed a phantom study based on a lung case planned under periodic tracking for four-pass (4-Pass) BgRT and then introduced transient translational shifts to the phantom motion continuously under treatment. By comparing the dose delivered under a normal periodic sinusoidal tumor motion to the dose delivered under a perturbed sinusoidal delivery, with a simple perturbation situation characterized by a perturbation introduced at the end of the second pass of the 4-Pass delivery and a more complex situation with perturbation introduced at each of the four passes of the 4-Pass delivery, we assessed the robustness and adaptability of the RefleXion X1 SCINTIX™ system in delivering the correct dose under such circumstances.
Cardiovascular disease (CVD) is the leading cause of non-cancer mortality in prostate cancer (PCa) patients. The management of CVD, including hypertension, holds equal significance to cancer treatment. However, the optimal antihypertensive agent for blood pressure management in PCa patients receiving abiraterone acetate (AA) is still unclear. This study aims to investigate the association between various antihypertensive regimens and survival outcomes in PCa patients treated with AA. We performed a post-hoc observational analysis using data from COU-AA-301 and COU-AA-302. Radiographic progression-free survival (rPFS), overall survival (OS) and prostate cancer-specific survival (PCSS) were evaluated using the Kaplan-Meier method. Cox proportional hazards models were used to obtain hazard ratios (HRs) and associated 95% confidence intervals (CIs). Among the AA groups of COU-AA-301 and COU-AA-302, angiotensin converting enzyme inhibitors/angiotensin receptor blockers (ACEI/ARB) monotherapy was associated with longer rPFS (HR 0.82, 95% CI 0.59-1.13; HR 0.71, 95% CI 0.53-0.95), OS (HR 0.66, 95% CI 0.41-1.06; HR 0.70, 95% CI 0.53-0.92) and PCSS (HR 0.72, 95% CI 0.44-1.19; HR 0.67, 95% CI 0.49-0.92). Multiple-class antihypertensive treatment regimens including ACEI/ARBs were associated with longer rPFS (HR 0.74, 95% CI 0.59-0.92; HR 0.71, 95% CI 0.54-0.94), OS (HR 0.76, 95% CI 0.57-1.01; HR 0.72, 95% CI 0.55-0.94) and PCSS (HR 0.71, 95% CI 0.51-0.99; HR 0.62, 95% CI 0.46-0.83). Multivariable analysis indicated that ACEI/ARBs were associated with improved rPFS (HR 0.72, 95% CI 0.60-0.86; HR 0.75, 95% CI 0.60-0.94), OS (HR 0.71, 95% CI 0.56-0.91; HR 0.70, 95% CI 0.56-0.88) and PCSS (HR 0.73, 95% CI 0.55-0.96; HR 0.64, 95% CI 0.50-0.82). In this post-hoc analysis, concomitant use of ACEI/ARBs was associated with longer rPFS, OS and PCSS in PCa patients treated with AA. The potential role of ACEI/ARB-containing antihypertensive regimens in these patients warrants further investigation. ClinicalTrials.gov Identifier: NCT00638690, NCT00887198.
The worldwide rise in antimicrobial resistance, along with the ongoing prevalence of cancer, underscores the pressing need for novel, safe, and multifunctional therapeutic candidates. Medicinal plants continue to serve as a valuable source of chemically diverse bioactive molecules that modulate multiple biological targets. In this investigation, the preliminary screening of the antibacterial and anticancer activities of an ethanolic extract of Alhagi maurorum (A. maurorum) was comprehensively evaluated using integrated chemical characterization, in vitro bioassays, and in silico approaches. A liquid chromatography-mass spectrometry (LC-MS) analysis demonstrated a rich phytochemical profile including glucosinolates, phenolic acids, gallotannins, fatty acids, alkaloids, carotenoid derivatives, and 2-hexyldecanoic acid-associated constituents. Antibacterial efficacy was assessed by disk diffusion and minimum inhibitory concentration (MIC) testing against Escherichia coli (E. coli) and Bacillus cereus (B. cereus), with the extract producing inhibition zones similar to those observed with streptomycin. Anticancer effects were determined using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assays with MCF-7 breast carcinoma cells and Hs27 normal fibroblasts over 24, 48, and 72 h, revealing a time-dependent, selective decrease in malignant cell viability with relatively limited toxicity towards normal cells. Induction of apoptosis was further verified by propidium iodide (PI) staining. A molecular docking analysis highlighted 2-hexyldecanoic acid as the principal active compound, with a strong binding affinity for critical bacterial targets (GyrA, GyrB, and RpoB). In silico toxicity and ADME (absorption, distribution, metabolism, and excretion) assessments indicated favorable drug-like properties, good gastrointestinal uptake, and acceptable safety profiles. Altogether, these results provide combined experimental and computational support for A. maurorum as a promising source of dual-purpose antibacterial and anticancer agents and lay a mechanistic foundation for subsequent preclinical studies.
Cancer cell metabolism represents a critical therapeutic target, particularly under conditions of metabolic stress induced by glycolysis inhibition. Nitroglycerin (glyceryl trinitrate, GTN), a nitric oxide donor, and 2-deoxy-D-glucose (2-DG), a glycolysis inhibitor, have individually demonstrated anticancer potential through modulation of cellular metabolism and redox balance. In this study, we investigated the cytotoxic and combined effects of GTN and caffeine under 2-DG-induced metabolic stress in human cancer cell lines (HeLa, A549, HT29, and MRC-5). Cell viability was assessed using the sulforhodamine B assay after 24 and 48 h treatments, while drug interactions were evaluated using the Chou-Talalay method and combination index (CI) values. 2-DG alone reduced cell viability in a concentration- and time-dependent manner, with IC50 values ranging from 2.01 to 7.05 mM depending on the cell line and exposure period. The combined treatment further enhanced cytotoxicity, particularly in A549 cells, where viability decreased to approximately 63% after 48 h and the calculated IC50 value for GTN in the presence of caffeine reached 0.143 μM. CI analysis demonstrated synergistic interactions in HeLa and A549 cells (CI < 1), whereas HT29 cells predominantly exhibited antagonistic responses (CI > 1). However, strong synergistic effects were also observed in MRC-5 fibroblasts, indicating limited selectivity toward cancer cells. Molecular docking suggested favorable in silico binding of GTN to aldehyde dehydrogenase 2 (ALDH2) and caffeine to the adenosine A2A receptor. Nevertheless, these findings should be considered exploratory and hypothesis-generating because target expression, enzymatic activity, and pathway activation were not experimentally validated. Overall, the results suggest that GTN enhances caffeine-induced cytotoxicity under metabolically stressed conditions through combined metabolic and redox perturbation, although the magnitude of the response depends on cellular context and warrants further mechanistic investigation.
To assess adherence to the recommended 12-month virological follow-up among women aged 30-65 years living in Brittany (France) who had a positive high-risk HPV test with normal cytology (hrHPV+ / Cytology-) within the French national program of organized cervical cancer screening, and to identify factors associated with follow-up compliance. We conducted a retrospective observational study using data from the Regional Cancer Screening Coordination Center of Brittany collected between July 2020 and March 2023. Women with hrHPV+/Cytology- screening result were included. The primary outcome was completion of a repeat hrHPV test between 6 and 12 months after the initial result, in accordance with French Health Authority (HAS) recommendations. Secondary outcomes included analyze of women characteristics according to age, geographical area, initial sampler taker, and declaration of a general practitioner. Among 762 113 eligible women, 12 985 (1.7%) had a hrHPV+/Cytology- result. At 1 year, 28.5% had no documented follow-up, and only 21.3% underwent follow-up in accordance with French recommendations, corresponding to 29.8% of women who were followed. Among women with appropriate follow-up, 53% remained hrHPV+, and 81.4% of these were referred for colposcopy. Loss of follow-up was more common among young women, those living in non-urban areas. Conversely, recommended follow-up was more frequent in areas with higher health care availability and among women managed by gynecologists. Implementation of guideline-recommended follow-up after hrHPV+/Cytology- screening remains suboptimal, despite well-documented increased risks of high grade precancerous lesions and invasive cancer in this population. Strategies to improve adherence include personalized reminders, use of self-sampling, personalized invitations to screening, harmonization of professional practices, and optimization of colposcopy referral pathways.
Background/Objectives: Pancreatic ductal adenocarcinoma (PDAC) is a devastating disease with limited therapeutic options, a high mortality rate, and poor overall survival, necessitating the development of new therapeutic and diagnostic strategies. This study investigated the potential of plasma-derived small extracellular vesicles (sEVs) as a source of molecular biomarkers associated with the treatment response. Methods: Plasma samples were obtained from patients with locally advanced and borderline resectable PDAC at baseline and following neoadjuvant chemotherapy, either FOLFIRINOX (5-FU [fluorouracil], leucovorin, oxaliplatin, and irinotecan) or GEM-ABRAX ( gemcitabine plus nab-paclitaxel), followed by stereotactic body radiation therapy (SBRT). sEVs were isolated from plasma at baseline, after neoadjuvant chemotherapy, and following SBRT, and were characterized by nanoparticle tracking analysis (NTA), transmission electron microscopy (TEM), nano-flow cytometry, and real-time PCR (RT-PCR). Results: The isolated sEVs exhibited an average size of <200 nm, expressed canonical exosome markers (CD63 and CD9), and exhibited pancreatic cancer (PanC)-associated markers, including cholecystokinin A receptor (CCK-AR) and carbohydrate antigen 19-9 (CA19-9). The sEV cargo included several PanC-associated microRNAs (miRNAs). Notably, the expression profiles of these miRNAs demonstrated interpatient variability, though a subset of miRNAs showed statistically significant changes following treatment. Conclusions: These findings support the feasibility of sEV isolation and molecular profiling from patient plasma and warrant further investigation as a potential source of biomarkers in pancreatic cancer.
High body-mass index (BMI) defined in the Global Burden of Disease Study as BMI above the theoretical minimum risk exposure level, is an established modifiable risk factor for ovarian cancer, particularly among older women. However, a comprehensive assessment of the global disease burden attributable to high BMI, including its spatiotemporal evolution and underlying drivers, remains lacking, particularly for older women. Using data from the Global Burden of Disease Study 2021, we analyzed disability-adjusted life years (DALYs) and deaths from ovarian cancer attributable to high BMI among women aged ≥55 years from 1990 to 2021. We examined temporal trends, geographic disparities by Socio-Demographic Index (SDI), region, and nation, and performed decomposition analyses to identify contributions from population growth, aging, and epidemiological changes. Globally, the attributable burden increased from 1990 to 2021, with population growth as the main driver. of rising absolute DALYs (86.72) and deaths (85.17). Marked socioeconomic disparities were observed. While high-SDI regions had the highest age-standardized rates in 2021, they showed declining trends., whereas low-middle and low-SDI regions experienced the most rapid increases. Regionally, the fastest increases occurred in South Asia, Southeast Asia, and East Asia, while nationally the largest rises were observed in Timor-Leste, Viet Nam, and Bangladesh. In these settings, epidemiological changes were the dominant contributor to increasing burden. The global burden of ovarian cancer due to high BMI is rising and unequally distributed across SDI regions. While population growth drives the overall increase, escalating obesity prevalence is the key driver in rapidly developing regions. Targeted obesity prevention, improved early detection, and strengthened health-care systems should be prioritized, particularly in high-growth regions. Future studies should improve data quality in low-resource settings and explore cost-effective interventions.
Background/Objectives: To evaluate the prognostic significance of automated, volumetric body composition analysis (BCA) derived from pretreatment thoracic computed tomography (CT) scans in patients with head and neck cancer (HNC). Methods: We retrospectively assessed 160 patients (median age: 63 years; 26.9% women) undergoing primary treatment. BCA quantified various tissue volumes, including bone (B), skeletal muscle (SM), and subcutaneous adipose tissue (SAT). Optimal sex-specific cutoffs for BCA metrics were established via maximally selected log-rank tests. Internal validation of BCA cutoffs was conducted via bootstrap resampling. Kaplan-Meier survival analysis and Cox proportional hazards modeling were used to investigate progression-free survival (PFS). Results: The median PFS for all patients was 51.7 months (95% confidence interval (CI): 31.4-68.8). Among the continuous BCA parameters, only SM/B was significant across the total cohort (hazard ratio (HR): 0.23; 95%CI: 0.12-0.46; p < 0.0001, males (p = 0.0009), females (p = 0.004)). Internal validation of gender-specific cutoffs demonstrated strong-to-intermediate stability for SM/B across both sexes and for SAT/B in males. In contrast, SAT/B exhibited only weak stability among female participants. In univariate PFS analysis, dichotomized SM/B, SAT/B, Union for International Cancer Control (UICC) stage, Eastern Cooperative Oncology Group (ECOG) status, higher body mass index (BMI), normal albumin, and Charlson Comorbidity Index were identified as significant predictors of PFS. Multivariable analysis identified high SM/B (HR: 0.53; 95% CI: 0.3-0.93; p = 0.026) and high SAT/B (HR: 0.58; 95% CI: 0.35-0.95; p = 0.029) as independent prognostic factors, alongside lower UICC stage (p = 0.045) and lower Charlson Comorbidity Index (p = 0.038). Patients with high SM/B and SAT/B ratios had the longest median PFS (65.9 months, 95%CI: 51.7-.), compared to 36.4 months (95%CI: 19.4-.) for high SM/B or SAT/B and 12.6 months (95%CI: 4.2-25.1) for low SM/B and SAT/B (p < 0.0001). Conclusions: Although the BCA parameters SM/B and, to a lesser extent, SAT/B appear to be promising biomarkers, external validation and investigation within well-defined patient subgroups are warranted to establish their generalizability in clinical practice.
The IGF-1Eb isoform has been proposed as a stress-responsive variant of IGF-1, yet its significance in cancer remains unclear. This investigation aims to clarify its role across breast, prostate and liver cancer cell lines and determine whether its loss or supplementation is associated with alterations in cellular behavior and stress adaptation. Eb expression was modulated through targeted silencing and exogenous peptide addition. Cellular responses were evaluated under normal conditions and UV stress using proliferation, viability and rescue experiments, wound healing, immunofluorescence for Eb-knockdown confirmation, qRT-PCR, Annexin V/PI apoptosis, and PI cell-cycle evaluation. Across six cancer cell lines, Eb peptide given before UV stress was associated with partial protective effects, whereas post-UV treatment was associated with improved recovery and partial restoration of proliferative capacity. The rescue effect differed by cell type, with prostate and breast cells showing the strongest responses and liver-derived lines displaying more modest improvements. Eb knockdown revealed clear cell-type-specific dependencies. PC3 cells showed markedly reduced proliferation (p < 0.01) and sharply decreased post-UV viability (p < 0.0001). HepG2 cells maintained higher growth without UV but displayed reduced recovery following UV exposure, whereas MDA-MB-231 exhibited elevated apoptosis (p < 0.05) with limited additional UV sensitivity. Eb peptide may exert a dual, timing-dependent role, supporting protection before UV damage and facilitating recovery-associated responses afterward, with its impact differing across cell lines.
Background: The current guidelines recommend that women at elevated risk for breast cancer (BC), defined as lifetime BC risk ≥ 20%, undergo annual screening with breast magnetic resonance imaging (MRI) and mammogram. However, limited evidence exists in the literature to guide the optimal timing of the MRI relative to the mammogram. Our study evaluated women undergoing high-risk BC screenings to determine the impact of timing for supplemental MRI on BC detection. Methods: Patients who completed high-risk screening MRI at a single institution from January 2019 through June 2022 were included. Baseline characteristics and clinical outcomes were collected through retrospective chart review. MRI exams were divided into two groups based on timing of MRI: concurrent (<90 days from mammogram) and staggered (≥90 days from mammogram). Results: Of 1115 patients initially identified, 770 met inclusion criteria, with a total of 3707 screening exams performed (2073 mammograms and 1634 MRIs). The final analysis included 1355 MRI exams for 712 patients, where a prior mammogram and MRI were available. Of the MRIs included, 784 (57.9%) were concurrent and 571 (42.1%) were staggered. Additional imaging was performed for 12.5% (98/784) of concurrent MRIs and 9.6% (55/571) of staggered MRIs. Biopsy rates were 9.8% (77/784) for concurrent and 7.0% (40/571) for staggered MRIs. In this high-risk population, there were surprisingly low BC detection rates, with a BC incremental detection rate of 0.5% in both the concurrent and staggered groups (p = 1.0), with the median size of detected invasive BCs equaling 5 mm in the concurrent group and 4 mm in the staggered group (p = 0.72). Conclusions: When comparing concurrent and staggered MRI regimens, there were no significant differences in incremental cancer detection rate, tumor size, rates of additional imaging, or negative biopsies. Further investigation with prospective analysis is needed to validate these findings.
H. Xu, Y.-L. Hao, L.-N. Xu, L. Chen and F.-W. Xu, "Tanshinone sensitized the antitumor effects of irradiation on laryngeal cancer via JNK pathway," Cancer Medicine 7, no. 10 (2018): 5187-5193, https://doi.org/10.1002/cam4.1781. The above article, published online on 21 September 2018 in Wiley Online Library (wileyonlinelibrary.com), has been retracted by agreement between the journal Editor-in-Chief, Stephen Tait; and John Wiley & Sons Ltd. The retraction has been agreed following concerns raised by a third party. An investigation identified several instances of image duplication. Specifically, in Figure 4A, parts of the PBS panel were to be found duplicated in another article published later by a different author group. In addition, some western blot bands presented in Figure 5A were found to be duplicated in five other articles, three of which were published prior to this article. In one instance, the duplicated bands were used to represent different proteins. The authors were contacted to comment on the concerns and provide supporting data, but no response was received. The editors therefore consider the results and conclusions of this article to be compromised. The authors did not respond to our notice of retraction.