Körperliche Aktivität unterstützt die physische und psychosoziale Rehabilitation nach Krebs. Die Aktivierung von Patienten mit Kopf-Hals-Tumoren gelingt bislang nur schwer. In der Studie wurde der Zusammenhang zwischen der subjektiv eingeschätzten Wichtigkeit, körperlich aktiver zu werden, und dem aktuellen Aktivitätsniveau sowie soziodemografischen und klinischen Faktoren untersucht. In einer prospektiven Querschnittstudie wurden ambulante Patienten mit Kopf-Hals-Tumoren (≥ 18 Jahre) eingeschlossen. Erfasst wurden soziodemografische Daten, die Symptomschwere (u. a. Fatigue, Schmerz) mittels visueller Analogskalen (VAS, 0–10), Dyspnoe (mMRC-Skala [Modified British Medical Research Council]) sowie die Wichtigkeit der Aktivitätssteigerung (VAS 0–10). Die körperliche Aktivität wurde per 7‑tägiger Akzelerometrie erfasst (inkludiert: ≥ 10 h/Tag an ≥ 4 Tagen). Die Auswertung erfolgte uni-, bi- und multivariat. Insgesamt wurden 51 Patienten (82

Altered immune states at the time of cancer diagnosis remain insufficiently characterized. Although circulating immune biomarkers offer a promising, non-invasive way of analysing systemic tumour-host interactions, their potential remains poorly defined. Here, we present an integrated multi-omics analysis of peripheral blood mononuclear cells from treatment-naïve cancer patients, minimizing confounding by therapy-induced immune changes, combining immune phenotyping (flow cytometry, FC), multiplex cytokine profiling, and single-cell RNA sequencing (scRNA-seq). Compared with healthy donors, patients exhibited widespread immune dysregulation, including expansion of FOXP3+ regulatory T cells, depletion of CD16+CD11b+ monocytes and CD56^dim^ Natural killer (NK) cells, and elevated plasma IL-6 and IL-4 levels. scRNA-seq identified cancer-associated immune signatures, notably consistent upregulation of THBS1 and CH25H, indicative of systemic imprinting by tumour-derived cues. We further developed machine learning-guided models integrating single-cell multi-omics data (sc-FC and scRNA-seq) to characterize cancer-associated immune patterning and cancer type-related signal structure, while providing biologically interpretable feature attribution across modalities. The models achieved robust classification performance within the cohort and revealed modality-spanning features linked to immune state alterations. Together, these findings establish a framework for immune-based, multi-omics profiling of peripheral blood and provide a resource for discovering circulating cancer-associated immune signatures. This supports future development of immune-based diagnostics and disease monitoring approaches.

BackgroundPhysical activity is associated with improved clinical outcomes across the cancer continuum. However, adherence to recommended activity levels among cancer survivors remains low. Digital health technologies such as smartwatches may support patients and survivors in achieving sufficient daily activity through continuous monitoring and feedback. Patients with head and neck cancer (HNC) often experience persistent functional limitations, yet evidence regarding the utility of wearable-based monitoring in this population remains limited. Therefore, the MOVE-1 study evaluated the feasibility of smartwatch-based monitoring in HNC survivors.MethodsMOVE-1 was a cross-sectional study investigating smartwatch use in HNC survivors. Participants were instructed to wear a smartwatch continuously for seven days (24 hours per day, 168 hours in total). Heart rate and step count were recorded and visible to participants via the smartwatch display. Feasibility parameters evaluated included recruitment rate, adherence assessed by heart rate data availability, frequency of display use (4-point Likert scale) and usability (System Usability Scale, SUS). Demographic and clinical characteristics were collected. Screened individuals who declined participation were analyzed separately regarding age, sex and reasons for refusal.ResultsThe recruitment rate was 50%. There were no significant differences between participants and non-participants regarding sex or age. Common reasons for non-participation included lack of interest, sufficient self-reported physical activity, time constraints and low affinity for technology. Thirty-five HNC survivors were enrolled (median age 63 ± 6 years). Median smartwatch wearing time was 111 hours, out of a total of 168 hours (67%). Display functions were used “often” or “very often” by 60% of participants. Perceived usability was rated as good, with a mean SUS score of 74 (percentile rank 69, grade B). Reported dissatisfaction mainly concerned wristband handling, while three participants experienced difficulties operating the smartwatch. The median daily step count was 7,298 steps.ConclusionModerate-to-good adherence and good usability suggest that smartwatch-based monitoring of physical activity and vital parameters is feasible in HNC survivors, although alternative wristband designs may improve usability. The observed step counts indicate that included individuals were more physically active than average. These findings support future interventional studies using smartwatches to promote physical activity in this patient cohort.

MicroRNAs (miRNAs) play pivotal roles in glioblastoma (GBM) progression and therapy resistance. Among them, miR-25-3p has emerged as a key oncogenic miRNA that promotes tumor growth, invasiveness, and resistance to temozolomide (TMZ). In this study, we profiled miRNA expression in primary GBM specimens (n = 50) stratified by MGMT methylation and TP53 mutation status and assessed the functional impact of miR-25-3p inhibition in seven patient-derived GBM cell lines. Quantitative PCR analysis revealed upregulation of miR-135b in MGMT-methylated tumors and miR-10b in TP53-mutant cases. Both miR-25-3p and miR-10b were significantly elevated in 3D spheroid cultures compared to 2D monolayers. Notably, both miRNAs were secreted via tumor-derived extracellular vesicles, implicating a role in cell-cell communication. Inhibition of miR-25-3p in GBM cell lines consistently suppressed β-catenin and re-induced FBXW7 expression across all cases, correlating with inhibitor uptake. In four of seven cell lines, miR-25-3p inhibition enhanced TMZ sensitivity and reduced invasiveness, although the anti-invasive effect was not further potentiated by the addition of TMZ. In addition, RNA-Seq and methylome analyses revealed genetic and epigenetic reprograming toward a less aggressive, less invasive phenotype with reduced stemness potential. These findings highlight the interplay between tumor microenvironment and molecular heterogeneity in shaping miRNA dynamics in GBM. Collectively, our results identify miR-25-3p as a promising dual-action therapeutic target to mitigating both invasion and chemoresistance in GBM, warranting further translational investigation. miRNA-mediated regulation of invasion, protein synthesis, and drug sensitivity in glioblastoma. Schematic overview of miRNA-mediated regulation of glioblastoma cell behavior. miRNAs modulate mRNA targets and protein synthesis, influencing β-catenin signaling, invasion capacity, and temozolomide sensitivity through FBXW7-associated pathways, ultimately affecting apoptosis.

Glioblastoma (GBM) is an aggressive, World Health Organization grade 4 brain tumor with a poor prognosis, largely due to its complex, treatment-resistant microenvironment. To better model this environment for preclinical testing, we developed a three-dimensional (3D) biomimetic bioprinting platform using patient-derived GBM cells. Two hydrogels, alginate/gelatin (AlgGel; 1.5%/7.5%) and gelatin methacryloyl (10%), were evaluated for biocompatibility. GBM cells (GBM06, GBM14, and GBM15), transduced with iRFP-680 for viability tracking, were embedded in the hydrogels and printed. Tumor growth and viability were monitored for 28 days using fluorescence microscopy, complemented by electron microscopy (EM) for structural analysis. Drug response testing included temozolomide (TMZ; 10 mu M) and the cyclin-dependent kinases 4/6 inhibitor abemaciclib (1 mu M). Cell viability and extracellular vesicle (EV) release were quantified. Efficacy was further assessed in a co-culture with astrocytes. The AlgGel hydrogel supported superior long-term viability and growth. EM analysis of AlgGel scaffolds revealed preserved cellular architecture and adherence to the bioprinted extracellular matrix. Drug response assays confirmed findings previously observed in 2D and 3D cultures. Two cycles of abemaciclib reduced GBM cell viability in AlgGel scaffolds, accompanied by a significant decrease in EV secretion. TMZ, in contrast, did not significantly affect cell viability. The reduction in viability remained pronounced in co-culture with astrocytes, without compromising astrocyte viability. In this study, we present a 3D biomimetic bioprinting model that successfully mimics key aspects of the GBM microenvironment. This model demonstrates strong potential as a preclinical drug screening tool, enabling improved mechanistic insight into cell-matrix interactions that govern nutrient/metabolite diffusion and therapeutic responses

BACKGROUND:Physical activity (PA) supports physical and psychosocial rehabilitation after cancer. However, motivating patients with head and neck cancer (HNC) to become more active remains challenging. This study investigated the association of the self-rated importance of increasing PA with current activity levels as well as sociodemographic and clinical factors. METHODS:In this prospective cross-sectional study, outpatient HNC patients (≥ 18 years) were included. Sociodemographic data, symptom burden (e.g., fatigue, pain) using visual analog scales (VAS; 0-10), dyspnea (modified Medical Research Council scale, mMRC), and the perceived importance of becoming more active (VAS 0-10) were recorded. Current PA was assessed via 7‑day accelerometry (valid if ≥ 10 h/day on ≥ 4 days). Analyses were conducted using univariate, bivariate, and multivariate methods. RESULTS:A total of 51 patients (82% male; mean age 67 ± 19 years) were included; 39 provided valid accelerometry data. Increasing PA was rated as important or very important by 68% of participants. On average, participants were physically active for 179 ± 89 min per day. The perceived importance of becoming more active was higher among those living alone (p = 0.033) and tended to be higher in participants with greater dyspnea (p = 0.056) or more severe pain (p = 0.068). CONCLUSION:The average activity level in this sample was low, with around 3 h of movement per day. For the majority of participants, increasing activity was important. Further research is needed to clarify why higher symptom burden and social factors are associated with a greater perceived importance of becoming more active.

BackgroundMyeloproliferative neoplasms (MPNs) comprise a heterogeneous group of clonal hematopoietic stem cell disorders with distinct molecular pathogenesis and treatment strategies. Across all MPN subtypes, patients experience a substantial and persistent symptom burden that impairs health-related quality of life (HrQoL). Because MPNs are typically chronic diseases, lifelong symptom management and supportive therapies play a central role in patient care. Supportive care primarily targets disease- and treatment-related symptoms rather than the underlying malignancy itself. However, it remains unclear whether symptom profiles are comparable across MPN subtypes independent of disease phenotype. Therefore, this analysis aimed to identify symptom severity clusters (SSCs) in a cohort of patients with MPN.MethodsA multicenter cross-sectional survey was conducted. Patients with MPN aged ≥18 years completed questionnaires assessing sociodemographic and disease-specific variables (e.g., sex, age, diagnosis, and current therapies) as well as the severity of 14 symptoms (e.g., fatigue, musculoskeletal pain, and itching), rated on continuous scales ranging from 0 (absent) to 100 (worst imaginable). Hierarchical and K-means cluster analysis as well as multinomial logistic regression were used to identify SSCs and their associations with patient characteristics.ResultsThe sample comprised 644 patients (63% female; mean age 56.8 ± 13.4 years), including 187 patients with chronic myeloid leukemia, 174 with polycythemia vera, 154 with essential thrombocythemia, and 129 with myelofibrosis. Four SSCs were identified: very high, high, middle, and low symptom severity. Compared with the low SSC, membership in the very high SSC was associated with younger age (95% CI: −0.04 to 0.00) and lower educational level (95% CI: −1.17 to −0.04). Membership in the high SSC was associated with female sex (95% CI: 1.26 to 2.60), higher body mass index (95% CI: 0.00 to 0.11), and lower educational level (95% CI: −1.20 to −0.19). Membership in the very high, high, or middle SSCs, compared with the low SSC, was not associated with diagnostic group.ConclusionSymptom severity in patients with MPN appears to be comparable across disease subtypes. These findings support a shift toward symptom-focused, multimodal supportive care approaches (e.g., exercise and psychological support) in patients with MPN.

Introduction Overexpression of anti-apoptotic protein BCL-2 and hypermethylation are hallmarks of acute lymphoblastic leukemia (ALL) and can be pharmacologically addressed by venetoclax (VEN) and hypomethylating agents (HMA) such as azacytidine (AZA) or decitabine (DEC). Combined VEN and HMA application was recently successfully implemented into the clinical treatment regimen of acute myeloid leukemia but has so far not been investigated in ALL. Methods We therefore analyzed the anti-leukemic potential of VEN + HMA in four ALL cell lines and identified potential modes of synergy to overcome mono-drug-induced resistance using proliferation, metabolism, methylation and apoptotic protein expression assays. Single cell RNAseq of a VEN-treated PDX model was used to gain deeper insights into metabolic reprograming. Results All substances influenced proliferation and induced apoptosis in a subset of cell lines. Combined VEN and HMA application resulted in significantly reduced metabolic activity. In contrast, no synergistic effects were observed regarding the BCL-2 protein and methyltransferase expression or global methylation. Single cell RNAseq revealed that VEN interferes with both main energy supply routes, oxidative phosphorylation as well as glycolysis, to impede the cells’ metabolism and mitochondrial activity. The addition of HMA, especially DEC, increased anti-metabolic effects, leading to a strong reduction of respiration, ATP production and proton leakage. AZA-induced metabolic suppression and overall anti-leukemic activity alone and in combination with VEN was generally weaker compared to DEC. Conclusion Altogether, we herein demonstrate that combined VEN and HMA application acts synergistically and significantly reduces the leukemic burden in ALL cell lines via impairment of tumor cell metabolism and mitochondrial function.

[This corrects the article DOI: 10.3389/fonc.2026.1802050.].

Despite ongoing research, realistic in vitro models for acute lymphoblastic leukemia (ALL) that can mimic the complex pathology are still not available, highlighting the need for continuous animal-based investigation. As part of the 3R principles, constant refinement of animal experiments is mandatory. Therefore, reviewing the effectiveness of used analgesics is essential for animal model-specific refinement. Here we evaluate whether metamizole-previously used in our institute-or tramadol is more suitable as on-demand analgesia in mouse models of ALL. The murine orthotopic xenograft models were induced by intravenous injection of either the human precursor ALL cell lines RS4;11 or SEM into immune-deficient male and female NSG mice. Mice were weighed and checked daily for basic behavior and well-being, while detailed welfare parameters, such as burrowing behavior, nesting activity, perianal temperature, liquid intake, fecal corticosterone metabolites, mouse grimace scale and tumor cell proliferation were monitored weekly. Upon leukemic progression, when signs of pain or discomfort were observed, metamizole (3 mg/ml) or tramadol (1 mg/ml) was administered via drinking water for analgesic treatment, and detailed welfare parameters were assessed daily. Following the initiation of treatment, mice receiving either metamizole or tramadol continued to show a decline in body weight, liquid intake and other welfare parameters, suggesting that neither drug was sufficient to fully counteract the effects of late-stage ALL. Combining the data with the relative severity assessment algorithm revealed that metamizole treatment appeared less effective than tramadol in mitigating the detrimental effects of the disease. Therefore, the opioid tramadol should replace metamizole as the analgesic compound of choice for hematological xenograft models to improve animal welfare in future studies.

BACKGROUND:FDA-approved immune checkpoint inhibitors (ICIs) are the state-of-the-art treatment for mismatch-repair deficient tumors (dMMR). Their immunomodulatory effects in a preventive setting, are poorly studied. In this study, we used two ICIs against PD-L1 or LAG-3 in a preclinical mouse model of dMMR-driven carcinogenesis. METHODS:Msh2loxP/loxP; TgTg(Vil1-cre mice without clinical signs of tumor development (i.e. age <12 weeks) received repeated applications (n = 8, 28-day interval) of anti-PD-L1, anti-LAG-3 (2.5 mg/kg bw, i.p.) or isotype (anti-IgG1, 2.5 mg/kg bw, i.p.). Blood phenotyping, tumor microenvironment, and hematopoiesis, and presence of procoagulant extracellular vesicles (EV) were studied. RESULTS:Prophylactic ICI application significantly prolonged overall survival (OS) of Msh2loxP/loxP; TgTg(Vil1-cre mice (OS: anti-PD-L1: 54.4 wks and anti-LAG-3: 58.4 wks vs. ctrl 35.8 wks). Circulating exhausted and regulatory T cells were significantly lower in the ICI groups. Splenic exhaustion markers showed correlating results. Outgrowing tumors showed an inflammatory response-related gene signature. Accompanying immunofluorescence confirmed data and identified reduced numbers of tumor-infiltrating regulatory granulocytes in late-onset tumors. Alterations in bone marrow hematopoiesis accompanied this massive immune modulation, indicating successful prevention of myeloid-shifted hematopoiesis. Plasma coagulation of EVs was not significantly altered in the ICI groups. CONCLUSION:Preventive ICI prolongs overall survival of cancer-prone mice. The sustained immune modulation and normal bone marrow hematopoiesis may pre-sensitize late-onset dMMR tumors to a second round of immunotherapy. Hence, we highlight the importance of preventive strategies for germline MMR mutation carriers and recommend improved screening of patients eligible for prophylactic ICIs to improve long-term outcomes.

Given the selection of elderly patients with AML in first complete remission (CR1) the advantage of consolidation with allogeneic hematopoietic cell transplantation (HCT) over chemotherapy is still unclear. Newly diagnosed AML patients in CR1 aged 60-75 years were registered and a donor search initiated. After one consolidation cycle, patients with a matched donor were randomized to HCT with fludarabine/low-dose total body irradiation and cyclosporine/mycophenolate mofetil immunosuppression or conventional non-HCT. Primary outcome was restricted mean leukemia-free survival (RM-LFS) up to 5 years. Between 2010 and 2017, 245 patients (median age 67 years) were registered at CR1. After one consolidation, 26.9% of patients failed inclusion criteria. Of the 179 (73%) patients still on study, 75.4% had an HLA identical donor. Ten ineligible patients were excluded, and 125 randomized to HCT (N=83) or non-HCT (N=42). The primary outcome RM-LFS up to 5 years was 24.5 months (95% confidence interval [CI]: 18.9-30.1) in the HCT and 15.6 months (95% CI: 10.4-20.8) in the non-HCT arm (P=0.022) due to a decrease in cumulative relapse incidence from 91.1% (95% CI: 80.7-100.0) after non-HCT to 37.8% (95% CI: 27.2-48.4) after HCT (P<0.0001). The secondary endpoints RM-OS up to 5 years was 27.8 months (95% CI:22.3-33.2) in the HCT as compared to 28.6 months (95% CI: 22.2-35.0) in the non-HCT arm; non-relapse mortality at 5 years was 33.4% (95% CI: 23.0-43.9) with HCT and 0% without. In older patients with AML in CR1 5-year RM-LFS is better with HCT than with non-HCT consolidation treatment. The long-term RM-LFS benefit did not translate into a better RM-OS during the study period.

Imatinib (IMA) plus chemotherapy followed by allogeneic hematopoietic cell transplantation (HCT) is established treatment for Philadelphia chromosome positive (Ph+) acute lymphoblastic leukemia (ALL). We investigated the use of dasatinib (DASA) combined with intensive chemotherapy in ALL (18-55 years) first-line in a prospective, multicenter phase II trial by the GMALL study group. 140 mg DASA QD was used with a pediatric-based induction and consolidation chemotherapy according to GMALL 07/2003 protocol with recommended consecutive HCT. Nineteen of 20 planned patients were enrolled in 12 centers. The hematologic CR rate after induction was 79% with an overall MRD negativity rate of 62.5%. Six patients died during induction and two discontinued therapy. This regimen achieved deep molecular responses but was associated with a higher than expected early mortality (21%) and was stopped prematurely due to toxicities. The GMALL therefore adopted a combination of low intensity chemotherapy plus IMA as its current induction regimen.