BMC CancerPub Date : 2026-11-03DOI: 10.1186/s12885-026-16367-7
Wang Yingchen, Wu Yinhang, Zhuang Jing, Chu Jian, Wu Zheng, Liu Jiang, Han Shuwen
{"title":"NaB-induced inhibition of HDAC4 and TUG1: a novel strategy for reversing oxaliplatin resistance in colorectal cancer.","authors":"Wang Yingchen, Wu Yinhang, Zhuang Jing, Chu Jian, Wu Zheng, Liu Jiang, Han Shuwen","doi":"10.1186/s12885-026-16367-7","DOIUrl":"10.1186/s12885-026-16367-7","url":null,"abstract":"<p><strong>Background: </strong>Oxaliplatin (OXA) resistance affects the efficacy of colorectal cancer (CRC) treatment.</p><p><strong>Methods: </strong>Gene expression profiles of OXA-resistant and OXA-sensitive cells were compared to identify differentially expressed non-coding RNAs. A dual-luciferase assay was used to research the targeting relationship and binding region of TUG1 and miR-449a. SiRNA interference was used to construct cell models of OXA-resistant cells with low expression of TUG1 and OXA-sensitive cells with high expression of HDAC, as well as animal models based on these two types of cells. Then, cellular function was assessed. Histopathologic conditions were assessed by immunohistochemistry.</p><p><strong>Results: </strong>TUG1, miR-449a and Histone Deacetylase 4 (HDAC4) were all upregulated in OXA-resistant cells, and the increase of HDAC4 was accompanied by a decrease in acetylation level. TUG1 binds to miR-449a, and TUG1 was located in the cytoplasm of OXA-resistant cells. Downregulated expression of TUG1 could inhibit proliferation and induce apoptosis in OXA-resistant cells and reverse OXA resistance. Downregulated expression of HDAC4 could reduce the expression of TUG1, and inhibit proliferation and induce apoptosis of OXA-resistant cells. Treatment with 2 mmol/L sodium butyrate (NaB), a histone deacetylase inhibitor, markedly suppressed tumor cell growth through regulation of TUG1 compared with 0.01 mmol/L NaB. The OXA-resistant tumor-bearing mouse experiment further confirmed the inhibitory effect of NaB on tumor.</p><p><strong>Conclusion: </strong>High-dose NaB can inhibit the expression of HDAC4, and then reduce the expression of TUG1 through acetylation modification, thereby inhibiting the development of CRC and reversing OXA resistance in CRC.</p>","PeriodicalId":9131,"journal":{"name":"BMC Cancer","volume":"26 1","pages":""},"PeriodicalIF":4.1,"publicationDate":"2026-11-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13729348/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149317984","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
BMC CancerPub Date : 2026-11-03DOI: 10.1186/s12885-026-17298-z
Anna Thomsen, Nourane Trigui, Jonas Rast, Emily Newton-Tanzer, Mireia Gonzalez Donate, Markus Hoffmann, Susanne Wiegand
{"title":"Living longer or living better - priorities among head and neck cancer survivors.","authors":"Anna Thomsen, Nourane Trigui, Jonas Rast, Emily Newton-Tanzer, Mireia Gonzalez Donate, Markus Hoffmann, Susanne Wiegand","doi":"10.1186/s12885-026-17298-z","DOIUrl":"10.1186/s12885-026-17298-z","url":null,"abstract":"<p><strong>Background: </strong>Head and neck cancer and its treatment can profoundly affect physical function, psychosocial well-being, and overall quality of life (QoL). As survival rates improve, integrating patient-reported outcomes and individual treatment preferences into clinical decision-making has become increasingly important. This study aimed to assess the preferences of head and neck cancer (HNC) survivors regarding QoL versus life prolongation in order to better inform patient-centered treatment decisions.</p><p><strong>Methods: </strong>Adult head and neck cancer survivors completed validated questionnaires assessing health-related QoL (EORTC QLQ-C30), distress (Distress Thermometer), and preferences for QoL versus life prolongation (QQ questionnaire). Multivariable regression analyses were used to identify predictors of QoL and distress, while associations between patient characteristics and treatment preference were examined using group comparisons.</p><p><strong>Results: </strong>The study included 207 patients (70.5% male; mean age 66.2 years). The median global health status (QLQ-C30) was 66.6, and the median distress score was 3, indicating a relatively good overall QoL and a comparatively low level of psychological distress. In multivariable analysis, lower distress and employment (both p < 0.001) as well as surgical treatment and lower comorbidity (both p < 0.05) were independently associated with better QoL. Independent predictors of distress included sex, global health status, tumor stage, educational level, and treatment modality (all p < 0.05). Regarding preferences (n = 202), 53.0% of patients prioritized QoL, 21.8% favored life prolongation, and 25.2% reported no clear preference. Preference was significantly associated with age (p = 0.035), with older patients favoring QoL, and with tumor stage (p = 0.032), with the differences between options diminishing in advanced stages.</p><p><strong>Conclusion: </strong>QoL in head and neck cancer survivors is shaped by both clinical and psychosocial factors. Lower distress, employment, surgical treatment, and lower comorbidity were associated with better QoL, while most patients prioritized QoL over life prolongation, particularly at older age. These findings emphasize the need to align treatment strategies with patient values, placing QoL at the center of clinical decision-making.</p>","PeriodicalId":9131,"journal":{"name":"BMC Cancer","volume":"26 1","pages":""},"PeriodicalIF":4.1,"publicationDate":"2026-11-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13729282/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149317981","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
BMC CancerPub Date : 2026-11-02DOI: 10.1186/s12885-026-17190-w
Nina Schraps, Muriel Torzewski, Clara von Bargen, Fiete Gehrisch, Anne Menz, Florian Lutz, Viktoria Chirico, Florian Viehweger, David Dum, Ria Schlichter, Andrea Hinsch, Christoph Fraune, Christian Bernreuther, Seyma Büyücek, Martina Kluth, Claudia Hube-Magg, Georgia Makrypidi-Fraune, Katharina Möller, Andreas M Luebke, Patrick Lebok, Guido Sauter, Maximilian Lennartz, Till Clauditz, Andreas H Marx, Thilo Hackert, Ronald Simon, Eike Burandt, Natalia Gorbokon, Maria Christina Tsourlakis, Sarah Minner, Till Krech, Morton Freytag, Viktor Reiswich, Stefan Steurer
{"title":"Expression of nestin in cancer: a tissue microarray study involving 13,318 cancers from 148 tumor entities.","authors":"Nina Schraps, Muriel Torzewski, Clara von Bargen, Fiete Gehrisch, Anne Menz, Florian Lutz, Viktoria Chirico, Florian Viehweger, David Dum, Ria Schlichter, Andrea Hinsch, Christoph Fraune, Christian Bernreuther, Seyma Büyücek, Martina Kluth, Claudia Hube-Magg, Georgia Makrypidi-Fraune, Katharina Möller, Andreas M Luebke, Patrick Lebok, Guido Sauter, Maximilian Lennartz, Till Clauditz, Andreas H Marx, Thilo Hackert, Ronald Simon, Eike Burandt, Natalia Gorbokon, Maria Christina Tsourlakis, Sarah Minner, Till Krech, Morton Freytag, Viktor Reiswich, Stefan Steurer","doi":"10.1186/s12885-026-17190-w","DOIUrl":"10.1186/s12885-026-17190-w","url":null,"abstract":"<p><strong>Background: </strong>Nestin (neuroepithelial stem cell protein) is a class VI intermediate filament protein which is transiently expressed in subsets of precursor cells of various tissues during development. Nestin expression can be reinduced in the adult during pathological situations.</p><p><strong>Methods: </strong>To better comprehend the prevalence of nestin in different cancer types, nestin was analyzed by immunohistochemistry on tissue microarrays (TMAs) containing 17,285 samples from 148 different tumor types. Our antibody was validated using a second independent antibody on 76 different normal tissues, ensuring a broad range of proteins to be tested for cross-reactivity.</p><p><strong>Results: </strong>Of 13,318 analyzable tumors, nestin staining was absent in 11,677 (87.7%), weak in 961 (7.2%), moderate in 360 (2.7%), and strong in 320 (2.4%) cases. Of 148 tumor categories, 119 showed nestin staining in at least one case, and 57 included at least one sample with strong positivity. Nestin positivity was most seen in tumors of the salivary glands (up to 100%), gastrointestinal stromal tumors (GIST) (93.8%), tumors of the peripheral nerves (up to 93.8%) and malignant melanomas (81.8%). High nestin expression was linked to high grade (p < 0.0001), estrogen (p = 0.0054), and progesterone receptor negativity (p = 0.0051), as well as a triple negative phenotype (p = 0.0028) in invasive breast cancer NST, in papillary as well as poor ISUP (p=0.0149), Fuhrman (p=0.0006) and Thoenes grades (p=0.0099) in clear cell renal cell carcinoma, invasive tumor growth in urothelial carcinoma of the urinary bladder (pTa vs. pT2-4; p < 0.0001), and advanced pT stage (p = 0.0477) in serous carcinoma of the ovary.</p><p><strong>Conclusions: </strong>The data from this study provide an overview of nestin expression in human cancer and demonstrate that increased nestin levels can occur in many different tumor entities. Significant associations with unfavorable tumor characteristics in multiple entities argue for a role of nestin in driving cancer aggressiveness, which may further support the concept of exploring nestin as a drug target.</p>","PeriodicalId":9131,"journal":{"name":"BMC Cancer","volume":"26 1","pages":""},"PeriodicalIF":4.1,"publicationDate":"2026-11-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13729484/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149317977","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
BMC CancerPub Date : 2026-10-27DOI: 10.1186/s12885-026-17245-y
Anna Fleischer, Sabine-Anna Bergert, Patrick-Pascal Strunz, Barbara Huber, Nadine Schassberger, Miriam Benz, Elisabeth Jentschke, Florian Eisele, Yoko Tamamushi, Hermann Einsele, Leo Rasche, Michael Hudecek, Johannes Duell, Max Topp, Imad Maatouk
{"title":"Longitudinal psychosocial burden, quality of life, and digital supportive care preferences before and after CAR T-cell therapy: a prospective single-center observational study.","authors":"Anna Fleischer, Sabine-Anna Bergert, Patrick-Pascal Strunz, Barbara Huber, Nadine Schassberger, Miriam Benz, Elisabeth Jentschke, Florian Eisele, Yoko Tamamushi, Hermann Einsele, Leo Rasche, Michael Hudecek, Johannes Duell, Max Topp, Imad Maatouk","doi":"10.1186/s12885-026-17245-y","DOIUrl":"https://doi.org/10.1186/s12885-026-17245-y","url":null,"abstract":"<p><strong>Background: </strong>Prospective studies of CAR T-cell therapy have described changes in patient-reported outcomes, but these are rarely examined alongside supportive care preferences and patients' own accounts. We examined these components together across the treatment course.</p><p><strong>Methods: </strong>This prospective single-center study included adults scheduled for CAR T-cell therapy at a German tertiary hospital. Of 52 patients in the screening/recruitment log, 32 who completed at least three of four assessments formed the longitudinal cohort. Assessments occurred before treatment (T0), during post-infusion hospitalization (T1), at or around discharge (T2), and seven to eight weeks after discharge (T3). Standardized measures assessed quality of life, anxiety/depression, loneliness, fear of progression, somatic symptoms, and social support. Unadjusted generalized estimating equations examined longitudinal change; supportive care items were summarized descriptively and open-ended responses analyzed thematically.</p><p><strong>Results: </strong>The cohort included 17 male and 15 female participants; median age was 61.0 years (IQR 53.0-65.5), and 23/32 (71.9%) had multiple myeloma. Global health status/quality of life showed an overall time effect (p = 0.001), with the lowest mean at T2 and recovery by T3. Physical functioning was nominally lower at T2 (β = -14.450, p = 0.046); fatigue was nominally higher at T1 and T2 (β = 11.990, p = 0.015; β = 15.574, p = 0.008), and the QLQ-C30 summary score lower at T1 and T2 (β = -7.772, p = 0.006; β = -6.954, p = 0.035). Loneliness was nominally higher at T1 (β = 0.795, p = 0.009), whereas PHQ-4 scores changed little. Across timepoints, 60.0% to 70.0% considered post-discharge psycho-oncological support useful and 66.7% to 79.3% considered peer contact useful. Five themes concerned treatment uncertainty, physical decline, multidimensional support needs, accessible individualized digital support, and incomplete treatment understanding.</p><p><strong>Conclusions: </strong>Patient-reported physical and functional burden was greatest during hospitalization and around discharge and improved by seven to eight weeks after discharge. Brief anxiety/depression scores captured only part of participants' support needs. The findings can inform co-design and prospective evaluation of longitudinal supportive care approaches without establishing intervention effectiveness.</p>","PeriodicalId":9131,"journal":{"name":"BMC Cancer","volume":"26 1","pages":""},"PeriodicalIF":4.1,"publicationDate":"2026-10-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13723932/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149317982","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
BMC CancerPub Date : 2026-10-27DOI: 10.1186/s12885-026-17180-y
Branko Calukovic, Katrin Benzler, Martin Schulze, Florian Battke, Lars Zender, Ulrich M Lauer, Saskia Biskup, Christoph K W Deinzer
{"title":"Association of tumor-informed circulating tumor DNA dynamics with radiologic disease assessment in a single-center real-world sarcoma cohort.","authors":"Branko Calukovic, Katrin Benzler, Martin Schulze, Florian Battke, Lars Zender, Ulrich M Lauer, Saskia Biskup, Christoph K W Deinzer","doi":"10.1186/s12885-026-17180-y","DOIUrl":"10.1186/s12885-026-17180-y","url":null,"abstract":"<p><strong>Background: </strong>Sarcomas are rare and heterogeneous malignant tumors for which reliable blood-based biomarkers for longitudinal disease monitoring remain limited. Circulating tumor DNA (ctDNA) has emerged as a minimally invasive biomarker in several solid tumors, but its clinical utility in sarcoma remains incompletely defined because of biological heterogeneity, variable ctDNA shedding, and the limited availability of recurrent, panel-coverable genomic alterations across different subtypes.</p><p><strong>Methods: </strong>We conducted a retrospective real-world study of patients with bone and soft tissue sarcomas treated at a certified high-volume sarcoma center. Patients underwent tumor-normal molecular profiling to identify tumor-informed ctDNA targets. Longitudinal plasma monitoring was performed using a unique molecular identifier (UMI)-based targeted sequencing approach in patients with an identifiable target. ctDNA findings were compared with radiologic assessment, treatment response, and clinical outcomes. In two selected patients with extended longitudinal follow-up, whole-genome-based molecular residual disease (MRD) analysis was performed as an exploratory analysis.</p><p><strong>Results: </strong>Twenty patients were screened, of whom 14 (70%) had an identifiable tumor-informed ctDNA target and were included in the longitudinal analysis. A total of 67 longitudinal plasma samples were analyzed, with a median of 4 samples per patient (range: 2-10). A total of 67 paired liquid biopsy-radiologic assessments were included in the concordance analysis. Concordant assessments were observed in 59 of 67 cases (88.1%), corresponding to substantial agreement between ctDNA and imaging (Cohen's κ = 0.755; 95% CI, 0.598-0.913). Using radiologic assessment as the reference standard, ctDNA demonstrated a sensitivity of 80.0% and specificity of 94.6% for detecting progressive disease. These assessment-level estimates were descriptive and did not account for repeated measurements within patients. Descriptive review of the longitudinal ctDNA identified patterns consistent with radiologic and clinical disease course in individual patients. In a 3-month landmark analysis, patients with ctDNA-defined progression had numerically shorter progression-free survival than patients without ctDNA-defined progression (9.0 vs. 16.0 months), although the difference was not statistically significant. Exploratory whole-genome MRD analysis was concordant with radiologic disease course in two selected patients.</p><p><strong>Conclusions: </strong>Tumor-informed ctDNA monitoring was feasible in 70% of screened patients and showed high concordance with radiologic disease assessment in this real-world sarcoma cohort. These findings support prospective evaluation of ctDNA as an adjunct to imaging for longitudinal disease monitoring in patients with a suitable tumor-informed target, while broader tumor-informed approaches may be required for patients whose tumo","PeriodicalId":9131,"journal":{"name":"BMC Cancer","volume":"26 1","pages":""},"PeriodicalIF":4.1,"publicationDate":"2026-10-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13715185/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149285235","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
BMC CancerPub Date : 2026-10-26DOI: 10.1186/s12885-026-17178-6
Michael Stoffel, Katharina Baschun, Melina Kehl, Jörg Ellinger, Niklas Klümper, Sebastian Kadzik, Franziska I Winterhagen, Manuel Ritter, Michael Hölzel, Glen Kristiansen, Marieta I Toma
{"title":"Endothelial p16 expression identifies a subgroup of clear cell renal cell carcinoma with favorable prognosis.","authors":"Michael Stoffel, Katharina Baschun, Melina Kehl, Jörg Ellinger, Niklas Klümper, Sebastian Kadzik, Franziska I Winterhagen, Manuel Ritter, Michael Hölzel, Glen Kristiansen, Marieta I Toma","doi":"10.1186/s12885-026-17178-6","DOIUrl":"10.1186/s12885-026-17178-6","url":null,"abstract":"<p><strong>Background: </strong>Clear cell renal cell carcinoma (ccRCC) is characterized by extensive angiogenesis and marked architectural heterogeneity. While vascular density has been investigated as a prognostic parameter in ccRCC, little is known about the biological characteristics of intratumoral endothelial cells.</p><p><strong>Methods: </strong>In this study, we analyzed the p16 expression in a tissue microarray cohort comprising 347 ccRCC cases with clinicopathological and survival data and related the vascular p16 expression to previously described tumor architecture subtypes.</p><p><strong>Results: </strong>Tumor architecture could be assessed in 315 cases and was classified into nine predominant growth patterns. Tumors with thick trabecular/insular or solid sheet architecture were grouped as high-risk patterns and were associated with higher tumor grade and shorter overall survival (p < 0.001). Tumor cell p16 expression was infrequent and showed no association with clinicopathological parameters or survival. In contrast, endothelial p16 expression was commonly observed in intratumoral blood vessels, with a median of 35% positive vessels per case. Higher endothelial p16 expression, both in extent and intensity, was significantly associated with lower tumor grade, lower pT stage, favorable architectural patterns, and prolonged overall survival. Furthermore, the prognostic impact of architectural growth patterns was most pronounced in tumors with low endothelial p16 expression, whereas tumors with high endothelial p16 expression showed comparable survival independent of architectural subtype.</p><p><strong>Conclusion: </strong>Endothelial p16 expression is common in ccRCC and is associated with favorable clinicopathological characteristics and prolonged survival. These findings suggest that endothelial p16 expression may complement architectural tumor stratification in ccRCC, identifying cases with good prognosis.</p>","PeriodicalId":9131,"journal":{"name":"BMC Cancer","volume":"26 1","pages":""},"PeriodicalIF":4.1,"publicationDate":"2026-10-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13711708/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149262716","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
BMC CancerPub Date : 2026-10-22DOI: 10.1186/s12885-026-17186-6
Anna Thunström Salzer, Chloe Williams, Samuel Skoluda, Marios Stylianou, Jonathan D Gilthorpe, Constantin F Urban
{"title":"Neutrophils alter the metabolic profile of a coculture model of triple-negative breast cancer and stromal cells.","authors":"Anna Thunström Salzer, Chloe Williams, Samuel Skoluda, Marios Stylianou, Jonathan D Gilthorpe, Constantin F Urban","doi":"10.1186/s12885-026-17186-6","DOIUrl":"10.1186/s12885-026-17186-6","url":null,"abstract":"<p><strong>Background: </strong>Breast cancer is one of the most common cancer types. Triple-negative breast cancer (TNBC), one of the most lethal breast cancer subtypes, is characterized by substantial neutrophil accumulation in the tumor microenvironment (TME), although the impact of neutrophils on disease progression remains unclear.</p><p><strong>Methods: </strong>To model interactions between cancer cells and stromal cells, we used a coculture system combining a TNB Ccell line with breast fibroblasts and exposed these cultures to neutrophils isolated from healthy donors.</p><p><strong>Results: </strong>Coculture generated a pro-inflammatory environment, with increased levels of pro-inflammatory cytokines resembling cytokine profiles reported in cancer patients. Coculture-conditioned medium attracted neutrophils and activated them to produce reactive oxygen species (ROS). Coculture also altered metabolic activity, as measured by the Seahorse Extracellular Flux Assay, compared with the corresponding monocultures.</p><p><strong>Conclusions: </strong>Adding neutrophils to the coculture increased mitochondrial activity, suggesting that neutrophils may promote a metabolic shift in the coculture system: Together, our results support further investigation of neutrophil-driven changes in energy metabolism in TNBC microenvironments.</p>","PeriodicalId":9131,"journal":{"name":"BMC Cancer","volume":"26 1","pages":""},"PeriodicalIF":4.1,"publicationDate":"2026-10-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13693121/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149242880","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Decoupling T cell cytotoxicity: a CCL21+ICAM1-based synthetic immune niche enhances tumor elimination by accelerating lytic hit delivery.","authors":"Manish Kumar Gupta, Rawan Zoabi, Sofi Yado, Jörn Starruß, Benjamin Geiger, Haralampos Hatzikirou","doi":"10.1186/s12885-026-16748-y","DOIUrl":"10.1186/s12885-026-16748-y","url":null,"abstract":"<p><p>Preserving T cell cytotoxic function during ex vivo expansion remains a major challenge for adoptive cancer immunotherapy. A synthetic immune niche (SIN) composed of immobilized CCL21 and ICAM1 was shown to improve T cell expansion while preserving cytotoxicity; however, it remains unclear which specific step of the T cell killing process is enhanced by the SIN stimulation. Here, we combined advanced imaging based on time-lapse microscopy with a mean-field model to analyze the distinct stages in killing of B16 melanoma cells by CD8[Formula: see text] T cells. This framework enabled us to resolve the tumor cell killing process into discrete steps throughout target cell engagement with SIN-treated T cells and lytic hit delivery. We found that tumor cell death is best explained by a multi-hit process, requiring approximately four discrete hits to trigger cell death. Model-based analysis identified a significant increase in the lytic hit-delivery rate, [Formula: see text], as the main kinetic change associated with the enhanced cytotoxicity of SIN-treated T cells. The target encounter rate, [Formula: see text], could not be reliably compared between conditions because it was practically non-identifiable in the untreated dataset. Global sensitivity analysis further showed that increasing lytic hit delivery has a stronger effect on tumour control than increasing target encounter rates. These findings fundamentally reorient our understanding of optimized T cell manufacturing, suggesting that the lytic execution step may be the primary rate-limiting bottleneck in this in-vitro system, and that engineering strategies targeting granule polarization or discharge warrant prioritization alongside affinity-enhancement approaches.</p>","PeriodicalId":9131,"journal":{"name":"BMC Cancer","volume":"26 1","pages":""},"PeriodicalIF":4.1,"publicationDate":"2026-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13670589/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149179403","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
BMC CancerPub Date : 2026-10-15DOI: 10.1186/s12885-026-17170-0
Eya Khadhraoui, Leon Schmidt, Stefan Klebingat, I Erol Sandalcioglu, Roland Schwab, Philipp Arndt, Daniel Behme, Klaus-Peter Stein, Sebastian Johannes Müller
{"title":"Late enhancement and washout maps for distinguishing tumor progression from radiation necrosis in malignant brain tumors: an exploratory study.","authors":"Eya Khadhraoui, Leon Schmidt, Stefan Klebingat, I Erol Sandalcioglu, Roland Schwab, Philipp Arndt, Daniel Behme, Klaus-Peter Stein, Sebastian Johannes Müller","doi":"10.1186/s12885-026-17170-0","DOIUrl":"10.1186/s12885-026-17170-0","url":null,"abstract":"<p><strong>Background: </strong>Distinguishing between tumor progression and radiation necrosis during brain tumor follow-up is challenging. Advanced MR imaging techniques, such as perfusion, diffusion-weighted imaging (DWI), and spectroscopy, can help differentiate between these conditions. In our clinic, we established a novel technique, the rapid washout and late-enhancement map. This study investigated the value of this map in distinguishing true progression from radiation necrosis.</p><p><strong>Methods: </strong>Patients with a histologically confirmed initial diagnosis of glioblastoma, high-grade astrocytoma, primary central nervous system lymphoma, or brain metastasis who were undergoing radiochemotherapy and participated in our MRI protocol, including MR perfusion and rapid washout imaging, between January 1, 2024, and December 31, 2025, were included in the study. We volumetrically measured late enhancement and washout in brain tumors at all follow-up examinations and analyzed the resulting volumes. Additionally, we evaluated diffusion-weighted imaging and MR perfusion images.</p><p><strong>Results: </strong>A total of 33 patients (25 with glioblastoma, two with astrocytoma grade 4, two with astrocytoma grade 3, one with CNS lymphoma, and three with brain metastasis) were included. Diagnostic confirmation was obtained by histopathological assessment in 20 patients, MRI follow-up in 13 patients, with additional fluorodeoxyglucose-positron emission tomography in two. Among these patients, 23 were diagnosed with tumor recurrence, four with mixed pathology comprising \"radiation necrosis with scattered active tumor cells\", and six with radiation necrosis. The mean washout ratio (± standard deviation) was 31 ± 18 % for progressive disease, 35 ± 20 % for mixed pathology, and 10 ± 7 % for radiation necrosis, respectively.</p><p><strong>Conclusions: </strong>The washout ratio can enhance the differentiation between recurrent tumor growth and radiation necrosis during post-treatment monitoring of malignant brain tumors. As MR perfusion can yield inconclusive results in this setting, the proposed method offers complementary information that supports initial diagnostic decision making. Diagnostic discrimination may be strengthened by combining the relative cerebral blood volume with washout ratio analysis, rather than relying on a single imaging marker.</p>","PeriodicalId":9131,"journal":{"name":"BMC Cancer","volume":"26 1","pages":""},"PeriodicalIF":4.1,"publicationDate":"2026-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13673850/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149191191","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
BMC CancerPub Date : 2026-10-15DOI: 10.1186/s12885-026-17177-7
Julian P Maier, Carlotta Pietsch, Hagen Schmal, Ioannis Ntanasis-Stathopoulos, Evangelos Terpos, Gabriele Ihorst, Ralph Wäsch, Monika Engelhardt, Georg W Herget
{"title":"Patient-reported outcomes and skeletal symptoms in multiple myeloma stratified by proteasome inhibitor-based therapy: a prospective interdisciplinary cohort study.","authors":"Julian P Maier, Carlotta Pietsch, Hagen Schmal, Ioannis Ntanasis-Stathopoulos, Evangelos Terpos, Gabriele Ihorst, Ralph Wäsch, Monika Engelhardt, Georg W Herget","doi":"10.1186/s12885-026-17177-7","DOIUrl":"https://doi.org/10.1186/s12885-026-17177-7","url":null,"abstract":"<p><strong>Background: </strong>Multiple myeloma (MM) frequently causes osteolytic bone disease and skeletal symptoms. Proteasome inhibitors (PIs) are central to MM treatment and in routine practice, PI-based therapy is preferentially selected for patients with more active or symptomatic disease. Hereby, PIs may also exert bone-modulating effects beyond their antimyeloma activity. Whether these biological effects are reflected in patient-reported outcomes or skeletal symptoms during routine care remains unclear.</p><p><strong>Methods: </strong>We prospectively enrolled 209 patients with MM during routine interdisciplinary follow-up and stratified them by current PI-based versus non-PI-based treatment status. Sixty-nine patients were reassessed after at least 6 months. Patient-reported outcomes and skeletal symptoms were evaluated using multivariable regression and sensitivity analyses addressing baseline imbalances and treatment selection.</p><p><strong>Results: </strong>Seventy-eight patients (37%) were currently receiving PI-based treatment. In adjusted analyses, current PI-based treatment status was not associated with Quality of Life (β = -0.08, 95% CI -0.45 to 0.29; p = 0.662), health-related status (β = -0.06, 95% CI -0.42 to 0.30; p = 0.740), bone pain (OR 0.92, 95% CI 0.48 to 1.74; p = 0.791), or prevalent osteolytic lesions (OR 1.26, 95% CI 0.53 to 2.96; p = 0.601). QoL and health-related status remained comparable during follow-up. MM-related bone pain was numerically more frequent among patients currently receiving PI-based treatment (46% vs. 33%), although the association did not reach statistical significance after multivariable adjustment (OR 1.80, 95% CI 0.93 to 3.48; p = 0.081).</p><p><strong>Conclusions: </strong>In this prospective real-world cohort, current PI-based treatment status was not associated with measurable differences in global patient-reported outcomes, overall bone pain, or prevalent osteolytic lesions compared with non-PI-based treatment. MM-related bone pain was numerically more frequent among patients currently receiving PI-based treatment, although the association did not reach statistical significance after multivariable adjustment. These findings provide a real-world description of patient-reported and skeletal outcomes according to current treatment status but do not establish whether the biological effects of proteasome inhibitors on bone remodeling translate into clinically meaningful patient-reported or structural skeletal benefits.</p>","PeriodicalId":9131,"journal":{"name":"BMC Cancer","volume":"26 1","pages":""},"PeriodicalIF":4.1,"publicationDate":"2026-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13695283/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149262702","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}