BMC Cancer最新文献

{"title":"Single- versus multi-fraction spine stereotactic radiosurgery (ALL-STAR) for patients with spinal metastases: a randomized phase III trial protocol.","authors":"Aniket Pratapneni, Daniella Klebaner, Scott Gerard Soltys, Elham Rahimy, Iris Catrice Gibbs, Steven Daniel Chang, Gordon Li, Melanie Hayden Gephart, Anand Veeravagu, Gregory Arthur Szalkowski, Xuejun Gu, Lei Wang, Cynthia Chuang, Lianli Liu, Scott Jackson, Rong Lu, Jillian Adele Skerchak, Kelly Zhe Huang, Samantha Wong, Eleanor Brown, Erqi Liu Pollom","doi":"10.1186/s12885-025-13655-6","DOIUrl":"10.1186/s12885-025-13655-6","url":null,"abstract":"<p><strong>Background: </strong>For patients with spine metastases, stereotactic radiosurgery (SRS) provides excellent local control and pain response. Despite increasing use of this treatment modality, there is no consensus on the optimal dose and fractionation of spine SRS for efficacy and toxicity. We have initiated a single-center phase III randomized trial that compares two dose regimens with similar biological equivalent dose (BED) to determine the isolated effect of SRS fractionation on local control.</p><p><strong>Methods: </strong>Patients with one to three cervical, thoracic, or lumbar spine metastases spanning no more than two contiguous vertebral levels in need of radiation will be eligible for enrollment. Patients will be assigned 1:1 to receive either 22 Gy in 1 fraction or 28 Gy in 2 fractions. Biased coin randomization will be used to randomly assign patients while balancing the following stratifying variables between the two treatment arms at baseline: gastrointestinal histology (yes/no), paraspinal tissue extension (yes/no), epidural compression (low-/high-grade), and number of sites treated (one to three). The primary endpoint is one-year local control, defined per Spine Response Assessment in Neuro-Oncology (SPINO) criteria. The secondary endpoints include patient-reported health-related quality of life (HRQOL), pain associated with the treated site, vertebral compression fracture (VCF), and two-year local control. Patients will be followed for these outcomes at one to two weeks, one month, three months, and six months after treatment, and every six months thereafter until 24 months after treatment. While on the study, patients will receive routine co-interventions as clinically indicated.</p><p><strong>Discussion: </strong>The studies published thus far comparing the single- and multi-fraction SRS are lacking long-term local control outcomes and are limited by selection bias as well as single-fraction arms with higher BED, which is correlated with improved local control. Our study will isolate the effect of fractionation by comparing one-year local control in patients treated with single- and multi-fraction SRS with equivalent BED. We anticipate that the results of this, as well as secondary endpoints such as pain response, adverse effects, and quality of life will provide much-needed guidance regarding optimal dose and fractionation for both maximizing local control and minimizing toxicity.</p><p><strong>Clinical trial information: </strong>NCT#06173401. Approved by Stanford Scientific Review Committee (study ID: BRN0060) on 9/12/2023 and Stanford Institutional Review Board (study ID: IRB-72248) on 11/14/2023.</p>","PeriodicalId":9131,"journal":{"name":"BMC Cancer","volume":"25 1","pages":"323"},"PeriodicalIF":3.4,"publicationDate":"2025-02-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11846292/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143472142","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":"Dosimetric effects of bladder volume changes in MR-guided radiotherapy for cervical cancer.","authors":"Kaiwen Zhou, Cong Wang, Junfeng Zhao, Jinhu Chen, Xingwei An, Yong Yin, Zhenjiang Li","doi":"10.1186/s12885-025-13442-3","DOIUrl":"10.1186/s12885-025-13442-3","url":null,"abstract":"<p><strong>Purpose: </strong>Bladder volume variations during radiotherapy can significantly influence dose distribution to both target volumes and surrounding organs-at-risk (OARs). This study aims to assess the dosimetric impact of variable bladder volume on the clinical target volume (CTV) and OARs in cervical cancer patients undergoing MR-guided radiotherapy.</p><p><strong>Method: </strong>A total of 27 cervical cancer patients were included in this study: 12 received radical radiotherapy, and 15 underwent postoperative radiotherapy. All patients were treated with the Elekta Unity MR-linac system. The dose requirement was 95-100% of the prescribed dose to the PTV(45 Gy/25 sessions/5 weeks). Daily images were acquired at the time of treatment using the MR-linac. For this study, MR images from the first three treatments of each patient were selected to contour the CTV and OAR (bladder, small bowel, rectum, right and left lateral femoral heads), and the treatment plan was recalculated using the Monaco TPS. The dosimetric effects of bladder volume changes on the CTV and OAR were analyzed by SPSS.</p><p><strong>Result: </strong>Regarding the dosimetric effects on the CTV, in the postoperative radiotherapy group, D₉₈ and D₉₅ of the CTV decreased as the bladder filled. In contrast, for patients undergoing radical radiotherapy, the mean dose of the CTV increased from 5223.55 cGy to 5273.93 cGy as the bladder filled. For the dosimetric effects on the bladder, in the postoperative radiotherapy group, V₃₀ and V₂₀ of the bladder decreased as the bladder filled. In the radical radiotherapy group, the minimum dose of the bladder decreased with increasing bladder volume, but the maximum dose increased from 5347.68 cGy to 5581.63 cGy. For the rectum and small bowel, in the postoperative radiotherapy group, changes in bladder volume did not significantly affect the dose of the small bowel and rectum. However, in the radical radiotherapy group, the minimum and mean doses to the rectum and the D₂ of the small bowel decreased with bladder filling.</p><p><strong>Conclusion: </strong>This study evaluated the dosimetric and volumetric impact of bladder filling on the Clinical Target Volume (CTV) and Organs at Risk (OAR) using daily magnetic resonance (MR) images from the MR-linac. The findings indicate that variations in bladder filling significantly affect dose distribution to both the CTV and OAR.</p>","PeriodicalId":9131,"journal":{"name":"BMC Cancer","volume":"25 1","pages":"324"},"PeriodicalIF":3.4,"publicationDate":"2025-02-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11846216/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143472285","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":"Metabolic and multi-model intravoxel incoherent motion parameters based ¹⁸F-FDG PET/MRI for predicting subtypes of inoperable non-small cell lung cancer.","authors":"Zhun Huang, Huihui Wang, Fang Ting, Yang Chen, Hengquan Fan, Xiaochen Li, Fangfang Fu, Jianmin Yuan, Yang Yang, Zhe Wang, Meiyun Wang","doi":"10.1186/s12885-025-13543-z","DOIUrl":"10.1186/s12885-025-13543-z","url":null,"abstract":"<p><strong>Background: </strong>To differentiate inoperable non-small cell lung cancer (NSCLC) subtypes by mono-exponential (MEM), bi-exponential (BEM), and stretched- exponential models (SEM) intravoxel incoherent motion (IVIM), and ¹⁸F-FDG PET parameters.</p><p><strong>Materials and methods: </strong>A total of 106 cases of NSCLC were included in this analysis, of which 68 cases were adenocarcinoma (AC) and 38 cases were squamous cell carcinoma (SCC). MEM derived parameter ADC; BEM derived parameters D, D*, and f, SEM derived parameters α, DDC; and ¹⁸F-FDG PET derived parameters MTV, SUV_max, and TLG were recorded and compared. Area under the receiver operating characteristic curve (AUC) was performed for diagnostic efficacy.</p><p><strong>Results: </strong>SUV_max, MTV and TLG were lower and ADC, f, D and DDC were higher in AC than in SCC (p all < 0.001), whereas D* and α were not significantly different (p = 0.824, 0.152). Logistic regression analysis showed that the stage, ADC, and TLG were independent predictors for identification of SCC and AC, and when combined they showed best diagnostic result (AUC, 0.906; sensitivity, 79.41%; specificity, 94.74%), which was higher than any single clinical factor (maximum diameter, sex smoking, stage, and CT readout; AUC = 0.725, 0.686, 0.707, 0.721, and 0.666, respectively), IVIM (ADC, f, and D; AUC = 0.772, 0.686, and 0.696, respectively) or ¹⁸F-FDG PET-derived variable (SUV_max, MTV, and TLG; AUC = 0.693, 0.712, and 0.774, respectively).</p><p><strong>Conclusion: </strong>The stage, ADC, and TLG were independent predictors for differentiating subtypes of inoperable NSCLC, and when combined they showed optimal diagnostic performance and could be a superior imaging marker.</p>","PeriodicalId":9131,"journal":{"name":"BMC Cancer","volume":"25 1","pages":"322"},"PeriodicalIF":3.4,"publicationDate":"2025-02-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11846224/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143472294","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":"The potential of thermal imaging as an early predictive biomarker of radiation dermatitis during radiotherapy for head and neck cancer: a prospective study.","authors":"Ye-In Park, Seo Hee Choi, Min-Seok Cho, Junyoung Son, Changhwan Kim, Min Cheol Han, Hojin Kim, Ho Lee, Dong Wook Kim, Jin Sung Kim, Chae-Seon Hong","doi":"10.1186/s12885-025-13734-8","DOIUrl":"10.1186/s12885-025-13734-8","url":null,"abstract":"<p><strong>Background: </strong>Predicting radiation dermatitis (RD), a common radiotherapy toxicity, is essential for clinical decision-making regarding toxicity management. This prospective study aimed to develop and validate a machine-learning model to predict the occurrence of grade ≥ 2 RD using thermal imaging in the early stages of radiotherapy in head and neck cancer.</p><p><strong>Methods: </strong>Thermal images of neck skin surfaces were acquired weekly during radiotherapy. A total of 202 thermal images were used to calculate the difference map of neck skin temperature and analyze to extract thermal imaging features. Changes in imaging features during treatment were assessed in the two RD groups, grade ≥ 2 and grade ≤ 1 RD, classified according to the Common Terminology Criteria for Adverse Events (CTCAE) guidelines. Feature importance analysis was performed to select thermal imaging features correlated with grade ≥ 2 RD. A predictive model for grade ≥ 2 RD occurrence was developed using a machine learning algorithm and cross-validated. Area under the receiver-operating characteristic curve (AUC), precision, and sensitivity were used as evaluation metrics.</p><p><strong>Results: </strong>Of the 202 thermal images, 54 images taken before the occurrence of grade ≥ 2 RD were used to develop the predictive model. Thermal radiomics features related to the homogeneity of image texture were selected as input features of the machine learning model. The gradient boosting decision tree showed an AUC of 0.84, precision of 0.70, and sensitivity of 0.75 in models trained using thermal features acquired before skin dose < 10 Gy. The support vector machine achieved a mean AUC of 0.71, precision of 0.68, and sensitivity of 0.70 for predicting grade ≥ 2 RD using thermal images obtained in the skin dose range of 10-20 Gy.</p><p><strong>Conclusions: </strong>Thermal images acquired from patients undergoing radiotherapy for head and neck cancer can be used as an early predictor of grade ≥ 2 RD and may aid in decision support for the management of acute skin toxicity from radiotherapy. However, our results should be interpreted with caution, given the limitations of this study.</p>","PeriodicalId":9131,"journal":{"name":"BMC Cancer","volume":"25 1","pages":"309"},"PeriodicalIF":3.4,"publicationDate":"2025-02-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11844184/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143467001","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":"The ATLAS/NOA-29 study protocol: a phase III randomized controlled trial of anterior temporal lobectomy versus gross-total resection in newly-diagnosed temporal lobe glioblastoma.","authors":"Matthias Schneider, Anna-Laura Potthoff, Yahya Ahmadipour, Valeri Borger, Hans Clusmann, Stephanie E Combs, Marcus Czabanka, Lasse Dührsen, Nima Etminan, Thomas M Freiman, Ruediger Gerlach, Florian Gessler, Frank A Giordano, Eleni Gkika, Roland Goldbrunner, Erdem Güresir, Hussam Hamou, Peter Hau, Sebastian Ille, Max Jägersberg, Naureen Keric, Maryam Khaleghi-Ghadiri, Ralph König, Jürgen Konczalla, Harald Krenzlin, Sandro Krieg, Aaron Lawson McLean, Julian P Layer, Jens Lehmberg, Vesna Malinova, Bernhard Meyer, Hanno S Meyer, Dorothea Miller, Oliver Müller, Christian Musahl, Barbara E F Pregler, Ali Rashidi, Florian Ringel, Constantin Roder, Karl Rössler, Veit Rohde, I Erol Sandalcioglu, Niklas Schäfer, Christina Schaub, Nils Ole Schmidt, Gerrit A Schubert, Clemens Seidel, Corinna Seliger, Christian Senft, Julia Shawarba, Joachim Steinbach, Veit Stöcklein, Walter Stummer, Ulrich Sure, Ghazaleh Tabatabai, Marcos Tatagiba, Niklas Thon, Marco Timmer, Johannes Wach, Arthur Wagner, Christian Rainer Wirtz, Katharina Zeiler, Thomas Zeyen, Patrick Schuss, Rainer Surges, Christine Fuhrmann, Daniel Paech, Matthias Schmid, Yvonne Borck, Torsten Pietsch, Rafael Struck, Alexander Radbruch, Christoph Helmstaedter, Robert Németh, Ulrich Herrlinger, Hartmut Vatter","doi":"10.1186/s12885-025-13682-3","DOIUrl":"10.1186/s12885-025-13682-3","url":null,"abstract":"<p><strong>Background: </strong>The discovery of cellular tumor networks in glioblastoma, with routes of malignant communication extending far beyond the detectable tumor margins, has highlighted the potential of supramarginal resection strategies. Retrospective data suggest that these approaches may improve long-term disease control. However, their application is limited by the proximity of critical brain regions and vasculature, posing challenges for validation in randomized trials. Anterior temporal lobectomy (ATL) is a standardized surgical procedure commonly performed in patients with pharmacoresistant temporal lobe epilepsy. Translating the ATL approach from epilepsy surgery to the neuro-oncological field may provide a model for investigating supramarginal resection in glioblastomas located in the anterior temporal lobe.</p><p><strong>Methods: </strong>The ATLAS/NOA-29 trial is a prospective, multicenter, multinational, phase III randomized controlled trial designed to compare ATL with standard gross-total resection (GTR) in patients with newly-diagnosed anterior temporal lobe glioblastoma. The primary endpoint is overall survival (OS), with superiority defined by significant improvements in OS and non-inferiority in the co-primary endpoint, quality of life (QoL; \"global health\" domain of the European organization for research and treatment of cancer (EORTC) QLQ-C30 questionnaire). Secondary endpoints include progression-free survival (PFS), seizure outcomes, neurocognitive performance, and the longitudinal assessment of six selected domains from the EORTC QLQ-C30 and BN20 questionnaires. Randomization will be performed intraoperatively upon receipt of the fresh frozen section result. A total of 178 patients will be randomized in a 1:1 ratio over a 3-year recruitment period and followed-up for a minimum of 3 years. The trial will be supervised by a Data Safety Monitoring Board, with an interim safety analysis planned after the recruitment of the 57th patient to assess potential differences in modified Rankin Scale (mRS) scores between the treatment arms 6 months after resection. Assuming a median improvement in OS from 17 to 27.5 months, the trial is powered at > 80% to detect OS differences with a two-sided log-rank test at a 5% significance level.</p><p><strong>Discussion: </strong>The ATLAS/NOA-29 trial aims to determine whether ATL provides superior outcomes at equal patients' Qol compared to GTR in anterior temporal lobe glioblastoma, potentially establishing ATL as the surgical approach of choice for isolated temporal glioblastoma and redefining the standard of care for this patient population.</p><p><strong>Trial registration: </strong>German Clinical Trials Register (DRKS00035314), registered on October 18, 2024.</p>","PeriodicalId":9131,"journal":{"name":"BMC Cancer","volume":"25 1","pages":"306"},"PeriodicalIF":3.4,"publicationDate":"2025-02-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11843818/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143466994","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":"Pathology-based deep learning features for predicting basal and luminal subtypes in bladder cancer.","authors":"Zongtai Zheng, Fazhong Dai, Ji Liu, Yongqiang Zhang, Zhenwei Wang, Bangqi Wang, Xiaofu Qiu","doi":"10.1186/s12885-025-13688-x","DOIUrl":"10.1186/s12885-025-13688-x","url":null,"abstract":"<p><strong>Background: </strong>Bladder cancer (BLCA) exists a profound molecular diversity, with basal and luminal subtypes having different prognostic and therapeutic outcomes. Traditional methods for molecular subtyping are often time-consuming and resource-intensive. This study aims to develop machine learning models using deep learning features from hematoxylin and eosin (H&E)-stained whole-slide images (WSIs) to predict basal and luminal subtypes in BLCA.</p><p><strong>Methods: </strong>RNA sequencing data and clinical outcomes were downloaded from seven public BLCA databases, including TCGA, GEO datasets, and the IMvigor210C cohort, to assess the prognostic value of BLCA molecular subtypes. WSIs from TCGA were used to construct and validate the machine learning models, while WSIs from Shanghai Tenth People's Hospital (STPH) and The Affiliated Guangdong Second Provincial General Hospital of Jinan University (GD2H) were used as external validations. Deep learning models were trained to obtained tumor patches within WSIs. WSI level deep learning features were extracted from tumor patches based on the RetCCL model. Support vector machine (SVM), random forest (RF), and logistic regression (LR) were developed using these features to classify basal and luminal subtypes.</p><p><strong>Results: </strong>Kaplan-Meier survival and prognostic meta-analyses showed that basal BLCA patients had significantly worse overall survival compared to luminal BLCA patients (hazard ratio = 1.47, 95% confidence interval: 1.25-1.73, P < 0.001). The LR model based on tumor patch features selected by Resnet50 model demonstrated superior performance, achieving an area under the curve (AUC) of 0.88 in the internal validation set, and 0.81 and 0.64 in the external validation sets from STPH and GD2H, respectively. This model outperformed both junior and senior pathologists in the differentiation of basal and luminal subtypes (AUC: 0.85, accuracy: 74%, sensitivity: 66%, specificity: 82%).</p><p><strong>Conclusions: </strong>This study showed the efficacy of machine learning models in predicting the basal and luminal subtypes of BLCA based on the extraction of deep learning features from tumor patches in H&E-stained WSIs. The performance of the LR model suggests that the integration of AI tools into the diagnostic process could significantly enhance the accuracy of molecular subtyping, thereby potentially informing personalized treatment strategies for BLCA patients.</p>","PeriodicalId":9131,"journal":{"name":"BMC Cancer","volume":"25 1","pages":"310"},"PeriodicalIF":3.4,"publicationDate":"2025-02-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11844054/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143466991","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":"Comprehensive characterization of pathogenic missense CTRP6 variants and their association with cancer.","authors":"Muhammad Zubair Mehboob, Arslan Hamid, Jeevotham Senthil Kumar, Xia Lei","doi":"10.1186/s12885-025-13685-0","DOIUrl":"10.1186/s12885-025-13685-0","url":null,"abstract":"<p><strong>Background: </strong>Previous genome-wide association studies have linked three missense single nucleotide polymorphisms (SNPs) in C1q/TNF-related protein 6 (CTRP6) to diseases such as type 1 diabetes and autoimmune diseases. However, the potential association of newly identified missense CTRP6 variants with diseases, especially cancer, remains unclear.</p><p><strong>Methods: </strong>We used several pathogenicity prediction algorithms to identify deleterious mutations within the highly conserved C1q domain of human CTRP6, following the retrieval of all SNPs from the Ensembl database. We systematically analyzed the effects of these mutations on the protein's stability, flexibility, structural conformation, compactness, stiffness, and overall functionality using various bioinformatics tools. Additionally, we investigated the association of these mutations with different cancer types using the cBioPortal and canSAR databases.</p><p><strong>Results: </strong>We identified 11 detrimental missense SNPs within the C1q domain, a region critical for this protein's functionality. Using various computational methods, we predicted the functional impact of these missense variants and assessed their effects on the stability and flexibility of the CTRP6 structure. Molecular dynamics simulations revealed significant structural differences between the native and mutated structures, including changes in structural conformation, compactness, solvent accessibility, and flexibility. Additionally, our study shows a strong association between two mutations, G181S and R247W, and certain types of cancer: colon adenocarcinoma and uterine corpus endometrial carcinoma, respectively. We also found that the mutational status of CTRP6 and other cancer-related genes, such as MAP2K3, p16, TP53, and JAK1, affected each other's expression, potentially contributing to cancer development.</p><p><strong>Conclusions: </strong>Our screening and predictive analysis of pathogenic missense variants in CTRP6 advance the understanding of the functional implications of these mutations, potentially facilitating more focused and efficient research in the future.</p>","PeriodicalId":9131,"journal":{"name":"BMC Cancer","volume":"25 1","pages":"304"},"PeriodicalIF":3.4,"publicationDate":"2025-02-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11840981/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143466986","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":"Up-regulation of m⁶A writer METTL14 inhibits tumorigenesis by suppressing glycolysis in colorectal cancer.","authors":"Lulu Li, Rong Zhang, Yongsheng Li","doi":"10.1186/s12885-025-13532-2","DOIUrl":"10.1186/s12885-025-13532-2","url":null,"abstract":"<p><strong>Background: </strong>Colorectal cancer (CRC) is a common malignant tumor. N⁶-Methyladenosine (m⁶A) modification plays an important role in the regulation of glycolysis in tumor cells and may be a potential target for tumor therapy.</p><p><strong>Methods: </strong>The role of METTL14, an m⁶A writer, in CRC was investigated through functional assays including cell viability, colony formation, and glycolysis-related measurements (glucose uptake, lactate production, extracellular acidification rate (ECAR) and oxygen consumption rate (OCR)). The target gene regulated by METTL14 in an m⁶A-dependent manner was identified using molecular biology techniques. In addition, CRC cells overexpressing METTL14 were subcutaneously injected into mice to verify the regulatory effect of METTL14 on tumor growth in vivo.</p><p><strong>Results: </strong>Our data suggested that METTL14 was up-regulated in CRC cell lines, and over-expression of METTL14 suppressed cell proliferation and glycolysis. Meanwhile, ATF2 m⁶A level was significantly up-regulated by over-expression of METTL14, and the binding relationship between ATF2 and METTL14 was further verified. METTL14-m⁶A regulated ATF2 in CRC cells participates in the regulation of glycolysis. METTL14 also suppressed tumorigenesis of nude mice.</p><p><strong>Conclusion: </strong>Intervention with METTL14 mediated m⁶A modifications or its associated protein ATF2 may provide new strategies for CRC therapy.</p>","PeriodicalId":9131,"journal":{"name":"BMC Cancer","volume":"25 1","pages":"305"},"PeriodicalIF":3.4,"publicationDate":"2025-02-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11844156/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143466424","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":"The impact of functional MDM2-polymorphisms on neutrophil counts in breast cancer patients during neoadjuvant chemotherapy.","authors":"Nora D Hatletvedt, Christina Engebrethsen, Jürgen Geisler, Stephanie Geisler, Turid Aas, Per E Lønning, Liv B Gansmo, Stian Knappskog","doi":"10.1186/s12885-025-13675-2","DOIUrl":"10.1186/s12885-025-13675-2","url":null,"abstract":"<p><strong>Background: </strong>Functional polymorphisms in the MDM2 promoters have been linked to cancer risk and several non-malignant conditions. Their potential role in bone marrow function during chemotherapy is largely unknown.</p><p><strong>Methods: </strong>We investigated the potential associations between genotypes of MDM2 SNP309 (rs2279744), SNP285 (rs117039649) and del1518 (rs3730485) and neutrophil counts in breast cancer patients receiving neoadjuvant sequential epirubicin and docetaxel, with additional G-CSF, in the DDP-trial (NCT00496795). We applied longitudinal ratios, post vs. pre-treatment, of neutrophil counts as our main measure. Differences by genotypes were tested by Jonckheere-Terpstra test for ranked alternatives, while dominant and recessive models were tested by Mann-Whitney U test, and additional sub-analyses were performed for genotype combinations.</p><p><strong>Results: </strong>The SNP309 reference T-allele was associated with a better sustained neutrophil count (p = 0.035). A similar association was observed for the alternative del-allele of the del1518 (p = 0.049). Additionally, in combined genotype-analyses, patients with the SNP309 TT genotype and at least one copy of the del1518 del-allele had particularly favorable sustained neutrophil counts during chemotherapy treatment (p = 0.005).</p><p><strong>Conclusions: </strong>Our study provides evidence that MDM2 promoter polymorphisms may be associated with neutrophil counts and bone marrow recovery during chemotherapy treatment in breast cancer patients.</p><p><strong>Trial registration: </strong>The DDP-trial was registered at ClinicalTrials.gov (NCT00496795; registration date 2007-07-04).</p>","PeriodicalId":9131,"journal":{"name":"BMC Cancer","volume":"25 1","pages":"308"},"PeriodicalIF":3.4,"publicationDate":"2025-02-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11843751/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143466998","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":"Incidence and risk factors of serious infections occurred in patients with lung cancer following immune checkpoint blockade therapy.","authors":"Xiao Wang, Yu-Xiao Wu, Wei-Ping Hu, Jing Zhang","doi":"10.1186/s12885-025-13743-7","DOIUrl":"10.1186/s12885-025-13743-7","url":null,"abstract":"<p><strong>Background: </strong>Immune checkpoint inhibitors (ICIs) therapy has revolutionized anti-cancer therapy, with lung cancer exhibiting sustained clinical responses to it. However, there remains a lack of research into the risk factors of serious infections in patients with lung cancer following ICIs therapy. Therefore, we aimed to investigate the incidence and risk factors of serious infections in these patients.</p><p><strong>Methods: </strong>Medical records were retrospectively collected and reviewed from 710 patients with lung cancer receiving ICIs therapy at Zhongshan Hospital between January 2021 and February 2023. Serious infections were defined as infections requiring hospitalization or parenteral antimicrobials occurring at any time from the initiation of the ICIs therapy to 3 months after its discontinuation.</p><p><strong>Results: </strong>Among the study population, 191 patients had suffered from serious infections, with an overall infection rate of 26.90% during an average follow-up period of (432.62 ± 377.09) days. The predominant site of infection was the lung (75.61%), and the most prevalent pathogens were bacteria (85.07%), followed by Mycobacterium tuberculosis (6.47%), viruses (4.98%), and fungi (3.48%). In addition to chronic obstructive pulmonary disease (COPD), asthma, and systemic glucocorticoids use, low lymphocyte count and CD4/CD8 ratio were identified as independent risk factors (all p < 0.05).</p><p><strong>Conclusion: </strong>Laboratory parameters may serve as strong predictors for serious infections in patients with lung cancer following ICIs therapy. Chronic airway diseases including COPD and asthma should be managed effectively. Systemic glucocorticoids should be used prudently to prevent serious infections in these patients.</p>","PeriodicalId":9131,"journal":{"name":"BMC Cancer","volume":"25 1","pages":"307"},"PeriodicalIF":3.4,"publicationDate":"2025-02-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11843754/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143466989","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}