Cancer Medicine最新文献

{"title":"PUF60-Regulated Isoform Switching of MAZ Modulates Gastric Cancer Cell Migration","authors":"Dong Xing,&nbsp;Ting Zhao,&nbsp;Chenchen Mao,&nbsp;Zheng Han,&nbsp;Wanxia Cai,&nbsp;Teming Zhang,&nbsp;Dianfeng Mei,&nbsp;Wangkai Xie,&nbsp;Jiaye Yu,&nbsp;Zhonghan Wu,&nbsp;Zhiyuan Chen,&nbsp;Shiyu Feng,&nbsp;Xian Shen,&nbsp;Xiangyang Xue,&nbsp;Dan Xiang","doi":"10.1002/cam4.70977","DOIUrl":"https://doi.org/10.1002/cam4.70977","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>As an essential transcription factor, Myc-associated zinc-finger protein (MAZ) is frequently upregulated in many human tumors and is a well-documented oncogene. However, we found high expression of MAZ was closely associated with good survival outcomes in patients with stomach adenocarcinoma (STAD), and the underlying mechanism involved remains to be elucidated. We hypothesize that alternative splicing of MAZ plays an important role.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Pan-cancer analysis of MAZ expression and prognostic significance was performed using The Cancer Genome Atlas (TCGA) data, with emphasis on its divergent prognostic impact in gastric cancer (GC). MAZ protein levels were further validated in 356 GC tissue samples via immunohistochemistry. Functional investigations encompassed MAZ knockout (KO) and isoform-specific rescue experiments to assess GC cell migration, alongside quantification of MAZ alternative splicing rates (PSI). Additionally, RNA immunoprecipitation sequencing (RIP-seq) identified PUF60-mediated regulation of MAZ isoforms.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>MAZ was upregulated in GC but served as an independent protective prognostic factor. MAZ-KO enhanced GC cell migration, while isoform-specific re-expression revealed divergent roles: MAZ-2 promoted migration, whereas MAZ-1 and MAZ-3 suppressed it. Notably, MAZ-2 is highly expressed in GC and is associated with poor survival prognosis of patients. Lower PSI values of MAZ-2 were detected in GC. MAZ transcripts were directly bound by PUF60. PUF60 knockdown caused MAZ splice isoform switch, thereby enhancing GC cell migration.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>The prognostic difference of MAZ in GC stems from isoform-specific functional antagonism, with cell migration phenotypes governed by the MAZ-1/3 versus MAZ-2 ratio. Targeting MAZ alternative splicing, particularly via PUF60 modulation, represents a novel therapeutic strategy.</p>\u0000 </section>\u0000 </div>","PeriodicalId":139,"journal":{"name":"Cancer Medicine","volume":"14 11","pages":""},"PeriodicalIF":2.9,"publicationDate":"2025-05-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/cam4.70977","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144126000","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":"Tertiary Lymphoid Structures as Independent Predictors of Favorable Prognosis in Muscle-Invasive Bladder Cancer","authors":"Xiaodong Teng,&nbsp;Zhen Chen,&nbsp;Yanfeng Bai,&nbsp;Hui Cao,&nbsp;Jing Zhang,&nbsp;Liming Xu,&nbsp;Kaihua Liu,&nbsp;Yuqian Shi,&nbsp;Yang Shao","doi":"10.1002/cam4.70978","DOIUrl":"https://doi.org/10.1002/cam4.70978","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Tertiary lymphoid structure (TLS) has been reported to be associated with prognosis and immunotherapy in certain cancers. The objective of our study was to investigate the prognostic significance of Tertiary Lymphoid Structures (TLS) within the context of Muscle-Invasive Bladder Cancer (MIBC), while concurrently examining the clinicopathological and molecular determinants influencing TLS formation.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Immunohistochemistry was used to detect the expression of TLS, CD8+ T cells, B cells, and plasma cells in 119 MIBC cases, of which 80 cases were tested by next generation sequencing (NGS) for analyzing the differences in gene alterations between TLS-negative and TLS-positive.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>TLS were identified in 52.1% (62/119) of the MIBC cases studied. Patients exhibiting TLS demonstrated reduced T and TNM staging and prolonged overall survival (OS) compared to those lacking TLS. Multivariate analysis showed that TLS was an independent prognostic factor. Densities of B cells, CD8+ T cells, and plasma cells in tumors were significantly correlated with TLS, but in the cases with low-density B cells, high-density CD8+ T cells, or high-density plasma cells, differences in OS between the tumors with TLS and without TLS were not significant. Compared with TLS-negative tumors, TLS-positive tumors had a lower frequency of <i>TP53</i> mutations and higher frequencies of <i>FAT1</i> and <i>CDKN1A</i> mutations. Tumor mutational burden (TMB) was not significantly different between the two groups but was significantly associated with TLS in <i>TP53</i> wild-type tumors.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>TLS emerged as an independent harbinger of favorable prognosis in MIBC, predominantly mediating antitumor responses via B cells. Moreover, <i>TP53</i> mutations were identified as a potential inhibitor of TLS formation.</p>\u0000 </section>\u0000 </div>","PeriodicalId":139,"journal":{"name":"Cancer Medicine","volume":"14 10","pages":""},"PeriodicalIF":2.9,"publicationDate":"2025-05-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/cam4.70978","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144100879","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":"AKR1B1 Expression in the Colorectal Tumor Microenvironment Contributes Towards Its Prognostic Significance","authors":"Seçil Demirkol Canlı,&nbsp;Güneş Güner,&nbsp;Aynur Işık,&nbsp;Branka Sosic-Jurjevi,&nbsp;Aleksandra Djikic Rom,&nbsp;Esin Gülce Seza,&nbsp;Ömer Dizdar,&nbsp;Sandra Dragicevic,&nbsp;Aleksandra Nikolic,&nbsp;Aytekin Akyol,&nbsp;Sreeparna Banerjee","doi":"10.1002/cam4.70974","DOIUrl":"https://doi.org/10.1002/cam4.70974","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>AKR1B1, a member of the aldo-keto reductase enzyme family involved in the polyol pathway of aldehyde metabolism, is aberrantly expressed in colorectal cancer (CRC). Our previous studies demonstrated that AKR1B1 knockdown reduced the motility and proliferation of CRC cell lines, and its elevated expression was correlated with increased mesenchymal marker expression, inflammation, and poor prognosis in CRC patient cohorts. However, whether stromal cells also express AKR1B1 and whether stromal expression can affect clinical outcomes has not been examined.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Objectives</h3>\u0000 \u0000 <p>To evaluate the expression of AKR1B1 within the tumor microenvironment (TME) of CRC, with a paticular focus on stromal cells, and to assess its association with clinical outcomes.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>We assessed AKR1B1 expression in colorectal tumors utilizing publicly available transcriptomic data from CRC tumors. Single-cell RNA-sequencing data from CRC samples were analyzed to determine cell type-specific expression. Immunohistochemistry based assessment of AKR1B1 expression was performed in Turkish and Serbian cohorts. Co-localization of AKR1B1 and CD163 (M2 macrophage marker) was evaluated by immunoflourescence.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>AKR1B1 was expressed in both the epithelial and stromal components of colorectal tumors, with higher expression observed in the stroma. Single-cell transcriptomic analysis revealed AKR1B1 expression in myeloid cells, T and NK cells, B cells, dendritic cells, fibroblasts, and epithelial cells. Notably, AKR1B1-expressing macrophages were predominantly of the M2 phenotype, and AKR1B1 expression and M2 marker expression showed strong positive correlation in bulk transcriptomic data. Immunofluorescence confirmed the colocalization of CD163 and AKR1B1 in stromal macrophages. Moreover, immunohistochemical analysis of AKR1B1 expression in tumor stroma from a cohort of Turkish patients revealed that its expression was associated with favorable overall survival, particularly in tumors with higher stromal infiltration.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Overall, our findings underscore the significant influence of the TME composition on the relationship between AKR1B1 expression and clinical outcomes.</p>\u0000 </section>\u0000 </div>","PeriodicalId":139,"journal":{"name":"Cancer Medicine","volume":"14 10","pages":""},"PeriodicalIF":2.9,"publicationDate":"2025-05-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/cam4.70974","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144100880","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":"Correction to “Expression of Cancer-Testis Antigens MAGE-A1, MAGE-A4, NY-ESO-1 and PRAME in Bone and Soft Tissue Sarcomas: The Experience From a Single Center in China”","authors":"","doi":"10.1002/cam4.70971","DOIUrl":"https://doi.org/10.1002/cam4.70971","url":null,"abstract":"<p>Chen A, Qiu Y, Yen YT, et al. Expression of Cancer-Testis Antigens MAGE-A1, MAGE-A4, NY-ESO-1, and PRAME in Bone and Soft Tissue Sarcomas: The Experience From a Single Center in China. <i>Cancer Med</i>. 2025;14(7):e70750. https://doi.org/10.1002/cam4.70750</p><p>In the affiliation section of the manuscript, all of the affiliations were incorrect. The correct affiliations should be: “¹Department of Oncology, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, China. ²The Comprehensive Cancer Center, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, China. ³Department of Pathology, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, China.”</p><p>We apologize for this error.</p>","PeriodicalId":139,"journal":{"name":"Cancer Medicine","volume":"14 10","pages":""},"PeriodicalIF":2.9,"publicationDate":"2025-05-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/cam4.70971","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144100613","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":"Risk of Second Primary Neoplasms Among Cancer Survivors: A Population-Based, Cohort Study in Golestan Province, Northern Iran, 2004–2019","authors":"Susan Hasanpour-Heidari,&nbsp;Shahryar Semnani,&nbsp;Abdolreza Fazel,&nbsp;Mohammad Naeimi-Tabiei,&nbsp;Mahshid Mehrjerdian,&nbsp;SeyedMehdi Sedaghat,&nbsp;Hamideh Sadeghzadeh,&nbsp;Faezeh Salamat,&nbsp;Nastaran Jafari-Delouei,&nbsp;Fatemeh Ghasemi-Kebria,&nbsp;Honeyehsadat Mirkarimi,&nbsp;Nesa Shokouhifar,&nbsp;Behnoush Abedi-Ardekani,&nbsp;Elisabete Weiderpass,&nbsp;Gholamreza Roshandel,&nbsp;Reza Malekzadeh","doi":"10.1002/cam4.70926","DOIUrl":"https://doi.org/10.1002/cam4.70926","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Recent reports of the Golestan population-based cancer registry (GPCR) suggested increasing trends in the incidence and survival rates of cancers in Golestan, Northern Iran. We investigated the risk of developing second primary neoplasms (SPNs) among cancer survivors in Golestan.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>The GPCR cases for whom a first primary cancer was diagnosed between 2004 and 2019 were included as cohort participants. The cohort members were followed by the end of 2020, and the occurrence of a second primary neoplasm (SPN) was considered as the study outcome event. The standardized incidence ratios (SIRs) and the Absolute excess risks (AERs), with corresponding 95% confidence intervals (95% CI) were calculated to evaluate the risk of SPNs.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Of the total 32,980 cases with first primary cancer, with a median follow-up of 3.4 years, 772 (2.3%) SPNs were registered. Our findings suggested a significantly higher risk of occurring new neoplasms among cancer survivors, with a SIR of 4.6 (95% CI: 4.3–4.9) and an AER of 41.8 per 10,000 person-years (95% CI: 37.6–46.0). Rural residents had a higher risk of SPN (SIR = 5.48) than urban dwellers (SIR = 3.99). Patients with first primary cancers of the ovary (SIR = 6.83) and prostate (SIR = 6.72) had the highest risk of any SPNs. The highest risk of site-specific SPNs was observed for the SPNs of the ovary (SIR = 8.11) and NHL (SIR = 7.07).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Our results suggest that cancer patients are at significantly higher risk of getting a new neoplasm than the general population. These findings highlight the need for designing and implementing efficient surveillance programs for cancer survivors.</p>\u0000 </section>\u0000 </div>","PeriodicalId":139,"journal":{"name":"Cancer Medicine","volume":"14 10","pages":""},"PeriodicalIF":2.9,"publicationDate":"2025-05-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/cam4.70926","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144091592","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":"Physical Activity Patterns According to Demographic, Social, and Clinical Correlates Among Breast Cancer Survivors","authors":"Michael A. Kebede,&nbsp;Charles E. Matthews,&nbsp;Matthew R. Dunn,&nbsp;Natasha R. Burse,&nbsp;Annie G. Howard,&nbsp;Kelly R. Evenson,&nbsp;Melissa A. Troester","doi":"10.1002/cam4.70884","DOIUrl":"https://doi.org/10.1002/cam4.70884","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Introduction</h3>\u0000 \u0000 <p>Moderate to vigorous physical activity (MVPA) after breast cancer diagnosis is associated with improved survivorship. However, differences in MVPA by race among breast cancer survivors are not well described in population-based studies.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>We analyzed data from Carolina Breast Cancer Study Phase 3 (<i>n</i> = 2994, 50% Black) participants to evaluate the trajectory of MVPA from pre-diagnosis to 18-month post-diagnosis. Participants self-reported MVPA at baseline (pre-diagnosis) and 6- and 18-month post-diagnosis and were classified as having any MVPA (&gt; 0 min/week) or no MVPA. Associations between MVPA and demographic, social, and clinical variables were estimated using multivariable logistic regression.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>At baseline, 84.0% of participants reported any MVPA pre-diagnosis, which dropped to 55.4% at 6-month post-diagnosis, then rebounded to 85.1% by 18-month post-diagnosis. Among those who had no MVPA pre-diagnosis, 32.5% and 71.0% became active at 6- and 18-month post-diagnosis, respectively. Higher income [adjusted odds ratio (aOR) = 1.33, 95% confidence interval (CI) (1.02, 1.74) &gt; $30K vs. &lt; 15K], lower body mass index [aOR = 1.30, 95% CI (1.00, 1.73) &lt; 25 vs. &gt; 30], low area deprivation [aOR = 1.35, 95% CI (1.08, 1.67) vs. high], high area assets [aOR = 1.54, 95% CI (1.23, 1.93) vs. low], and stage I breast cancer [aOR = 1.72, 95% CI (1.22, 2.43) vs. 3 or 4] were associated with any MVPA at 18-month post-diagnosis.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>We identified several demographic and social correlates of any MVPA at 18-month post-diagnosis, and together with established clinical correlates (such as late disease), these factors may contribute to breast cancer disparities.</p>\u0000 </section>\u0000 </div>","PeriodicalId":139,"journal":{"name":"Cancer Medicine","volume":"14 10","pages":""},"PeriodicalIF":2.9,"publicationDate":"2025-05-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/cam4.70884","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144100538","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":"Lipid Metabolism in Gastrointestinal Malignancies: Exploring Dysregulation, Biomarkers, and Treatment Strategies","authors":"Yan An,&nbsp;Huihui Song,&nbsp;Hongyan Qiu,&nbsp;Jun Jiang,&nbsp;Junfeng Shi","doi":"10.1002/cam4.70975","DOIUrl":"https://doi.org/10.1002/cam4.70975","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Gastrointestinal malignancies are a major public health concern worldwide, characterized by high incidence and mortality rates. Despite continuous advancements in existing treatment methods, overall survival rates remain low. Lipid metabolism plays a crucial role in the occurrence, progression, and treatment of gastrointestinal malignancies. Its involvement in the metabolic reprogramming of tumor cells, regulation of the tumor microenvironment, and drug response has become a research hotspot.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Materials &amp; Methods</h3>\u0000 \u0000 <p>This review summarizes current research related to lipid metabolism mechanisms, biomarkers, and therapies in GI cancers, with emphasis on its interaction with the tumor microenvironment.</p>\u0000 </section>\u0000 </div>","PeriodicalId":139,"journal":{"name":"Cancer Medicine","volume":"14 10","pages":""},"PeriodicalIF":2.9,"publicationDate":"2025-05-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/cam4.70975","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144091593","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":"GRB2 Promotes Malignant Behaviors of Breast Cancer by Modulating the Global Expression and Alternative Splicing Profiles in SK-BR-3 Cells Through Binding mRNA","authors":"Wei Liu,&nbsp;Yumian Huang,&nbsp;Lei Qiao,&nbsp;Le Chong,&nbsp;Luhua Xia,&nbsp;Aikeremu Abudurehaman,&nbsp;Hongyu Li","doi":"10.1002/cam4.70905","DOIUrl":"https://doi.org/10.1002/cam4.70905","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Purpose</h3>\u0000 \u0000 <p>The flexible protein GRB2 interacts with HER1–4 on the cell surface and regulates the development of tumor cells; meanwhile, it is also an RBP that plays an important role in post-transcriptional regulation in eukaryotes, which affects every stage of mRNA synthesis, modification, splicing, and stabilization. Although some studies have found a connection between GRB2 and HER2-overexpression breast cancer, highlighting the potential of GRB2 as a novel biomarker that stimulates tumor growth, limited data were available to elaborate on their interaction mechanisms.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>In this research, we found 396 different gene expressions between the Grb2-knockdown group and the SK-BR-3 group by the RNA sequencing approach. After GRB2 was knocked down, 956 alternative splicing events occurred.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>The fRIP-seq results showed that GRB2-binding reads were significantly enriched in the intron region, indicating that UUAGC and UUGGUUGG might be the binding motifs. An integration analysis of DEGs with the peak genes of fRIP-seq revealed that 63 genes possess GRB2 binding sites on their mRNAs or antisense RNAs. By integration analysis of AS events with the peak genes of fRIP-seq, 66 genes related to AS events were found.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Above, these AS events may be regulated by GRB2 to promote the progression of HER2-overexpression breast cancer.</p>\u0000 </section>\u0000 </div>","PeriodicalId":139,"journal":{"name":"Cancer Medicine","volume":"14 10","pages":""},"PeriodicalIF":2.9,"publicationDate":"2025-05-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/cam4.70905","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144085346","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":"Mapping of Functional Metabolic Phenotypes in Acute Myeloid Leukemia","authors":"Sissel Dyrstad,&nbsp;Kimberley Joanne Hatfield,&nbsp;Endre Stigen,&nbsp;Marte Karen Brattås,&nbsp;Karl Johan Tronstad,&nbsp;Håkon Reikvam","doi":"10.1002/cam4.70950","DOIUrl":"https://doi.org/10.1002/cam4.70950","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Acute myeloid leukemia (AML) is an aggressive hematologic malignancy with a poor prognosis, particularly in older patients. AML is highly heterogeneous, influenced by various chromosomal, genetic, and epigenetic alterations.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>This study investigated the metabolic profiles of primary AML cells from 46 patients, focusing on mitochondrial respiration and glycolysis. We hypothesized that the metabolic profiles would reflect distinct disease characteristics. Using Seahorse technology, we measured the oxygen consumption rate (OCR) for mitochondrial respiration and the extracellular acidification rate (ECAR) for glycolysis.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Our results showed significant variability in metabolic activity, with some samples relying more on glycolysis than mitochondrial respiration. Mature AML cells (FAB M4/M5, CD34 negative) exhibited increased rates of both mitochondrial respiration and glycolysis, indicating distinct metabolic adaptations. Higher glycolytic activity was observed in patients with adverse cytogenetic abnormalities. However, no clear associations were found between metabolic profiles and mutations in <i>FLT3</i> or <i>NPM1</i>.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>These findings highlight the role of metabolic variability in AML and suggest that targeting specific metabolic pathways could offer therapeutic opportunities, particularly for subgroups like FAB M4/M5 with unique metabolic features. Further studies are needed to refine these therapeutic strategies for clinical application.</p>\u0000 </section>\u0000 </div>","PeriodicalId":139,"journal":{"name":"Cancer Medicine","volume":"14 10","pages":""},"PeriodicalIF":2.9,"publicationDate":"2025-05-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/cam4.70950","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144085490","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":"Optimization of Tumor Treating Fields (TTFields) Frequency and Treatment Duration in Colorectal Cancer Cells","authors":"Menglan Liu,&nbsp;Zhaoran Su,&nbsp;Paul-Philipp Hagemann,&nbsp;Malte Fischer,&nbsp;Michael Linnebacher","doi":"10.1002/cam4.70976","DOIUrl":"https://doi.org/10.1002/cam4.70976","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Introduction</h3>\u0000 \u0000 <p>Colorectal cancer (CRC) is one of the most prevalent malignancies worldwide. Tumor Treating Fields (TTFields), a novel anticancer therapy using intermediate frequency and low-intensity alternating electric fields, has demonstrated efficacy in various cancers, but its application in CRC remains underexplored.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Objective</h3>\u0000 \u0000 <p>To determine the optimal frequency and treatment duration of TTFields therapy for CRC through in vitro experiments.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Four human CRC cell lines (2 MSI: HROC110 T1 M7, HROC285 T0 M2; 2 MSS: HROC450, HROC463) were treated using the inovitro TTFields system. Frequencies (100, 200, 300 kHz) and daily exposure durations (16, 20, 24 h/day) were varied. Cell viability was assessed after 72 h using crystal violet staining and spectrophotometry. Data were analyzed using <i>t</i>-tests or ANOVA, with <i>p</i> &lt; 0.05 considered statistically significant.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>TTFields significantly reduced cell viability at all tested frequencies. The 100 kHz frequency yielded the most pronounced effects, especially in MSI cell lines (<i>p</i> &lt; 0.001). Treatment duration of 24 h/day led to the greatest viability reduction across all cell lines (<i>p</i> &lt; 0.01), while 16 h/day and 20 h/day showed comparatively weaker effects.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Our study demonstrates that TTFields effectively reduce CRC cell viability, supporting their therapeutic potential. Further studies are needed to understand their mechanisms and synergy with existing treatments</p>\u0000 </section>\u0000 </div>","PeriodicalId":139,"journal":{"name":"Cancer Medicine","volume":"14 10","pages":""},"PeriodicalIF":2.9,"publicationDate":"2025-05-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/cam4.70976","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144085335","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}