Cancer Medicine最新文献

{"title":"Comparison of Survival Prognostic Tools in Terminal-Stage Tumor Patients: A Multicenter Prospective Cohort Study.","authors":"Ziluo Cheng, Lu Jin, Zhen Mei, Yeping Wang","doi":"10.1002/cam4.72283","DOIUrl":"10.1002/cam4.72283","url":null,"abstract":"<p><strong>Aim: </strong>Previous studies have discussed the effectiveness of the Karnofsky Performance Scale (KPS), Palliative Performance Scale (PPS), Palliative Prognostic Index (PPI), and Delirium-Palliative Prognostic Score (D-PaP) in predicting the survival of patients with terminal-stage tumors, but their effectiveness in the Chinese terminal-stage tumor population still needs to be explored. Therefore, we conducted this prospective cohort study to investigate the applicability of KPS, PPS, PPI, and D-PaP in predicting survival in Chinese patients with terminal-stage tumors.</p><p><strong>Methods: </strong>This is a prospective cohort study that collected data from 449 terminal-stage tumor patients across four medical institutions in China from January to December 2024. The feasibility of using KPS, PPS, PPI, and D-PaP to predict the 7-day and 30-day survival of terminal-stage tumor patients was discussed through ROC curves. Kaplan-Meier survival curves were used to examine the survival differences of terminal-stage tumor patients using four survival prediction tools with new cut-off values.</p><p><strong>Results: </strong>The study ultimately included 449 patients with terminal-stage tumors. For the prediction of 30-day survival, the area under the ROC curve of KPS, PPI, PPS, and D-PaP was 0.842, 0.749, 0.778, and 0.898, respectively. In our study cohort, the optimal cut-off values were 25, 3, 35, and 9.25. Their corresponding sensitivity was 86.3%, 92.3%, 77.7%, and 76.0%, while their specificity was 69.7%, 44.4%, 67.7%, and 93.9%, respectively.</p><p><strong>Conclusion: </strong>The results of this multicenter cohort analysis reveal that in terminal-stage tumor patients in China, KPS, PPS, PPI, and D-PaP are all effective for predicting survival. Specifically, D-PaP is more applicable for predicting 30-day survival. Although D-PaP showed the most significant predictive power, its accuracy in predicting 7-day and 30-day survival outcomes was not significantly superior to that of experienced palliative care professionals. Therefore, future research still needs to develop or update scoring tools with better predictive performance.</p>","PeriodicalId":139,"journal":{"name":"Cancer Medicine","volume":"15 10","pages":"e72283"},"PeriodicalIF":3.5,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13654485/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149163361","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":"Integrated Spatial and Bulk Transcriptomic Analysis Identifies a Multicellular Ecosystem Involved in Progression of Young Breast Cancer.","authors":"Xiaolin Chen, Zhuozhi Liang, Xinming Chen, Qian Ouyang, Qianru Chen, Liling Zhu, Shunrong Li, Kai Chen","doi":"10.1002/cam4.72367","DOIUrl":"https://doi.org/10.1002/cam4.72367","url":null,"abstract":"<p><p>Young breast cancer (YBC), defined as diagnosis at or before the age of 40 years, is characterized by an aggressive phenotype and poor prognosis. The tumor microenvironment (TME), comprising immune and stromal cells, plays a critical role in tumor initiation and progression and is closely associated with clinical outcomes. However, alterations in cell states and the organization of multicellular ecosystems within the YBC microenvironment remain poorly understood. We analyzed 7379 bulk transcriptome samples and spatial transcriptomic data from eight samples using EcoTyper and complementary spatial analyses. The abundance of CD4+ T cells (S07), fibroblasts (S05), monocytes/macrophages (S09), and epithelial cells (S05) was significantly lower in young than in older patients with breast cancer. CD4+ T cells (S07), fibroblasts (S05), and monocytes/macrophages (S09) formed a spatially organized multicellular ecosystem with putative interactions involving CDH1-PTPRF/ERBB3. Lower ecosystem abundance was associated with poorer prognosis, including among patients who did not achieve a pathological complete response after neoadjuvant therapy. These findings identify a distinct multicellular ecosystem within the YBC microenvironment, providing insights into the microenvironmental features associated with disease progression.</p>","PeriodicalId":139,"journal":{"name":"Cancer Medicine","volume":"15 10","pages":"e72367"},"PeriodicalIF":3.5,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149222854","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"CBX4 and NOX4 Expression Are Associated With Chemoradiotherapy Response and Overall Survival in Locally Advanced Cervical Squamous Cell Carcinoma.","authors":"Xianfang Pang, Xiyun Qin, Lilin Que, Weiye Li, Zixuan Yang, Weili Yi, Jiao Tang, Yong Zhang, Shanshan Ma, Linjiang Pan, Fang Wu","doi":"10.1002/cam4.72402","DOIUrl":"https://doi.org/10.1002/cam4.72402","url":null,"abstract":"<p><strong>Background: </strong>Tissue biomarkers may improve risk stratification in locally advanced cervical cancer before definitive concurrent chemoradiotherapy (CCRT). We evaluated pretreatment expression of chromobox 4 (CBX4), NADPH oxidase 4 (NOX4), specificity protein 1 (SP1), and copper transporter 1 (CTR1) in relation to CCRT response and overall survival.</p><p><strong>Methods: </strong>In this retrospective 1:1 matched case-control study, pretreatment biopsies from 40 patients with locally advanced cervical squamous cell carcinoma (20 CCRT-resistant, 20 CCRT-sensitive) were quantified by AI-assisted digital pathology using H-scores. A parsimonious CBX4 + NOX4 logistic model was evaluated by apparent ROC, leave-one-out cross-validation (LOOCV), repeated stratified 5-fold cross-validation, and bootstrap optimism correction. Overall survival analyses were exploratory.</p><p><strong>Results: </strong>CBX4 and NOX4 expression was lower in CCRT-resistant tumors (median H-score: CBX4, 40.47 vs. 79.62; NOX4, 7.00 vs. 53.93; both p < 0.001), whereas SP1 and CTR1 did not differ. Apparent AUCs were 0.840 for CBX4 and 0.843 for NOX4. The two-marker model had an apparent AUC of 0.903, LOOCV AUC 0.845, repeated 5-fold CV AUC 0.854 ± 0.022, and bootstrap-corrected AUC 0.883. High CBX4 and NOX4 expression was associated with better 5-year overall survival; in joint Cox models, hazard ratios per 1-SD increase were 0.31 (95% CI 0.13-0.74) for CBX4 and 0.48 (0.26-0.90) for NOX4. No histochemically detectable copper deposits were observed.</p><p><strong>Conclusions: </strong>Lower pretreatment CBX4 and NOX4 expression was associated with a CCRT-resistant phenotype and poorer overall survival in this small, response-enriched cohort. Internal resampling suggested discrimination, but same-dataset marker selection may introduce residual optimism and does not establish generalizability. Independent validation in a consecutively recruited cohort is required before clinical application. No mechanisms involving DNA repair, ROS, or chemoradiotherapy sensitivity were established.</p>","PeriodicalId":139,"journal":{"name":"Cancer Medicine","volume":"15 10","pages":"e72402"},"PeriodicalIF":3.5,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149222900","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Assessment of Factors and Trends Affecting Different Pathological Types of Cervical Cancer in China From 2013 to 2022.","authors":"Yufei Li, Runhua Li, Rufei Duan, Xiaofen Gu, Jia You, Hong Wang, Tingting Zuo, Zhe Wang, Weizhao Lin, Li Li, Bo Zhu, Shaokai Zhang, Wen Yang, Shuai Yuan, Hongping Zhang, Lingbin Du, Jian Yin, Huan Yang, Youlin Qiao","doi":"10.1002/cam4.72259","DOIUrl":"10.1002/cam4.72259","url":null,"abstract":"<p><strong>Objective: </strong>Cervical cancer poses a significant burden globally, particularly in developing countries, with China accounting for 20% of the global incidence. This study aimed to examine temporal changes in the pathological distribution of cervical cancer, particularly squamous cell carcinoma (SCC) and adenocarcinoma (ADC), in China from 2013 to 2022.</p><p><strong>Methods: </strong>A nationwide, multicenter, retrospective study analyzed 6645 cervical cancer cases diagnosed between 2013 and 2022 across seven tertiary hospitals in China. The study analyzed demographic, obstetric, and reproductive factors to identify trends in the proportions of SCC and ADC. Multivariable logistic regression was further performed among women with SCC or ADC to identify factors independently associated with histological type.</p><p><strong>Results: </strong>SCC accounted for 86.9% and ADC for 10.4% of invasive cervical cancer (ICC) cases. Although no significant change in SCC proportion was observed overall, declines were observed in specific subgroups-unemployed women, premenopausal women, and those with a history of reproductive system disease (p_trend = 0.012, 0.021, and 0.011, respectively). In multivariable analysis, compared with Central China, the odds of ADC relative to SCC were significantly higher in North China, Southwest China, East China, and South China, whereas menopausal women, Uyghur women, and rural residents showed lower odds of ADC relative to SCC.</p><p><strong>Conclusions: </strong>Although the overall proportion of SCC among ICC cases remained statistically stable during 2013-2022, SCC showed a decreasing trend in several high-risk subpopulations. Compared with our 2005-2010 series, the present 2013-2022 study showed a higher ADC proportion and a lower SCC proportion. These findings suggest a gradual shift in the pathological landscape of ICC in China and provide up-to-date nationwide multicenter data that may help refine future screening and prevention strategies.</p>","PeriodicalId":139,"journal":{"name":"Cancer Medicine","volume":"15 10","pages":"e72259"},"PeriodicalIF":3.5,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13620289/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149072811","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":"Quality of Life in Adults With Metastatic Breast Cancer: The Impact of Between- and Within-Person Changes in Symptoms and Positive Affect.","authors":"Brenna Mossman, Brent J Small, Elizabeth L Addington, Judith Tedlie Moskowitz, Mikaela A Velazquez-Sosa, Jennifer D Rodriguez, Aigner Bobbitt, Alene Mathurin, Lesley Glenn, Shontè Drakeford, Roxana Guerra, Claudine Isaacs, Ami Chitalia, Christopher Gallagher, Deena Graham, Nina Kadan-Lottick, Suzanne C O'Neill, Claire C Conley","doi":"10.1002/cam4.72338","DOIUrl":"10.1002/cam4.72338","url":null,"abstract":"<p><strong>Introduction: </strong>Quality of life (QoL) is important for patients with metastatic breast cancer (MBC). We examined QoL in daily life among patients with MBC using ecological momentary assessment (EMA).</p><p><strong>Methods: </strong>From 2023 to 2024, patients with MBC were recruited from 5 Mid-Atlantic sites. Eligible patients were English- or Spanish-speaking, with a life expectancy > 6 months and access to a smartphone. Participants were invited to complete 12 EMAs over 4 weeks. EMAs assessed global QoL, symptom severity (depression, anxiety, pain, fatigue, slowed cognition, appetite loss, nausea, gastrointestinal distress, decreased libido), and positive affect (social connection, peace, joy). Multilevel mixed-effects models analyzed the relationships between QoL and between-person and within-person variations in symptom severity and positive affect. We also explored associations between QoL and years since MBC diagnosis at the time of study entry.</p><p><strong>Results: </strong>Participants (N = 108; Mean age 57.8 years) were a mean of 4.4 years post-diagnosis (range = 0.06-20.65 years). Between-person effects indicated QoL was worse among individuals reporting more nausea (β = -0.109, p = 0.035) and less joy (β = 0.593, p < 0.001). Within-person effects indicated individuals' QoL was lower at times when they had more depression (β = -0.177, p < 0.001), anxiety (β = -0.049, p = 0.023), fatigue (β = -0.052, p = 0.009), appetite loss (β = -0.053, p = 0.028), and decreased libido (β = -0.058, p = 0.036) and less social connectedness (β = 0.091, p = 0.001), joy (β = 0.055, p = 0.047), and peace (β = 0.107, p < 0.001) than their personal average. QoL was not associated with years since MBC diagnosis (β = 0.106, p = 0.956). Age (β = 0.482, p = 0.013) and being partnered (β = 13.356, p = 0.005) at baseline were positively associated with estimated QoL at MBC diagnosis. Changes in QoL per year since MBC diagnosis were positively associated with being employed at baseline (β = 2.453, p < 0.001) and negatively associated with HR positive disease (β = -1.334, p = 0.001).</p><p><strong>Conclusions: </strong>Both within-person and between-person variations in symptom severity and positive affect are associated with QoL, highlighting the need for adaptive, targeted intervention strategies to optimize QoL for all patients.</p>","PeriodicalId":139,"journal":{"name":"Cancer Medicine","volume":"15 10","pages":"e72338"},"PeriodicalIF":3.5,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13624535/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149079385","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":"Extranodal Organ Involvement in Chronic Lymphocytic Leukemia: Clinical Features and Outcomes With Bruton Tyrosine Kinase and BCL-2 Inhibitors.","authors":"Finn J Schulze, Evgenii Shumilov, Akhil Behringer, Andrea Kerkhoff, Matthias Eckhardt, Simone Bätker, Markus Maulhardt, Georg Lenz, Alexander Pohlmann","doi":"10.1002/cam4.72341","DOIUrl":"https://doi.org/10.1002/cam4.72341","url":null,"abstract":"<p><strong>Background: </strong>Although chronic lymphocytic leukemia (CLL) typically follows an indolent course involving blood, lymph nodes, and bone marrow, extranodal organ involvement is rare and poorly characterized.</p><p><strong>Methods: </strong>We retrospectively analyzed 19 patients with histologically confirmed extranodal CLL or small lymphocytic lymphoma (SLL), assessing organ involvement, clinical features, genetic risk factors, and response to therapy.</p><p><strong>Results: </strong>Different organs were affected, most frequently the kidneys (7/19). Median age at initial CLL diagnosis was 54 years, median time from CLL diagnosis to extranodal manifestation was 3 years. Genetic risk factors were comparable to typical CLL cohorts. Per treatment episode, exploratory overall response rate (ORR) for Bruton tyrosine kinase inhibitors (BTKi) was 88.9% (8/9); median progression-free survival (PFS) from treatment initiation was 29 months. For venetoclax-based regimens, ORR was 83.3% (5/6) and median PFS 52 months.</p><p><strong>Conclusions: </strong>These data suggest meaningful activity of BTK and BCL-2 inhibitors in CLL/SLL with extranodal organ involvement.</p>","PeriodicalId":139,"journal":{"name":"Cancer Medicine","volume":"15 10","pages":"e72341"},"PeriodicalIF":3.5,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13635478/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149101560","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":"Low-Dose Cytarabine Plus G-CSF Induction in Pediatric M2 Acute Myeloid Leukemia: A Multicenter Study.","authors":"Wenxin Ou, Xiaohua Zhu, Jun Lu, Hongsheng Wang, Ning Liao, Yufeng Liu, Hua Jiang, Qi An, Xiaojun Yuan, Hailong He, Ningling Wang, Jixia Luo, Xiuli Ju, Qian-Fei Wang, Minghua Yang, Cheng Cheng, Peifang Xiao, Liangchun Yang, Li Gao, Raul C Ribeiro, Shaoyan Hu, Xiaowen Zhai","doi":"10.1002/cam4.72349","DOIUrl":"https://doi.org/10.1002/cam4.72349","url":null,"abstract":"<p><p>This retrospective secondary analysis of the multicenter randomized CALS III-AML18 trial evaluated the efficacy and safety of low-dose chemotherapy (LDC) compared with standard-dose chemotherapy (SDC) in children with M2 acute myeloid leukemia (AML-M2). A total of 221 children were included, with 109 in the LDC arm and 112 in the SDC arm. The complete remission (CR)/CR with incomplete recovery (CRi) rates after induction I and II were 67.0% versus 70.5% (p = 0.568) and 84.4% versus 89.3% (p = 0.740), respectively. The 3 year overall survival (OS) rates were 81.2% ± 3.9% and 86.9% ± 3.3% in the LDC and SDC arms, respectively (p = 0.304). The corresponding 3 year relapse-free survival (RFS) rates were 82.0% ± 3.8% and 88.1% ± 3.1% (p = 0.205), and the 3 year event-free survival (EFS) rates were 62.1% ± 4.8% and 70.8% ± 4.4% (p = 0.218). Among patients with KIT mutations, outcomes were poorer in the LDC arm than in the SDC arm, including 3 year OS (67.1% ± 8.7% vs. 91.5% ± 4.1%, p = 0.011), RFS (70.6% ± 7.8% vs. 87.5% ± 4.8%, p = 0.038), and EFS (49.2% ± 8.7% vs. 81.0% ± 5.7%, p = 0.002). Among patients who developed sepsis, grade 3-5 events were less frequent in the LDC arm than in the SDC arm (33.3% vs. 78.8%, p < 0.001). LDC was also associated with faster neutrophil and platelet recovery, lower transfusion requirements, and reduced treatment costs during induction. No statistically significant differences in remission or survival outcomes were observed between LDC and SDC, while the LDC regimen showed a lower treatment-related burden. These findings support further evaluation of LDC as a toxicity-sparing induction strategy in selected pediatric patients with AML-M2. The poorer outcomes observed among patients with KIT mutations warrant caution when considering treatment de-intensification in this subgroup.</p>","PeriodicalId":139,"journal":{"name":"Cancer Medicine","volume":"15 10","pages":"e72349"},"PeriodicalIF":3.5,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13627885/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149101649","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":"Self-Reported Cancer-Related Cognitive Impairment and Psychosocial Symptom Burden in Survivors of Head and Neck Cancer.","authors":"Matthew E Lin, Jake Stenzel, Desiree Delavary, Maie A St John, Deborah J Wong, Patricia A Ganz, Eden R Brauer","doi":"10.1002/cam4.72316","DOIUrl":"https://doi.org/10.1002/cam4.72316","url":null,"abstract":"<p><strong>Background: </strong>Cancer-related cognitive impairment (CRCI) is an increasingly recognized survivorship concern, yet its prevalence and associated clinical and psychosocial factors among survivors of head and neck cancer (HNC) remain poorly characterized.</p><p><strong>Methods: </strong>This cross-sectional study recruited survivors of HNC, who were at least 1-year post-diagnosis, from an institutional tumor registry to complete a comprehensive survey. Self-reported cognitive function was assessed using the PROMIS Cognitive Function Short Form 8a, with a T-score < 40 indicating cognitive impairment. Symptom burden was assessed using the EORTC QLQ-HN43, PROMIS short forms, and the Insomnia Severity Index. Social role functioning was assessed using the PROMIS Satisfaction with Participation in Social Roles short form. Multivariable linear and logistic regression examined factors independently associated with self-reported cognitive impairment.</p><p><strong>Results: </strong>Of 337 survey respondents, 41 survivors (12.2%) met criteria for self-reported moderate to severe cognitive impairment. Cognitively impaired survivors reported significantly higher symptom burden and lower social role functioning than survivors within normal limits. In multivariable linear regression (R² = 0.520), poorer cognitive function was significantly associated with anxiety (β = -0.362, p < 0.001), fatigue (β = -0.223, p < 0.001), sleep disturbance (β = -0.261, p < 0.001), and social isolation (β = -0.178, p = 0.002). In logistic regression, anxiety (OR = 1.07, p = 0.035), fatigue (OR = 1.08, p = 0.021), and high-intensity treatment (OR = 2.62, p = 0.028) were independently associated with impairment.</p><p><strong>Conclusions: </strong>Approximately one in eight HNC survivors reported moderate-to-severe cognitive impairment. Self-reported cognitive difficulty was associated with psychosocial symptom burden and multimodal treatment, and co-occurred with poorer social role functioning. These findings support concurrent assessment of cognitive and psychosocial symptoms in HNC survivorship care.</p>","PeriodicalId":139,"journal":{"name":"Cancer Medicine","volume":"15 10","pages":"e72316"},"PeriodicalIF":3.5,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13628158/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149101662","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":"Impact of p53 Target Genes on Drug Resistance in TP53-Mutated B-Cell Precursor Acute Lymphoblastic Leukemia.","authors":"Thao T T Nguyen, Minori Tamai, Koshi Akahane, Chiaki Komatsu, Keiko Kagami, Xuekang Qi, Luay Aswad, Kunio Miyake, Shin Kasai, Shinpei Somazu, Atsushi Watanabe, Kumiko Goi, Koichi Oshima, Hiroshi Imanaga, Yuichiro Semba, Masashi Sanada, Janne Lehtiö, Hiroaki Goto, Masayoshi Minegishi, Toshiya Inaba, Shotaro Iwamoto, Takahiro Maeda, Rozbeh Jafari, Takeshi Inukai","doi":"10.1002/cam4.72386","DOIUrl":"10.1002/cam4.72386","url":null,"abstract":"<p><p>TP53 mutations are linked to poor prognoses in B-cell precursor acute lymphoblastic leukemia (BCP-ALL), indicating that specific p53 target genes may contribute to drug resistance. Although the impact of specific genetic alterations on drug sensitivity has been reported in BCP-ALL, the effects of TP53 mutations on sensitivity to individual agents remain poorly defined in the clinical setting because of the use of combination chemotherapy regimens. In the present study, we addressed this issue through two complementary analyses using a large panel of BCP-ALL cell lines. Initially, 30 cell lines harboring TP53 mutations demonstrated significantly greater resistance to daunorubicin (DNR), mafosfamide (MAF; an active analog of cyclophosphamide), 6-mercaptopurine (6-MP), and prednisolone compared to 46 cell lines without mutations. Second, 11 CRISPR/Cas9-mediated TP53-knockout sublines derived from cell lines with wild-type TP53 recapitulated resistance to DNR, MAF, and 6-MP, as well as to vincristine (VCR) and cytarabine (Ara-C). Consistent with these findings, re-evaluation of genome-wide CRISPR screening datasets revealed significant enrichment of TP53 gRNAs in cells treated with DNR, MAF, 6-MP, Ara-C, and VCR. Furthermore, transcriptomic and proteomic analyses of p53 target genes in the two cell line models, along with re-evaluation of genome-wide CRISPR screening datasets, identified BAX, BBC3, and FDXR as key p53 target genes associated with multidrug resistance. These results highlight the potential value of targeting these p53 downstream pathways to improve outcomes in TP53-mutated BCP-ALL cases.</p>","PeriodicalId":139,"journal":{"name":"Cancer Medicine","volume":"15 10","pages":"e72386"},"PeriodicalIF":3.5,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13662230/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149178151","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":"Changes in the Age Distribution of Radical Prostatectomy and Radical Cystectomy During the Diffusion of Robot-Assisted Surgery in Japan.","authors":"Taku Mochizuki, Takashi Kawahara, Akihito Hashizume, Masanobu Yamazaki, Teppei Takeshima, Hiroji Uemura, Kazuhide Makiyama, Jun-Ichi Teranishi","doi":"10.1002/cam4.72370","DOIUrl":"https://doi.org/10.1002/cam4.72370","url":null,"abstract":"<p><strong>Objective: </strong>To examine how the age distribution of radical prostatectomy and radical cystectomy changed in Japan during the period in which robot-assisted surgery spread.</p><p><strong>Methods: </strong>We used the National Database Open Data for fiscal years 2014 to 2024 (Japanese fiscal year, April to March). Procedures were identified by procedure code and classified as robot-assisted or conventional. Rates per 100,000 population were calculated, and the rate in each age group was expressed relative to that in patients aged 70 to 74 years. Cells with fewer than 10 claims are suppressed in the source tables; sensitivity analyses imputed 0, 5 or 9 procedures into these cells.</p><p><strong>Results: </strong>Radical prostatectomy increased from 20,222 to 29,239 procedures and radical cystectomy from 3545 to 4793. Rates in patients younger than 75 years rose only about 1.2-fold. For prostatectomy, the rate ratio in men aged 75 to 79 years rose from 0.40 to 0.93, while that in men aged 80 to 84 years reached only 0.22. For cystectomy, the ratio in patients aged 80 to 84 years rose from 0.74 to 0.95, while no clear increase was seen in patients aged 85 years or older (0.18 to 0.20, p = 0.791). In men aged 80 years or older, robot-assisted prostatectomy increased from 94 to 1239 procedures, whereas conventional surgery changed from 64 to 97. These findings were unchanged when suppressed cells were imputed as 5 or 9.</p><p><strong>Conclusions: </strong>Between fiscal years 2014 and 2024, the age distribution of radical prostatectomy and radical cystectomy in Japan shifted toward older patients. The increase was concentrated in men aged 75 to 84 years for prostatectomy and in patients aged 80 to 84 years for cystectomy, and was accounted for mainly by robot-assisted procedures.</p>","PeriodicalId":139,"journal":{"name":"Cancer Medicine","volume":"15 10","pages":"e72370"},"PeriodicalIF":3.5,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13654486/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149163892","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}