Cancer Medicine最新文献

{"title":"Epigenetic Ageing and Breast Cancer Risk: A Systematic Review","authors":"Emily McLennan,&nbsp;Danmeng Lily Li,&nbsp;Melissa C. Southey,&nbsp;Pierre-Antoine Dugué","doi":"10.1002/cam4.70355","DOIUrl":"10.1002/cam4.70355","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Age is one of the strongest risk factors for breast cancer. Measures of biological age based on DNA methylation have gained popularity for their strong association with risk of many diseases, including cancer, which may help to identify high-risk subgroups for targeted prevention.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>We carried out a systematic review of prospective studies that examined the association of methylation-based markers of ageing with risk of invasive breast cancer in healthy (breast cancer-free) women, published up to May 2023. The search of three databases (MEDLINE, EMBASE and Web of Science) identified 2913 individual abstracts eligible for screening. Risk of bias assessment was conducted using ROBINS-E.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Ten prospective studies met the eligibility criteria, and these were heterogeneous in design and findings. The most frequently assessed epigenetic ageing measures were Horvath's first-generation clock, <i>PhenoAge</i> and <i>GrimAge</i>. Four studies reported mainly positive associations, five null associations and one reported a negative association. These associations were generally weak and the results were not consistent across epigenetic ageing measures.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>The summarised evidence is insufficient to support a role for current epigenetic ageing measures to stratify breast cancer risk.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <p><b>PROSPERO Registration:</b> This systematic review was registered in the International Prospective Register of Systematic Reviews (PROSPERO: CRD42023417559)</p>\u0000 </section>\u0000 </div>","PeriodicalId":139,"journal":{"name":"Cancer Medicine","volume":"13 21","pages":""},"PeriodicalIF":2.9,"publicationDate":"2024-11-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11555139/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142612716","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":"Is Centralisation of Cancer Services Associated With Under-Treatment of Patients With High-Risk Prostate Cancer?—A National Population-Based Study","authors":"Lu Han,&nbsp;Emily Mayne,&nbsp;Joanna Dodkins,&nbsp;Richard Sullivan,&nbsp;Adrian Cook,&nbsp;Matthew Parry,&nbsp;Julie Nossiter,&nbsp;Thomas E. Cowling,&nbsp;Alison Tree,&nbsp;Noel Clarke,&nbsp;Jan van der Meulen,&nbsp;Ajay Aggarwal","doi":"10.1002/cam4.70403","DOIUrl":"10.1002/cam4.70403","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Centralising prostate cancer surgical and radiotherapy services, requires some patients to travel longer to access treatment, but its impact on actual treatment utilisation and outcomes is unknown.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Using national cancer registry records linked to administrative hospital data, we identified all patients with high risk and locally advanced prostate cancer diagnosed between 1 April 2019 and 31 March 2020 in the English National Health Service (<i>n</i> = 15,971). Estimated travel times from the patient residential areas to the nearest hospital providing surgery or radiotherapy were estimated for journeys by car and by public transport. Multivariable logistic regression was used to model relationships between travel time and receipt of care with adjustment for patient characteristics.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>10,693 (67%) men received radical surgery or radiotherapy (RT) within 12 months of diagnosis. Average travel time to the nearest hospital providing prostatectomy or RT was 23.2 min by private car and 58.2 min by public transport. We found no association between travel time, either by car or public transport and the likelihood of receiving curative treatment. Patients living in the most socially deprived areas, those aged over 70, those with two or more comorbidities, and those of black ethnic origin, were less likely to receive curative treatment (<i>p</i>&amp; =&amp; 0.001 for all associations).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>The current configuration of national prostate cancer services is not associated with the likelihood of receiving curative treatment. Further increases in capacity will unlikely improve utilisation rates beyond addressing sociodemographic barriers.</p>\u0000 </section>\u0000 </div>","PeriodicalId":139,"journal":{"name":"Cancer Medicine","volume":"13 21","pages":""},"PeriodicalIF":2.9,"publicationDate":"2024-11-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11551782/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142612846","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":"Predicting Pancreatic Cancer in New-Onset Diabetes Cohort Using a Novel Model With Integrated Clinical and Genetic Indicators: A Large-Scale Prospective Cohort Study","authors":"Yongji Sun,&nbsp;Chaowen Hu,&nbsp;Sien Hu,&nbsp;Hongxia Xu,&nbsp;Jiali Gong,&nbsp;Yixuan Wu,&nbsp;Yiqun Fan,&nbsp;Changming Lv,&nbsp;Tianyu Song,&nbsp;Jianyao Lou,&nbsp;Kai Zhang,&nbsp;Jian Wu,&nbsp;Xiawei Li,&nbsp;Yulian Wu","doi":"10.1002/cam4.70388","DOIUrl":"10.1002/cam4.70388","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Introduction</h3>\u0000 \u0000 <p>Individuals who develop new-onset diabetes have been identified as a high-risk cohort for pancreatic cancer (PC), exhibiting an incidence rate nearly 8 times higher than the general population. Hence, the targeted screening of this specific cohort presents a promising opportunity for early pancreatic cancer detection. We aimed to develop and validate a novel model capable of identifying high-risk individuals among those with new-onset diabetes.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Employing the UK Biobank cohort, we focused on those developing new-onset diabetes during follow-up. Genetic and clinical characteristics available at registration were considered as candidate predictors. We conducted univariate regression analysis to identify potential indicators and used a 5-fold cross-validation method to select optimal predictors for model development. Five machine learning algorithms were used for model development.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Among 12,735 patients with new-onset diabetes, 100 (0.8%) were diagnosed with PC within 2 years. The final model (area under the curve, 0.897; 95% confidence interval, 0.865–0.929) included 5 clinical predictors and 24 single nucleotide polymorphisms. Two threshold cut-offs were established: 1.28% and 5.26%. The recommended 1.28% cut-off, based on model performance, reduces definitive testing to 13% of the total population while capturing 76% of PC cases. The high-risk threshold is 5.26%. Utilizing this threshold, only 2% of the population needs definitive testing, capturing nearly half of PC cases.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>We, for the first time, combined clinical and genetic data to develop and validate a model to determine the risk of pancreatic cancer in patients with new-onset diabetes using machine learning algorithms. By reducing the number of unnecessary tests while ensuring that a substantial proportion of high-risk patients are identified, this tool has the potential to improve patient outcomes and optimize healthcare sources.</p>\u0000 </section>\u0000 </div>","PeriodicalId":139,"journal":{"name":"Cancer Medicine","volume":"13 21","pages":""},"PeriodicalIF":2.9,"publicationDate":"2024-11-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11551786/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142612858","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":"Combination Immunotherapy With Radiotherapy in Non-Small Cell Lung Cancer: A Review of Evidence","authors":"Justin L. Burr,&nbsp;Kurtis C. Johnson,&nbsp;Joseph J. Carmicheal,&nbsp;Chi Lin,&nbsp;Apar Kishor Ganti","doi":"10.1002/cam4.70402","DOIUrl":"10.1002/cam4.70402","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Radiotherapy plays a fundamental role in the treatment of patients with all stages of non-small-cell lung cancer (NSCLC). The emergence of immune checkpoint inhibitors (ICIs) has transformed the standard of care in these patients. The use of ICIs is increasingly utilized in the definitive setting as an adjunct to chemoradiotherapy or surgery and remains a vital component in the treatment of metastatic disease. Despite improvements in patient survival, the use of immunotherapy as monotherapy has shown limited overall response rates with susceptibility to resistance. Radiotherapy has been identified as a viable option to enhance the response rate to ICI and improve outcomes in NSCLC.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>We queried the English PubMed database utilizing variably combined search items including “radiation,” “chemoradiation,” “immune checkpoint,” “immunotherapy,” “stereotactic body radiotherapy,” and “non-small-cell lung”. We additionally searched various acceptable alternative terms for similar keywords such as “radiotherapy” in place of “radiation.” These results were subsequently curated for relevance and impact on current treatment paradigms.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>In this review, we discuss preclinical and clinical studies relating to combinatorial use of immunotherapy and radiation in NSCLC. These studies are presented in the context of early-stage, operable stage III, unresectable stage III, and metastatic disease. The majority of the data illustrate promising results regarding the additive or synergistic effects of radiation and immunotherapy with a suggestion that the timing of these treatment modalities is crucial to optimizing outcomes.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>While there is now evidence regarding the favorable interplay between radiation and immunotherapy in NSCLC, there remain multiple unanswered questions which are expected to be addressed in ongoing clinical trials.</p>\u0000 </section>\u0000 </div>","PeriodicalId":139,"journal":{"name":"Cancer Medicine","volume":"13 21","pages":""},"PeriodicalIF":2.9,"publicationDate":"2024-11-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11551781/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142612686","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":"Identification and Experimental Validation of Prognostic miRNA Signature and Ferroptosis-Related Key Genes in Cervical Squamous Cell Carcinoma","authors":"Yan Guo,&nbsp;Yana Han,&nbsp;Junjie Zhang,&nbsp;Yanbin Zhou,&nbsp;Meiyan Wei,&nbsp;Lijun Yu","doi":"10.1002/cam4.70415","DOIUrl":"10.1002/cam4.70415","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Objectives</h3>\u0000 \u0000 <p>This study aimed to investigate the prognostic value of miRNAs and ferroptosis-related genes in cervical squamous cell carcinoma.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>We mined data from public databases for differentially expressed miRNAs, ferroptosis-related genes, and clinical parameters and constructed a prognostic risk model. The predictive performance of the model was evaluated using survival and receiver operating characteristic curve analyses. We combined the clinicopathological features to construct a nomogram and evaluated its efficacy using calibration and clinical decision curves. The correlation between miRNA characteristics, risk score, and the tumor microenvironment was also studied. Next, consensus and key genes were screened, and their biological functions were analyzed using KEGG, GO, GSEA, and drug sensitivity analysis. Finally, the expression of miRNAs and key genes was detected using qRT-PCR and western blotting to verify the prediction results.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Seven miRNA signatures (miR-100-3p, miR-301a-5p, miR-331-3p, miR-425-5p, miR-502-3p, miR-505-5p, and miR-629-3p) were generated, and prognostic risk and nomogram models were successfully constructed. These models exhibited good accuracy. miRNA signatures correlated with the tumor microenvironment. Twelve consensus genes and three key genes (SLC2A1, ANO6, and TXNIP) were screened and their biofunctional diversity was identified using various analytical methods. qRT-PCR and western blotting were used to verify the expression of miR-301a-5p, miR-505-5p, SLC2A1, and TXNIP in cervical squamous carcinoma. The results were consistent with those of bioinformatics analyses.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Seven miRNAs may serve as prognostic biomarkers of cervical squamous cell carcinoma. SLC2A1, ANO6, and TXNIP are associated with cervical squamous cell carcinoma and may serve as ferroptosis-related markers of the disease.</p>\u0000 </section>\u0000 </div>","PeriodicalId":139,"journal":{"name":"Cancer Medicine","volume":"13 21","pages":""},"PeriodicalIF":2.9,"publicationDate":"2024-11-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11551785/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142612727","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":"Pan-Cancer Single-Cell Transcriptomic Analysis Reveals Divergent Expression of Embryonic Proangiogenesis Gene Modules in Tumorigenesis","authors":"Zeshuai Wang,&nbsp;Yiyi Su,&nbsp;Lisha Zhao,&nbsp;Wei Liu,&nbsp;Jiaqi Zhang,&nbsp;Wei Yang,&nbsp;Hanjie Li,&nbsp;Mingqian Feng,&nbsp;Hao Wang,&nbsp;Zhuo Song","doi":"10.1002/cam4.70373","DOIUrl":"10.1002/cam4.70373","url":null,"abstract":"&lt;div&gt;\u0000 \u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;h3&gt; Background&lt;/h3&gt;\u0000 \u0000 &lt;p&gt;Angiogenesis is indispensable for the sustained survival and progression of both embryonic development and tumorigenesis. This intricate process is tightly regulated by a multitude of pro-angiogenic genes. The presence of gene modules facilitating angiogenesis has been substantiated in both embryonic development and the context of tumor proliferation. However, it remains unresolved whether the pro-angiogenic gene modules expressed during embryonic development also exist in tumors.&lt;/p&gt;\u0000 &lt;/section&gt;\u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;h3&gt; Methods&lt;/h3&gt;\u0000 \u0000 &lt;p&gt;This study performed a pan-cancer single-cell RNA sequencing (scRNA-seq) analysis on samples from 332 patients across seven cancer types: thyroid carcinoma, lung cancer, breast cancer, hepatocellular carcinoma, colorectal cancer, ovarian carcinoma, and prostate adenocarcinoma. Data processing was carried out using the Seurat R package, with rigorous quality control to filter high-quality cells and mitigate batch effects across datasets. We used principal component analysis (PCA), shared nearest neighbor graph-based clustering, and Uniform Manifold Approximation and Projection (UMAP) to visualize cell types and identify distinct cell clusters. Myeloid cell subpopulations were further analyzed for the expression of embryonic pro-angiogenic gene modules (EPGM) and tumor pro-angiogenic gene modules (TPGM).&lt;/p&gt;\u0000 &lt;/section&gt;\u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;h3&gt; Results&lt;/h3&gt;\u0000 \u0000 &lt;p&gt;The analysis identified nine major cell types within the tumor microenvironment, with myeloid cells consistently exhibiting elevated expression of both tumor pro-angiogenic gene modules (TPGM) and EPGM across all tumor types. In particular, myeloid cells, including macrophages and monocytes, showed high EPGM expression, indicating an active role of embryonic pro-angiogenesis pathways in tumors. A subset analysis revealed 20 distinct myeloid subtypes with varying EPGM and TPGM expression across different cancers. Treatment and disease stage influenced these gene expressions, with certain subtypes, such as HSPAhi/STAT1+ macrophages in breast cancer, displaying reduced pro-angiogenic gene activity post-treatment.&lt;/p&gt;\u0000 &lt;/section&gt;\u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;h3&gt; Conclusion&lt;/h3&gt;\u0000 \u0000 &lt;p&gt;This study provides evidence that tumors may exploit EPGM to enhance vascularization and support sustained growth, as evidenced by the elevated EPGM expression in tumor-associated myeloid cells. The consistent presence of EPGM in TAMs across multiple cancer types suggests a conserved mechanism wherein tumors harness embryonic angiogenic pathways to facilitate their progression. Distinct EPG","PeriodicalId":139,"journal":{"name":"Cancer Medicine","volume":"13 21","pages":""},"PeriodicalIF":2.9,"publicationDate":"2024-11-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11551789/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142612852","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 “Clinical Outcome of Induction Treatment in the Era of Novel Agents and the Impact of the Number of High-Risk Cytogenetic Abnormalities (HRA) on Prognosis of Patients With Newly Diagnosed Multiple Myeloma (NDMM): Insights From a Multicenter Study”","authors":"","doi":"10.1002/cam4.70406","DOIUrl":"10.1002/cam4.70406","url":null,"abstract":"<p>This corrects the article “Clinical Outcome of Induction Treatment in the Era of Novel Agents and the Impact of the Number of High-Risk Cytogenetic Abnormalities (HRA) on Prognosis of Patients With Newly Diagnosed Multiple Myeloma (NDMM): Insights From a Multicenter Study” PMID: 39422477 PMCID: PMC11487677 DOI: 10.1002/cam4.70270</p><p>The correct affiliations for Xiaojin Li are as follows:</p><p>2. Faculty of Environmental Science and Engineering, Kunming University of Science and Technology, Kunming, Yunnan, China</p><p>3. The Affiliated Hospital of Yunnan University, Kunming, Yunnan, China</p><p>The correct title of Table 4 is “Baseline characteristics of patients without HRA, those with 1 HRA and those with ≥ 2 HRA”</p><p>We apologize for these errors.</p>","PeriodicalId":139,"journal":{"name":"Cancer Medicine","volume":"13 21","pages":""},"PeriodicalIF":2.9,"publicationDate":"2024-11-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11551253/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142612689","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":"CaMKII Exacerbates Doxorubicin-Induced Cardiotoxicity by Promoting Ubiquitination Through USP10 Inhibition","authors":"Yitong Yang,&nbsp;Zhenyi Wang,&nbsp;Nisha Wang,&nbsp;Jian Yang,&nbsp;Lifang Yang","doi":"10.1002/cam4.70286","DOIUrl":"10.1002/cam4.70286","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Doxorubicin (DOX) is an effective anticancer drug, but it has a problem of cardiotoxicity that cannot be ignored. Ca²⁺/calmodulin-dependent protein kinase II (CaMKII) is tightly associated with the pathological progression of DOX-induced cardiotoxicity. Ubiquitin-specific protease 10 (USP10) plays an important role in many biological processes and cancers. However, its association with DOX-induced cardiotoxicity and CaMKII remains unclear.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>H9C2 cells, HL-1 cells and C57BL/6 mice were used to establish the DOX-induced cardiotoxicity model, and the CaMKII-specific inhibitor KN-93 and USP10 specific inhibitor Spautin-1 were used to observe the CaMKII and USP10 effect. In cell experiments, CCK-8 method was used to assess cell viability, LDH kit was used to assess lactate dehydrogenase expression, DCFH-DA staining was used to observe changes in active oxygen content, TUNEL staining was used to observe cell apoptosis, and Western blotting method was used to detect relevant protein markers. The expression of p-CaMKII and USP10 was assessed by immunofluorescence staining. In animal experiments, mouse echocardiograph was used were used to evaluate cardiac function, and HE staining and Masson staining were used to evaluate myocardial injury. Cardiomyocyte apoptosis was detected by TUNEL staining. Western blotting method was used to detect relevant protein markers.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Our results demonstrated that activation of CaMKII and inhibition of USP10 pathway related to DOX-induced cardiotoxicity. Inhibition of CaMKII with KN-93 ameliorated DOX-induced cardiac dysfunction and cytotoxicity. In addition, CaMKII inhibition prevented DOX-induced apoptosis and ubiquitination. Furthermore, CaMKII inhibition increased USP10 expression in DOX-treated mouse hearts, H9C2 cells and HL-1 cells. At last, the USP10 inhibitor, Spautin-1, blocked the regulatory effect of CaMKII inhibition on apoptosis and ubiquitination in DOX-induced cardiotoxicity.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Our findings revealed that DOX-induced myocardial apoptosis and activated CaMKII through cellular and animal levels, while providing a novel probe into the mechanism of CaMKII action: promoting ubiquitination by inhibiting USP10 aggravated apoptosis.</p>\u0000 </section>\u0000 </div>","PeriodicalId":139,"journal":{"name":"Cancer Medicine","volume":"13 21","pages":""},"PeriodicalIF":2.9,"publicationDate":"2024-11-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11549063/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142612736","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":"Genetic Alterations in Chromatin Regulatory Genes in Upper Tract Urothelial Carcinoma and Urothelial Bladder Cancer","authors":"Shuo Wang,&nbsp;Xuzhi Yan,&nbsp;Weihua Lan,&nbsp;Yapeng Wang,&nbsp;Ze Wang,&nbsp;Dali Tong,&nbsp;Yao Zhang,&nbsp;Qiang Ran,&nbsp;Haoyang Li,&nbsp;Junhao Jin,&nbsp;Haiyang Xiao,&nbsp;Jing Xu,&nbsp;Qian Yan,&nbsp;Dianzheng Zhang,&nbsp;Qiang Ma,&nbsp;Hualiang Xiao,&nbsp;Jun Qin,&nbsp;Luofu Wang,&nbsp;Jun Jiang,&nbsp;Qiuli Liu","doi":"10.1002/cam4.70398","DOIUrl":"10.1002/cam4.70398","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Purpose</h3>\u0000 \u0000 <p>Upper tract urothelial carcinoma (UTUC) and urothelial carcinoma of the bladder (UCB) share histomorphological and therapeutic features but distinct epidemiologic and clinicopathologic characteristics. We examined alterations of chromatin regulatory genes in molecular subtypes, clonal relatedness, and T-cell receptor (TCR) diversity in UTUC and UCB.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Materials and Methods</h3>\u0000 \u0000 <p>Targeted next-generation sequencing or whole-exome DNA sequencing and TCR sequencing were conducted with 34 UTUC and 49 UCB specimens from 63 patients. Tumors were subtyped based on the expression of CK5 and GATA3. Results of tissue microarray of 78 muscle-invasive bladder cancer (MIBC) samples were used as prognostic factors of different subtypes of MIBC.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Chromatin regulatory genes were frequently mutated in both UTUC and UCB. Rapid relapse and progression of non-MIBC are correlated with alterations of <i>KMT2C</i> and <i>EP300</i>. Frequency of alterations in chromatin regulatory genes is higher in UTUC patients with SBS22 and SBS2 signatures and lower in UCB patients with SBS2 and SBS6 signatures. GATA3 and CK5 double-positive patients with higher frequencies of <i>SMARCA4</i>, <i>ARID1A</i>, and <i>EP300</i> mutations have better prognoses than patients with basal subtypes. Although UTUC and UCB in the same patient can be either clonally related or developed independently, mutated genes in chromatin pathway were enriched in the related clones. Compared to UTUC, UCB had more deleterious mutations in DNA damage repair (DDR) genes, higher levels of tumor mutation burden (TMB) and copy number variations (CNVs), as well as higher TCR clonality and lower TCR diversity.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Since genetic alterations of the chromatin pathway genes are important in both UTUC and UCB, they could serve as potential biomarkers for predicting disease progression and therapeutic targets. Differences in mutation frequencies of DDR pathway, TMB, CNV, and TCR might be the contributing factors for the distinct responses to immune checkpoint inhibitor (ICI) between UTUC and UCB.</p>\u0000 </section>\u0000 </div>","PeriodicalId":139,"journal":{"name":"Cancer Medicine","volume":"13 21","pages":""},"PeriodicalIF":2.9,"publicationDate":"2024-11-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11544325/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142602210","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":"Pretreatment Quality of Life and Substance Use Among Patients Diagnosed With Head and Neck Cancer","authors":"Eric Adjei Boakye,&nbsp;Sami I. Nassar,&nbsp;Suma J. Alzouhayli,&nbsp;Amy M. Williams,&nbsp;Steven S. Chang,&nbsp;Tamer A. Ghanem,&nbsp;Marissa Gilbert,&nbsp;Suhael Momin,&nbsp;Farzan Siddiqui,&nbsp;Vivian F. Wu,&nbsp;Samantha H. Tam","doi":"10.1002/cam4.70399","DOIUrl":"10.1002/cam4.70399","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>There is a paucity of research on the effects of commonly used substances, such as cannabis and other drugs, on quality of life as a contributor to head and neck cancer (HNC) prognosis. We examined associations between non-alcohol or tobacco substance use (cannabis and other illicit drug) and self-reported quality of life in patients with HNC prior to starting treatment.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>This was a cross-sectional study of patients who presented for routine psych-oncologevaluation prior to treatment between 11/2015 and 9/2022. Primary exposures were cannabis use (never, past, or current users) and current illicit drug use (yes/no). The primary outcome measure was the Functional Assessment of Cancer Therapy—Head and Neck (FACT-HN) subscales (physical, social/family, functional and emotional). Linear regression models examined associations between pretreatment substance use and FACT-HN subscales adjusting for demographic, socioeconomic, and clinical factors.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Of 570 patients, 13.9% endorsed current cannabis and 13.9% current illicit drug use. The mean (SD) scores for FACT-HN subscales were physical well-being = 22.8 (5.0), social well-being = 22.7 (5.5), emotional well-being = 17.5 (4.5), and functional well-being = 18.7 (6.9). In the adjusted models, cannabis use was not independently associated with any FACT-HN subscales. However, patients who currently used illicit drugs reported worse emotional well-being (<i>β</i> = −1.32; 95% CI −2.45 to −0.20). No independent association was found between current illicit drug use and other subscales (physical, social, and functional).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Illicit drug use, but not cannabis use, is negatively associated with pretreatment emotional well-being in patients with HNC. Further research exploring the relationships between longitudinal cannabis and illicit drug use and methods of consumption on QoL and cancer outcomes in patients with head and neck cancer is warranted.</p>\u0000 </section>\u0000 </div>","PeriodicalId":139,"journal":{"name":"Cancer Medicine","volume":"13 21","pages":""},"PeriodicalIF":2.9,"publicationDate":"2024-11-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11544131/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142602214","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}