British Journal of Cancer最新文献

{"title":"Effects of tamoxifen on cognitive function in patients with primary breast cancer.","authors":"Maryse J Luijendijk, Sanne M Buijs, Agnes Jager, Stijn L W Koolen, Elsken van der Wall, Sanne B Schagen, Ron H J Mathijssen","doi":"10.1038/s41416-024-02914-1","DOIUrl":"https://doi.org/10.1038/s41416-024-02914-1","url":null,"abstract":"<p><strong>Introduction: </strong>Tamoxifen may adversely affect cognitive function by interfering with estrogen action in the brain. Despite growing evidence for a relationship between tamoxifen and cognitive problems, findings remain inconclusive. While some tamoxifen-related side effects seem exposure-dependent with concentrations of tamoxifen or its main metabolite, endoxifen, this has never been investigated for cognitive function. We investigated cognitive function after two years of tamoxifen and its association with tamoxifen and endoxifen exposure.</p><p><strong>Methods: </strong>135 women with breast cancer completed the Amsterdam Cognition Scan (ACS), an online neuropsychological test battery, after two years of tamoxifen. Test scores were converted to standardized Z-scores based on a matched 'no-cancer' control group. Tamoxifen and endoxifen concentrations and tamoxifen dose were regressed separately on cognitive functioning.</p><p><strong>Results: </strong>Patients reported mild cognitive complaints and had worse verbal learning, processing speed, executive functioning, and motor functioning compared to matched controls. After correcting for age, mean tamoxifen and endoxifen levels, as well as tamoxifen dose, were associated with worse performance on several cognitive domains.</p><p><strong>Conclusion: </strong>Tamoxifen is adversely associated with objective as well as self-reported cognitive function, which may depend on the level of exposure to tamoxifen and endoxifen. Further research is warranted to confirm this hypothesis.</p>","PeriodicalId":9243,"journal":{"name":"British Journal of Cancer","volume":" ","pages":""},"PeriodicalIF":6.4,"publicationDate":"2024-11-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142726108","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"SKP2 inhibition activates tumor cell-intrinsic immunity by inducing DNA replication stress and genomic instability.","authors":"Yuchong Peng, Xuli Qi, Liuyang Ding, Jingjing Huang, Youhong Liu, Rirong Zheng, Yongming Fu, Linglong Yin, Tanggang Deng, Yubing Ye, Size Chen, Xiong Li","doi":"10.1038/s41416-024-02909-y","DOIUrl":"https://doi.org/10.1038/s41416-024-02909-y","url":null,"abstract":"<p><strong>Background: </strong>S-phase kinase-associated protein 2 (SKP2) is a typical oncogene aberrantly overexpressing in a variety of cancer types, but it remains elusive whether SKP2 regulates the antitumor immunity of triple-negative breast cancer.</p><p><strong>Methods: </strong>The efficacy of anti-PD-1 was evaluated in the orthotopic xenografts of immunocompetent mice models. The infiltration of cytotoxic T cells in tumor microenvironment(TME) were assessed by immunofluorescence staining. The levels of pro-inflammatory chemokines were analyzed by ELISA. The protein interaction was analyzed by co-immunoprecipitation and GST pull-down. The genomic instability was analyzed by fluorescent microscopy.</p><p><strong>Results: </strong>SKP2 inhibition significantly improved the antitumor efficacy of immune checkpoint blockade (ICB). Furthermore, SKP2 inhibition activated the cGAS/STING signal pathway and induced the secretion of pro-inflammatory chemokines, thereby promoting cytotoxic T cell infiltration. Additionally, we identified CDC6, a DNA replication licensing factor as a novel substrate of SKP2 in addition to CDT1. SKP2 induced protein degradation of CDC6 and CDT1 through the ubiquitin-proteasome pathway. Conversely, SKP2 inhibition elevated CDC6 and CDT1 protein levels, which caused DNA aberrant replication, DNA damage and genomic instability, thereby resulting in the accumulation of cytosolic DNA, activating cGAS/STING signaling pathway and improving antitumor immunity.</p><p><strong>Conclusion: </strong>SKP2 may be used as an effective therapeutic target to enable ICB antitumor immunotherapy.</p><p><strong>Social media: </strong>Peng et al. found that SKP2 inhibition improved the antitumor immunotherapy by activating tumor cell-intrinsic immunity, thereby providing evidences that SKP2 may be used as an effective therapeutic target to enable ICB antitumor immunotherapy.</p>","PeriodicalId":9243,"journal":{"name":"British Journal of Cancer","volume":" ","pages":""},"PeriodicalIF":6.4,"publicationDate":"2024-11-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142709292","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Associations of blood lipids and LDL cholesterol lowering drug-targets with colorectal cancer risk: a Mendelian randomisation study.","authors":"Wing Ching Chan, Lili Liu, Emmanouil Bouras, Verena Zuber, Wanqing Wen, Jirong Long, Dipender Gill, Neil Murphy, Marc J Gunter, Themistocles L Assimes, Luis Bujanda, Stephen B Gruber, Sébastien Küry, Brigid M Lynch, Conghui Qu, Minta Thomas, Emily White, Michael O Woods, Ulrike Peters, Christopher I Li, Andrew T Chan, Hermann Brenner, Konstantinos K Tsilidis, Wei Zheng","doi":"10.1038/s41416-024-02900-7","DOIUrl":"10.1038/s41416-024-02900-7","url":null,"abstract":"<p><strong>Background: </strong>Whether blood lipids are causally associated with colorectal cancer (CRC) risk remains unclear.</p><p><strong>Methods: </strong>Using two-sample Mendelian randomisation (MR), our study examined the associations of genetically-predicted blood concentrations of lipids and lipoproteins (primary: LDL-C, HDL-C, triglycerides, and total cholesterol), and genetically-proxied inhibition of HMGCR, NPC1L1, and PCSK9 (which mimic therapeutic effects of LDL-lowering drugs), with risks of CRC and its subsites. Genetic associations with lipids were obtained from the Global Lipids Genetics Consortium (n = 1,320,016), while genetic associations with CRC were obtained from the largest existing CRC consortium (n = 58,221 cases and 67,694 controls). Our main analysis was a multivariable MR (MVMR) with mutual adjustments for LDL-C, HDL-C, and triglycerides. Secondary analyses, including MVMR additionally-adjusting for BMI or diabetes, were also performed.</p><p><strong>Results: </strong>Genetically-predicted LDL-C was positively associated with CRC risk in the MVMR adjusted for HDL-C and triglycerides (OR = 1.09; 95%CI 1.02-1.16 per SD increase) and additionally-adjusted for BMI (OR = 1.12; 95%CI 1.05-1.21) or diabetes (OR = 1.09; 95%CI 1.02-1.17). Associations were generally consistent across anatomical subsites. No clear evidence of association was found for other lipids, lipoproteins, or LDL-lowering drug-targets.</p><p><strong>Conclusions: </strong>We found evidence of a weak positive association between LDL-C and CRC that did not appear to be explained by potential pleiotropic pathways such as via HDL-C, triglycerides, BMI, or diabetes.</p>","PeriodicalId":9243,"journal":{"name":"British Journal of Cancer","volume":" ","pages":""},"PeriodicalIF":6.4,"publicationDate":"2024-11-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142695214","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Adaptive Universal Principles for Real-world Observational Studies (AUPROS): an approach to designing real-world observational studies for clinical, epidemiologic, and precision oncology research.","authors":"Samir H Barghout, Nicholas Meti, Simren Chotai, Christina J H Kim, Devalben Patel, M Catherine Brown, Katrina Hueniken, Luna J Zhan, Stavroula Raptis, Faisal Al-Agha, Christopher Deutschman, Benjamin Grant, Martha Pienkowski, Patrick Moriarty, John de Almeida, David P Goldstein, Scott V Bratman, Frances A Shepherd, Ming S Tsao, Andrew N Freedman, Wei Xu, Geoffrey Liu","doi":"10.1038/s41416-024-02899-x","DOIUrl":"https://doi.org/10.1038/s41416-024-02899-x","url":null,"abstract":"<p><p>The field of precision oncology has witnessed several advances that stimulated the development of new clinical trial designs and the emergence of real-world data (RWD) as an important resource for evidence generation in healthcare decision-making. Here, we highlight our experience with an innovative approach to a set of Adaptive, Universal Principles for Real-world Observational Studies (AUPROS). To demonstrate the utility of these principles, we used a mixed-methods approach to assess three studies that follow AUPROS at Princess Margaret Cancer Centre: (1) Molecular Epidemiology of ThorAcic Lesions (METAL), (2) Translational Head And NecK Study (THANKS), and (3) CAnadian CAncers With Rare Molecular Alterations (CARMA; NCT04151342). We performed resource assessments, stakeholder-directed surveys and discussions, analysis of funding, research output, collaborations, and a Strengths-Weaknesses-Opportunities-Threats (SWOT) analysis. Based on these analyses, AUPROS is an approach that is applicable to a wide range of observational study designs. The universality of AUPROS allows for multi-purpose analyses of various RWD, and the adaptive nature creates opportunities for multi-source funding and collaborations. Following AUPROS can offer cost and logistical benefits and may lead to increased research productivity. Several challenges were identified pertinent to ethics approvals, sustainability, complex coordination, and data quality that require local adaptation of these principles.</p>","PeriodicalId":9243,"journal":{"name":"British Journal of Cancer","volume":" ","pages":""},"PeriodicalIF":6.4,"publicationDate":"2024-11-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142686183","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cancer care for migrant people.","authors":"Edward Christopher Dee","doi":"10.1038/s41416-024-02911-4","DOIUrl":"https://doi.org/10.1038/s41416-024-02911-4","url":null,"abstract":"","PeriodicalId":9243,"journal":{"name":"British Journal of Cancer","volume":" ","pages":""},"PeriodicalIF":6.4,"publicationDate":"2024-11-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142680409","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Editorial Expression of Concern: Identification of DNA hypermethylation of SOX9 in association with bladder cancer progression using CpG microarrays","authors":"A. Aleman,&nbsp;L. Adrien,&nbsp;L. Lopez-Serra,&nbsp;C. Cordon-Cardo,&nbsp;M. Esteller,&nbsp;T. J. Belbin,&nbsp;M. Sanchez-Carbayo","doi":"10.1038/s41416-024-02903-4","DOIUrl":"10.1038/s41416-024-02903-4","url":null,"abstract":"","PeriodicalId":9243,"journal":{"name":"British Journal of Cancer","volume":"131 12","pages":"1946-1946"},"PeriodicalIF":6.4,"publicationDate":"2024-11-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s41416-024-02903-4.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142667358","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Breast cancer metastasis progression is associated with elevated activity of kynurenine monooxygenase and kynureninase","authors":"Hemaasri-Neya Girithar,&nbsp;Shivani Krishnamurthy,&nbsp;Luke Carroll,&nbsp;Anna Guller,&nbsp;Ayse A. Bilgin,&nbsp;Laurence Gluch,&nbsp;Gilles J. Guillemin,&nbsp;Seong Beom Ahn,&nbsp;Benjamin Heng","doi":"10.1038/s41416-024-02889-z","DOIUrl":"10.1038/s41416-024-02889-z","url":null,"abstract":"Metastasis remains the major cause of death in breast cancer (BrCa) and lacks specific treatment strategies. The kynurenine pathway (KP) has been suggested as a key mechanism facilitating progression of BrCa. While KP activity has been explored in primary BrCa, its role in metastasis remains unclear. To better understand this, we examined changes in the KP of BrCa with no metastasis compared to BCa that produced local or distant metastases. Given that the cancer cell secretome plays a role in metastasis, we also investigated the relationship between changes in KP activity and serum proteins of patients with local or distant metastases. To investigate changes in the KP in BrCa, with and without metastasis, we quantified KP metabolites in blood sera collected from patients with stage 1 BrCa (n = 34), BrCa with local metastases (n = 46), BrCa with distant metastases (n = 20) and healthy controls (n = 39). The serum protein profile of the BrCa patients with local or distant metastasis was determined before correlation analyses were carried out to examine the relationship between changes in the KP and cancer serum proteins using SPSS. We found that the KP was elevated in BrCa patients with local and distant metastasis compared to healthy controls and stage 1 BrCa patients. The activity of kynurenine monooxygenase (KMO) and kynureninase (KYNU) A was positively associated with disease stage and was higher compared to healthy controls. Proteome analysis in patients with local or distant metastasis revealed the dysregulation of 14 proteins, 9 of which were up-regulated and 5 down-regulated at the distant metastasis stage. Importantly, three of these proteins have not been previously linked to BrCa metastasis. In the correlation studies between the KP profile, cancer serum proteins and metastasis status, KYNU A had the greatest number of significant associations with cancer serum protein, followed by KMO. Our findings reveal that the KP was regulated differently at various stages of BrCa and was more dysregulated in patients with local or distant metastasis. These KP activity changes showed a significant association with cancer serum proteins in BrCa patients with local or distant metastasis, highlighting the potential role of KP in BrCa metastasis.","PeriodicalId":9243,"journal":{"name":"British Journal of Cancer","volume":"131 12","pages":"1881-1892"},"PeriodicalIF":6.4,"publicationDate":"2024-11-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142667332","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Understanding genetic architecture of breast cancer: how can proteome-wide association studies contribute?","authors":"Yijia Sun,&nbsp;Dezheng Huo","doi":"10.1038/s41416-024-02905-2","DOIUrl":"10.1038/s41416-024-02905-2","url":null,"abstract":"Proteome-wide association studies (PWAS) address gaps in post-transcriptional modifications that previous genome- and transcriptome-wide association studies could not capture. Zhao and colleagues conducted the first breast tissue-based PWAS and identified proteins associated with breast cancer risk, providing insights into the role of protein expression in breast cancer development.","PeriodicalId":9243,"journal":{"name":"British Journal of Cancer","volume":"131 12","pages":"1869-1870"},"PeriodicalIF":6.4,"publicationDate":"2024-11-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s41416-024-02905-2.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142667322","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Editorial Expression of Concern: Temozolomide induces senescence but not apoptosis in human melanoma cells","authors":"N. M. Mhaidat,&nbsp;X. D. Zhang,&nbsp;J. Allen,&nbsp;K. A. Avery-Kiejda,&nbsp;R. J. Scott,&nbsp;P. Hersey","doi":"10.1038/s41416-024-02907-0","DOIUrl":"10.1038/s41416-024-02907-0","url":null,"abstract":"","PeriodicalId":9243,"journal":{"name":"British Journal of Cancer","volume":"131 12","pages":"1947-1947"},"PeriodicalIF":6.4,"publicationDate":"2024-11-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s41416-024-02907-0.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142667361","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Correction: Modelled mortality benefits of multi-cancer early detection screening in England","authors":"Peter Sasieni,&nbsp;Rebecca Smittenaar,&nbsp;Earl Hubbell,&nbsp;John Broggio,&nbsp;Richard D. Neal,&nbsp;Charles Swanton","doi":"10.1038/s41416-024-02836-y","DOIUrl":"10.1038/s41416-024-02836-y","url":null,"abstract":"","PeriodicalId":9243,"journal":{"name":"British Journal of Cancer","volume":"131 12","pages":"1942-1944"},"PeriodicalIF":6.4,"publicationDate":"2024-11-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s41416-024-02836-y.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142667355","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}