British Journal of Cancer最新文献

{"title":"Editorial Expression of Concern: Identification of DNA hypermethylation of SOX9 in association with bladder cancer progression using CpG microarrays.","authors":"A Aleman, L Adrien, L Lopez-Serra, C Cordon-Cardo, M Esteller, T J Belbin, 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":" ","pages":""},"PeriodicalIF":6.4,"publicationDate":"2024-11-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","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":"","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, Shivani Krishnamurthy, Luke Carroll, Anna Guller, Ayse A Bilgin, Laurence Gluch, Gilles J Guillemin, Seong Beom Ahn, Benjamin Heng","doi":"10.1038/s41416-024-02889-z","DOIUrl":"10.1038/s41416-024-02889-z","url":null,"abstract":"<p><strong>Introduction: </strong>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.</p><p><strong>Methods: </strong>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.</p><p><strong>Results: </strong>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.</p><p><strong>Conclusion: </strong>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.</p>","PeriodicalId":9243,"journal":{"name":"British Journal of Cancer","volume":" ","pages":""},"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, Dezheng Huo","doi":"10.1038/s41416-024-02905-2","DOIUrl":"10.1038/s41416-024-02905-2","url":null,"abstract":"","PeriodicalId":9243,"journal":{"name":"British Journal of Cancer","volume":" ","pages":""},"PeriodicalIF":6.4,"publicationDate":"2024-11-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","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":"","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, X D Zhang, J Allen, K A Avery-Kiejda, R J Scott, 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":" ","pages":""},"PeriodicalIF":6.4,"publicationDate":"2024-11-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","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":"","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, Rebecca Smittenaar, Earl Hubbell, John Broggio, Richard D Neal, 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":" ","pages":""},"PeriodicalIF":6.4,"publicationDate":"2024-11-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","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":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Germline BRCA1/2 status and chemotherapy response score in high-grade serous ovarian cancer.","authors":"Robert D Morgan, Xin Wang, Bethany M Barnes, Laura Spurgeon, Aurore Carrot, Daniel Netto, Jurjees Hasan, Claire Mitchell, Zena Salih, Sudha Desai, Joseph Shaw, Brett Winter-Roach, Helene Schlecht, George J Burghel, Andrew R Clamp, Richard J Edmondson, Benoit You, D Gareth R Evans, Gordon C Jayson, Stephen S Taylor","doi":"10.1038/s41416-024-02874-6","DOIUrl":"10.1038/s41416-024-02874-6","url":null,"abstract":"<p><strong>Background: </strong>High-grade serous ovarian cancer (HGSOC) can be treated with platinum-based neoadjuvant chemotherapy (NACT) and delayed primary surgery (DPS). Histopathological response to NACT can be assessed using Böhm's chemotherapy response score (CRS). We investigated whether germline BRCA1/2 (gBRCA1/2) genotype associated with omental CRS phenotype.</p><p><strong>Methods: </strong>A retrospective study of patients with newly diagnosed FIGO stage IIIC/IV HGSOC prescribed NACT and tested for gBRCA1/2 pathogenic variants (PVs) between September 2017 and December 2022 at The Christie Hospital. The Cox proportional hazards model evaluated the association between survival and key clinical factors. The chi-square test assessed the association between CRS3 (no/minimal residual tumour) and gBRCA1/2 status.</p><p><strong>Results: </strong>Of 586 eligible patients, 393 underwent DPS and had a CRS reported. Independent prognostic factors by multivariable analysis were gBRCA1/2 status (PV versus wild type [WT]), CRS (3 versus 1 + 2), surgical outcome (complete versus optimal/suboptimal) and first-line poly (ADP-ribose) polymerase-1/2 inhibitor maintenance therapy (yes versus no) (all P < 0.05). There was a non-significant trend for tumours with a gBRCA2 PV having CRS3 versus WT (odds ratio [OR] = 2.13, 95% confidence intervals [CI] 0.95-4.91; P = 0.0647). By contrast, tumours with a gBRCA1 PV were significantly less likely to have CRS3 than WT (OR = 0.35, 95%CI 0.14-0.91; P = 0.0291).</p><p><strong>Conclusions: </strong>Germline BRCA1/2 genotype was not clearly associated with superior omental CRS. Further research is required to understand how HGSOC biology defines CRS.</p>","PeriodicalId":9243,"journal":{"name":"British Journal of Cancer","volume":" ","pages":""},"PeriodicalIF":6.4,"publicationDate":"2024-11-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142643389","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":"UK guidelines for the management of bone sarcomas.","authors":"Craig Gerrand, Fernanda Amary, Hanny A Anwar, Bernadette Brennan, Palma Dileo, Maninder Singh Kalkat, Martin G McCabe, Anna Louise McCullough, Michael C Parry, Anish Patel, Beatrice M Seddon, Jennifer M Sherriff, Roberto Tirabosco, Sandra J Strauss","doi":"10.1038/s41416-024-02868-4","DOIUrl":"https://doi.org/10.1038/s41416-024-02868-4","url":null,"abstract":"<p><p>This document is an update of the British Sarcoma Group guidelines (2016) and provides a reference standard for the clinical care of UK patients with primary malignant bone tumours (PMBT) and giant cell tumours (GCTB) of bone. The guidelines recommend treatments that are effective and should be available in the UK, and support decisions about management and service delivery. The document represents a consensus amongst British Sarcoma Group members in 2024. Key recommendations are that bone pain, or a palpable mass should always lead to further investigation and that patients with clinical or radiological findings suggestive of a primary bone tumour at any anatomic site should be referred to a specialist centre and managed by an accredited bone sarcoma multidisciplinary team. Treatment recommendations are provided for the major tumour types and for localised, metastatic and recurrent disease. Follow-up schedules are suggested.</p>","PeriodicalId":9243,"journal":{"name":"British Journal of Cancer","volume":" ","pages":""},"PeriodicalIF":6.4,"publicationDate":"2024-11-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142643393","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":"Integrated proteomics and scRNA-seq analyses of ovarian cancer reveal molecular subtype-associated cell landscapes and immunotherapy targets.","authors":"Rong Tan, Ming Wen, Wenqing Yang, Dongdong Zhan, Nairen Zheng, Mingwei Liu, Fang Zhu, Xiaodan Chen, Meng Wang, Siyu Yang, Bin Xie, Qiongqiong He, Kai Yuan, Lunquan Sun, Yi Wang, Jun Qin, Yu Zhang","doi":"10.1038/s41416-024-02894-2","DOIUrl":"https://doi.org/10.1038/s41416-024-02894-2","url":null,"abstract":"<p><strong>Background: </strong>Epithelial ovarian cancer (EOC) represents the most lethal gynaecological malignancy, yet understanding the connections between its molecular subtypes and their therapeutic implications remains incomplete.</p><p><strong>Methods: </strong>We conducted mass spectrometry-based proteomics analyses of 154 EOC tumour samples and 29 normal fallopian tubes, and single-cell RNA sequencing (scRNA-seq) analyses of an additional eight EOC tumours to classify proteomic subtypes and assess their cellular ecosystems and clinical significance. The efficacy of identified therapeutic targets was evaluated in patient-derived xenograft (PDX) and orthotopic mouse models.</p><p><strong>Results: </strong>We identified four proteomic subtypes with distinct clinical relevance: malignant proliferative (C1), immune infiltrating (C2), Fallopian-like (C3) and differentiated (C4) subtypes. C2 subtype was characterized by lymphocyte infiltration, notably an increased presence of GZMK CD8+ T cells and phagocytosis-like MRC+ macrophages. Additionally, we identified CD40 as a specific prognostic factor for C2 subtype. The interaction between CD40+ phagocytosis-like macrophages and CD40RL+ IL17R CD4+ T cells was correlated with a favourable prognosis. Finally, we established a druggable landscape for non-immune EOC patients and verified a TYMP inhibitor as a promising therapeutic strategy.</p><p><strong>Conclusions: </strong>Our study refines the current immune subtype for EOC, highlighting CD40 agonists as promising therapies for C2 subtype patients and targeting TYMP for non-immune patients.</p>","PeriodicalId":9243,"journal":{"name":"British Journal of Cancer","volume":" ","pages":""},"PeriodicalIF":6.4,"publicationDate":"2024-11-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142638293","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":"Phenotypical differences of neutrophils patrolling tumour-draining lymph nodes in head and neck cancer.","authors":"Sandra Ekstedt, Krzysztof Piersiala, Aeneas Kolev, Pedro Farrajota Neves da Silva, Gregori Margolin, Susanna Kumlien Georén, Lars-Olaf Cardell","doi":"10.1038/s41416-024-02891-5","DOIUrl":"https://doi.org/10.1038/s41416-024-02891-5","url":null,"abstract":"<p><strong>Background: </strong>The complexity and heterogeneity of neutrophils are recognized, especially their roles in modulating inflammation and cancer immune responses. The detailed functions of neutrophils in human tumour-draining lymph nodes (TDLNs), specifically in the context of head and neck cancer, remain inadequately characterized.</p><p><strong>Aim: </strong>This study aims to delineate the phenotypic diversity of neutrophils in TDLNs, non-tumour-draining lymph nodes (nTDLNs) from patients with oral squamous cell carcinoma (OSCC), and to evaluate their correlation with clinical outcomes.</p><p><strong>Methods: </strong>A flow cytometry-based investigation.</p><p><strong>Results: </strong>Neutrophils manifest a tissue-specific heterogeneity with significant phenotypic differences between compartments. A substantial fraction of neutrophils displayed an activated CD16^highCD62L^dim profile in TDLNs, more prominent in patients with advanced T stages, implicating their involvement in the disease's progression. Notably, the presence of this activated neutrophil phenotype in TDLNs was strongly associated with poorer patient prognosis.</p><p><strong>Conclusions: </strong>The study confirms the heterogeneity of neutrophils in human TDLNs, aligning with findings from animal models but extending them to show clinical relevance in human disease. The correlation of neutrophil phenotypes with cancer progression and prognosis emphasizes the importance of these cells in the tumour-microenvironment. The data suggests a future possibility to develop targeted therapies that modulate the neutrophilic response in OSCC.</p>","PeriodicalId":9243,"journal":{"name":"British Journal of Cancer","volume":" ","pages":""},"PeriodicalIF":6.4,"publicationDate":"2024-11-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142615132","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":"The abscopal effects of sonodynamic therapy in cancer.","authors":"Victoria G Collins, Dana Hutton, Kismet Hossain-Ibrahim, James Joseph, Sourav Banerjee","doi":"10.1038/s41416-024-02898-y","DOIUrl":"https://doi.org/10.1038/s41416-024-02898-y","url":null,"abstract":"<p><p>The abscopal effect is a phenomenon wherein localised therapy on the primary tumour leads to regression of distal metastatic growths. Interestingly, various pre-clinical studies utilising sonodynamic therapy (SDT) have reported significant abscopal effects, however, the mechanism remains largely enigmatic. SDT is an emerging non-invasive cancer treatment that uses focussed ultrasound (FUS) and a sonosensitiser to induce tumour cell death. To expand our understanding of abscopal effects of SDT, we have summarised the preclinical studies that have found SDT-induced abscopal responses across various cancer models, using diverse combination strategies with nanomaterials, microbubbles, chemotherapy, and immune checkpoint inhibitors. Additionally, we shed light on the molecular and immunological mechanisms underpinning SDT-induced primary and metastatic tumour cell death, as well as the role and efficacy of different sonosensitisers. Notably, the observed abscopal effects underscore the need for continued investigation into the SDT-induced 'vaccine-effect' as a potential strategy for enhancing systemic anti-tumour immunity and combating metastatic disease. The results of the first SDT human clinical trials are much awaited and are hoped to enable the further evaluation of the safety and efficacy of SDT, paving the way for future studies specifically designed to explore the potential of translating SDT-induced abscopal effects into clinical reality.</p>","PeriodicalId":9243,"journal":{"name":"British Journal of Cancer","volume":" ","pages":""},"PeriodicalIF":6.4,"publicationDate":"2024-11-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142615133","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}