BJC Reports最新文献

{"title":"Targeting PLOD2 suppresses invasion and metastatic potential in radiorecurrent prostate cancer","authors":"Gavin Frame, Hon Leong, Roni Haas, Xiaoyong Huang, Jessica Wright, Urban Emmenegger, Michelle Downes, Paul C. Boutros, Thomas Kislinger, Stanley K. Liu","doi":"10.1038/s44276-024-00085-3","DOIUrl":"10.1038/s44276-024-00085-3","url":null,"abstract":"Metastatic relapse of prostate cancer after radiotherapy is a significant cause of prostate cancer-related morbidity and mortality. PLOD2 is a mediator of invasion and metastasis that we identified as being upregulated in our highly aggressive radiorecurrent prostate cancer cell line. Patient dataset analysis was conducted using a variety of prostate cancer cohorts. Prostate cancer cell lines were treated with siRNA, or the drug PX-478 prior to in vitro invasion, migration, or in vivo chick embryo (CAM) extravasation assay. Protein levels were detected by western blot. For RNA analysis, RNA sequencing was conducted on PLOD2 knockdown cells and validated by qRT-PCR. PLOD2 is a negative prognostic factor associated with biochemical relapse, driving invasion, migration, and extravasation in radiorecurrent prostate cancer. Mechanistically, HIF1α upregulation drives PLOD2 expression in our radiorecurrent prostate cancer cells, which is effectively inhibited by HIF1α inhibitor PX-478 to reduce invasion, migration, and extravasation. Finally, the long non-coding RNA LNCSRLR acts as a promoter of invasion downstream of PLOD2. Together, our results demonstrate for the first time the role of PLOD2 in radiorecurrent prostate cancer invasiveness, and point towards its potential as a therapeutic target to reduce metastasis and improve survival outcomes in prostate cancer patients.","PeriodicalId":135222,"journal":{"name":"BJC Reports","volume":" ","pages":"1-11"},"PeriodicalIF":0.0,"publicationDate":"2024-08-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s44276-024-00085-3.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142041747","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Retrospective evaluation of plasma protein tumour markers for early lung cancer detection","authors":"Michael Peter Alan Davies, Ruwanthi Kolamunnage-Dona, Suzannah Phillips, Angela Lambert, Stephanie Tate, John Kirkpatrick Field","doi":"10.1038/s44276-024-00082-6","DOIUrl":"10.1038/s44276-024-00082-6","url":null,"abstract":"Blood-based biomarkers might help lung cancer diagnosis. A panel of serum tumour markers (TM) has been validated for hospital referrals due to clinical suspicion of lung cancer. We have compared plasma from a cohort enriched for early-stage lung cancer, including controls from a healthy population cohort. TM assays for CEA, CYFRA 21-1, CA15.3, ProGRP and SCC were run on a Roche Elecsys 2010 Immunoassay Analyser for a retrospective, nested case-control cohort from the Liverpool Lung Project. The primary endpoints were the sensitivity and specificity of a pre-defined TM panel using published thresholds. Except for ProGRP, TM levels were significantly higher in cases and ROC AUC values demonstrated significant discriminant power. Accuracy and levels were higher for late-stage cancers, except for ProGRP which was highest in stage 1 cancers. Although providing similar sensitivity (82.4% vs 88.5%), TMs performed worse for specificity (39.3% vs 82%) and overall (Youden’s Index 0.22 vs 0.77) and this was not improved by threshold optimisation or binary logistic regression. Although the TMs were associated with lung cancer status and discriminatory with a high sensitivity when combined, performance was compromised in early-stage disease, which casts some doubt on utility in the screening setting.","PeriodicalId":135222,"journal":{"name":"BJC Reports","volume":" ","pages":"1-8"},"PeriodicalIF":0.0,"publicationDate":"2024-08-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s44276-024-00082-6.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142002629","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Chromosomal copy number based stratification of gastric cancer has added prognostic value to Lauren’s histological classification","authors":"H. D. Biesma, T. T. D. Soeratram, H. F. van Essen, J. M. P. Egthuijsen, J. B. Poell, E. van Dijk, E. Meershoek - Klein Kranenbarg, H. H. Hartgrink, C. J. H. van de Velde, M. A. van de Wiel, B. Ylstra, N. C. T. van Grieken","doi":"10.1038/s44276-024-00078-2","DOIUrl":"10.1038/s44276-024-00078-2","url":null,"abstract":"The Cancer Genome Atlas (TCGA) recognizes four molecular subgroups of gastric cancer: Epstein-Barr virus (EBV) positive, microsatellite instable (MSI), genomically stable (GS), and chromosomal instable (CIN). Since a GS/CIN classifier is lacking, alternative markers such as Lauren’s histopathology or CDH1/p53 immunohistochemistry are commonly applied. Here we compared survival of gastric cancer subgroups determined by four methods. 309 EBV negative and microsatellite stable tumors were included from the Dutch D1/D2 trial and assigned to subgroups by: (i) TCGA’s specific chromosomal copy number aberrations, (ii) genome instability index (GII), (iii) Lauren’s classification, and (iv) CDH1/p53 immunohistochemistry. Subgroups were associated with cancer-related survival (CRS). Five-year CRS was 42.0% for diffuse and 49.5% for patients with intestinal type tumors, and 57.8% for GS and 41.6% for patients with CIN tumors. Classification by GII or CDH1/p53 IHC did not correlate with CRS. The combination of TCGA and Lauren classifications resulted in four distinct subgroups. Five-year CRS for GS-intestinal (n = 24), GS-diffuse (n = 57), CIN-intestinal (n = 142) and CIN-diffuse (n = 86) was 61.4%, 56.5%, 47.6%, and 31.5%, respectively. TCGA’s GS and CIN subgroups have additional prognostic value to Lauren’s classification in resectable gastric cancer. GS-intestinal, GS-diffuse, CIN-intestinal and CIN-diffuse are suggested stratification variables for future studies.","PeriodicalId":135222,"journal":{"name":"BJC Reports","volume":" ","pages":"1-8"},"PeriodicalIF":0.0,"publicationDate":"2024-08-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s44276-024-00078-2.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142002623","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The impact of VEGF signalling pathway inhibitors and/or immune checkpoint inhibitors on kidney function over time: a single centre retrospective analysis","authors":"Benjamin M. P. Elyan, Michael K. Sullivan, James Hedley, Nicole De La Mata, Angela C. Webster, Balaji Venugopal, Rob J. Jones, Ninian N. Lang, Patrick B. Mark, Jennifer S. Lees","doi":"10.1038/s44276-024-00081-7","DOIUrl":"10.1038/s44276-024-00081-7","url":null,"abstract":"Drugs targeting angiogenesis and immunotherapy have transformed outcomes in renal cancer but may contribute to progressive kidney disease. We linked healthcare databases in the West of Scotland (spanning 2010–2020) to identify adults with renal cancer who received one or both classes of drugs. Over two years following initiation, estimated glomerular filtration rate (eGFR) slope was modelled using linear mixed-effects models. Additional renal outcomes used competing risk regression considering the competing risk of death. Amongst 357 adults (62.5% male; median age 63.0 years, IQI 55.0–71.0), there was no significant change in eGFR (annual eGFR change +1.03 mL/min/1.73 m²/year, 95%CI −1.64 to +3.70), nor in subgroups of patients who had nephrectomy, metastatic cancer or an eGFR < 60 mL/min/1.73 m² prior to systemic therapy. A ≥ 40% decline in eGFR occurred in 82 people (23.0%) within one year of starting systemic therapy and was associated with pre-existing diabetes (subhazard ratio 1.89, 95%CI 1.05–3.41). Anti-angiogenic and immune therapy had no substantial impact on the average change in eGFR but people with diabetes are at higher risk of clinically significant renal events. With appropriate monitoring, more widespread use of these agents in patients with renal impairment may be warranted.","PeriodicalId":135222,"journal":{"name":"BJC Reports","volume":" ","pages":"1-9"},"PeriodicalIF":0.0,"publicationDate":"2024-08-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s44276-024-00081-7.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141986133","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Source credibility: a necessary North Star in cancer care","authors":"Seamus O’Reilly, Karie Dennehy, Dearbhaile C. Collins","doi":"10.1038/s44276-024-00075-5","DOIUrl":"10.1038/s44276-024-00075-5","url":null,"abstract":"","PeriodicalId":135222,"journal":{"name":"BJC Reports","volume":" ","pages":"1-3"},"PeriodicalIF":0.0,"publicationDate":"2024-08-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s44276-024-00075-5.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141968577","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Alternative cancer clinics’ use of Google listings and reviews to mislead potential patients","authors":"Marco Zenone, Jeremy Snyder, May van Schalkwyk, Jean-Christophe Bélisle-Pipon, Greg Hartwell, Timothy Caulfield, Nason Maani","doi":"10.1038/s44276-024-00071-9","DOIUrl":"10.1038/s44276-024-00071-9","url":null,"abstract":"Alternative cancer clinics, who provide treatment associated with earlier time to death, actively seek to create favorable views of their services online. An unexplored means where alternative cancer clinics can shape their appeal is their Google search results. We retrieved the Google listing and Google reviews of 47 prominent alternative cancer clinics on August 22, 2022. We then conducted a content analysis to assess the information cancer patients are faced with online. Google listings of alternative treatment providers rarely declared the clinic was an alternative clinic versus a conventional primary cancer treatment provider (12.8% declared; 83.0% undeclared). The clinics were highly rated (median, 4.5 stars of 5). Reasons for positive reviews included treatment quality (n = 519), care (n = 420), and outcomes (n = 316). 288 reviews presented the clinics to cure or improve cancer. Negative reviews presented alternative clinics to financially exploit patients with ineffective treatment (n = 98), worsen patients’ condition (n = 72), provide poor care (n = 41), and misrepresent outcomes (n = 23). The favorable Google listing and reviews of alternative clinics contribute to harmful online ecosystems. Reviews provide compelling narratives but are an ineffective indicator of treatment outcomes. Google lacks safeguards for truthful reviews and should not be used for medical decision-making.","PeriodicalId":135222,"journal":{"name":"BJC Reports","volume":" ","pages":"1-8"},"PeriodicalIF":0.0,"publicationDate":"2024-08-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11303243/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141908836","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Different efficacy of tyrosine kinase inhibitors by KIT and PGFRA mutations identified in circulating tumor DNA for the treatment of refractory gastrointestinal stromal tumors","authors":"Tadayoshi Hashimoto, Yoshiaki Nakamura, Yoshito Komatsu, Satoshi Yuki, Naoki Takahashi, Naohiro Okano, Hidekazu Hirano, Koushiro Ohtsubo, Takashi Ohta, Eiji Oki, Tomohiro Nishina, Hisateru Yasui, Hisato Kawakami, Taito Esaki, Nozomu Machida, Ayako Doi, Shogen Boku, Toshihiro Kudo, Yoshiyuki Yamamoto, Akiyoshi Kanazawa, Tadamichi Denda, Masahiro Goto, Naoko Iida, Hiroshi Ozaki, Taro Shibuki, Mitsuho Imai, Takao Fujisawa, Hideaki Bando, Yoichi Naito, Takayuki Yoshino","doi":"10.1038/s44276-024-00073-7","DOIUrl":"10.1038/s44276-024-00073-7","url":null,"abstract":"While advanced gastrointestinal stromal tumors (GISTs) are primarily treated with tyrosine kinase inhibitors (TKIs), acquired resistance from specific mutations in KIT or PDGFRA frequently occurs. We aimed to assess the utility of circulating tumor DNA (ctDNA) as a modality of therapeutic decision-making in advanced GIST. We conducted a pooled analysis of SCRUM-Japan studies for advanced GIST patients. We compared patient characteristics analyzed with tissue and blood samples, assessed gene alteration profiles, and evaluated prognostic implications from ctDNA status. In 133 patients, tissue and blood samples were analyzed for 89 and 44 patients, respectively. ctDNA was detected in 72.7% of cases; no prior treatment or progressive disease was significantly associated with ctDNA-positivity. ctDNA-positive patients had significantly shorter progression-free survival compared with ctDNA-negative patients (hazard ratio = 3.92; P = 0.007). ctDNA genotyping revealed a complex landscape of gene alterations, characterized by multi-exonic mutations in KIT, compared with tissue-based analysis. Patients who received TKIs matched to the identified KIT mutation in ctDNA demonstrated significantly longer PFS than those with unmatched treatment (median, 8.23 vs. 2.43 months; P < 0.001). ctDNA-based analysis facilitates assessment of disease status and genomic profiles, thus potentially assisting in identifying optimal therapeutic strategies for advanced GIST patients.","PeriodicalId":135222,"journal":{"name":"BJC Reports","volume":" ","pages":"1-10"},"PeriodicalIF":0.0,"publicationDate":"2024-07-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s44276-024-00073-7.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141802720","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"BOADICEA model: updates to the BRCA2 breast cancer risks for ages 60 years and older","authors":"Lorenzo Ficorella, Xin Yang, Douglas F. Easton, Antonis C. Antoniou","doi":"10.1038/s44276-024-00079-1","DOIUrl":"10.1038/s44276-024-00079-1","url":null,"abstract":"Breast cancer risks in older BRCA2 pathogenic variant carriers are understudied. Recent studies show a marked decline in the relative risk at older ages. We used data from two large studies to update the breast cancer risks in the BOADICEA model for BRCA2 carriers 60 years and older.","PeriodicalId":135222,"journal":{"name":"BJC Reports","volume":" ","pages":"1-3"},"PeriodicalIF":0.0,"publicationDate":"2024-07-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11269170/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141790796","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"System transferability of Raman-based oesophageal tissue classification using modern machine learning to support multi-centre clinical diagnostics","authors":"Nathan Blake, Riana Gaifulina, Martin Isabelle, Jennifer Dorney, Manuel Rodriguez-Justo, Katherine Lau, Stéphanie Ohrel, Gavin Lloyd, Neil Shepherd, Aaran Lewis, Catherine A. Kendall, Nick Stone, Ian Bell, Geraint Thomas","doi":"10.1038/s44276-024-00080-8","DOIUrl":"10.1038/s44276-024-00080-8","url":null,"abstract":"The clinical potential of Raman spectroscopy is well established but has yet to become established in routine oncology workflows. One barrier slowing clinical adoption is a lack of evidence demonstrating that data taken on one spectrometer transfers across to data taken on another spectrometer to provide consistent diagnoses. We investigated multi-centre transferability using human oesophageal tissue. Raman spectra were taken across three different centres with different spectrometers of the same make and model. By using a common protocol, we aimed to minimise the difference in machine learning performance between centres. 61 oesophageal samples from 51 patients were interrogated by Raman spectroscopy at each centre and classified into one of five pathologies. The overall accuracy and log-loss did not significantly vary when a model trained upon data from any one centre was applied to data taken at the other centres. Computational methods to correct for the data during pre-processing were not needed. We have found that when using the same make and model of spectrometer, together with a common protocol, across different centres it is possible to achieve system transferability without the need for additional computational instrument correction.","PeriodicalId":135222,"journal":{"name":"BJC Reports","volume":" ","pages":"1-8"},"PeriodicalIF":0.0,"publicationDate":"2024-07-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s44276-024-00080-8.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141811877","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Ropeginterferon alfa-2b shows anti-polycythaemia vera activity without causing clinically significant anaemia","authors":"Keita Kirito, Albert Qin, Shanshan Suo, Rongfeng Fu, Daoxiang Wu, Toshiaki Sato, Oleh Zagrijtschuk, Kazuya Shimoda, Norio Komatsu, Jie Jin","doi":"10.1038/s44276-024-00076-4","DOIUrl":"10.1038/s44276-024-00076-4","url":null,"abstract":"Anaemia could develop in polycythemia vera (PV) due to phlebotomy-caused iron-deficiency and cytotoxic effect of cytoreductive therapy. Ropeginterferon alfa-2b treatment was not associated with ≥grade 3 anaemia in two recent clinical studies of 78 patients with PV. Only four cases of grade 2 anaemias occurred, the anaemia resolved. The mean haemoglobin levels were above 120.0 g/L. Therefore, ropeginterferon alfa-2b treatment does not lead to clinically significant anaemia and appears to manage PV without affecting normal erythropoiesis. “Both trials were registered at clinicaltrials.gov (A19-201: NCT04182100; A20-202: NCT05485948)”.","PeriodicalId":135222,"journal":{"name":"BJC Reports","volume":" ","pages":"1-3"},"PeriodicalIF":0.0,"publicationDate":"2024-07-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s44276-024-00076-4.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141597199","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}