BJC Reports最新文献

{"title":"Small extracellular vesicles as biomarkers of response in recurrent/metastatic HNSCC patients treated with immunotherapy","authors":"Dan P. Zandberg, Chang-Sook Hong, Andrew Swartz, Ronan Hsieh, Jennifer Anderson, Robert L. Ferris, Brenda Diergaarde, Theresa L. Whiteside","doi":"10.1038/s44276-024-00096-0","DOIUrl":"10.1038/s44276-024-00096-0","url":null,"abstract":"Biomarkers that effectively predict response to anti-PD-1 mAb therapy in cancer patients are an unmet need. We evaluated the utility of small extracellular vesicles (sEV) as biomarkers of response to immunotherapy in recurrent/metastatic (R/M) head and neck squamous cell carcinoma (HNSCC) patients. Plasma sEV were isolated from 24 R/M HNSCC patients prior to immunotherapy initiation. sEV were separated by immune capture into T cell-derived CD3(+) and tumor-enriched CD3(−) subsets. Stimulatory and suppressive profiles of CD3(−) sEV were determined by on-bead flow cytometry. Differences were assessed using nonparametric tests. Multivariable Cox regression was used to evaluate the relationship with overall (OS) and progression free survival (PFS). CD3(−)CD44v3(+) sEV represented the majority of plasma sEV; the T-cell-derived CD3(+) fraction was significantly smaller. High CD3(+) sEV was associated with better OS and PFS. Total CD3(−)CD44v3(+) sEV was not associated with outcome. However, suppressive and stimulatory profiles were associated with OS; the suppressive/stimulatory ratio was associated with best response. Exploration of individual proteins on CD3(−) sEV showed that high PD-L1 and high CTLA-4 were associated with better outcomes. Evaluation of the T cell-derived-CD3(+) and tumor-enriched CD3(−) plasma sEV subsets indicated their potential utility as biomarkers of response to immunotherapy.","PeriodicalId":135222,"journal":{"name":"BJC Reports","volume":" ","pages":"1-9"},"PeriodicalIF":0.0,"publicationDate":"2024-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s44276-024-00096-0.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142231145","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":"Cannabidiol and fluorinated derivative anti-cancer properties against glioblastoma multiforme cell lines, and synergy with imidazotetrazine agents","authors":"Alice Brookes, Nicholas Kindon, David J. Scurr, Morgan R. Alexander, Pavel Gershkovich, Tracey D. Bradshaw","doi":"10.1038/s44276-024-00088-0","DOIUrl":"10.1038/s44276-024-00088-0","url":null,"abstract":"Glioblastoma multiforme (GBM) is an aggressive cancer with poor prognosis, partly due to resistance to the standard chemotherapy treatment, temozolomide (TMZ). Phytocannabinoid cannabidiol (CBD) has exhibited anti-cancer effects against GBM, however, CBD’s ability to overcome common resistance mechanisms to TMZ have not yet been investigated. 4’-Fluoro-cannabidiol (4’-F-CBD, or HUF-101/PECS-101) is a derivative of CBD, that exhibits increased activity compared to CBD during in vivo behavioural studies. This anti-cancer activity of cannabinoids against GBM cells sensitive to and representing major resistance mechanisms to TMZ was investigated. Cannabinoids were also studied in combination with imidazotetrazine agents, and advanced mass spectrometry with the 3D OrbiSIMS was used to investigate the mechanism of action of CBD. CBD and 4’-F-CBD were found to overcome two major resistance mechanisms (methylguanine DNA-methyltransferase (MGMT) overexpression and DNA mismatch repair (MMR)-deficiency). Synergistic responses were observed when cells were exposed to cannabinoids and imidazotetrazine agents. Synergy increased with T25 and 4’-F-CBD. 3D OrbiSIMS analysis highlighted the presence of methylated-DNA, a previously unknown anti-cancer mechanism of action of CBD. This work demonstrates the anti-cancer activity of 4’-F-CBD and the synergy of cannabinoids with imidazotetrazine agents for the first time and expands understanding of CBD mechanism of action.","PeriodicalId":135222,"journal":{"name":"BJC Reports","volume":" ","pages":"1-10"},"PeriodicalIF":0.0,"publicationDate":"2024-09-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s44276-024-00088-0.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142231127","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 elective cervical lymph node treatment on the tumour immune response in head and neck squamous cell carcinoma: time for a change in treatment strategy?","authors":"Karl Payne, Pablo Nenclares, Clare Schilling","doi":"10.1038/s44276-024-00095-1","DOIUrl":"10.1038/s44276-024-00095-1","url":null,"abstract":"The elective ablation of cervical lymph nodes, via surgery or irradiation, is a mainstay in the treatment of head and neck squamous cell carcinoma (HNSCC). In this setting, the decision to treat the clinically node negative neck is based upon risk analysis of various factors, primarily derived from tumour features. However, the impact of ablation of tumour-draining lymph nodes upon the tumour-immune response and immunocompetence is largely unknown. In this review we highlight recent evidence of the communication between tumour and tumour-draining lymph nodes and the fundamental importance of this axis. We will provide a perspective of how recent cancer biology discoveries may juxtapose with current treatment pathways, with potential translational line of site for future research. In particular, neo-adjuvant therapy or biomarkers from tumour-draining lymph nodes may present opportunities to preserve lymphatics and harness improved immunocompetence in HNSCC patients.","PeriodicalId":135222,"journal":{"name":"BJC Reports","volume":" ","pages":"1-5"},"PeriodicalIF":0.0,"publicationDate":"2024-09-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s44276-024-00095-1.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142231144","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":"Predictive model of castration resistance in advanced prostate cancer by machine learning using genetic and clinical data: KYUCOG-1401-A study","authors":"Masaki Shiota, Shota Nemoto, Ryo Ikegami, Shuichi Tatarano, Toshiyuki Kamoto, Keita Kobayashi, Hideki Sakai, Tsukasa Igawa, Tomomi Kamba, Naohiro Fujimoto, Akira Yokomizo, Seiji Naito, Masatoshi Eto","doi":"10.1038/s44276-024-00093-3","DOIUrl":"10.1038/s44276-024-00093-3","url":null,"abstract":"The predictive power of the treatment efficacy and prognosis in primary androgen deprivation therapy (ADT) for advanced prostate cancer is not satisfactory. The objective of this study was to integrate genetic and clinical data to predict castration resistance in primary ADT for advanced prostate cancer by machine learning (ML). Clinical and single nucleotide polymorphisms (SNP) data obtained in the KYUCOG-1401-A study (UMIN000022852) that enrolled Japanese patients with advanced prostate cancer were used. All patients were treated with primary ADT. A point-wise linear (PWL) algorithm, logistic regression with elastic-net regularization, and eXtreme Gradient Boosting were the ML algorithms used in this study. Area under the curve for castration resistance and C-index for prognoses were calculated to evaluate the utility of the models. Among the three ML algorithms, the area under the curve values to predict castration resistance at 2 years was highest for the PWL algorithm with all the datasets. Three predictive models (clinical model, small SNPs model, and large SNPs model) were created by the PWL algorithm using the clinical data alone, and 2 and 46 SNPs in addition to clinical data. C-indices for overall survival by the clinical, small SNPs, and large SNPs models were 0.636, 0.621, and 0.703, respectively. The results demonstrated that the SNPs models created by ML produced excellent prediction of castration resistance and prognosis in primary ADT for advanced prostate cancer, and will be helpful in treatment choice.","PeriodicalId":135222,"journal":{"name":"BJC Reports","volume":" ","pages":"1-8"},"PeriodicalIF":0.0,"publicationDate":"2024-09-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s44276-024-00093-3.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142231158","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":"Towards replicability and sustainability in cancer research","authors":"David Robert Grimes","doi":"10.1038/s44276-024-00090-6","DOIUrl":"10.1038/s44276-024-00090-6","url":null,"abstract":"High-quality cancer research is crucial to both save lives and improve quality of life. Spurious findings, however, impedes these laudable goals by misleading research efforts and creating research waste that is inherently difficult to counteract. Irreproducible research is intrinsically wasteful, and unsustainable over the long term. In this perspective piece, we elucidate the extent of the current replication crisis and the underlying causes, identifying practices that lend themselves to unsustainable spurious findings, and the factors that underpin these practices. Finally we outline some remedies to the problem of irreproducible research, and how we might move towards more sustainable and trustworthy research in biomedical science.","PeriodicalId":135222,"journal":{"name":"BJC Reports","volume":" ","pages":"1-5"},"PeriodicalIF":0.0,"publicationDate":"2024-09-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s44276-024-00090-6.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142130468","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":"Phase 1b/2 study of the liposomal formulation of eribulin (E7389-LF) in combination with nivolumab: Results from the phase 2 esophageal cancer cohort","authors":"Takashi Oshima, Sachiko Yamamoto, Hisato Kawakami, Tomoki Makino, Akihito Kawazoe, Toshiki Masuishi, Takahiro Tsushima, Motohiro Hirao, Masahiro Tsuda, Kaori Hino, Noboru Yamamoto, Hiroki Hara, Shota Kaname, Daiko Matsuoka, Yohei Otake, Keisuke Yasuda, Takao Takase, Shuya Takashima, Taro Semba, Akira Ooki","doi":"10.1038/s44276-024-00066-6","DOIUrl":"10.1038/s44276-024-00066-6","url":null,"abstract":"Esophageal cancer is one of the most common types of cancer in Japan. Herein, we report the efficacy and safety of E7389-LF plus the immune checkpoint inhibitor, nivolumab, from the esophageal cancer cohort of the phase 2 part of Study 120. Eligible patients received E7389-LF 2.1 mg/m2 plus nivolumab 360 mg intravenously Q3W. The primary objective was to evaluate the objective response rate (ORR); other objectives included safety, progression-free survival (PFS), and overall survival (OS). Of the 35 Japanese patients enrolled, 7 (20.0%) had a partial response as their best overall response, and 14 (40.0%) had stable disease. The ORR was 20.0% (95% CI 8.4–36.9). The duration of response was 5.6 months (95% CI 1.7–not estimable [NE]). The median PFS was 2.81 months (95% CI 1.31–4.17). The median OS was not reached (95% CI 6.54 months–NE). The most common treatment-emergent adverse events were neutropenia (65.7%), pyrexia (60.0%), and leukopenia (57.1%). Select plasma endothelial cell markers levels increased from day 1 of cycle 1 and changes were pronounced between days 8–15 of each cycle. E7389-LF plus nivolumab showed antitumor activity in patients with unresectable and pretreated esophageal cancer and should be evaluated further in a broader population. NCT04078295.","PeriodicalId":135222,"journal":{"name":"BJC Reports","volume":" ","pages":"1-7"},"PeriodicalIF":0.0,"publicationDate":"2024-09-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s44276-024-00066-6.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142130465","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":"Publisher Correction: Real-world effectiveness of CDK 4/6 inhibitors in estrogen-positive metastatic breast cancer","authors":"Mathilde Louise Gehrchen, Tobias Berg, Rasmus Garly, Maj-Britt Jensen, Saskia Eßer-Naumann, Jeanette Dupont Rønlev, Hanne Melgaard Nielsen, Ann Knoop, Iben Kümler","doi":"10.1038/s44276-024-00083-5","DOIUrl":"10.1038/s44276-024-00083-5","url":null,"abstract":"","PeriodicalId":135222,"journal":{"name":"BJC Reports","volume":" ","pages":"1-5"},"PeriodicalIF":0.0,"publicationDate":"2024-09-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s44276-024-00083-5.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142130467","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":"Calcium intake and genetic variants in the calcium sensing receptor in relation to colorectal cancer mortality: an international consortium study of 18,952 patients","authors":"Evertine Wesselink, William Gauderman, Sonja I. Berndt, Hermann Brenner, Daniel D. Buchanan, Peter T. Campbell, Andrew T. Chan, Jenny Chang-Claude, Michelle Cotterchoi, Marc J. Gunter, Michael Hoffmeister, Amit D. Joshi, Christina C. Newton, Rish K. Pai, Andrew J. Pellatt, Amanda I. Phipps, Mingyang Song, Caroline Y. Um, Bethany van Guelpen, Emily White, Ulrike Peters, Fränzel J. B. van Duijnhoven","doi":"10.1038/s44276-024-00077-3","DOIUrl":"10.1038/s44276-024-00077-3","url":null,"abstract":"Research on calcium intake as well as variants in the calcium sensor receptor (CaSR) gene and their interaction in relation to CRC survival is still limited. Data from 18,952 CRC patients, were included. Associations between primarily pre-diagnostic dietary (n = 13.085), supplemental (n = 11,837), total calcium intake (n = 5970) as well as 325 single nucleotide polymorphisms (SNPs) of the CaSR gene (n = 15,734) in relation to CRC-specific and all-cause mortality were assessed using Cox proportional hazard models. Also interactions between calcium intake and variants in the CaSR gene were assessed. During a median follow-up of 4.8 years (IQR 2.4–8.4), 6801 deaths occurred, of which 4194 related to CRC. For all-cause mortality, no associations were observed for the highest compared to the lowest sex- and study-specific quartile of dietary (HR 1.00, 95%CI 0.92–1.09), supplemental (HR 0.97, 95%CI 0.89–1.06) and total calcium intake (HR 0.99, 95%CI 0.88–1.11). No associations with CRC-specific mortality were observed either. Interactions were observed between supplemental calcium intake and several SNPs of the CaSR gene. Calcium intake was not associated with all-cause or CRC-specific mortality in CRC patients. The association between supplemental calcium intake and all-cause and CRC-specific mortality may be modified by genetic variants in the CaSR gene.","PeriodicalId":135222,"journal":{"name":"BJC Reports","volume":" ","pages":"1-12"},"PeriodicalIF":0.0,"publicationDate":"2024-09-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s44276-024-00077-3.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142123438","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":"Temporal evolution and inter-patient heterogeneity in primary and recurrent head and neck squamous cell carcinoma","authors":"Luisa Bresadola, David Weber, Christoph Ritzel, Martin Löwer, Valesca Bukur, Özlem Akilli-Öztürk, Christian Schuster, Alessandra Gargano, Julia Becker, Hisham Mehanna, Barbara Schrörs, Fulvia Vascotto, Ugur Sahin, Anthony Kong","doi":"10.1038/s44276-024-00091-5","DOIUrl":"10.1038/s44276-024-00091-5","url":null,"abstract":"Head and neck squamous cell carcinomas (HNSCCs) are heterogeneous in terms of origin and aetiology. In addition, there is uncertainty about the genetic evolution from initial diagnosis to recurrence after primary treatments and further disease progression following systemic treatment. Changes in the genetic profile have implications on the selection of appropriate treatments for patients, especially in the era of targeted therapies and immunotherapies. We analysed a cohort of nine HNSCC patients with metachronous recurrence. All patients had paired primary and recurrent samples suitable for whole-exome sequencing, while transcriptomic data from seven patients could be analysed (multiple recurrent samples collected at different time points were available for three patients). At the genomic level, the recurrences shared a fraction of the somatic single nucleotide variants (SNVs) with the index primary tumours, but they also acquired many additional mutations, while losing only a few others. A similar behaviour was also observed when examining the changes of mutational signatures between primary and recurrent samples. Overall, recurrences appeared thus more genetically diverse than the respective primary tumours. The transcriptomic analysis showed that recurrent samples had lower immune cell presence, which was also confirmed by the multiplex immunofluorescence (IF) histology assays performed on the PhenoCycler platform. Several genes related to immune response were significantly downregulated compared to the primary samples. Our results underline the importance of analysing multiple samples per patient to obtain a more complete picture of the patient’s tumour and advocate a re-biopsy in the event of recurrence and treatment failure, in order to select the most appropriate therapeutic strategy.","PeriodicalId":135222,"journal":{"name":"BJC Reports","volume":" ","pages":"1-11"},"PeriodicalIF":0.0,"publicationDate":"2024-08-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s44276-024-00091-5.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142100553","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":"Estimating cure proportion in cancer clinical trials using flexible parametric cure models","authors":"Yuka Sano, Shiro Tanaka, Tosiya Sato","doi":"10.1038/s44276-024-00092-4","DOIUrl":"10.1038/s44276-024-00092-4","url":null,"abstract":"In the context of survival analysis in recent cancer clinical trials, there has been an increasing interest in the proportion of patients who are not susceptible to the event, known as the cure proportion. To estimate it, cure models implicitly specify the time point when patients are considered cured, although the impact of the cure point position on cure proportion estimates is unclear. Sensitivity of cure proportion estimates to the knot number and placement in flexible parametric cure models was examined using data from a clinical trial of CheckMate 141, an immuno-oncology compound. The performance of the model and procedures to determine the cure point position were evaluated using a simulation study. Analysis of the CheckMate 141 data showed the impact of the last knot position on the cure proportion estimate and model fit. Simulations revealed that the flexible parametric cure model with the last knot at the last observed event time overestimated the cure proportion. This bias was reduced when the last knot was placed later. For cure proportion estimation in clinical trials with survival outcomes, the flexible parametric cure model can be an attractive alternative to the Kaplan–Meier method.","PeriodicalId":135222,"journal":{"name":"BJC Reports","volume":" ","pages":"1-7"},"PeriodicalIF":0.0,"publicationDate":"2024-08-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s44276-024-00092-4.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142100558","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}