Oncotarget最新文献_第4页

Immune-mediated adverse events following atezolizumab and bevacizumab in a multinational Latin American cohort of unresectable hepatocellular carcinoma. 在一项拉丁美洲多国不可切除肝细胞癌队列中，阿特唑单抗和贝伐单抗后免疫介导的不良事件

Oncotarget Pub Date : 2025-05-19 DOI: 10.18632/oncotarget.28721

Leonardo Gomes da Fonseca, Federico Piñero, Margarita Anders, Carla Bermudez, Ezequiel Demirdjian, Adriana Varón, Daniela Perez, Jorge Rodriguez, Oscar Beltrán, Ezequiel Ridruejo, Pablo Caballini, Alexandre Araujo, Juan Diego Torres Florez, Juan Ignacio Marín, Marina Villa, Federico Orozco, Jaime Poniachik, Sebastián Marciano, Fernando Bessone, Manuel Mendizabal

{"title":"Immune-mediated adverse events following atezolizumab and bevacizumab in a multinational Latin American cohort of unresectable hepatocellular carcinoma.","authors":"Leonardo Gomes da Fonseca, Federico Piñero, Margarita Anders, Carla Bermudez, Ezequiel Demirdjian, Adriana Varón, Daniela Perez, Jorge Rodriguez, Oscar Beltrán, Ezequiel Ridruejo, Pablo Caballini, Alexandre Araujo, Juan Diego Torres Florez, Juan Ignacio Marín, Marina Villa, Federico Orozco, Jaime Poniachik, Sebastián Marciano, Fernando Bessone, Manuel Mendizabal","doi":"10.18632/oncotarget.28721","DOIUrl":"10.18632/oncotarget.28721","url":null,"abstract":"Aims: Latin America has been underrepresented in trials evaluating immunotherapy for hepatocellular carcinoma (HCC). We aimed to describe the incidence of immune-related adverse events (irAEs) and their impact on outcomes in a Latin American cohort.Methods: A multicenter prospective study was conducted in Argentina, Brazil, Chile, and Colombia, including patients who received atezolizumab plus bevacizumab. A time-covarite proportional hazard analysis evaluated the effect of irAEs.Results: 99 patients were included. The median treatment duration was 6 months, with a median survival of 17.0 months (95% CI: 12.6-19.8). The irAE incidence rate was 2.1 cases per 100 persons-months (cumulative incidence 18.1% (95% CI: 11.1-27.2%)). Median time to irAE was 2.3 months (range 1.4-4.8), most frequently hepatitis (n = 6), thyroiditis (n = 5), and 8/18 required steroids. Follow-up, treatment duration, and overall survival were similar regardless of the occurrence of irAEs (HR = 1.71, 95% CI: 0.76-3.86; P = 0.19). Baseline alpha-feto protein ≥400 ng/ml (HR: 2.9 (95% CI: 1.1-7.6)) was independently associated with irAE.Conclusion: The incidence of irAEs in this cohort is lower than reported in controlled trials, withouut impact on survival outcomes. Education and early recognition are crucial to ensure that these events are identified and addressed.","PeriodicalId":19499,"journal":{"name":"Oncotarget","volume":"16 ","pages":"348-360"},"PeriodicalIF":0.0,"publicationDate":"2025-05-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12088043/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144093628","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}

引用次数: 0

PRDX1 protects ATM from arsenite-induced proteotoxicity and maintains its stability during DNA damage signaling. PRDX1保护ATM免受亚砷酸盐诱导的蛋白质毒性，并在DNA损伤信号传导过程中维持其稳定性。

Oncotarget Pub Date : 2025-05-19 DOI: 10.18632/oncotarget.28720

Reem Ali, Mashael Algethami, Amera Sheha, Shatha Alqahtani, Ahmad Altayyar, Ayat Lashen, Emad Rakha, Abdallah Alhaj Sulaiman, Srinivasan Madhusudan, Dindial Ramotar

{"title":"PRDX1 protects ATM from arsenite-induced proteotoxicity and maintains its stability during DNA damage signaling.","authors":"Reem Ali, Mashael Algethami, Amera Sheha, Shatha Alqahtani, Ahmad Altayyar, Ayat Lashen, Emad Rakha, Abdallah Alhaj Sulaiman, Srinivasan Madhusudan, Dindial Ramotar","doi":"10.18632/oncotarget.28720","DOIUrl":"10.18632/oncotarget.28720","url":null,"abstract":"Redox regulation and DNA repair coordination are essential for genomic stability. Peroxiredoxin 1 (PRDX1) is a thiol-dependent peroxidase and a chaperone that protects proteins from excessive oxidation. ATM kinase (Ataxia-Telangiectasia Mutated) and the MRN (MRE11-RAD50-NBS1) complex are DNA damage signaling and repair proteins. We previously showed that cells lacking PRDX1 are sensitive to arsenite, a toxic metal that induces DNA single- and double-strand breaks (DSBs). Herein, we showed that PRDX1 interacts with ATM. PRDX1-deleted cells have reduced ATM, MRE11, and RAD50 protein levels, but not NBS1. In control cells treated with arsenite, we observed γH2AX foci formation due to arsenite-induced DSBs, and not from PRDX1-deleted cells. Arsenite caused profound depletion of ATM in PRDX1-deleted cells, suggesting that PRDX1 protects and stabilizes ATM required to form γH2AX foci. Importantly, arsenite pretreatment of PRDX1-deleted cells caused hypersensitivity to chemotherapeutic agents that generate DSBs. Analysis of a clinical cohort of ovarian cancers treated with platinum chemotherapy revealed that tumours with high PRDX1/high ATM or high PRDX1/high MRE11 expression manifested aggressive phenotypes and poor patient survival. The data suggest that PRDX1 can predict responses to chemotherapy, and targeting PRDX1 could be a viable strategy to improve the efficacy of platinum chemotherapy.","PeriodicalId":19499,"journal":{"name":"Oncotarget","volume":"16 ","pages":"362-378"},"PeriodicalIF":0.0,"publicationDate":"2025-05-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12088036/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144093644","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}

引用次数: 0

Retraction: Inhibition of protein phosphatase 2A with a small molecule LB100 radiosensitizes nasopharyngeal carcinoma xenografts by inducing mitotic catastrophe and blocking DNA damage repair. 小分子LB100抑制蛋白磷酸酶2A通过诱导有丝分裂突变和阻断DNA损伤修复使鼻咽癌异种移植物放射增敏。

Oncotarget Pub Date : 2025-05-19 DOI: 10.18632/oncotarget.28727

Peng Lv, Yue Wang, Jie Ma, Zheng Wang, Jing-Li Li, Christopher S Hong, Zhengping Zhuang, Yi-Xin Zeng

引用次数: 0

Analytical validation of a circulating tumor DNA assay using PhasED-Seq technology for detecting residual disease in B-cell malignancies. 利用PhasED-Seq技术检测b细胞恶性肿瘤残留疾病的循环肿瘤DNA分析验证

Oncotarget Pub Date : 2025-05-09 DOI: 10.18632/oncotarget.28719

Nina Klimova, Sandra Close, David M Kurtz, Richard D Hockett, Laura Hyland

{"title":"Analytical validation of a circulating tumor DNA assay using PhasED-Seq technology for detecting residual disease in B-cell malignancies.","authors":"Nina Klimova, Sandra Close, David M Kurtz, Richard D Hockett, Laura Hyland","doi":"10.18632/oncotarget.28719","DOIUrl":"https://doi.org/10.18632/oncotarget.28719","url":null,"abstract":"Background: Circulating tumor DNA (ctDNA) can be used as a tool to detect minimal residual disease (MRD) which can provide important prognostic information in diffuse large B-cell lymphomas (DLBCL). Here, we present an ultra-sensitive MRD assay reliant on Phased Variant Enrichment and Detection Sequencing (PhasED-Seq), which leverages phased variants to detect ctDNA.Methods: Blank plasma samples were used to assess assay specificity and a limiting dilution series with a DLBCL clinical-contrived sample was performed to assess assay sensitivity and precision. DLBCL plasma patient samples with MRD comparator assay results were tested with PhasED-Seq technology to assess assay accuracy.Results: The assay's false positive rate was 0.24% and the background error rate was 1.95E-08. The limit of detection at 95% detection rate with 120 ng of input DNA was 0.7 parts in 1,000,000 and precision was >96%. Positive percent agreement for the MRD assay was 90.62% (95% CI 74.98%, 98.02%) and negative percent agreement was 77.78% (95% CI 52.73, 93.59) using a single nucleotide variant-based method as reference.Conclusions: The PhasED-Seq-based MRD assay has strong analytical and clinical performance in B-cell malignancies. Improved ctDNA detection methods such as this may improve patient outcomes through detection of residual disease or early relapse.","PeriodicalId":19499,"journal":{"name":"Oncotarget","volume":"16 ","pages":"329-336"},"PeriodicalIF":0.0,"publicationDate":"2025-05-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12068320/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144023452","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}

引用次数: 0

Retraction: Downregulation of long non-coding RNA ANRIL suppresses lymphangiogenesis and lymphatic metastasis in colorectal cancer. 撤回：下调长链非编码RNA ANRIL抑制结直肠癌的淋巴管生成和淋巴转移。

Oncotarget Pub Date : 2025-05-09 DOI: 10.18632/oncotarget.28725

Zhenqiang Sun, Chunlin Ou, Weiguo Ren, Xiang Xie, Xiayu Li, Guiyuan Li

引用次数: 0

Relationship between ABO blood group antigens and Rh factor with breast cancer: A systematic review and meta-analysis. ABO血型抗原和Rh因子与乳腺癌的关系：系统回顾和荟萃分析。

Oncotarget Pub Date : 2025-05-09 DOI: 10.18632/oncotarget.28718

Rahaf Alchazal, Khaled J Zaitoun, Mohammad Al-Qudah, Ghena Zaitoun, Amira M Taha, Othman Saleh, Mohammad Alqudah, Mohammad Abuawwad, Mohammad Taha, Abdullah Yousef Aldalati

{"title":"Relationship between ABO blood group antigens and Rh factor with breast cancer: A systematic review and meta-analysis.","authors":"Rahaf Alchazal, Khaled J Zaitoun, Mohammad Al-Qudah, Ghena Zaitoun, Amira M Taha, Othman Saleh, Mohammad Alqudah, Mohammad Abuawwad, Mohammad Taha, Abdullah Yousef Aldalati","doi":"10.18632/oncotarget.28718","DOIUrl":"10.18632/oncotarget.28718","url":null,"abstract":"Background: Breast cancer is a type of cancer that can affect both males and females, but it is widespread among women. Blood types may be associated with breast cancer, as many studies have reported on this relationship but rarely described it. The primary objective of our research is to summarize and analyze the available evidence to produce comprehensive and accurate information that can be used to make evidence-based decisions.Methods: Researchers searched for studies on breast cancer patients and ABO blood groups across four major databases: PubMed, Scopus, Web of Science, and Google. The outcomes of the studies were presented as a relative risk and odds ratio with a 95% confidence interval.Results: Twenty-nine case-control studies with 13029 breast cancer patients. Blood type A was the most common blood type among patients. For blood type A, there was an association with breast cancer (OR = 1.18, 95% CI: 1.03-1.36). Blood types B, AB, and Rh factor showed no significant association with breast cancer (OR = 0.97, 95% CI: 0.86-1.11, OR = 1.05, 95% CI: 0.89-1.25, and OR = 1.14, 95% CI: 0.81-1.60 respectively) in compare to blood type A.Conclusions: This study highlights the potential of blood type A as a risk factor for breast cancer compared to blood type O. This relationship was insignificant for blood types B, AB, or Rh. Further studies are needed to understand the mechanisms behind the blood type and breast cancer correlation.","PeriodicalId":19499,"journal":{"name":"Oncotarget","volume":"16 ","pages":"311-326"},"PeriodicalIF":0.0,"publicationDate":"2025-05-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12068321/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143997243","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}

引用次数: 0

Retraction: Ginkgo biloba extract EGb 761-induced upregulation of LincRNA-p21 inhibits colorectal cancer metastasis by associating with EZH2. 撤回：银杏叶提取物EGb 761诱导LincRNA-p21上调，通过与EZH2相关抑制结直肠癌转移。

Oncotarget Pub Date : 2025-05-08 DOI: 10.18632/oncotarget.28525

Tingting Liu, Junzhong Zhang, Zhongqiu Chai, Gang Wang, Naiqiang Cui, Bing Zhou

引用次数: 0

METTL3 promotes oral squamous cell carcinoma by regulating miR-146a-5p/SMAD4 axis. METTL3通过调节miR-146a-5p/SMAD4轴促进口腔鳞状细胞癌。

Oncotarget Pub Date : 2025-05-08 DOI: 10.18632/oncotarget.28717

Jayasree Peroth Jayaprakash, Pragati Karemore, Piyush Khandelia

{"title":"METTL3 promotes oral squamous cell carcinoma by regulating miR-146a-5p/SMAD4 axis.","authors":"Jayasree Peroth Jayaprakash, Pragati Karemore, Piyush Khandelia","doi":"10.18632/oncotarget.28717","DOIUrl":"https://doi.org/10.18632/oncotarget.28717","url":null,"abstract":"N6-methyladenosine (m6A), one of the most prominent and reversible internal modifications of eukaryotic RNAs, has emerged as a critical regulator of gene expression in various cancers including oral squamous cell carcinoma (OSCC), wherein it shapes the tumor-specific epitranscriptomic gene-regulatory networks. METTL3, the primary m6A RNA methyltransferase, is significantly upregulated in OSCC cells leading to increased global m6A levels. Interestingly, METTL3 positively regulates miRNA biogenesis by modulating the processing of primary miRNAs in a m6A-dependent manner. We identified miR-146a-5p, an oncogenic miRNA as one of the METTL3-regulated miRNAs in OSCC. METTL3-depletion or inhibition of its catalytic activity leads to a reduction of miR-146a-5p and an appreciable accumulation of primary miR-146a in OSCC cells. Functional assays examining the effects of miR-146a-5p inhibition or overexpression confirm its oncogenic role in OSCC pathophysiology. Further, SMAD4, a central transducer in TGF-β signaling, was identified as a miR-146a-5p target. In OSCC cells, SMAD4-depletion exacerbates the oncogenic traits, whereas its overexpression exerts the opposite effect. Additionally, METTL3-depletion dysregulates SMAD4-regulated genes suggesting its potential involvement in SMAD4-dependent TGF-β signaling. Taken together, we report that METTL3, an oncogene regulates the expression of SMAD4, a tumor-suppressor via miR-146a-5p, thus unveiling a novel regulatory axis of METTL3/miR-146a-5p/SMAD4 in OSCC, which can potentially have therapeutic implications.","PeriodicalId":19499,"journal":{"name":"Oncotarget","volume":"16 ","pages":"291-309"},"PeriodicalIF":0.0,"publicationDate":"2025-05-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12060920/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144017463","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}

引用次数: 0

Retraction: MicroRNA-300 inhibited glioblastoma progression through ROCK1. 缩回：MicroRNA-300通过ROCK1抑制胶质母细胞瘤的进展。

Oncotarget Pub Date : 2025-04-24 DOI: 10.18632/oncotarget.28716

Fucheng Zhou, Yang Li, Zhen Hao, Xuanxi Liu, Liang Chen, Yu Cao, Zuobin Liang, Fei Yuan, Jie Liu, Jianjiao Wang, Yongri Zheng, Deli Dong, Shan Bian, Baofeng Yang, Chuanlu Jiang, Qingsong Li

引用次数: 0

PD-L1 and FOXP3 expression in high-grade squamous intraepithelial lesions of the anogenital region. PD-L1和FOXP3在肛门生殖器区高级别鳞状上皮内病变中的表达。

Oncotarget Pub Date : 2025-04-24 DOI: 10.18632/oncotarget.28715

Humberto Carvalho Carneiro, Rodrigo de Andrade Natal, José Vassallo, Fernando Augusto Soares

{"title":"PD-L1 and FOXP3 expression in high-grade squamous intraepithelial lesions of the anogenital region.","authors":"Humberto Carvalho Carneiro, Rodrigo de Andrade Natal, José Vassallo, Fernando Augusto Soares","doi":"10.18632/oncotarget.28715","DOIUrl":"https://doi.org/10.18632/oncotarget.28715","url":null,"abstract":"Host immunosurveillance is an important factor in the progression of high-grade squamous intraepithelial lesions (HSIL) into high-risk human papillomavirus (HR-HPV)-related squamous cell carcinoma. Immune escape by forkhead box protein P3 (FOXP3+) immunoregulatory T cells and the programmed death-ligand 1 (PD1/PD-L1) axis, mechanisms best described in the context of invasive neoplasms, may play a role in the evolution of pre-malignant lesions. This morphological study aimed to characterize the inflammatory response and expression of FOXP3 and PD-L1 in anal, vulvar, and penile HSILs and compare them with those in low-grade SILs co-infected with HR-HPV (LSILHR). The study group comprised 157 samples from 95 male and 55 female patients (median age = 35.5 years), including 122 HSILs and 35 LSILsHR. Dense inflammatory infiltrates and high counts of FOXP3+ cells were significantly more frequent in patients with HSILs than in those with LSILsHR (p = 0.04 and 0.02, respectively). HSILs also exhibited higher PD-L1 expression (padj < 0.01 and < 0.01 for the SP142 and 22C3 clones, respectively), based on the Poisson generalized linear model. In addition, concordant higher PD-L1 expression was observed in cases with a greater number of FOXP3+ cells (p < 0.05). Our findings indicate a putative role of transcriptionally active HR-HPV in evoking an inflammatory response and immune evasion in the early phases of carcinogenesis in a subset of non-cervical anogenital HSILs.","PeriodicalId":19499,"journal":{"name":"Oncotarget","volume":"16 ","pages":"277-290"},"PeriodicalIF":0.0,"publicationDate":"2025-04-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12060918/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143984887","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}

引用次数: 0