Cancer Biology & Therapy最新文献

{"title":"PINCH-1 promotes tumor growth and metastasis by enhancing DRP1-mediated mitochondrial fission in head and neck squamous cell carcinoma.","authors":"Ruxian Tian, Hao Song, Jiaxuan Li, Ting Yuan, Jiahui Liu, Yaqi Wang, Yumei Li, Xicheng Song","doi":"10.1080/15384047.2025.2477365","DOIUrl":"10.1080/15384047.2025.2477365","url":null,"abstract":"<p><strong>Purpose: </strong>Abnormal expression of PINCH-1 has been observed in various types of human cancers. However, the clinical importance and mechanism underlying its role in head and neck squamous cell carcinoma (HNSCC) is yet to be fully elucidated.</p><p><strong>Methods: </strong>This study evaluated the expression of PINCH-1 in HNSCC samples through immunohistochemical staining and Western blotting. AMC-HN-8, Cal27, and SCC7 cell lines were utilized for cellular function experiments, both in vivo and in vitro. CCK8, colony-formation assay, flow cytometry, wound-healing assay, and transwell assay were employed to investigate the effects of alterations in target proteins on the growth and metastasis of cancer cells. Mito-Tracker Deep Red FM was used to track mitochondrial morphology.</p><p><strong>Results: </strong>PINCH-1 was found to be overexpressed in HNSCC and closely associated with lymph node metastasis and poor pathologic differentiation. Its upregulation promoted proliferation, inhibited apoptosis, and enhanced migration and invasion in HNSCC cells. It also promoted mitochondrial fission. We conducted a mechanism analysis, which showed that PINCH-1 knockdown inhibited mitochondrial fission by reducing the expression of DRP1. Furthermore, inhibition of mitochondrial fission could impede the proliferation and metastasis of HNSCC cells. Re-expression of DRP1 reversed the inhibitory effect of PINCH-1 knockdown on mitochondrial fission, cell proliferation, and metastasis in HNSCC cells.</p><p><strong>Conclusions: </strong>PINCH-1 plays a critical oncogenic role in HNSCC by enhancing DRP1-mediated mitochondrial fission, which may serve as a novel therapeutic target for HNSCC.</p>","PeriodicalId":9536,"journal":{"name":"Cancer Biology & Therapy","volume":"26 1","pages":"2477365"},"PeriodicalIF":4.4,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11901378/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143596397","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Bibliometric analysis of autophagy in the diagnosis and treatment of osteosarcoma: a bibliometric analysis (2007-2023).","authors":"Min Zhu, Wei Xiang, Zhoujun Zhu, Bingjie Nie, Xinyue Zhen, Chen Chen, Tianhai Wang","doi":"10.1080/15384047.2025.2484825","DOIUrl":"10.1080/15384047.2025.2484825","url":null,"abstract":"<p><p>Osteosarcoma is the most common primary bone tumor in children and adolescents. Its pathogenesis is complex and poses difficulties in treatment. Autophagy is a cell biological process that plays a crucial role in the mechanistic study and treatment of osteosarcoma. The objective of this study is to evaluate the past research progress from 2007 to 2023 and visualize the key research directions through bibliometric methods. Relevant publications published from the start of 2007 to the end of 2023 were searched and screened in the Web of Science Core Collection. They were analyzed and visualized using CiteSpace and the Bibliometric online analysis platform in terms of country, institution, author, journal, cited references, and keywords. In total, 619 publications from 522 journals with 682 authors from 42 countries were screened. The country with the highest number of publications is China (<i>n</i> = 445, 71.890%), followed by the United States (<i>n</i> = 60, 9.693%). The research institution with the highest number of publications is Shanghai Jiao Tong University (<i>n</i> = 42, 6.785%). The author with the highest number of publications is Cai, Zhengdong (<i>n</i> = 7), while the most cited author is Mizushimma N (<i>n</i> = 93). Among many journals, AUTOPHAGY has the most citations (<i>n</i> = 342), while CANCER LETT shows the greatest centrality (Centrality = 0.05). \"Autophagy\" is the most cited keyword (<i>n</i> = 177), and the keyword with the largest burst intensity is \"cancer cells\" (Strength = 6.27), which lasted from 2011 to 2014. China is a major contributor to autophagy research in the field of osteosarcoma, followed by the United States. All publications are in high-quality journals. \"Autophagy\" is a hot research topic in this field.</p>","PeriodicalId":9536,"journal":{"name":"Cancer Biology & Therapy","volume":"26 1","pages":"2484825"},"PeriodicalIF":4.4,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11951729/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143718137","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Functional validation of somatic variability in <i>TP53</i> and <i>KRAS</i> for prediction of platinum sensitivity and prognosis in epithelial ovarian carcinoma patients.","authors":"Al Obeed Allah Mohammad, Ali Esraa, Krus Ivona, Holý Petr, Haničinec Vojtěch, Ambrozkiewicz Filip, Rob Lukáš, Hruda Martin, Mrhalová Marcela, Kopečková Kateřina, Bartáková Alena, Bouda Jiří, Spálenková Alžběta, Souček Pavel, Václavíková Radka","doi":"10.1080/15384047.2025.2543105","DOIUrl":"10.1080/15384047.2025.2543105","url":null,"abstract":"<p><p>Concerning the dismal prognosis of chemoresistant patients with epithelial ovarian carcinoma (EOC), we aimed to follow up the findings of a previous whole-exome sequencing study using an orthogonal Sanger sequencing on the same patients and a separate set of 127 EOC patients (<i>N</i> = 177, all fresh frozen tumor samples). We focused on TP53 as a frequently mutated gene relevant for chemosensitivity, included KRAS as an additional therapeutically relevant target, complemented the study with transcript levels of both genes, and compared results with clinical parameters. All variants in TP53 and KRAS detected by exome sequencing were confirmed. KRAS mutated patients had significantly more frequent FIGO stages I or II (<i>p</i> = .002) and other than high-grade serous tumor subtypes (nonHGSCs) (<i>p</i> < .001), which was connected with lower KRAS transcript levels (<i>p</i> = .004). Patients with nonHGSC subtypes had less frequent TP53 mutations (<i>p</i> = .002). Carriers of TP53 variants disrupting the DNA binding loop had significantly longer platinum-free intervals than the rest (<i>p</i> = .037). Tumors bearing nonsense, frameshift, or splice site TP53 variants had a significantly lower TP53 transcript level, while those with missense variants had significantly higher levels than wild types (<i>p</i> < .001). The normalized intratumoral TP53 and KRAS transcript levels were correlated, and patients with co-mutated genes had poorer overall survival than others (<i>p</i> = .015). Protein levels of both genes significantly correlated with their respective transcripts (<i>p</i> = .028 and <i>p</i> = .001, respectively). Our study points to <i>KRAS</i> as a target for future therapy of nonHGSCs and reveals the prognostic value of <i>TP53</i> variants in the DNA binding loop.</p>","PeriodicalId":9536,"journal":{"name":"Cancer Biology & Therapy","volume":"26 1","pages":"2543105"},"PeriodicalIF":4.6,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12341051/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144815808","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Efficacy and pharmacodynamic effect of anti-CD73 and anti-PD-L1 monoclonal antibodies in combination with cytotoxic therapy: observations from mouse tumor models.","authors":"Brajesh P Kaistha, Gozde Kar, Andreas Dannhorn, Amanda Watkins, Grace Opoku-Ansah, Kristina Ilieva, Stefanie Mullins, Judith Anderton, Elena Galvani, Fabien Garcon, Jean-Martin Lapointe, Lee Brown, James Hair, Tim Slidel, Nadia Luheshi, Kelli Ryan, Elizabeth Hardaker, Simon Dovedi, Rakesh Kumar, Robert W Wilkinson, Scott A Hammond, Jim Eyles","doi":"10.1080/15384047.2023.2296048","DOIUrl":"10.1080/15384047.2023.2296048","url":null,"abstract":"<p><p>CD73 is a cell surface 5'nucleotidase (NT5E) and key node in the catabolic process generating immunosuppressive adenosine in cancer. Using a murine monoclonal antibody surrogate of Oleclumab, we investigated the effect of CD73 inhibition in concert with cytotoxic therapies (chemotherapies as well as fractionated radiotherapy) and PD-L1 blockade. Our results highlight improved survival in syngeneic tumor models of colorectal cancer (CT26 and MC38) and sarcoma (MCA205). This therapeutic outcome was in part driven by cytotoxic CD8 T-cells, as evidenced by the detrimental effect of CD8 depleting antibody treatment of MCA205 tumor bearing mice treated with anti-CD73, anti-PD-L1 and 5-Fluorouracil+Oxaliplatin (5FU+OHP). We hypothesize that the improved responses are tumor microenvironment (TME)-driven, as suggested by the lack of anti-CD73 enhanced cytopathic effects mediated by 5FU+OHP on cell lines <i>in vitro</i>. Pharmacodynamic analysis, using imaging mass cytometry and RNA-sequencing, revealed noteworthy changes in specific cell populations like cytotoxic T cells, B cells and NK cells in the CT26 TME. Transcriptomic analysis highlighted treatment-related modulation of gene profiles associated with an immune response, NK and T-cell activation, T cell receptor signaling and interferon (types 1 & 2) pathways. Inclusion of comparator groups representing the various components of the combination allowed deconvolution of contribution of the individual therapeutic elements; highlighting specific effects mediated by the anti-CD73 antibody with respect to immune-cell representation, chemotaxis and myeloid biology. These pre-clinical data reflect complementarity of adenosine blockade with cytotoxic therapy, and T-cell checkpoint inhibition, and provides new mechanistic insights in support of combination therapy.</p>","PeriodicalId":9536,"journal":{"name":"Cancer Biology & Therapy","volume":"25 1","pages":"2296048"},"PeriodicalIF":3.6,"publicationDate":"2024-12-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10793677/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139416454","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"TOP2A modulates signaling via the AKT/mTOR pathway to promote ovarian cancer cell proliferation.","authors":"Kaiwen Zhang, Xingyu Zheng, Yiqing Sun, Xinyu Feng, Xirong Wu, Wenlu Liu, Chao Gao, Ye Yan, Wenyan Tian, Yingmei Wang","doi":"10.1080/15384047.2024.2325126","DOIUrl":"10.1080/15384047.2024.2325126","url":null,"abstract":"<p><p>Ovarian cancer (OC) is a form of gynecological malignancy that is associated with worse patient outcomes than any other cancer of the female reproductive tract. Topoisomerase II α (TOP2A) is commonly regarded as an oncogene that is associated with malignant disease progression in a variety of cancers, its mechanistic functions in OC have yet to be firmly established. We explored the role of TOP2A in OC through online databases, clinical samples, in vitro and in vivo experiments. And initial analyses of public databases revealed high OC-related TOP2A expression in patient samples that was related to poorer prognosis. This was confirmed by clinical samples in which TOP2A expression was elevated in OC relative to healthy tissue. Kaplan-Meier analyses further suggested that higher TOP2A expression levels were correlated with worse prognosis in OC patients. In vitro, TOP2A knockdown resulted in the inhibition of OC cell proliferation, with cells entering G1 phase arrest and undergoing consequent apoptotic death. In rescue assays, TOP2A was confirmed to regulate cell proliferation and cell cycle through AKT/mTOR pathway activity. Mouse model experiments further affirmed the key role that TOP2A plays as a driver of OC cell proliferation. These data provide strong evidence supporting TOP2A as an oncogenic mediator and prognostic biomarker related to OC progression and poor outcomes. At the mechanistic level, TOP2A can control tumor cell growth via AKT/mTOR pathway modulation. These preliminary results provide a foundation for future research seeking to explore the utility of TOP2A inhibitor-based combination treatment regimens in platinum-resistant recurrent OC patients.</p>","PeriodicalId":9536,"journal":{"name":"Cancer Biology & Therapy","volume":"25 1","pages":"2325126"},"PeriodicalIF":3.6,"publicationDate":"2024-12-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10936659/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140038743","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Correction.","authors":"","doi":"10.1080/15384047.2024.2375109","DOIUrl":"10.1080/15384047.2024.2375109","url":null,"abstract":"","PeriodicalId":9536,"journal":{"name":"Cancer Biology & Therapy","volume":"25 1","pages":"2375109"},"PeriodicalIF":4.4,"publicationDate":"2024-12-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11218795/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141476013","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Correction.","authors":"","doi":"10.1080/15384047.2024.2392996","DOIUrl":"10.1080/15384047.2024.2392996","url":null,"abstract":"","PeriodicalId":9536,"journal":{"name":"Cancer Biology & Therapy","volume":"25 1","pages":"2392996"},"PeriodicalIF":4.4,"publicationDate":"2024-12-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11340761/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141999471","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Correction.","authors":"","doi":"10.1080/15384047.2024.2352926","DOIUrl":"10.1080/15384047.2024.2352926","url":null,"abstract":"","PeriodicalId":9536,"journal":{"name":"Cancer Biology & Therapy","volume":"25 1","pages":"2352926"},"PeriodicalIF":4.4,"publicationDate":"2024-12-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11789723/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140944101","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Cdk inhibitor dinaciclib as a promising anti-tumorigenic agent in biliary tract cancer.","authors":"Celina Ablinger, Daniel Neureiter, Theresa Mähr, Christian Mayr, Tobias Kiesslich, Nicole Maeding, Irina Valenta, Maximilian Ardelt, Fabian Wilhelm, Elen Neureiter, Markus Ritter, Johanna Pachmayr, Petra Huber-Cantonati","doi":"10.1080/15384047.2024.2439057","DOIUrl":"10.1080/15384047.2024.2439057","url":null,"abstract":"<p><p>Biliary tract cancer (BTC) is a rare malignancy with rising incidence. The therapeutic options are limited and the overall survival remains poor. Cyclin-dependent kinases, drivers of cell cycle and transcription have numerous biological functions and are known to be dysregulated in numerous tumor entities. Dinaciclib is a selective Cdk1/2/5/9 inhibitor with anti-tumor activity. In the present study, the efficacy of dinaciclib was tested on a comprehensive BTC cell-line model. The results indicate a heterogeneous expression pattern of Cdk1/2/5/9, as well as various differentiation tumor markers in BTC cells. We demonstrated that dinaciclib reduces cell viability, ATP levels, and proliferation rates. Moreover, dinaciclib induces apoptosis via increased caspase 3/7 activity and reduced expression levels of the anti-apoptotic protein Mcl-1 in a concentration- and cell line -dependent manner. 3D cell culture confirms the cytotoxic impact of dinaciclib under more physiologic tumor conditions. Additionally, dinaciclib affects different cell growth regulators like EGFR and STAT3 on gene and protein level, thus decreasing tumor growth. In summary, our study indicates that dinaciclib acts as a promising anti-tumorigenic agent in 2D and 3D <i>in vitro</i> BTC models and thus encourages further investigation.</p>","PeriodicalId":9536,"journal":{"name":"Cancer Biology & Therapy","volume":"25 1","pages":"2439057"},"PeriodicalIF":4.4,"publicationDate":"2024-12-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11789727/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142817426","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Tumor microenvironment in primary central nervous system lymphoma (PCNSL).","authors":"Qiqi Jin, Haoyun Jiang, Ye Han, Litian Zhang, Cuicui Li, Yurong Zhang, Ye Chai, Pengyun Zeng, Lingling Yue, Chongyang Wu","doi":"10.1080/15384047.2024.2425131","DOIUrl":"10.1080/15384047.2024.2425131","url":null,"abstract":"<p><p>Primary central nervous system lymphoma (PCNSL) is one of the rare lymphomas limited to the central nervous system. With the availability of immunotherapy, the tumor microenvironment (TME) attracts much attention nowadays. However, the systematic studies on the TME of PCNSL are lacking. By reviewing the existing research, we found that the TME of PCNSL is infiltrated with abundant TAMs and TILs, among which cytotoxic T cells (CTLs) and M2-polarized macrophages are principal. However, the counts of immune cells infiltrated in the TME of PCNSL are significantly lower than systemic diffuse large B-cell lymphoma (DLBCL). In addition, PCNSL can attract the infiltration of immunosuppressive cells and the loss of HLA I/II expression, overexpress inhibitory immune checkpoints, and release immunosuppressive cytokines to form an immunosuppressive TME. The immunosuppressive effect of TME in PCNSL is significantly stronger than that in systemic DLBCL. These characteristics of TME highlight the immunosuppression of PCNSL.</p>","PeriodicalId":9536,"journal":{"name":"Cancer Biology & Therapy","volume":"25 1","pages":"2425131"},"PeriodicalIF":4.4,"publicationDate":"2024-12-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11581175/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142646873","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}