Cancer Biology & Therapy最新文献

{"title":"Role of glutaminyl-peptide cyclotransferase in breast cancer doxorubicin sensitivity.","authors":"Bin Xu, Liu Yang, Lixian Yang, Ahmed Al-Maamari, Jingyu Zhang, Heng Song, Meiqi Wang, Suwen Su, Zhenchuan Song","doi":"10.1080/15384047.2024.2321767","DOIUrl":"10.1080/15384047.2024.2321767","url":null,"abstract":"<p><p>Doxorubicin (DOX) is one of the most effective and widely used chemotherapeutic drugs. However, DOX resistance is a critical risk problem for breast cancer treatment. Previous studies have demonstrated that metadherin (MTDH) involves in DOX resistance in breast cancer, but the exact mechanism remains unclear. In this study, we found that glutaminyl-peptide cyclotransferase (QPCT) was a MTDH DOX resistance-related downstream gene in breast cancer. Elevated expression of QPCT was found in the GEPIA database, breast cancer tissue, and breast cancer cells. Clinical data showed that QPCT expression was positively associated with poor prognosis in DOX-treated patients. Overexpression of QPCT could promote the proliferation, invasion and migration, and reduce DOX sensitivity in MCF-7 and MDA-MB-231 cells. Mechanistically, MTDH positively regulates the expressions of NF-κB (p65) and QPCT, and NF-κB (p65) directly regulates the expression of QPCT. Therefore, MTDH/NF-κB (p65)/QPCT signal axis was proposed. Collectively, our findings delineate the mechanism by which the MTDH/NF-κB (p65) axis regulate QPCT signaling and suggest that this complex may play an essential role in breast cancer progression and affect DOX sensitivity.</p>","PeriodicalId":9536,"journal":{"name":"Cancer Biology & Therapy","volume":null,"pages":null},"PeriodicalIF":3.6,"publicationDate":"2024-12-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10903679/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139989415","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":"M6A-mediated molecular patterns and tumor microenvironment infiltration characterization in nasopharyngeal carcinoma.","authors":"Yong Wang, Lisha Peng, Feng Wang","doi":"10.1080/15384047.2024.2333590","DOIUrl":"10.1080/15384047.2024.2333590","url":null,"abstract":"<p><p>N6-methyladenosine (m6A) is the most predominant RNA epigenetic regulation in eukaryotic cells. Numerous evidence revealed that m6A modification exerts a crucial role in the regulation of tumor microenvironment (TME) cell infiltration in several tumors. Nevertheless, the potential role and mechanism of m6A modification in nasopharyngeal carcinoma (NPC) remains unknown. mRNA expression data and clinical information from GSE102349, and GSE53819 datasets obtained from Gene Expression Omnibus (GEO) was used for differential gene expression and subsequent analysis. Consensus clustering was used to identify m6A-related molecular patterns of 88 NPC samples based on prognostic m6A regulators using Univariate Cox analysis. The TME cell-infiltrating characteristics of each m6A-related subclass were explored using single-sample gene set enrichment (ssGSEA) algorithm and CIBERSORT algotithm. DEGs between two m6A-related subclasses were screened using edgeR package. The prognostic signature and predicated nomogram were constructed based on the m6A-related DEGs. The cell infiltration and expression of prognostic signature in NPC was determined using immunohistochemistry (IHC) analysis. Chi-square test was used to analysis the significance of difference of the categorical variables. And survival analysis was performed using Kaplan-Meier plots and log-rank tests. The NPC samples were divided into two m6A-related subclasses. The TME cell-infiltrating characteristics analyses indicated that cluster 1 is characterized by immune-related and metabolism pathways activation, better response to anit-PD1 and anti-CTLA4 treatment and chemotherapy. And cluster 2 is characterized by stromal activation, low expression of HLA family and immune checkpoints, and a worse response to anti-PD1 and anti-CTLA4 treatment and chemotherapy. Furthermore, we identified 1558 DEGs between two m6A-related subclasses and constructed prognostic signatures to predicate the progression-free survival (PFS) for NPC patients. Compared to non-tumor samples, REEP2, TMSB15A, DSEL, and ID4 were upregulated in NPC samples. High expression of REEP2 and TMSB15A showed poor survival in NPC patients. The interaction between REEP2, TMSB15A, DSEL, ID4, and m6A regulators was detected. Our finding indicated that m6A modification plays an important role in the regulation of TME heterogeneity and complexity.</p>","PeriodicalId":9536,"journal":{"name":"Cancer Biology & Therapy","volume":null,"pages":null},"PeriodicalIF":3.6,"publicationDate":"2024-12-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10978033/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140292890","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":"Comparative analysis of the tumor microbiome, molecular profiles, and immune cell abundances by HPV status in mucosal head and neck cancers and their impact on survival.","authors":"Rituraj Upadhyay, Aastha Dhakal, Caroline Wheeler, Rebecca Hoyd, Malvenderjit Jagjit Singh, Vidhya Karivedu, Priyanka Bhateja, Marcelo Bonomi, Sasha Valentin, Mauricio E Gamez, David J Konieczkowski, Sujith Baliga, John C Grecula, Dukagjin M Blakaj, Emile Gogineni, Darrion L Mitchell, Nicholas C Denko, Daniel Spakowicz, Sachin R Jhawar","doi":"10.1080/15384047.2024.2350249","DOIUrl":"10.1080/15384047.2024.2350249","url":null,"abstract":"<p><p>Head and Neck Squamous Cell Carcinoma (HNSCC) comprises a diverse group of tumors with variable treatment response and prognosis. The tumor microenvironment (TME), which includes microbiome and immune cells, can impact outcomes. Here, we sought to relate the presence of specific microbes, gene expression, and tumor immune infiltration using tumor transcriptomics from The Cancer Genome Atlas (TCGA) and associate these with overall survival (OS). RNA sequencing (RNAseq) from HNSCC tumors in TCGA was processed through the exogenous sequences in tumors and immune cells (exotic) pipeline to identify and quantify low-abundance microbes. The detection of the Papillomaviridae family of viruses assessed HPV status. All statistical analyses were performed using R. A total of 499 RNAseq samples from TCGA were analyzed. HPV was detected in 111 samples (22%), most commonly Alphapapillomavirus 9 (90.1%). The presence of Alphapapillomavirus 9 was associated with improved OS [HR = 0.60 (95%CI: 0.40-0.89, <i>p</i> = .01)]. Among other microbes, <i>Yersinia pseudotuberculosis</i> was associated with the worst survival (HR = 3.88; <i>p</i> = .008), while <i>Pseudomonas viridiflava</i> had the best survival (HR = 0.05; <i>p</i> = .036). Microbial species found more abundant in HPV- tumors included several gram-negative anaerobes. HPV- tumors had a significantly higher abundance of M0 (<i>p</i> < .001) and M2 macrophages (<i>p</i> = .035), while HPV+ tumors had more T regulatory cells (<i>p</i> < .001) and CD8+ T-cells (<i>p</i> < .001). We identified microbes in HNSCC tumor samples significantly associated with survival. A greater abundance of certain anaerobic microbes was seen in HPV tumors and pro-tumorigenic macrophages. These findings suggest that TME can be used to predict patient outcomes and may help identify mechanisms of resistance to systemic therapies.</p>","PeriodicalId":9536,"journal":{"name":"Cancer Biology & Therapy","volume":null,"pages":null},"PeriodicalIF":3.6,"publicationDate":"2024-12-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11086009/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140897367","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 interplay between the tumor microenvironment and tumor-derived small extracellular vesicles in cancer development and therapeutic response.","authors":"Xuanyu Guo, Jiajun Song, Miao Liu, Xinyi Ou, Yongcan Guo","doi":"10.1080/15384047.2024.2356831","DOIUrl":"10.1080/15384047.2024.2356831","url":null,"abstract":"<p><p>The tumor microenvironment (TME) plays an essential role in tumor cell survival by profoundly influencing their proliferation, metastasis, immune evasion, and resistance to treatment. Extracellular vesicles (EVs) are small particles released by all cell types and often reflect the state of their parental cells and modulate other cells' functions through the various cargo they transport. Tumor-derived small EVs (TDSEVs) can transport specific proteins, nucleic acids and lipids tailored to propagate tumor signals and establish a favorable TME. Thus, the TME's biological characteristics can affect TDSEV heterogeneity, and this interplay can amplify tumor growth, dissemination, and resistance to therapy. This review discusses the interplay between TME and TDSEVs based on their biological characteristics and summarizes strategies for targeting cancer cells. Additionally, it reviews the current issues and challenges in this field to offer fresh insights into comprehending tumor development mechanisms and exploring innovative clinical applications.</p>","PeriodicalId":9536,"journal":{"name":"Cancer Biology & Therapy","volume":null,"pages":null},"PeriodicalIF":3.6,"publicationDate":"2024-12-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11110713/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141064959","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":"Jmjd2c maintains the ALDH^bri+ cancer stemness with transcription factor SOX2 in lung squamous cell carcinoma.","authors":"Min Wang, Yuling Hu, Feng Cai, Lili Guo, Yimin Mao, Yingmin Zhang","doi":"10.1080/15384047.2024.2373447","DOIUrl":"10.1080/15384047.2024.2373447","url":null,"abstract":"<p><p>Lung squamous cell carcinoma (LSCC) is a deadly cancer in the world. Histone demethylase Jmjd2c is a key epigenetic regulator in various tumors, while the molecular mechanism underlying Jmjd2c regulatory in LSCC is still unclear. We used the aldehyde dehydrogenasebright (ALDH^bri+) subtype as a research model for cancer stem cells (CSCs) in LSCC and detected the sphere formation ability and the proportion of ALDH^bri+ CSCs with Jmjd2c interference and caffeic acid (CA) treatment. Additionally, we carried out bioinformatic analysis on the expression file of Jmjd2c RNAi mice and performed western blotting, qRT-PCR, Co-IP and GST pull-down assays to confirm the bioinformatic findings. Moreover, we generated Jmjd2c-silenced and Jmjd2c-SOX2-silenced ALDH^bri+ tumor-bearing BALB/c nude mice to detect the effects on tumor progression. The results showed that Jmjd2c downregulation inhibited the sphere formation and the proportion of ALDH^bri+ CSCs. The SOX2 decreased expression significantly in Jmjd2c RNAi mice, and they were positively co-expressed according to the bioinformatic analysis. In addition, SOX2 expression decreased in Jmjd2c shRNA ALDH^bri+ CSCs, Jmjd2c and SOX2 proteins interacted with each other. Furthermore, Jmjd2c interference revealed significant blocking effect, and Jmjd2c-SOX2 interference contributed even stronger inhibition on ALDH^bri+ tumor progression. The Jmjd2c and SOX2 levels were closely related to the development and prognosis of LSCC patients. This study indicated that Jmjd2c played key roles on maintaining ALDH^bri+ CSC activity in LSCC by interacting with transcription factor SOX2. Jmjd2c might be a novel molecule for therapeutic targets and biomarkers in the diagnosis and clinical treatment of lung cancer.</p>","PeriodicalId":9536,"journal":{"name":"Cancer Biology & Therapy","volume":null,"pages":null},"PeriodicalIF":4.4,"publicationDate":"2024-12-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11232651/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141554140","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":"Autophagic degradation of CDK4 is responsible for G0/G1 cell cycle arrest in NVP-BEZ235-treated neuroblastoma.","authors":"Zhen Liu, Xiao-Yang Wang, Han-Wei Wang, Shan-Ling Liu, Chao Zhang, Feng Liu, Ying Guo, Feng-Hou Gao","doi":"10.1080/15384047.2024.2385517","DOIUrl":"10.1080/15384047.2024.2385517","url":null,"abstract":"<p><strong>Background: </strong>CDK4 is highly expressed and associated with poor prognosis and decreased survival in advanced neuroblastoma (NB). Targeting CDK4 degradation presents a potentially promising therapeutic strategy compared to conventional CDK4 inhibitors. However, the autophagic degradation of the CDK4 protein and its anti-proliferation effect in NB cells has not been mentioned.</p><p><strong>Results: </strong>We identified autophagy as a new pathway for the degradation of CDK4. Firstly, autophagic degradation of CDK4 is critical for NVP-BEZ235-induced G0/G1 arrest, as demonstrated by the overexpression of CDK4, autophagy inhibition, and blockade of autophagy-related genes. Secondly, we present the first evidence that p62 binds to CDK4 and then enters the autophagy-lysosome to degrade CDK4 in a CTSB-dependent manner in NVP-BEZ235 treated NB cells. Similar results regarding the interaction between p62 and CDK4 were observed in the NVP-BEZ235 treated NB xenograft mouse model.</p><p><strong>Conclusions: </strong>Autophagic degradation of CDK4 plays a pivotal role in G0/G1 cell cycle arrest in NB cells treated with NVP-BEZ235.</p>","PeriodicalId":9536,"journal":{"name":"Cancer Biology & Therapy","volume":null,"pages":null},"PeriodicalIF":4.4,"publicationDate":"2024-12-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11296530/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141859077","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":"T-Cell redirecting bispecific antibodies: a review of a novel class of immuno-oncology for advanced prostate cancer.","authors":"Julia Palecki, Amman Bhasin, Andrew Bernstein, Patrick J Mille, William J Tester, Wm Kevin Kelly, Kevin K Zarrabi","doi":"10.1080/15384047.2024.2356820","DOIUrl":"10.1080/15384047.2024.2356820","url":null,"abstract":"<p><p>Novel T-cell immunotherapies such as bispecific T-cell engagers (BiTEs) are emerging as promising therapeutic strategies for prostate cancer. BiTEs are engineered bispecific antibodies containing two distinct binding domains that allow for concurrent binding to tumor-associated antigens (TAAs) as well as immune effector cells, thus promoting an immune response against cancer cells. Prostate cancer is rich in tumor associated antigens such as, but not limited to, PSMA, PSCA, hK2, and STEAP1 and there is strong biologic rationale for employment of T-cell redirecting BiTEs within the prostate cancer disease space. Early generation BiTE constructs employed in clinical study have demonstrated meaningful antitumor activity, but challenges related to drug delivery, immunogenicity, and treatment-associated adverse effects limited their success. The ongoing development of novel BiTE constructs continues to address these barriers and to yield promising results in terms of efficacy and safety. This review will highlight some of most recent developments of BiTE therapies for patients with advanced prostate cancer and the evolving data surrounding BiTE constructs undergoing clinical evaluation.</p>","PeriodicalId":9536,"journal":{"name":"Cancer Biology & Therapy","volume":null,"pages":null},"PeriodicalIF":3.6,"publicationDate":"2024-12-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11135853/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141154595","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":"Roles of TRPM channels in glioma.","authors":"Zhigang Chen, Han Xie, Jun Liu, JiaJia Zhao, Ruixiang Huang, Yufei Xiang, Haoyuan Wu, Dasheng Tian, Erbao Bian, Zhang Xiong","doi":"10.1080/15384047.2024.2338955","DOIUrl":"10.1080/15384047.2024.2338955","url":null,"abstract":"<p><p>Gliomas are the most common type of primary brain tumor. Despite advances in treatment, it remains one of the most aggressive and deadly tumor of the central nervous system (CNS). Gliomas are characterized by high malignancy, heterogeneity, invasiveness, and high resistance to radiotherapy and chemotherapy. It is urgent to find potential new molecular targets for glioma. The TRPM channels consist of TRPM1-TPRM8 and play a role in many cellular functions, including proliferation, migration, invasion, angiogenesis, etc. More and more studies have shown that TRPM channels can be used as new therapeutic targets for glioma. In this review, we first introduce the structure, activation patterns, and physiological functions of TRPM channels. Additionally, the pathological mechanism of glioma mediated by TRPM2, 3, 7, and 8 and the related signaling pathways are described. Finally, we discuss the therapeutic potential of targeting TRPM for glioma.</p>","PeriodicalId":9536,"journal":{"name":"Cancer Biology & Therapy","volume":null,"pages":null},"PeriodicalIF":3.6,"publicationDate":"2024-12-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11062369/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140851757","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":"CD8α Structural Domains Enhance GUCY2C CAR-T Cell Efficacy.","authors":"Trevor R Baybutt, Ariana A Entezari, Adi Caspi, Ross E Staudt, Robert D Carlson, Scott A Waldman, Adam E Snook","doi":"10.1080/15384047.2024.2398801","DOIUrl":"10.1080/15384047.2024.2398801","url":null,"abstract":"<p><p>Despite success in treating some hematological malignancies, CAR-T cells have not yet produced similar outcomes in solid tumors due, in part, to the tumor microenvironment, poor persistence, and a paucity of suitable target antigens. Importantly, the impact of the CAR components on these challenges remains focused on the intracellular signaling and antigen-binding domains. In contrast, the flexible hinge and transmembrane domains have been commoditized and are the least studied components of the CAR. Here, we compared the hinge and transmembrane domains derived from either the CD8ɑ or CD28 molecule in identical GUCY2C-targeted third-generation designs for colorectal cancer. While these structural domains do not contribute to differences in antigen-independent contexts, such as CAR expression and differentiation and exhaustion phenotypes, the CD8ɑ structural domain CAR has a greater affinity for GUCY2C. This results in increased production of inflammatory cytokines and granzyme B, improved cytolytic effector function with low antigen-expressing tumor cells, and robust anti-tumor efficacy <i>in vivo</i> compared with the CD28 structural domain CAR. This suggests that CD8α structural domains should be considered in the design of all CARs for the generation of high-affinity CARs and optimally effective CAR-T cells in solid tumor immunotherapy.</p>","PeriodicalId":9536,"journal":{"name":"Cancer Biology & Therapy","volume":null,"pages":null},"PeriodicalIF":4.4,"publicationDate":"2024-12-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11423665/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142307152","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 correlation between serum bone metabolism indexes and bone disease and survival in newly diagnosed multiple myeloma patients","authors":"Linlin Huang, Yi Zhong, Qingxiao Chen, Donghua He, Gaofeng Zheng, Yang Yang, Xiaoyan Han, Wenjun Wu, Yi Zhao, Yi Li, Li Yang, Zhen Cai, Jingsong He","doi":"10.1080/15384047.2024.2403205","DOIUrl":"https://doi.org/10.1080/15384047.2024.2403205","url":null,"abstract":"Objective Myeloma-related bone disease (MBD) is one of the most common complications of multiple myeloma (MM). This study aims to investigate the correlation between serum bone metabolism indexes (...","PeriodicalId":9536,"journal":{"name":"Cancer Biology & Therapy","volume":null,"pages":null},"PeriodicalIF":3.6,"publicationDate":"2024-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142250505","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}