Journal of oncology research and therapy最新文献

Comparative Assessment of Various Formats of TRAIL in Three-Dimensional Cell Culture and Patient-Derived Tumoroids of Colorectal Cancer. 结直肠癌三维细胞培养和患者源性类肿瘤中不同形式TRAIL的比较评估。

Journal of oncology research and therapy Pub Date : 2025-01-01 Epub Date: 2025-09-12 DOI: 10.29011/2574-710x.10302

Farzaneh Vafaeinik, Sarah Helmueller, Alexandra Gangi, Ja-Lok Ku, Roland Kontermann, Yong J Lee

{"title":"Comparative Assessment of Various Formats of TRAIL in Three-Dimensional Cell Culture and Patient-Derived Tumoroids of Colorectal Cancer.","authors":"Farzaneh Vafaeinik, Sarah Helmueller, Alexandra Gangi, Ja-Lok Ku, Roland Kontermann, Yong J Lee","doi":"10.29011/2574-710x.10302","DOIUrl":"10.29011/2574-710x.10302","url":null,"abstract":"Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) has emerged as a promising cytokine that selectively targets cancer cells while sparing normal tissues. Despite its favorable safety profile, clinical trials have demonstrated antitumor responses in only a small subset of patients. This limited efficacy has been largely attributed to the short plasma half-life of recombinant monomeric soluble TRAIL (rhTRAIL). To enhance its stability and therapeutic potential, researchers have developed modified versions, including an immunoglobulin Fc domain-fused TRAIL (Fc-TRAIL) and a dimeric Fc-fused single-chain variant (Fc-scTRAIL). In this study, we used the SNU-1746 three-dimensional (3D) multicellular layer culture model and a patient-derived colon cancer tumoroid model to evaluate the biological activity of these TRAIL formats (rhTRAIL, Fc-TRAIL, and Fc-scTRAIL). Treatment with rhTRAIL revealed that a longer exposure time (18-24 hours) was required to induce apoptosis in both 3D models, in contrast to monolayer cultures. Among the TRAIL formats, Fc-scTRAIL was the most potent in inducing apoptosis, as confirmed by immunoblotting analyses. Furthermore, artesunate (ART) enhanced TRAIL-induced apoptosis across all TRAIL formats, with the strongest synergistic effect observed in combination with Fc-scTRAIL. JC-1 staining assays indicated that mitochondrial membrane depolarization (a hallmark of the intrinsic apoptosis pathway) plays a key role in the cell death observed with the combination treatment in tumoroids. These findings provide compelling preclinical evidence supporting the potential of ART and Fc-scTRAIL combination therapy for future clinical evaluation.","PeriodicalId":73876,"journal":{"name":"Journal of oncology research and therapy","volume":"10 3","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12483094/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145208320","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

DZ-1-Artesunate Induces Apoptosis Via a Bid-, Bax-, and Bak-Independent Caspase-3 Activation Pathway. dz -1-青蒿素通过Bid-、Bax-和bak -非依赖性Caspase-3激活途径诱导细胞凋亡。

Journal of oncology research and therapy Pub Date : 2025-01-01 Epub Date: 2025-08-29

Badrinath Narayanasamy, Sarah Helmueller, Yi Zhang, Alexandra Gangi, Heuiran Lee, Cheryn Song, Ha-Na Woo, Yong J Lee

{"title":"DZ-1-Artesunate Induces Apoptosis Via a Bid-, Bax-, and Bak-Independent Caspase-3 Activation Pathway.","authors":"Badrinath Narayanasamy, Sarah Helmueller, Yi Zhang, Alexandra Gangi, Heuiran Lee, Cheryn Song, Ha-Na Woo, Yong J Lee","doi":"","DOIUrl":"","url":null,"abstract":"Artesunate (ART), a well-established antimalarial agent, has demonstrated promising anticancer activity in both in vitro and in vivo studies. Despite its potential, clinical application of ART in oncology is limited by modest efficacy and dose-limiting toxicity, likely due to nonspecific accumulation in normal tissues. Targeted delivery strategies are therefore essential to enhance therapeutic selectivity and reduce off-target effects. To this end, ART has been conjugated with targeting molecules such as aptamers, dyes, and polymers. DZ-1, a heptamethine cyanine dye, selectively accumulates in cancer cells through overexpression of organic anion transporting polypeptides (OATPs), offering a promising vehicle for tumor-specific delivery. In this study, we evaluated the anticancer efficacy and underlying mechanisms of a novel conjugate of DZ-1 and ART (DZ-1-ART) in three human cancer cell lines: colon cancer (HCT116), pancreatic cancer (BxPC-3), and breast cancer (MCF-7). DZ-1-ART induced time-dependent cytotoxicity across all tested cancer cell lines. Mechanistically, DZ-1-ART localized to both mitochondria and lysosomes, but functional studies indicated that lysosomes were not essential for its pro- apoptotic activity. Instead, DZ-1-ART triggered mitochondria-mediated apoptosis via a Bid-, Bax-, and Bak-independent pathway, leading to caspase-3 activation and cell death. Our findings demonstrate that DZ-1-ART undergoes intracellular trafficking through lysosomes and mitochondria, but induces apoptosis primarily through a mitochondrial, Bid-Bax/Bak- independent, caspase-3-dependent pathway. These results support the development of DZ-1- ART as a tumor-targeted anticancer agent with potential applications in theranostics.","PeriodicalId":73876,"journal":{"name":"Journal of oncology research and therapy","volume":"10 ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12662740/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145650220","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

The Nuclear-Encoded Cytochrome c Oxidase Subunit COX4-1 Enhances Hypoxia Tolerance in Glioblastoma Cells. 核编码细胞色素c氧化酶亚基COX4-1增强胶质母细胞瘤细胞的缺氧耐受性。

Journal of oncology research and therapy Pub Date : 2025-01-01 Epub Date: 2025-08-21 DOI: 10.29011/2574-710x.10299

Claudia R Oliva, Susanne Flor, Md Yousuf Ali, Corinne E Griguer

{"title":"The Nuclear-Encoded Cytochrome c Oxidase Subunit COX4-1 Enhances Hypoxia Tolerance in Glioblastoma Cells.","authors":"Claudia R Oliva, Susanne Flor, Md Yousuf Ali, Corinne E Griguer","doi":"10.29011/2574-710x.10299","DOIUrl":"10.29011/2574-710x.10299","url":null,"abstract":"Glioblastoma (GBM) is the most common and aggressive primary brain cancer in adults. While chemo- and radiotherapy are often effective in treating newly diagnosed GBM, increasing evidence suggests that treatment-induced metabolic alterations promote tumor recurrence and further resistance. In addition, GBM tumors are typically hypoxic, which further contributes to treatment resistance. Recent studies have shown that changes in glioma cell metabolism driven by a shift in the isoform expression of mitochondrial cytochrome c oxidase (CcO) subunit 4 (COX4), a key regulatory subunit of mammalian CcO, may underlie the treatment-induced metabolic alterations in GBM cells. However, the impact of hypoxia on GBM energetics is not fully understood. Using isogenic GBM cell lines expressing either COX4-1 or the alternative COX4 isoform, COX4-2, we found that COX4-1 expressing cells maintained a more oxidative metabolism under hypoxia, characterized by increased CcO activity and ATP production, enhanced assembly of CcO-containing mitochondrial supercomplexes, and reduced superoxide production. Furthermore, COX4-1 expression was sufficient to increase radioresistance under hypoxic conditions. Untargeted metabolomic analysis revealed that the most significantly upregulated pathways in COX4-1-expressing cells under hypoxia were purine and methionine metabolism. In contrast, COX4-2-expressing cells showed increased activation of glycolysis and the Warburg effect. Our study provides new insights into how CcO regulatory subunits influence cellular metabolic networks and radioresistance in GBM under hypoxia, identifying potential therapeutic targets for improved treatment strategies.","PeriodicalId":73876,"journal":{"name":"Journal of oncology research and therapy","volume":"10 3","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12435011/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145076698","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

Targeting DNA Repair Pathways in Orthotopic Glioblastoma Xenoplants 靶向直立型胶质母细胞瘤外植体中的 DNA 修复途径

Journal of oncology research and therapy Pub Date : 2024-07-15 DOI: 10.29011/2574-710x.10234

引用次数: 0

Effectiveness and Safety of Docetaxel in Combination with Nintedanib or Ramucirumab Following Chemoimmunotherapy in Patients with Metastatic Non-Small-Cell Lung Cancer 转移性非小细胞肺癌患者化疗免疫疗法后多西他赛联合 Nintedanib 或 Ramucirumab 的有效性和安全性

Journal of oncology research and therapy Pub Date : 2024-07-12 DOI: 10.29011/2574-710x.10232

引用次数: 0

Establishment of a New Radiological Prognostic Score in Patients with Osteosarcoma 为骨肉瘤患者建立新的放射预后评分标准

Journal of oncology research and therapy Pub Date : 2024-07-08 DOI: 10.29011/2574-710x.10230

引用次数: 0

Vaping, Smoking and Lung Cancer Risk 吸烟、吸烟与肺癌风险

Journal of oncology research and therapy Pub Date : 2024-07-04 DOI: 10.29011/2574-710x.10229

引用次数: 0

Anticancer Effect of Osmanthus Heterophilus Leaf Extract Through Inhibition of mTOR Phosphorylation And Upregulation of Cytokeratin 18 in Head and Neck Squamous Cell Carcinoma 桂花叶提取物通过抑制头颈部鳞状细胞癌中 mTOR 磷酸化和细胞角蛋白 18 的上调发挥抗癌作用

Journal of oncology research and therapy Pub Date : 2024-06-12 DOI: 10.29011/2574-710x.10225

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Desmoid-type Fibromatosis of the Breast. A Literature Review Based on 2 Case Reports 乳腺苔藓样纤维瘤病。基于 2 例病例报告的文献综述

Journal of oncology research and therapy Pub Date : 2024-05-14 DOI: 10.29011/2574-710x.10216

引用次数: 0

Molecular Targeting in Non-Small Cell Lung Cancer: Advances in EGFR, ROS1, ALK, and MET Pathways 非小细胞肺癌的分子靶向治疗：表皮生长因子受体、ROS1、ALK 和 MET 通路的研究进展

Journal of oncology research and therapy Pub Date : 2024-05-09 DOI: 10.29011/2574-710x.10214

引用次数: 0