{"title":"Hsa_circRNA_000166 Promotes Cell Proliferation, Migration and Invasion by Regulating miR-330-5p/ELK1 in Colon Cancer [Retraction]","authors":"Gang Zhao, Gong Jian Dai","doi":"10.2147/ott.s471178","DOIUrl":"https://doi.org/10.2147/ott.s471178","url":null,"abstract":"Retraction for the article Hsa_circRNA_000166 Promotes Cell Proliferation, Migration and Invasion by Regulating miR-330-5p/ELK1 in Colon Cancer","PeriodicalId":19534,"journal":{"name":"OncoTargets and therapy","volume":null,"pages":null},"PeriodicalIF":4.0,"publicationDate":"2024-04-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140566205","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}
{"title":"Circular RNA Hsa_circ_0023404 Promotes Proliferation, Migration and Invasion in Non-Small Cell Lung Cancer by Regulating miR-217/ZEB1 Axis [Retraction]","authors":"Chengjun Liu, Zuwang Zhang, Dongdong Qi","doi":"10.2147/ott.s471175","DOIUrl":"https://doi.org/10.2147/ott.s471175","url":null,"abstract":"Retraction for the article Circular RNA hsa_circ_0023404 promotes proliferation, migration and invasion in non-small cell lung cancer by regulating miR-217/ZEB1 axis","PeriodicalId":19534,"journal":{"name":"OncoTargets and therapy","volume":null,"pages":null},"PeriodicalIF":4.0,"publicationDate":"2024-04-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140565866","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}
Jieping Yan, Xue Zhang, Lili Yu, Meihua Ye, Yun Chen
{"title":"Long-Term Follow-Up of Combination Therapy with Sintilimab and Anlotinib in Gallbladder Follicular Dendritic Cell Sarcoma: A Rare Case Report","authors":"Jieping Yan, Xue Zhang, Lili Yu, Meihua Ye, Yun Chen","doi":"10.2147/ott.s449258","DOIUrl":"https://doi.org/10.2147/ott.s449258","url":null,"abstract":"<strong>Abstract:</strong> Follicular dendritic cell sarcoma (FDCS) is a rare malignant neoplasm for which a standardized treatment approach has yet to be established. The prevailing therapeutic strategy typically involves resection followed by adjuvant chemotherapy or radiation. This case report details the long-term follow-up of a 59-year-old Chinese male diagnosed with gallbladder FDCS and liver metastases. The patient received a combination therapy of sintilimab and anlotinib, resulting in a substantial partial response (PR) lasting for a noteworthy duration of 30 months. Notably, this is the first documented instance of gallbladder FDCS with liver metastases being treated with PD-1 antibody and antiangiogenic agents as first-line therapy. These findings suggest that this treatment regimen may offer a potential therapeutic option for patients with gallbladder FDCS and liver metastases, with a duration of PR lasting up to 30 months.<br/><br/><strong>Keywords:</strong> gallbladder follicular dendritic cell sarcoma, long-term follow-up, PD-1 antibody, antiangiogenic agents, first-line therapy, partial response<br/>","PeriodicalId":19534,"journal":{"name":"OncoTargets and therapy","volume":null,"pages":null},"PeriodicalIF":4.0,"publicationDate":"2024-04-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140566199","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}
{"title":"Overexpression of Mst1 Reduces Gastric Cancer Cell Viability by Repressing the AMPK-Sirt3 Pathway and Activating Mitochondrial Fission [Retraction]","authors":"Shiwei Yao, Wei Yan","doi":"10.2147/ott.s471173","DOIUrl":"https://doi.org/10.2147/ott.s471173","url":null,"abstract":"Retraction for the article Overexpression of Mst1 reduces gastric cancer cell viability by repressing the AMPK-Sirt3 pathway and activating mitochondrial fission","PeriodicalId":19534,"journal":{"name":"OncoTargets and therapy","volume":null,"pages":null},"PeriodicalIF":4.0,"publicationDate":"2024-04-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140566200","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}
{"title":"Efficacy and Safety of the MDM2–p53 Antagonist Brigimadlin (BI 907828) in Patients with Advanced Biliary Tract Cancer: A Case Series","authors":"Noboru Yamamoto, Anthony Tolcher, Navid Hafez, Iwona Lugowska, Rodryg Ramlau, Teresa Macarulla, Junxian Geng, Jian Li, Michael Teufel, Angela Märten, Patricia LoRusso","doi":"10.2147/ott.s440979","DOIUrl":"https://doi.org/10.2147/ott.s440979","url":null,"abstract":"<strong>Background:</strong> In patients with advanced biliary tract cancer (BTC), first-line chemotherapy plus immunotherapy has improved outcomes; however, second-line options that reflect the disease’s molecular heterogeneity are still needed. One emerging target is <em>MDM2</em>, amplified in ~5– 8% of BTC cases.<br/><strong>Methods:</strong> This is a subset analysis of two ongoing Phase Ia/Ib trials assessing patients treated with brigimadlin (BI 907828; a highly potent, oral MDM2–p53 antagonist) ± ezabenlimab (PD-1 inhibitor) ± BI 754111 (anti-LAG-3; n = 1).<br/><strong>Results:</strong> Results from 12 patients with BTC are shown (monotherapy: n = 6/combination: n = 6). Six patients achieved partial response (monotherapy: n = 2/combination: n = 4), four had stable disease; responses were durable. Brigimadlin had a manageable safety profile. Seven patients had dose reductions due to adverse events, but no treatment-related adverse events led to treatment discontinuation.<br/><strong>Conclusion:</strong> Brigimadlin demonstrated anti-tumor activity in patients with advanced <em>MDM2</em>-amplified BTC, and warrants further investigation.<br/><br/><strong>Plain Language Summary:</strong> Biliary tract carcinoma (BTC) is a cancer that affects the bile ducts which are part of the digestive system. Usually, the first treatment for advanced BTC (ie cannot be removed surgically and/or has spread) is chemotherapy in combination with immunotherapy. However, if chemotherapy does not work, or stops working, there are few treatment options available in second-line. Accordingly, intensive research is ongoing to try and find effective drugs. One potential medicine, called brigimadlin (or BI 907828), is a tablet that activates a molecule in tumor cells called p53. The normal function of p53 is to kill cells when they first start to become cancerous. However, if p53 is turned off by genetic mutations, or other mechanisms, then cancer can develop. Although p53 is rarely mutated in BTC tumors, it is inactivated by another molecule called MDM2 which is usually present at abnormally high levels in BTC. Brigimadlin prevents interaction between MDM2 and p53. This activates p53 and causes the cancer to die. Two clinical trials are currently assessing brigimadlin in a range of cancers, including BTC, with the aim of identifying a safe dose that can be examined in more detail in larger trials. So far, 12 patients with BTC have been treated. The patients’ tumors significantly shrank in six of these patients and remained stable in a further four patients. Side effects were as expected and could be tolerated by pausing treatment or lowering the dose. These results show that brigimadlin should be tested further in patients with advanced BTC.<br/><br/>","PeriodicalId":19534,"journal":{"name":"OncoTargets and therapy","volume":null,"pages":null},"PeriodicalIF":4.0,"publicationDate":"2024-03-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140322920","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}
Danfei Zhou, Jun Ying, Shanshan Hu, Jiangdong Li, Haijian Liu
{"title":"A Novel Intergenic Region (chr2: 30,316,870)-ALK Fusion in a Patient with Lung Adenocarcinoma Responding to Crizotinib Combined with Pemetrexed Treatment: A Case Report","authors":"Danfei Zhou, Jun Ying, Shanshan Hu, Jiangdong Li, Haijian Liu","doi":"10.2147/ott.s444624","DOIUrl":"https://doi.org/10.2147/ott.s444624","url":null,"abstract":"<strong>Background:</strong> Anaplastic lymphoma kinase (<em>ALK</em>) rearrangements have been reported as an important oncogenic driver in 5– 7% non-small cell lung cancer (NSCLC) patients. Reports about the intergenic region (IGR) as an <em>ALK</em> fusion partner are rare. In this study, we report a novel IGR (chr2: 30,316,870)-<em>ALK</em> fusion in an advanced lung adenocarcinoma patient that responded effectively to crizotinib combined with pemetrexed.<br/><strong>Case Presentation:</strong> A 68-year-old Chinese female was diagnosed with stage IV right lung adenocarcinoma (cT3N3M1c). The targeted next-generation sequencing (NGS) of 14 cancer-related genes identified an IGR (chr2: 30,316,870)-<em>ALK</em> fusion. Her lung lesions have been successfully converted from a partial response to a complete response after administrating crizotinib for 1 year combined with 6 cycles of chemotherapy with pemetrexed. So far, her progression-free-survival has reached 21 months.<br/><strong>Conclusion:</strong> In this case, we firstly report a novel IGR (chr2: 30,316,870)-<em>ALK</em> fusion by using targeted NGS, and highlight the efficacy of crizotinib combined with pemetrexed to reduce unbearable gastrointestinal adverse reactions. It provides valuable clinical guidance for the treatment of similar cases in the future.<br/><br/>","PeriodicalId":19534,"journal":{"name":"OncoTargets and therapy","volume":null,"pages":null},"PeriodicalIF":4.0,"publicationDate":"2024-03-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140314704","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}
{"title":"M2-Type Macrophages and Cancer-Associated Fibroblasts Combine to Promote Colorectal Cancer Liver Metastases","authors":"Yunpeng Feng, Shifeng Qiao, Jie Chen, Xin Wen, Yanlei Chen, Xiaoyu Song, Jiaxin Xu, Xiucheng Qiao, Jing Yang, Shenshen Zhang, Yang Feng, Yu Gao","doi":"10.2147/ott.s447502","DOIUrl":"https://doi.org/10.2147/ott.s447502","url":null,"abstract":"<strong>Purpose:</strong> This research explored the association between CD163-labeled M2-type macrophages and cancer-associated fibroblasts (CAFs) in the tumor microenvironment (TME) of 38 colorectal cancer (CRC) liver metastases. In addition, we investigated the correlation differences between M2-type macrophages and CAFs in the tumor microenvironments of 38 primary colorectal cancer patients with confirmed liver metastases and 946 colorectal cancer patients, as well as possible mechanisms of action between the two cells.<br/><strong>Methods:</strong> The Immunohistochemistry (IHC) method was applied to detect the expression levels of M2-type macrophages and CAFs in the tissues of 984 cases of CRC and to analyze the correlation between M2-type macrophages and CAFs in colorectal cancer tissues. The IHC method was also applied to detect the expression levels of M2-type macrophages and CAFs in the liver metastases of 38 cases of CRC in the experimental group and to analyze the correlation between the two cells in liver metastases.<br/><strong>Results:</strong> 1. M2-type macrophages and CAFs expression were significantly higher in 38 primary colorectal cancer patients compared to 946 controls, and the expression of M2-type macrophages was significantly positively correlated with CAFs. 2. In 984 CRC cases, M2-type macrophages and CAFs expression levels were significantly higher in the cancer tissues than in the paired paracancerous tissues. 3. The expression levels of M2-type macrophages and CAFs in primary colorectal cancer were significantly higher in the experimental group than in colorectal cancer tissues without distant metastasis.<br/><strong>Conclusion:</strong> M2-type macrophages and CAFs are involved in the development of the colorectal cancer tumor microenvironment, and their interaction influences the initiation and progression of liver metastasis in colorectal cancer. It may provide new clinical ideas for early diagnosis of CRC liver metastases and searching for immune targets.<br/><br/><strong>Keywords:</strong> M2-type macrophages, cancer-associated fibroblasts, colorectal cancer, liver metastasis<br/>","PeriodicalId":19534,"journal":{"name":"OncoTargets and therapy","volume":null,"pages":null},"PeriodicalIF":4.0,"publicationDate":"2024-03-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140298494","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}
Yixin Hou, Jianguo Yan, Ke Shi, Xiaoli Liu, Fangyuan Gao, Tong Wu, Peipei Meng, Min Zhang, Yuyong Jiang, Xianbo Wang
{"title":"Development and Validation of a Machine Learning-Based Model Used for Predicting Hepatocellular Carcinoma Risk in Patients with Hepatitis B-Related Cirrhosis: A Retrospective Study","authors":"Yixin Hou, Jianguo Yan, Ke Shi, Xiaoli Liu, Fangyuan Gao, Tong Wu, Peipei Meng, Min Zhang, Yuyong Jiang, Xianbo Wang","doi":"10.2147/ott.s444536","DOIUrl":"https://doi.org/10.2147/ott.s444536","url":null,"abstract":"<strong>Object:</strong> Our objective was to estimate the 5-year cumulative risk of HCC in patients with HBC by utilizing an artificial neural network (ANN).<br/><strong>Methods:</strong> We conducted this study with 1589 patients hospitalized at Beijing Ditan Hospital of Capital Medical University and People’s Liberation Army Fifth Medical Center. The training cohort consisted of 913 subjects from Beijing Ditan Hospital of Capital Medical University, while the validation cohort comprised 676 subjects from People’s Liberation Army Fifth Medical Center. Through univariate analysis, we identified factors that independently influenced the occurrence of HCC, which were then used to develop the ANN model. To evaluate the ANN model, we assessed its predictive accuracy, discriminative ability, and clinical net benefit using metrics such as the area under the receiver operating characteristic curve (AUC), concordance index (C-index), calibration curves.<br/><strong>Results:</strong> In total, we included nine independent risk factors in the development of the ANN model. Remarkably, the AUC of the ANN model was 0.880, significantly outperforming the AUC values of other existing models including mPAGE-B (0.719) (95% CI 0.670– 0.768), PAGE-B (0. 710) (95% CI 0.660– 0.759), FIB-4 (0.693) (95% CI 0.640– 0.745), and Toronto hepatoma risk index (THRI) (0.705) (95% CI 0.654– 0.756) (p< 0.001 for all). The ANN model effectively stratified patients into low, medium, and high-risk groups based on their 5-year In the training cohort, the positive predictive value (PPV) for low-risk patients was 26.2% (95% CI 25.0– 27.4), and the negative predictive value (NPV) was 98.7% (95% CI 95.2– 99.7). For high-risk patients, the PPV was 54.7% (95% CI 48.6– 60.7), and the NPV was 91.6% (95% CI 89.4– 93.4). These findings were validated in the independent validation cohort.<br/><strong>Conclusion:</strong> The ANNs model has good individualized prediction performance and may be helpful to evaluate the probability of the 5-year risk of HCC in patients with HBC.<br/><br/><strong>Keywords:</strong> machine learning-based model, hepatocellular carcinoma, risk, hepatitis B-related cirrhosis<br/>","PeriodicalId":19534,"journal":{"name":"OncoTargets and therapy","volume":null,"pages":null},"PeriodicalIF":4.0,"publicationDate":"2024-03-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140204508","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}
{"title":"Progerin Inhibits the Proliferation and Migration of Melanoma Cells by Regulating the Expression of Paxillin","authors":"Weixian Liu, Xinxian Huang, Weizhao Luo, Xinguang Liu, Weichun Chen","doi":"10.2147/ott.s442504","DOIUrl":"https://doi.org/10.2147/ott.s442504","url":null,"abstract":"<strong>Objective:</strong> Progerin, the underlying cause of Hutchinson-Gilford Progeria Syndrome (HGPS), has been extensively studied for its impact on normal cells and premature aging patients. However, there is a lack of research on its specific effects on tumor cells. Melanoma is one of the most common malignant tumors with high morbidity and mortality. This study aimed to elucidate the potential therapeutic role of progerin in melanoma.<br/><strong>Materials and Methods:</strong> We constructed the melanoma A375 cell line and M14 cell line with stable expression of progerin. The expression of progerin, paxillin, and epithelial-mesenchymal transition (EMT) marker proteins in each cell group was measured using Western blot. The migration, proliferation, and cell cycle of cancer cells were assessed using the transwell assay, wound healing assay, colony formation assay, CCK 8 assay, and flow cytometry. RT-qPCR technology was used to examine the impact of progerin overexpression on microRNA expression. Finally, we transfected paxillin into the progerin overexpression cell group to verify whether progerin regulates the phenotype of tumor cells through paxillin.<br/><strong>Results:</strong> Our study demonstrated that overexpression of progerin leads to decreased expression of paxillin and inhibits cancer cell migration, proliferation, EMT process and cell cycle progression. Additionally, rescue experiments revealed that the migration, proliferation ability, and EMT marker protein expression in progerin overexpressing cancer cells could be partially restored by transfecting a plasmid containing the paxillin gene. Mechanistic investigations further revealed that progerin achieves this inhibition of paxillin expression by upregulating miR-212.<br/><strong>Conclusion:</strong> This study reveals that progerin may inhibit the migration and proliferation of melanoma cells through the miR-212/paxillin axis, which provides a new approach for the future treatment of this disease.<br/><br/><strong>Keywords:</strong> progerin, paxillin, migration, proliferation, melanoma<br/>","PeriodicalId":19534,"journal":{"name":"OncoTargets and therapy","volume":null,"pages":null},"PeriodicalIF":4.0,"publicationDate":"2024-03-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140204593","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}