Anti-Cancer Drugs最新文献_第10页

Bergaptol inhibits glioma cell proliferation and induces apoptosis via STAT3/Bcl-2 pathway. 香柑醇能抑制胶质瘤细胞增殖，并通过 STAT3/Bcl-2 通路诱导细胞凋亡。

IF 2.3 4区医学

Anti-Cancer Drugs Pub Date : 2024-07-01 Epub Date: 2024-03-22 DOI: 10.1097/CAD.0000000000001603

Hao Huang, Junrong Zhang, Jianbing Wu, Chunfu Du, Bo Zheng, Zhangchao Guo, Ligang Chen, Deming Zhang, Luotong Liu

{"title":"Bergaptol inhibits glioma cell proliferation and induces apoptosis via STAT3/Bcl-2 pathway.","authors":"Hao Huang, Junrong Zhang, Jianbing Wu, Chunfu Du, Bo Zheng, Zhangchao Guo, Ligang Chen, Deming Zhang, Luotong Liu","doi":"10.1097/CAD.0000000000001603","DOIUrl":"10.1097/CAD.0000000000001603","url":null,"abstract":"Glioblastoma (GBM) is the most common primary malignant brain tumour and lacks therapeutic options with significant effects. The aberrant activation of STAT3 is a critical factor in glioma progression via activating multiple signalling pathways that promote glioma. Among them, the antiapoptotic gene Bcl-2 could be upregulated by p-STAT3, which is an important reason for the continuous proliferation of glioma. We previously reported that bergaptol, a natural furanocoumarin widely found in citrus products, exerts antineuroinflammatory effects by inhibiting the overactivation of STAT3. Here, we aimed to evaluate whether bergaptol could promote glioma apoptosis by inhibiting the STAT3/Bcl-2 pathway. This study found that bergaptol inhibited the proliferation and migration of GBM cell lines (U87 and A172) and promoted apoptosis in vitro. We also found that bergaptol significantly inhibited the STAT3/Bcl-2 pathway in GBM cells. U87 cells were implanted intracranially into nude mice to establish a glioma model, and glioma-bearing mice were treated with bergaptol (40 mg/kg). Bergaptol treatment significantly inhibited glioma growth and prolonged the glioma-bearing mice's survival time. In addition, bergaptol administration also significantly inhibited the STAT3/Bcl-2 pathway of tumour tissue in vivo. Overall, we found that bergaptol could effectively play an antiglioma role by inhibiting STAT3/Bcl-2 pathway, suggesting the potential efficacy of bergaptol in treating glioma.","PeriodicalId":7969,"journal":{"name":"Anti-Cancer Drugs","volume":" ","pages":"535-541"},"PeriodicalIF":2.3,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140288071","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}

引用次数: 0

Network meta-analysis of first-line systemic regimens for older patients with advanced NSCLC. 老年晚期 NSCLC 患者一线系统治疗方案的网络荟萃分析。

IF 1.8 4区医学

Anti-Cancer Drugs Pub Date : 2024-07-01 Epub Date: 2024-03-19 DOI: 10.1097/CAD.0000000000001602

Andrea Luciani, Lorenzo Dottorini, Elena Battaiotto, Fausto Petrelli

{"title":"Network meta-analysis of first-line systemic regimens for older patients with advanced NSCLC.","authors":"Andrea Luciani, Lorenzo Dottorini, Elena Battaiotto, Fausto Petrelli","doi":"10.1097/CAD.0000000000001602","DOIUrl":"10.1097/CAD.0000000000001602","url":null,"abstract":"Various immunotherapy treatments have received approval for the treatment of advanced non-small cell lung cancer (NSCLC), either as standalone or in conjunction with chemotherapy, contingent upon the extent of PD-L1 expression. These treatments are commonly utilized in clinical practice. However, a specific gap exists in direct comparisons of these regimens in elderly patients. The aim of this network meta-analysis (NMA) was to examine the effectiveness of PD-1/PD-L1 inhibitors, either alone or in conjunction with chemotherapy, as the initial treatment for elderly patients diagnosed with advanced NSCLC. We extensively searched PubMed, EMBASE and the Cochrane Library to gather randomized clinical trials that utilized PD-1/PD-L1 inhibitors as the first-line therapy for advanced NSCLC. By means of Bayesian NMA, we conducted an analysis on hazard ratios (HRs) related to overall survival (OS). A total of 5240 patients were included in the 21 trials. Across all studies, cemiplimab exhibited a noteworthy superiority to chemotherapy in terms of OS [HR = 0.48, 95% confidence interval (CI): 0.3-0.77]. In the subgroup analysis, it was observed that patients with PD-L1 expression of 50% or higher experienced the greatest OS benefit from cemiplimab (HR = 0.48, 95% CI: 0.3-0.77). Conversely, the cohort with unselected PD-L1 scores (>1 or any score) exhibited the greatest OS benefit when treated with pembrolizumab combined with chemotherapy, as indicated by a HR of 0.69 (95% CI: 0.52-0.9). Chemotherapy combined with pembrolizumab and cemiplimab monotherapy may represent the reference regimens for older patients with NSCLC with unselected and >50% PD-L1 expression, respectively.","PeriodicalId":7969,"journal":{"name":"Anti-Cancer Drugs","volume":" ","pages":"576-583"},"PeriodicalIF":1.8,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140288075","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}

引用次数: 0

USP3 promotes cisplatin resistance in non-small cell lung cancer cells by suppressing ACOT7-regulated ferroptosis. USP3 通过抑制 ACOT7 调控的铁凋亡促进非小细胞肺癌细胞对顺铂的耐药性。

IF 2.3 4区医学

Anti-Cancer Drugs Pub Date : 2024-07-01 Epub Date: 2024-03-15 DOI: 10.1097/CAD.0000000000001562

Rancen Tao, Zuo Liu, Zhenning Zhang, Zhenfa Zhang

{"title":"USP3 promotes cisplatin resistance in non-small cell lung cancer cells by suppressing ACOT7-regulated ferroptosis.","authors":"Rancen Tao, Zuo Liu, Zhenning Zhang, Zhenfa Zhang","doi":"10.1097/CAD.0000000000001562","DOIUrl":"10.1097/CAD.0000000000001562","url":null,"abstract":"This study aims to investigate the role and mechanism of ubiquitin-specific protease 3 (USP3) in cisplatin (DDP) in non-small cell lung cancer (NSCLC). USP3 expression in NSCLC cells was detected using reverse transcription quantitative PCR and Western blot. DDP-resistant cells were constructed and cell counting kit-8 assay determined the IC 50 of cells to DDP. USP3 expression was silenced in DDP-resistant cells, followed by detection of cell proliferation by clone formation assay, iron ion contents, ROS, MDA, and GSH levels by kits, GPX4 and ACSL4 protein expressions by Western blot. The binding between USP3 and ACOT7 was analyzed using Co-IP, and the ubiquitination level of ACOT7 was measured. USP3 and ACOT7 were highly expressed in NSCLC cells and further increased in drug-resistant cells. USP3 silencing reduced the IC 50 of cells to DDP and diminished the number of cell clones. Moreover, USP3 silencing suppressed GSH and GPX4 levels, upregulated iron ion contents, ROS, MDA, and ACSL4 levels, and facilitated ferroptosis. Mechanistically, USP3 upregulated ACOT7 protein expression through deubiquitination. ACOT7 overexpression alleviated the promoting effect of USP7 silencing on ferroptosis in NSCLC cells and enhanced DDP resistance. To conclude, USP3 upregulated ACOT7 protein expression through deubiquitination, thereby repressing ferroptosis in NSCLC cells and enhancing DDP resistance.","PeriodicalId":7969,"journal":{"name":"Anti-Cancer Drugs","volume":" ","pages":"483-491"},"PeriodicalIF":2.3,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140179189","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}

引用次数: 0

A comprehensive clinical evaluation of HER2-TKIs in patients with previously treated HER2-positive metastatic breast cancer. 对既往接受过治疗的 HER2 阳性转移性乳腺癌患者使用 HER2-TKIs 的综合临床评估。

IF 1.8 4区医学

Anti-Cancer Drugs Pub Date : 2024-07-01 Epub Date: 2024-04-11 DOI: 10.1097/CAD.0000000000001604

Wen-Jun Ji, Xuan Lu, Yu-Gang Wang, Lin-Wei Chen

{"title":"A comprehensive clinical evaluation of HER2-TKIs in patients with previously treated HER2-positive metastatic breast cancer.","authors":"Wen-Jun Ji, Xuan Lu, Yu-Gang Wang, Lin-Wei Chen","doi":"10.1097/CAD.0000000000001604","DOIUrl":"10.1097/CAD.0000000000001604","url":null,"abstract":"Human epidermal growth factor receptor 2-tyrosine kinase inhibitors (HER2-TKIs) have been extensively utilized for treating HER2-positive metastatic breast cancer (MBC), with numerous clinical trial reports available. We aim to systematically perform a comprehensive clinical evaluation on HER2-TKIs, provide a reference for the clinical rational use of drugs, and serve for the decision-making of the national drug policy. We performed comprehensive clinical evaluation in six dimensions including safety, effectiveness, economy, suitability, accessibility, and innovation through meta-analysis, literature review, drug administration websites, and other relevant medication data to analyze HER2-TKIs in treating HER2-positive MBC. For safety, the risk of ≥ grade 3 adverse events among pyrotinib, lapatinib, and neratinib is not significantly different. Furthermore, pyrotinib and neratinib were found to be higher in the risk of ≥ grade 3 diarrhea than lapatinib, however the risk could be reversed and prevented with loperamide. Regarding effectiveness and economy, pyrotinib was confirmed to have the best efficacy and cost-utility value, neratinib the second, and lapatinib the third. As regards innovation and suitability, pyrotinib showed better than other HER2-TKIs. In addition, pyrotinib received a higher recommendation than other HER2-TKIs in patients with HER2-positive MBC. The accessibility of pyrotinib was found to be the best with better urban, rural, and national affordability and lower annual treatment costs. Pyrotinib is more valuable in clinics with better safety, effectiveness, economy, suitability, accessibility, and innovation in HER2-positive MBC. This study could provide references for the clinical application of HER2-TKIs in treating HER2-positive MBC.","PeriodicalId":7969,"journal":{"name":"Anti-Cancer Drugs","volume":" ","pages":"584-596"},"PeriodicalIF":1.8,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140189399","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}

引用次数: 0

m 6 A reader IGF2BP1 reduces the sensitivity of nasopharyngeal carcinoma cells to Taxol by upregulation of AKT2. m6A 阅读器 IGF2BP1 通过上调 AKT2 降低了鼻咽癌细胞对 Taxol 的敏感性。

IF 2.3 4区医学

Anti-Cancer Drugs Pub Date : 2024-07-01 Epub Date: 2024-03-12 DOI: 10.1097/CAD.0000000000001591

Chong Zhao, Fang Zhang, Yang Tian, Bingjie Tang, Jing Luo, Jianhui Zhang

{"title":"m 6 A reader IGF2BP1 reduces the sensitivity of nasopharyngeal carcinoma cells to Taxol by upregulation of AKT2.","authors":"Chong Zhao, Fang Zhang, Yang Tian, Bingjie Tang, Jing Luo, Jianhui Zhang","doi":"10.1097/CAD.0000000000001591","DOIUrl":"10.1097/CAD.0000000000001591","url":null,"abstract":"Taxol is widely used in the treatment of nasopharyngeal carcinoma (NPC); nevertheless, the acquired resistance of NPC to Taxol remains one of the major obstacles in clinical treatment. In this study, we aimed to investigate the role and mechanism of insulin-like growth factor 2 mRNA-binding protein 1 (IGF2BP1) in Taxol resistance of NPC. Taxol-resistant NPC cell lines were established by exposing to gradually increased concentration of Taxol. Relative mRNA and protein levels were tested using qRT-PCR and western blot, respectively. NPC cell viability and apoptosis were assessed by cell counting kit-8 and flow cytometry analysis, respectively. Cell migration and invasion capacities were measured using transwell assay. Interaction between IGF2BP1 and AKT2 was examined by RNA immunoprecipitation assay. The N6-methyladenosine level of AKT2 was tested using methylated RNA immunoprecipitation-qPCR. IGF2BP1 expression was enhanced in Taxol-resistant NPC cell lines. Knockdown of IGF2BP1 strikingly enhanced the sensitivity of NPC cells to Taxol and repressed the migration and invasion of NPC cells. Mechanistically, IGF2BP1 elevated the expression of AKT2 by increasing its mRNA stability. Furthermore, overexpression of AKT2 reversed the inhibitory roles of IGF2BP1 silence on Taxol resistance and metastasis. Our results indicated that IGF2BP1 knockdown enhanced the sensitivity of NPC cells to Taxol by decreasing the expression of AKT2, implying that IGF2BP1 might be promising candidate target for NPC treatment.","PeriodicalId":7969,"journal":{"name":"Anti-Cancer Drugs","volume":" ","pages":"501-511"},"PeriodicalIF":2.3,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140118547","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}

引用次数: 0

Brigatinib combined with cetuximab in the fifth-line treatment of non-small cell lung cancer with EGFR p.C797S mutation in critically ill patients: a report of two cases and literature review. 布加替尼联合西妥昔单抗用于重症患者表皮生长因子受体 p.C797S 突变非小细胞肺癌的五线治疗：两例病例报告和文献综述。

IF 1.8 4区医学

Anti-Cancer Drugs Pub Date : 2024-07-01 Epub Date: 2024-03-15 DOI: 10.1097/CAD.0000000000001598

Juanjuan Liu, Hongtao Lei, Ding Zhang, Ning Zhang

{"title":"Brigatinib combined with cetuximab in the fifth-line treatment of non-small cell lung cancer with EGFR p.C797S mutation in critically ill patients: a report of two cases and literature review.","authors":"Juanjuan Liu, Hongtao Lei, Ding Zhang, Ning Zhang","doi":"10.1097/CAD.0000000000001598","DOIUrl":"10.1097/CAD.0000000000001598","url":null,"abstract":"For critically ill patients with non-small cell lung cancer (NSCLC) in need of life-saving treatment, there is currently no reported evidence regarding the use of medication specifically targeting epidermal growth factor receptor ( EGFR ) p.C797S mutation, which is known to cause resistance to third-generation tyrosine kinase inhibitors (TKIs). Our report aims to investigate and explore treatment strategies to overcome resistance associated with EGFR p.C797S mutation in order to provide potential therapeutic options for these patients. Here, we reported two cases with NSCLC who initially harbored an EGFR -sensitive mutation and were both treated with osimertinib, a third-generation TKI. Next-generation sequencing tests conducted prior to the initiation of fifth-line therapy in critically ill patients revealed the presence of EGFR p.C797S mutations in both patients, suggesting acquired resistance. In the course of fifth-line therapy, the administration of a combination of brigatinib and cetuximab proved vital in saving critically ill patients, moderately extending their overall survival period. Our findings suggested that a combined regimen of brigatinib and cetuximab could serve as a potentially life-saving therapeutic strategy for critically ill patients with NSCLC, particularly those demonstrating EGFR p.C797S-mediated resistance. Further studies, however, are required to validate and expand upon these promising findings.","PeriodicalId":7969,"journal":{"name":"Anti-Cancer Drugs","volume":" ","pages":"569-575"},"PeriodicalIF":1.8,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140288072","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}

引用次数: 0

Venetoclax combined with decitabine induced tumor lysis syndrome in a young patient with acute myeloid leukemia: a case report and literature review. 一名年轻急性髓性白血病患者的 Venetoclax 联合地西他滨诱发肿瘤溶解综合征：病例报告和文献综述。

IF 2.3 4区医学

Anti-Cancer Drugs Pub Date : 2024-06-01 Epub Date: 2024-02-23 DOI: 10.1097/CAD.0000000000001580

Hongyong Zhang, Jingdi Liu, Qiuling Wu, Linghui Xia

{"title":"Venetoclax combined with decitabine induced tumor lysis syndrome in a young patient with acute myeloid leukemia: a case report and literature review.","authors":"Hongyong Zhang, Jingdi Liu, Qiuling Wu, Linghui Xia","doi":"10.1097/CAD.0000000000001580","DOIUrl":"10.1097/CAD.0000000000001580","url":null,"abstract":"Venetoclax, in combination with hypomethylation agents (HMAs), is a novel treatment for leukemia patients with low chemotherapy tolerance. However, it has been reported to be a risk of causing tumor lysis syndrome (TLS) in chronic lymphocytic leukemia (CLL) and elderly acute myeloid leukemia (AML) patients. Here we report a rare case of a young adult AML patient who induced TLS after receiving a combination therapy of venetoclax with decitabine (DEC). A 36-year-old male patient presented with an unexplained fever and was diagnosed with AML-M5a. The patient was first treated with a combination of antibiotics, including voriconazole 300 mg Q12h. After the infection was relieved, he was treated with 100 mg venetoclax in combination with 75 mg/m 2 DEC. However, 12 h after the first treatment, he developed diarrhea, fatigue and other symptoms, and the laboratory results were consistent with the laboratory TLS. The patient stopped chemotherapy immediately, and TLS gradually improved after receiving rehydration, diuresis, dialysis and other treatments. Finally, the patient achieved complete remission. Based on the experience of this case and related studies, we recommend the prevention of TLS should not be limited to elderly patients taking venetoclax, and it is equally important in young patients. And reduce the dosage of venetoclax when using azole antifungal drugs.","PeriodicalId":7969,"journal":{"name":"Anti-Cancer Drugs","volume":" ","pages":"440-444"},"PeriodicalIF":2.3,"publicationDate":"2024-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139929669","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}

引用次数: 0

Nivolumab combined docetaxel versus nivolumab in patients with previously treated nonsmall cell lung cancer: a phase 2 study. 尼妥珠单抗联合多西他赛与尼妥珠单抗治疗既往接受过治疗的非小细胞肺癌患者：一项二期研究。

IF 2.3 4区医学

Anti-Cancer Drugs Pub Date : 2024-06-01 Epub Date: 2024-01-22 DOI: 10.1097/CAD.0000000000001569

Yang Wang, Qianyun Hao, Jun Nie, Ling Dai, Weiheng Hu, Jie Zhang, Xiaoling Chen, Xiangjuan Ma, Guangming Tian, Jindi Han, Sen Han, Di Wu, Jieran Long, Ziran Zhang, Jian Fang

{"title":"Nivolumab combined docetaxel versus nivolumab in patients with previously treated nonsmall cell lung cancer: a phase 2 study.","authors":"Yang Wang, Qianyun Hao, Jun Nie, Ling Dai, Weiheng Hu, Jie Zhang, Xiaoling Chen, Xiangjuan Ma, Guangming Tian, Jindi Han, Sen Han, Di Wu, Jieran Long, Ziran Zhang, Jian Fang","doi":"10.1097/CAD.0000000000001569","DOIUrl":"10.1097/CAD.0000000000001569","url":null,"abstract":"The current standard second-line treatment is immune checkpoint inhibitors monotherapy for nonsmall cell lung cancer (NSCLC) patients. The objective of this phase 2 study was to evaluate the efficacy and safety of nivolumab plus docetaxel compared with nivolumab monotherapy for second-line therapy in immunotherapy-naive patients with advanced NSCLC. Progression-free survival (PFS) was the primary endpoint of this phase 2 study. Patients were randomized to receive nivolumab plus docetaxel or nivolumab monotherapy. From July 2019 to June 2022, a total of 22 patients were recruited, with significantly longer median PFS observed in the nivolumab plus docetaxel group (4.0 months) compared to the nivolumab group (2.0 months), P = 0.0019. The study was closed in June 2022 due to slow recruitment. The objective response rate was 10.0% [95% confidence interval (CI), 0-28.6] in the nivolumab group and 25% (95% CI, 0.5-49.5) in the nivolumab + docetaxel group ( P = 0.346). Disease control was significantly higher in the nivolumab plus docetaxel arm (40.0% versus 83.3%, P = 0.035). There was also an improvement in overall survival (OS) in the nivolumab + docetaxel arm, but this was not statistically significant (10.0 months versus 7.2 months, P = 0.129). The addition of docetaxel to nivolumab was well-tolerated, with adverse events more common in the combination group. Despite the small sample size, the results suggest that the addition of docetaxel to nivolumab may be a promising treatment option for NSCLC patients progressing on platinum-based chemotherapy, with trends towards improved OS observed.","PeriodicalId":7969,"journal":{"name":"Anti-Cancer Drugs","volume":" ","pages":"412-417"},"PeriodicalIF":2.3,"publicationDate":"2024-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139490548","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}

引用次数: 0

A phase 1 study of regorafenib and sildenafil in adults with advanced solid tumors. 一项针对晚期实体瘤成人患者的瑞戈非尼和西地那非的 1 期研究。

IF 2.3 4区医学

Anti-Cancer Drugs Pub Date : 2024-06-01 Epub Date: 2024-03-08 DOI: 10.1097/CAD.0000000000001584

Andrew S Poklepovic, Sarah W Gordon, Sejal Kothadia, William P McGuire, Leroy R Thacker, Xiaoyan Deng, Mary Beth Tombes, Ellen Shrader, Daniel Hudson, Dipankar Bandyopadhyay, Alison A Ryan, Maciej Kmieciak, Steven Smith, Paul Dent

{"title":"A phase 1 study of regorafenib and sildenafil in adults with advanced solid tumors.","authors":"Andrew S Poklepovic, Sarah W Gordon, Sejal Kothadia, William P McGuire, Leroy R Thacker, Xiaoyan Deng, Mary Beth Tombes, Ellen Shrader, Daniel Hudson, Dipankar Bandyopadhyay, Alison A Ryan, Maciej Kmieciak, Steven Smith, Paul Dent","doi":"10.1097/CAD.0000000000001584","DOIUrl":"10.1097/CAD.0000000000001584","url":null,"abstract":"The purpose of this study is to establish the recommended phase 2 dose for regorafenib in combination with sildenafil for patients with advanced solid tumors. Secondary outcomes included identification of antitumor effects of regorafenib and sildenafil, toxicity of the combination, determination of PDE5 expression in tumor samples, and the impact of sildenafil on the pharmacokinetics of regorafenib. This study was a phase 1, open-label single-arm dose-escalation trial using a 3 + 3 design. Additional patients were enrolled at the maximum tolerated dose (MTD) until a total of 12 patients were treated at the MTD. A total of 29 patients were treated in this study. The median duration of treatment was 8 weeks. The recommended phase 2 doses determined in this study are regorafenib 160 mg daily with sildenafil 100 mg daily. The most common toxicities included palmar-plantar erythrodysesthesia syndrome (20 patients, 69%) and hypophosphatemia (18 patients, 62%). Two patients (7%) experienced grade 4 lipase increase. Objective responses were not observed; however, 14 patients (48%) had a period of stable disease during the study. Stable disease for up to 12 months was observed in patients with ovarian cancer as well as up to 20 months for a patient with cervical cancer. The combination of regorafenib and sildenafil at the recommended phase 2 dose is safe and generally well tolerated. Disease control in patients with gynecologic malignancies was especially encouraging. Further evaluation of the combination of regorafenib and sildenafil in gynecologic malignancies is warranted. Clinical Trial Registration Number: NCT02466802.","PeriodicalId":7969,"journal":{"name":"Anti-Cancer Drugs","volume":" ","pages":"450-458"},"PeriodicalIF":2.3,"publicationDate":"2024-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11168782/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140058493","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}

引用次数: 0

HMOX1 regulates ferroptosis via mic14 and its impact on chemotherapy resistance in small-cell lung cancer. HMOX1通过mic14调控铁突变及其对小细胞肺癌化疗耐药性的影响

IF 2.3 4区医学

Anti-Cancer Drugs Pub Date : 2024-06-01 Epub Date: 2024-03-11 DOI: 10.1097/CAD.0000000000001588

Yujie Sun, Jian Zhang

{"title":"HMOX1 regulates ferroptosis via mic14 and its impact on chemotherapy resistance in small-cell lung cancer.","authors":"Yujie Sun, Jian Zhang","doi":"10.1097/CAD.0000000000001588","DOIUrl":"10.1097/CAD.0000000000001588","url":null,"abstract":"This study aimed to investigate the role and molecular mechanism of heme oxygenase-1 (HMOX1) in chemotherapy resistance in small-cell lung cancer (SCLC). Employed bioinformatics, qPCR, and Western Blot to assess HMOX1 levels in SCLC versus normal tissues and its prognostic relevance. CCK-8, flow cytometry, and thiobarbituric acid assays determined HMOX1's impact on SCLC chemosensitivity, ferroptosis markers, lipid peroxidation, and mic14's role in chemoresistance. In the GSE40275 and GSE60052 cohorts, HMOX1 expression was downregulated in SCLC tissues compared to normal tissues. Higher HMOX1 expression was associated with improved prognosis in the Sun Yat-sen University Cancer Hospital cohort and GSE60052 cohort. The RNA and protein levels of HMOX1 were reduced in drug-resistant SCLC cell lines compared to chemosensitive cell lines. Upregulation of HMOX1 increased chemosensitivity and reduced drug resistance in SCLC, while downregulation of HMOX1 decreased chemosensitivity and increased drug resistance. Upregulation of HMOX1 elevated the expression of ferroptosis-related proteins ACSL4, CD71, Transferrin, Ferritin Heavy Chain, and Ferritin Light Chain, while decreasing the expression of GPX4 and xCT. Conversely, downregulation of HMOX1 decreased the expression of ACSL4, CD71, Transferrin, Ferritin Heavy Chain, and Ferritin Light Chain, while increasing the expression of GPX4 and xCT. Upregulation of HMOX1 promoted cellular lipid peroxidation, whereas downregulation of HMOX1 inhibited cellular lipid peroxidation. Upregulation of HMOX1 reduced the RNA level of mic14, while downregulation of HMOX1 increased the RNA level of mic14. mic14 exhibited inhibitory effects on cellular lipid peroxidation in SCLC cells and contributed to reduced chemosensitivity and increased drug resistance in chemoresistant SCLC cell lines. HMOX1 plays a role in ferroptosis by regulating mic14 expression, thereby reversing chemoresistance in SCLC.","PeriodicalId":7969,"journal":{"name":"Anti-Cancer Drugs","volume":" ","pages":"397-411"},"PeriodicalIF":2.3,"publicationDate":"2024-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140288074","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}

引用次数: 0