Anti-Cancer Drugs最新文献

筛选
英文 中文
Anlotinib for the treatment of pulmonary epithelioid inflammatory myofibroblastic sarcoma: a case report. 安洛替尼治疗肺上皮样炎性肌成纤维细胞肉瘤1例。
IF 2.2 4区 医学
Anti-Cancer Drugs Pub Date : 2025-09-01 Epub Date: 2025-05-12 DOI: 10.1097/CAD.0000000000001731
Huanling Zeng, Xin Li, Shengli Chen, Jiajian Xu, Yue Xiao, Yuhua Zhao
{"title":"Anlotinib for the treatment of pulmonary epithelioid inflammatory myofibroblastic sarcoma: a case report.","authors":"Huanling Zeng, Xin Li, Shengli Chen, Jiajian Xu, Yue Xiao, Yuhua Zhao","doi":"10.1097/CAD.0000000000001731","DOIUrl":"10.1097/CAD.0000000000001731","url":null,"abstract":"<p><p>Epithelioid inflammatory myofibroblastic sarcoma (EIMS) is a rare subtype of inflammatory myofibrosarcoma. Anlotinib has demonstrated efficacy in the treatment of sarcoma. Nevertheless, to our knowledge, its use in EIMS has not been reported. Herein, we present a case of pulmonary EIMS. The patient underwent two courses of chemotherapy with doxorubicin combined with ifosfamide; however, the treatment was switched to anlotinib due to leukocytopenia. After 11 months of treatment with anlotinib, the tumor was in partial remission. Subsequently, the patient developed an acute myocardial infarction, which resulted in the discontinuation of anlotinib. Four months after discontinuation, the tumor progressed and anlotinib therapy was resumed. Following treatment for 5 months, tumor assessment indicated partial remission until March 2024. During this period, the patient experienced an adverse effect (i.e. ostealgia), which led to two reductions in the dosage of anlotinib. This case report provides a novel strategy for treating EIMS.</p>","PeriodicalId":7969,"journal":{"name":"Anti-Cancer Drugs","volume":" ","pages":"678-681"},"PeriodicalIF":2.2,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12329802/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143966467","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
APG-115 synergizes with bortezomib to induce apoptosis in cervical cancer cells. APG-115与硼替佐米协同诱导宫颈癌细胞凋亡。
IF 2.2 4区 医学
Anti-Cancer Drugs Pub Date : 2025-09-01 Epub Date: 2025-06-03 DOI: 10.1097/CAD.0000000000001735
Chuanyue Sun, Xueqiong Meng, Xiaoxi Cui, Shihao Liang, Jie Sun, Binghui Zhang, Yanhong Cui, Yinzhen Zhao, Ning Chen, Kangli Tian, Yixiang Chen
{"title":"APG-115 synergizes with bortezomib to induce apoptosis in cervical cancer cells.","authors":"Chuanyue Sun, Xueqiong Meng, Xiaoxi Cui, Shihao Liang, Jie Sun, Binghui Zhang, Yanhong Cui, Yinzhen Zhao, Ning Chen, Kangli Tian, Yixiang Chen","doi":"10.1097/CAD.0000000000001735","DOIUrl":"10.1097/CAD.0000000000001735","url":null,"abstract":"<p><p>Despite significant advancements in vaccination, screening, and therapeutic strategies have substantially reduced cervical cancer incidence, effective treatment for this disease remains a major clinical challenge. This study reveals that APG-115, a murine double minute 2 (MDM2) inhibitor, upregulates the transcription and expression of MDM2, p53, and p21, effectively inhibiting cell proliferation and inducing apoptosis in cervical cancer cells. Mechanistically, APG-115 suppresses the activation of the AKT and ERK signaling pathways and reduces the expression of antiapoptotic proteins BCL-2, BCL-xL, and MCL-1, while promoting the expression of pro-apoptotic proteins BAK, BAX, and BIM. Notably, the combination of APG-115 with bortezomib enhances p53 and p21 expression, synergistically induces cell apoptosis. In the cervical cancer xenograft models, APG-115 and bortezomib significantly downregulated the expression of Ki67 and BCL-2 while markedly increasing p21 protein levels, effectively suppressing tumor growth and inducing apoptosis. The combination further amplified the effects on Ki67, BCL-2, and p21 expression, leading to enhanced tumor growth inhibition. In summary, this study demonstrates that APG-115 exerts antitumor effects in cervical cancer, and its combination with bortezomib further enhances this inhibitory effect, probably through maximal activation of p53 and inhibition of BCL-2, suggesting a potential application of APG-115 in the treatment of cervical cancer.</p>","PeriodicalId":7969,"journal":{"name":"Anti-Cancer Drugs","volume":" ","pages":"637-647"},"PeriodicalIF":2.2,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12329801/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144207468","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
Synthesis, characterization and evaluation of linoleic acid-loaded nano-carriers: a novel drug delivery system for efficient treatment of hepatocellular carcinoma. 载亚油酸纳米载体的合成、表征和评价:一种有效治疗肝细胞癌的新型药物传递系统。
IF 2.2 4区 医学
Anti-Cancer Drugs Pub Date : 2025-09-01 Epub Date: 2025-05-30 DOI: 10.1097/CAD.0000000000001734
Mahsa Ghasemzad, Haleh Bakhshandeh, Roghayeh Naserkhaki, Ibrahim Ghoytasi, Bahare Shokoohian, Alireza Fotouhi, Zohreh Miri-Lavasani, Elham Rismani, Nikoo Hossein-Khannazer, Abbas Piryaei, Massoud Vosough
{"title":"Synthesis, characterization and evaluation of linoleic acid-loaded nano-carriers: a novel drug delivery system for efficient treatment of hepatocellular carcinoma.","authors":"Mahsa Ghasemzad, Haleh Bakhshandeh, Roghayeh Naserkhaki, Ibrahim Ghoytasi, Bahare Shokoohian, Alireza Fotouhi, Zohreh Miri-Lavasani, Elham Rismani, Nikoo Hossein-Khannazer, Abbas Piryaei, Massoud Vosough","doi":"10.1097/CAD.0000000000001734","DOIUrl":"10.1097/CAD.0000000000001734","url":null,"abstract":"<p><p>Hepatocellular carcinoma is the main primary liver cancer. Due to the high recurrence rate and potential resistance to treatments, there is an urgent need to find more effective and targeted therapies. Combinational therapies and using advanced drug delivery methods are promising approaches. Niosomes are one of the popular types of nanoparticles in modern drug delivery systems and have recently attracted more attention. They are biodegradable, nonimmunogenic, and more stable carriers than liposomes. They can release anticancer drugs in an efficient and controlled manner. The aim of this study was to synthesize and characterize the physicochemical properties of linoleic acid (LA)-loaded niosomes and evaluate their anticancer effects on a hepatoma cell. We synthesized LA-loaded niosomes using a thin-film hydration method and characterized their size, polydispersity index (PDI), and zeta potential. The morphology of niosomes was evaluated by scanning electron microscopy. Finally, the viability, migration capacity, and colonization potential of Hep-3B hepatoma cells treated with 150 μM LA-loaded niosomes were investigated and compared to the control groups. The niosomes had a mean size of 266.9 nm, PDI of 0.271, and zeta potential of -26.1 mV. The LA-loaded niosomes released LA sustainably at 37 °C for 72 h. MTS assay indicated that the LA-loaded niosomes were more toxic than free LA. Hep-3B hepatoma cells treated with LA-loaded niosomes showed a remarkable decline in the migration ability and colony-formation capacity. Therefore, the use of LA-loaded niosomes in combination with conventional protocols may be a promising approach to target cancer cells.</p>","PeriodicalId":7969,"journal":{"name":"Anti-Cancer Drugs","volume":" ","pages":"629-636"},"PeriodicalIF":2.2,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144172455","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 case of diabetic ketoacidosis triggered by immune checkpoint inhibitors in the treatment of recurrent nasopharyngeal carcinoma. 免疫检查点抑制剂治疗复发性鼻咽癌引发糖尿病酮症酸中毒1例。
IF 2.2 4区 医学
Anti-Cancer Drugs Pub Date : 2025-09-01 Epub Date: 2025-05-30 DOI: 10.1097/CAD.0000000000001739
Shuting Xian, Liu Yang, Chunmiao Wang, Jinxin Cao, Danxian Jiang, Jing Huang
{"title":"A case of diabetic ketoacidosis triggered by immune checkpoint inhibitors in the treatment of recurrent nasopharyngeal carcinoma.","authors":"Shuting Xian, Liu Yang, Chunmiao Wang, Jinxin Cao, Danxian Jiang, Jing Huang","doi":"10.1097/CAD.0000000000001739","DOIUrl":"10.1097/CAD.0000000000001739","url":null,"abstract":"<p><p>Immune-related adverse events (irAEs) caused by immune checkpoint inhibitors (ICIs) have been widely documented. Diabetic ketoacidosis (DKA), a severe irAEs, has not been previously reported in patients with nasopharyngeal carcinoma (NPC). This case report describes the development of DKA during maintenance immunotherapy with tislelizumab in a patient with recurrent NPC. A 41-year-old female patient with recurrent NPC (rT3N0M0, 8 th edition of AJCC staging) experienced DKA during her 13 th session of maintenance treatment with the ICI tislelizumab. After urgent consultation with an endocrinologist, immune-related DKA was diagnosed, and immune checkpoint inhibitor-related diabetes was confirmed. Prompt treatment with hypoglycemic agents, fluid infusion, and correction of water-electrolyte and acid-base balance was administered. The patient's blood glucose was stabilized within 6 days, and she was discharged without complications. This is the first reported case of DKA in a patient with NPC receiving tislelizumab maintenance immunotherapy. Clinicians should enhance their understanding and monitoring of adverse events in patients treated with ICIs, focusing on early diagnosis and appropriate intervention.</p>","PeriodicalId":7969,"journal":{"name":"Anti-Cancer Drugs","volume":" ","pages":"694-697"},"PeriodicalIF":2.2,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144172414","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
Novel dibenzoylmethane derivative 2-allyl-1,3-diphenyl-1, 3-propanedione: a safe and effective topical treatment for melanoma. 新型二苯甲酰甲烷衍生物2-烯丙基-1,3-二苯基-1,3-丙二酮:一种安全有效的黑色素瘤局部治疗药物。
IF 2.2 4区 医学
Anti-Cancer Drugs Pub Date : 2025-09-01 Epub Date: 2025-06-17 DOI: 10.1097/CAD.0000000000001730
Jefferson Viktor de Paula Barros Baeta, Maria Aparecida Braga Rocha E Oliveira, Fernada Rodrigues Nascimento, Marcos Rodrigo de Oliveira, Virgínia Ramos Pizziolo, Tiago Antônio de Oliveira Mendes, Gaspar Diaz-Muñoz, Anésia Aparecida Dos Santos, Marisa Alves Nogueira Diaz
{"title":"Novel dibenzoylmethane derivative 2-allyl-1,3-diphenyl-1, 3-propanedione: a safe and effective topical treatment for melanoma.","authors":"Jefferson Viktor de Paula Barros Baeta, Maria Aparecida Braga Rocha E Oliveira, Fernada Rodrigues Nascimento, Marcos Rodrigo de Oliveira, Virgínia Ramos Pizziolo, Tiago Antônio de Oliveira Mendes, Gaspar Diaz-Muñoz, Anésia Aparecida Dos Santos, Marisa Alves Nogueira Diaz","doi":"10.1097/CAD.0000000000001730","DOIUrl":"10.1097/CAD.0000000000001730","url":null,"abstract":"<p><p>This study investigated 2-allyl-1,3-diphenyl-1,3-propanedione (DPAP), a dibenzoylmethane derivative, as a potentially more effective and safer alternative to dacarbazine for melanoma treatment. The antitumor activity of DPAP was assessed through comprehensive in-vitro, in-silico, and in-vivo experiments. In-vitro assays evaluated DPAP's IC 50 values against melanoma cells, benchmarking its efficacy against dacarbazine. Molecular analyses explored apoptosis mechanisms, emphasizing the roles of FAS receptors and caspase pathways. In-silico absorption, distribution, metabolism, excretion, and toxicity analysis provided insights into DPAP's pharmacokinetic profile, including absorption, distribution, metabolism, and toxicity. In-vivo studies examined its effects on tumor volume, vascular endothelial growth factor (VEGF) levels, and the histopathology of the liver, kidney, and lymph nodes. DPAP demonstrated significantly enhanced antitumor activity, reflected by markedly lower IC 50 values compared with dacarbazine, underscoring its superior efficacy and specificity toward tumor cells. Molecular assays confirmed that DPAP induces apoptosis through modulation of FAS receptors and activation of caspase pathways. In-silico results revealed favorable pharmacokinetic properties, including high intestinal absorption and good tissue distribution, with no evidence of carcinogenic potential. Notably, in-vivo experiments showed that DPAP effectively reduced tumor volume and VEGF levels, while also preventing hepatotoxicity and nephrotoxicity. In addition, it inhibited the migration of tumor cells to lymph nodes. These findings position DPAP as a promising candidate for melanoma treatment, particularly as a topical therapeutic, offering enhanced efficacy and safety compared with existing treatments. DPAP is a promising candidate for melanoma treatment, particularly through topical application, offering a safer and more effective alternative to current treatments.</p>","PeriodicalId":7969,"journal":{"name":"Anti-Cancer Drugs","volume":" ","pages":"607-621"},"PeriodicalIF":2.2,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144315774","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
Benefit of switching to firmonertinib following almonertinib-induced interstitial pneumonitis in a patient with advanced non-small-cell lung cancer: a case report. 阿莫那替尼诱导的晚期非小细胞肺癌间质性肺炎患者改用非莫那替尼的益处:1例报告
IF 2.2 4区 医学
Anti-Cancer Drugs Pub Date : 2025-09-01 Epub Date: 2025-06-04 DOI: 10.1097/CAD.0000000000001742
Lingying Wang, Pan Yang, Hu Luo
{"title":"Benefit of switching to firmonertinib following almonertinib-induced interstitial pneumonitis in a patient with advanced non-small-cell lung cancer: a case report.","authors":"Lingying Wang, Pan Yang, Hu Luo","doi":"10.1097/CAD.0000000000001742","DOIUrl":"10.1097/CAD.0000000000001742","url":null,"abstract":"<p><p>Almonertinib, a representative epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI), is the first-line standard treatment for EGFR-mutant advanced non-small-cell lung cancer; however, it may induce drug-related interstitial lung disease (ILD). This case report presents a 67-year-old female with advanced lung adenocarcinoma, who was diagnosed with an EGFR exon 19 deletion mutation. After 2 months of first-line almonertinib treatment (110 mg/day), a PR was achieved; however, progressive respiratory distress emerged. Chest computed tomography revealed ground-glass opacities accompanied by grid-like changes in both lungs, leading to a diagnosis of EGFR-TKI-related ILD (grade 2). Following glucocorticoid treatment and medication discontinuation, the lung lesions improved. Given the persistent tumor activity, the patient was switched to firmonertinib (80 mg/day) for targeted therapy. This switch did not lead to a recurrence of ILD symptoms, with a progression-free survival exceeding 5 months and good tolerability. This suggests that for patients with ILD associated with almonertinib and firmonertinib may serve as an effective and safe alternative. Closely monitoring ILD in clinical practice and promptly switching to similar drugs may avoid chemotherapy intervention and optimize treatment strategies. This case marks the first report of clinical experience achieving sustained remission by switching to a similar drug, firmonertinib, in patients with ILD related to almonertinib.</p>","PeriodicalId":7969,"journal":{"name":"Anti-Cancer Drugs","volume":" ","pages":"682-685"},"PeriodicalIF":2.2,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12329803/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144214662","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
Rapid radiological response of leptomeningeal carcinosis and prolonged survival to encorafenib and binimetinib in BRAF-mutated melanoma. braf突变的黑色素瘤对轻脑膜癌的快速放射反应和延长恩科非尼和比尼替尼的生存期。
IF 2.2 4区 医学
Anti-Cancer Drugs Pub Date : 2025-09-01 Epub Date: 2025-05-30 DOI: 10.1097/CAD.0000000000001737
Giacomo Corradi, Sara De Martino, Angela Rinaldi, Giambattista Siepe, Paola V Marchese, Barbara Melotti, Francesca Comito
{"title":"Rapid radiological response of leptomeningeal carcinosis and prolonged survival to encorafenib and binimetinib in BRAF-mutated melanoma.","authors":"Giacomo Corradi, Sara De Martino, Angela Rinaldi, Giambattista Siepe, Paola V Marchese, Barbara Melotti, Francesca Comito","doi":"10.1097/CAD.0000000000001737","DOIUrl":"10.1097/CAD.0000000000001737","url":null,"abstract":"<p><p>Among solid tumors, malignant melanoma (MM) has the highest risk of metastasis to the leptomeninges, for which a specific therapeutic regimen has not been established yet. This case report describes a rapid partial response to leptomeningeal disease (LMD) in a patient with a BRAF V600K-mutated MM. A 69-year-old man affected by metastatic melanoma was initially treated with benefit with targeted therapy with encorafenib and binimetinib, which was discontinued several times because of toxicity or intolerance, and then with dabrafenib and trametinib, which were also poorly tolerated. During the treatment pause, the patient, who had refused to receive immunotherapy developed LMD and was started again on targeted therapy with reduced dosage of encorafenib and binimetinib. A few days after starting this treatment, MRI showed an important reduction of the perilesional edema and then, after a few months, a disease response. The patient had a long survival of approximately 14 months from this diagnosis. To the best of our knowledge, this is the first report describing rapid radiological response, clinical benefit, and prolonged survival with encorafenib and binimetinib in patients affected by LMD from melanoma.</p>","PeriodicalId":7969,"journal":{"name":"Anti-Cancer Drugs","volume":" ","pages":"691-693"},"PeriodicalIF":2.2,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144172452","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
Complete response with trastuzumab in heavily pretreated HER2-positive metastatic salivary duct carcinoma. 曲妥珠单抗在重度预处理的her2阳性转移性涎管癌中的完全缓解。
IF 2.2 4区 医学
Anti-Cancer Drugs Pub Date : 2025-09-01 Epub Date: 2025-05-06 DOI: 10.1097/CAD.0000000000001733
Rumeysa Çolak, Caner Kapar, Mesut Yilmaz
{"title":"Complete response with trastuzumab in heavily pretreated HER2-positive metastatic salivary duct carcinoma.","authors":"Rumeysa Çolak, Caner Kapar, Mesut Yilmaz","doi":"10.1097/CAD.0000000000001733","DOIUrl":"10.1097/CAD.0000000000001733","url":null,"abstract":"<p><p>Salivary duct carcinoma (SDC), an aggressive and relatively rare tumor, accounts for approximately 10% of all salivary gland malignancies. We report a case of a patient with a metastatic, human epidermal growth factor receptor 2 (HER2)-positive parotid SDC efficiently treated with docetaxel and trastuzumab combination after multiple series of chemotherapies. A 61-year-old man presented with SDC. After adjuvant radiotherapy, imaging revealed multiple metastatic lesions in the lungs. Systemic treatment with carboplatin and paclitaxel was initiated. After disease progression, doxorubicin, vinorelbine, and capecitabine were performed. Neurotrophic tropomyosin receptor kinase and AR (androgen receptor) were negative. Immunohistochemistry determined a HER2-positive score of 3. After multiple chemotherapy, the patient was started with combination of docetaxel and trastuzumab. A complete response was obtained after 3 months of treatment in the patient. In conclusion, SDCs are highly aggressive malignant tumors. Targeted therapy with trastuzumab targeting HER2 overexpression is a reasonable option in metastatic settings.</p>","PeriodicalId":7969,"journal":{"name":"Anti-Cancer Drugs","volume":" ","pages":"675-677"},"PeriodicalIF":2.2,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143960405","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
Denticleless homolog-mediated ubiquitin-proteasome degradation of forkhead box O1 contributes to development of carboplatin resistance in retinoblastoma. 无齿同源介导的叉头盒O1泛素蛋白酶体降解有助于视网膜母细胞瘤中卡铂耐药的发展。
IF 2.2 4区 医学
Anti-Cancer Drugs Pub Date : 2025-09-01 Epub Date: 2025-06-03 DOI: 10.1097/CAD.0000000000001738
Xian Liu, Shou-Feng Jiao, Chun-Yi Liu, Rui Luo, Han Liu, Yong Chai
{"title":"Denticleless homolog-mediated ubiquitin-proteasome degradation of forkhead box O1 contributes to development of carboplatin resistance in retinoblastoma.","authors":"Xian Liu, Shou-Feng Jiao, Chun-Yi Liu, Rui Luo, Han Liu, Yong Chai","doi":"10.1097/CAD.0000000000001738","DOIUrl":"10.1097/CAD.0000000000001738","url":null,"abstract":"<p><p>This study aimed to investigate the role of forkhead box O1 (FOXO1) in carboplatin-resistant retinoblastoma (RB) cells, focusing on its subcellular distribution and regulation through ubiquitin-dependent degradation mediated by denticleless homolog (DTL). The study sought to elucidate the molecular mechanisms underlying carboplatin resistance in RB and explore potential therapeutic strategies to overcome chemoresistance. Carboplatin-resistant RB cell lines (Y79/CBP and WERI-Rb-1/CBP) were established by incremental drug exposure. Bioinformatics analysis of the GSE111168 dataset identified differentially expressed genes associated with ubiquitination pathways. DTL expression was modulated using adeno-associated virus-mediated knockdown and overexpression. FOXO1 protein levels, subcellular localization, and ubiquitination were assessed via western blotting, immunofluorescence, and coimmunoprecipitation (Co-IP). The effects of DTL knockdown and LOM612 treatment on cell proliferation, apoptosis, and tumor growth were evaluated in vitro and in vivo using xenograft models. FOXO1 expression and nuclear localization were significantly reduced in carboplatin-resistant RB cells, with elevated levels of FOXO1 ubiquitination. Proteasome inhibitors preserved FOXO1 protein levels, implicating the ubiquitin-proteasome system in its degradation. DTL was identified as a significantly overexpressed gene in both resistant cells and patient-derived samples. Silencing DTL increased FOXO1 protein expression and nuclear accumulation, while Co-IP confirmed the interaction between DTL and FOXO1, mediated by the WD40 domain of DTL. Combined DTL knockdown and LOM612 treatment synergistically inhibited cell proliferation and invasion, promoted apoptosis in vitro, and significantly reduced tumor growth and induced apoptosis in vivo. DTL-mediated ubiquitination and degradation of FOXO1 play a critical role in carboplatin resistance in RB. Dual targeting of DTL and FOXO1 nuclear translocation may represent a promising therapeutic strategy to overcome chemoresistance and improve clinical outcomes in RB.</p>","PeriodicalId":7969,"journal":{"name":"Anti-Cancer Drugs","volume":" ","pages":"648-663"},"PeriodicalIF":2.2,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144207469","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
α-Asarone attenuates tumor-associated macrophages-induced gemcitabine resistance in pancreatic carcinoma via the transforming growth factor-beta 1/growth factor independent 1 axis. α-细辛酮通过转化生长因子- β 1/生长因子独立1轴减弱肿瘤相关巨噬细胞诱导的胰腺癌吉西他滨耐药
IF 2.2 4区 医学
Anti-Cancer Drugs Pub Date : 2025-09-01 Epub Date: 2025-06-13 DOI: 10.1097/CAD.0000000000001740
Jiaqi Yu, Yuzhe Xue, Zhaofeng Gao, Lingyu Hu, Xiaorong Liu, Xuesong He, Xiaoguang Wang
{"title":"α-Asarone attenuates tumor-associated macrophages-induced gemcitabine resistance in pancreatic carcinoma via the transforming growth factor-beta 1/growth factor independent 1 axis.","authors":"Jiaqi Yu, Yuzhe Xue, Zhaofeng Gao, Lingyu Hu, Xiaorong Liu, Xuesong He, Xiaoguang Wang","doi":"10.1097/CAD.0000000000001740","DOIUrl":"10.1097/CAD.0000000000001740","url":null,"abstract":"<p><p>Pancreatic cancer is characterized by aggressiveness and poor prognosis. The development of gemcitabine resistance, especially tumor-associated macrophage (TAM) -induced resistance in the tumor microenvironment, has greatly limited its therapeutic effectiveness. This study investigates the effects and underlying mechanisms of the plant-derived bioactive compound α-asarone in reversing gemcitabine resistance induced by TAMs in pancreatic cancer, offering potential therapeutic alternatives. Flow cytometry was used to assess the cell cycle and apoptosis in pancreatic cancer cells. Transforming growth factor-beta 1 (TGF-β1) secretion was measured by ELISA, and Cell Counting Kit-8 assays to evaluate the survival of PANC-1 cells treated with gemcitabine. Western blotting and quantitative real-time PCR were used to analyze growth factor independent 1 (Gfi-1) expression and its association with gemcitabine resistance. α-Asarone effectively reversed gemcitabine resistance in pancreatic cancer cells. Treatment with α-asarone reduced TGF-β1 levels in TAM condition medium, which in turn led to the upregulation of Gfi-1 expression. Gfi-1 was found to negatively regulate the expression of drug resistance factors, including connective tissue growth factor (CTGF) and high mobility group box 1 (HMGB1), thereby reversing gemcitabine resistance in pancreatic cancer cells. Those results indicate that α-asarone enhances Gfi-1 expression, downregulates CTGF and HMGB1, and restores gemcitabine sensitivity by reducing TGF-β1 secretion from TAMs. α-Asarone can effectively reverse gemcitabine resistance in pancreatic cancer by reducing TGF-β1 secretion from TAMs, upregulating Gfi-1, and downregulating resistance factors such as CTGF and HMGB1. This restoration of gemcitabine sensitivity may improve the therapeutic efficacy of gemcitabine in pancreatic cancer treatment.</p>","PeriodicalId":7969,"journal":{"name":"Anti-Cancer Drugs","volume":" ","pages":"664-674"},"PeriodicalIF":2.2,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12329808/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144282231","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
0
×
引用
GB/T 7714-2015
复制
MLA
复制
APA
复制
导出至
BibTeX EndNote RefMan NoteFirst NoteExpress
×
提示
您的信息不完整,为了账户安全,请先补充。
现在去补充
×
提示
您因"违规操作"
具体请查看互助需知
我知道了
×
提示
确定
请完成安全验证×
相关产品
×
本文献相关产品
联系我们:info@booksci.cn Book学术提供免费学术资源搜索服务,方便国内外学者检索中英文文献。致力于提供最便捷和优质的服务体验。 Copyright © 2023 布克学术 All rights reserved.
京ICP备2023020795号-1
ghs 京公网安备 11010802042870号
Book学术文献互助
Book学术文献互助群
群 号:604180095
Book学术官方微信