Cancer Chemotherapy and Pharmacology最新文献

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Retraction Note: New recommendations for reversal of high-dose methotrexate cytotoxicity with folinic acid. 撤回注:新推荐用叶酸逆转高剂量甲氨蝶呤细胞毒性。
IF 2.7 4区 医学
Cancer Chemotherapy and Pharmacology Pub Date : 2025-07-25 DOI: 10.1007/s00280-025-04798-1
Jesper Heldrup, Archie Bleyer, Laura Ramsey, Lauren Schaff, Brooke Bernhardt, Stefan Schwartz, Etienne Chatelut, Miriam Hwang, Carolina Ten, Martin Guscott, Scott Howard
{"title":"Retraction Note: New recommendations for reversal of high-dose methotrexate cytotoxicity with folinic acid.","authors":"Jesper Heldrup, Archie Bleyer, Laura Ramsey, Lauren Schaff, Brooke Bernhardt, Stefan Schwartz, Etienne Chatelut, Miriam Hwang, Carolina Ten, Martin Guscott, Scott Howard","doi":"10.1007/s00280-025-04798-1","DOIUrl":"https://doi.org/10.1007/s00280-025-04798-1","url":null,"abstract":"","PeriodicalId":9556,"journal":{"name":"Cancer Chemotherapy and Pharmacology","volume":"95 1","pages":"77"},"PeriodicalIF":2.7,"publicationDate":"2025-07-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144706423","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
DNA-incorporated thioguanine to detect potential non-adherence to maintenance therapy in acute lymphoblastic leukemia. dna结合硫鸟嘌呤检测急性淋巴细胞白血病维持治疗的潜在不依从性。
IF 2.7 4区 医学
Cancer Chemotherapy and Pharmacology Pub Date : 2025-07-16 DOI: 10.1007/s00280-025-04784-7
Mathilde Rønne Koch, Anna Sofie Buhl Rasmussen, Bodil Als-Nielsen, Ximo Duarte, Gabriele Escherich, Mats Heyman, Kristi Lepik, Johan Malmros, Jacob Nersting, Inga Johannsdottir, Riitta Niinimäki, Malene Johanne Petersen, Heidi Segers, Inge Margriet van der Sluis, Maria Thastrup, Goda Vaitkeviciene, Kjeld Schmiegelow, Linea Natalie Toksvang
{"title":"DNA-incorporated thioguanine to detect potential non-adherence to maintenance therapy in acute lymphoblastic leukemia.","authors":"Mathilde Rønne Koch, Anna Sofie Buhl Rasmussen, Bodil Als-Nielsen, Ximo Duarte, Gabriele Escherich, Mats Heyman, Kristi Lepik, Johan Malmros, Jacob Nersting, Inga Johannsdottir, Riitta Niinimäki, Malene Johanne Petersen, Heidi Segers, Inge Margriet van der Sluis, Maria Thastrup, Goda Vaitkeviciene, Kjeld Schmiegelow, Linea Natalie Toksvang","doi":"10.1007/s00280-025-04784-7","DOIUrl":"10.1007/s00280-025-04784-7","url":null,"abstract":"<p><strong>Purpose: </strong>Adherence to 6-mercaptopurine (6-MP)/methotrexate maintenance treatment for acute lymphoblastic leukemia (ALL) is pivotal to preventing relapse, and the 6-MP metabolite DNA-incorporated thioguanine (DNA-TG) is associated with relapse risk. In the ALLTogether-1 (A2G1) Maintenance sub-study (EU CT nr 2022-501050-11-01), DNA-TG, thioguanine nucleotides (TGN), and methylated mercaptopurine metabolites (MeMP) are analyzed regularly. Upon levels below preset limits (TGN < 50, or MeMP < 200 or < 100 nmol/mmol hemoglobin for thiopurine S-methyltransferase (TPMT) wild type and heterozygous patients, respectively), the treating physician is informed of potential non-adherence. We investigated the feasibility of using DNA-TG as the primary flagging of potential non-adherence.</p><p><strong>Methods: </strong>We analyzed 6-MP metabolites in 3,074 blood samples from 368 children enrolled in the A2G1 Maintenance sub-study.</p><p><strong>Results: </strong>In 6% of samples, TGN (median 212, 95% range 40-642), MeMP (median 4,959, 95% range 135-23,880) or both were below the flagging potential non-adherence limits. DNA-TG was associated with TGN (estimate = 1.72, p < 0.0001), MeMP (estimate = 1.10, p < 0.0001), and prescribed 6-MP dose (estimate = 1.083 and 1.132, p < 0.0001, for TPMT wild type and heterozygous patients) in linear effects models, and the predicted probability of treatment interruption in logistic regression models. DNA-TG was below 200 fmol TG/µg DNA (13th percentile of all measurements, median 569, 95% range 73-1,823) in all samples with both TGN and MeMP below the flagging potential non-adherence limits.</p><p><strong>Conclusion: </strong>DNA-TG can provide a cost-effective guidance on when to measure TGN and MeMP to determine whether non-adherence should be suspected, which is an additional benefit to monitoring DNA-TG during maintenance therapy.</p>","PeriodicalId":9556,"journal":{"name":"Cancer Chemotherapy and Pharmacology","volume":"95 1","pages":"76"},"PeriodicalIF":2.7,"publicationDate":"2025-07-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12267380/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144641886","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
Unrecognized mutations in DPYD* 2 A wild-type rectal cancer patients receiving postoperative 5-FU-based chemotherapy - do they have a clinical impact? 接受术后5- fu化疗的DPYD* 2a野生型直肠癌患者中未被识别的突变-它们是否具有临床影响?
IF 2.7 4区 医学
Cancer Chemotherapy and Pharmacology Pub Date : 2025-07-15 DOI: 10.1007/s00280-025-04787-4
P Liersch, S Dierks, R Andag, T Liersch, C de Boer, J Kreutzer, A Hille, H Sülberg, A Leha, Julie Schanz
{"title":"Unrecognized mutations in DPYD* 2 A wild-type rectal cancer patients receiving postoperative 5-FU-based chemotherapy - do they have a clinical impact?","authors":"P Liersch, S Dierks, R Andag, T Liersch, C de Boer, J Kreutzer, A Hille, H Sülberg, A Leha, Julie Schanz","doi":"10.1007/s00280-025-04787-4","DOIUrl":"10.1007/s00280-025-04787-4","url":null,"abstract":"<p><strong>Purpose: </strong>The impact of the unrecognized mutational dihydropyrimidine-dehydrogenase-gene-(DPYD)-status on high-grade CTC-AE-grades ≥ 3 (NCI-Common Terminology Criteria for Adverse Events, vs. 3.0) was assessed in patients with upper rectal cancer (inferior tumor margin ≥ 12 cm above the anal verge) treated with upfront surgery and 5-Fluorouracil (5-FU) based adjuvant chemotherapy (CTx).</p><p><strong>Methods: </strong>75 participants of the GAST-05-phase-IIb-trial (ISRCTN35198481) were tested in this single center analysis for DPYD*2A-wildtype (WT) at staging. After surgery, 43 patients (stages II and III, according to the current 8th TNM/UICC-classification, 2017) received FOLFOX-CTx and entered follow-up (median: 101 months). According to recent recommendations of the European Medicines Agency (EMA) and national guidelines, post-hoc genotyping for DPYD*2A (c.1905 + 1G > A; IVS14 + 1G > A; rs3918290), DPYD*13 (c.1679T > G; rs55886062), polymorphism c.2846 A > T (rs67376798) and Haplotype B3 (HapB3) (c.1236G > A; c.1129-5923 C > G) was performed using cryopreserved blood samples and standardized PCR-techniques.</p><p><strong>Results: </strong>Five patients were found to have a heterozygous (het_) DPYD-HapB3-status. Across all patients, the adherence to CTx-cycles 1 to 4 was 100%, 97.7%, 95.3%, and 93.0%, respectively. Grade ≥ 3 CTC-AEs were observed in 0.9% of both het_HapB3- and WT-patients. The mean administered dose of 5-FU was 68.8% of the target in DPYD-HapB3 carriers, compared to 92.6% in 38 WT patients. Logistic regression analysis revealed that 5-FU dose reductions were significantly associated with DPYD-HapB3 carrier status (odds ratio [OR] 12.55, p = 0.044) and male sex (OR 0.23, p = 0.049). During follow-up het_HapB3-patients had a recurrence rate of 60.0%, compared to 13,6% for WT-patients. The disease-free survival (DFS) for het_HapB3-patients was significantly reduced vs. WT (p = 0.010). Multivariable analysis showed that het_HapB3-patients had an increased risk for reduced DFS (HR 3.774; p = 0.057). Interestingly, 5-FU dose reductions per se were not significantly associated with limited DFS in the total population.</p><p><strong>Conclusion: </strong>DPYD genotyping revealed a het_HapB3 variant in 11.6% of DPYD*2A-WT patients treated with FOLFOX. While not linked to increased toxicity, HapB3 status was associated with reduced DFS, suggesting an impact on treatment efficacy. These results support DPYD genotyping and highlight the need for adequate 5-FU plasma level assessment followed by subtile dose escalation (therapeutic drug monitoring) to personalize 5-FU dosing more precisely, safely and most effective.</p>","PeriodicalId":9556,"journal":{"name":"Cancer Chemotherapy and Pharmacology","volume":"95 1","pages":"75"},"PeriodicalIF":2.7,"publicationDate":"2025-07-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12259744/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144636229","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
Evaluation of the pharmacokinetics of enasidenib in patients with hepatic impairment. enasidenib在肝功能损害患者中的药代动力学评价。
IF 2.7 4区 医学
Cancer Chemotherapy and Pharmacology Pub Date : 2025-07-11 DOI: 10.1007/s00280-025-04797-2
Yiming Cheng, Jian Chen, Carlos Vigil, Shahram Khanzadeh, Anita Rampersad, Thomas Prebet, Yan Li
{"title":"Evaluation of the pharmacokinetics of enasidenib in patients with hepatic impairment.","authors":"Yiming Cheng, Jian Chen, Carlos Vigil, Shahram Khanzadeh, Anita Rampersad, Thomas Prebet, Yan Li","doi":"10.1007/s00280-025-04797-2","DOIUrl":"https://doi.org/10.1007/s00280-025-04797-2","url":null,"abstract":"","PeriodicalId":9556,"journal":{"name":"Cancer Chemotherapy and Pharmacology","volume":"95 1","pages":"74"},"PeriodicalIF":2.7,"publicationDate":"2025-07-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144607448","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 report: capillary leak syndrome in a patient receiving high-dose methotrexate, Tislelizumab and zanubrutinib for CNS lymphoma. 一例报告:接受大剂量甲氨蝶呤、替利单抗和扎鲁替尼治疗中枢神经系统淋巴瘤患者的毛细血管渗漏综合征。
IF 2.7 4区 医学
Cancer Chemotherapy and Pharmacology Pub Date : 2025-07-07 DOI: 10.1007/s00280-025-04796-3
Wenpeng Li, Yuxi Hou
{"title":"A case report: capillary leak syndrome in a patient receiving high-dose methotrexate, Tislelizumab and zanubrutinib for CNS lymphoma.","authors":"Wenpeng Li, Yuxi Hou","doi":"10.1007/s00280-025-04796-3","DOIUrl":"https://doi.org/10.1007/s00280-025-04796-3","url":null,"abstract":"<p><strong>Purpose: </strong>The high-dose methotrexate (MTX) regimen is a first-line treatment for primary central nervous system diffuse large B-cell lymphoma (PCNS-DLBCL). However, MTX-related kidney injury is a severe treatment complication. No cases of capillary leak syndrome (CLS) causing delayed MTX metabolism-associated renal failure have been reported.</p><p><strong>Case presentation: </strong>A 48-year-old female presented to Zibo Central Hospital in April 2024 with headaches. Contrast-enhanced magnetic resonance imaging (MRI) of the brain revealed a space-occupying lesion in the right occipital lobe. A stereotactic biopsy was performed to determine the nature of the lesion. Postoperative pathology confirmed DLBCL. The patient underwent a TZM regimen, which included Tislelizumab, MTX, and Zanubrutinib. On the first day following MTX, the patient developed generalized edema, shortness of breath, and reduced urine output. Laboratory tests revealed hypoxemia, low albumin levels, and acute kidney injury. Based on these findings, the patient was diagnosed with CLS. To quickly lower the blood MTX concentration, pleural effusion drainage and continuous renal replacement therapy (CRRT) were performed. The treatment was successful, and the patient recovered and was discharged.</p><p><strong>Conclusion: </strong>CLS is a serious complication for DLBCL patients receiving high-dose MTX therapy.</p>","PeriodicalId":9556,"journal":{"name":"Cancer Chemotherapy and Pharmacology","volume":"95 1","pages":"71"},"PeriodicalIF":2.7,"publicationDate":"2025-07-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144574888","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
Risk factors and prediction models for cardiotoxicity induced by anthracyclines in malignant chemotherapy. 蒽环类药物致恶性化疗心脏毒性的危险因素及预测模型。
IF 2.7 4区 医学
Cancer Chemotherapy and Pharmacology Pub Date : 2025-07-07 DOI: 10.1007/s00280-025-04795-4
Pengxiang Zhang, Yan Zhang, Zheng Xue, Dongchao Liu, Dongliang Li, Bing Duan, Meina Zhao, Liang Yin, Hongjie Gao, Bulang Gao, Jie Mi
{"title":"Risk factors and prediction models for cardiotoxicity induced by anthracyclines in malignant chemotherapy.","authors":"Pengxiang Zhang, Yan Zhang, Zheng Xue, Dongchao Liu, Dongliang Li, Bing Duan, Meina Zhao, Liang Yin, Hongjie Gao, Bulang Gao, Jie Mi","doi":"10.1007/s00280-025-04795-4","DOIUrl":"https://doi.org/10.1007/s00280-025-04795-4","url":null,"abstract":"","PeriodicalId":9556,"journal":{"name":"Cancer Chemotherapy and Pharmacology","volume":"95 1","pages":"73"},"PeriodicalIF":2.7,"publicationDate":"2025-07-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144574890","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
Protective effect of celecoxib against capecitabine induced hand and foot syndrome in patients with colorectal Cancer. 塞来昔布对卡培他滨诱导的结直肠癌患者手足综合征的保护作用。
IF 2.7 4区 医学
Cancer Chemotherapy and Pharmacology Pub Date : 2025-07-07 DOI: 10.1007/s00280-025-04794-5
Ahmed M Kettana, Tarek M Mostafa, Amr A Ghannam, Dalia R El-Afify
{"title":"Protective effect of celecoxib against capecitabine induced hand and foot syndrome in patients with colorectal Cancer.","authors":"Ahmed M Kettana, Tarek M Mostafa, Amr A Ghannam, Dalia R El-Afify","doi":"10.1007/s00280-025-04794-5","DOIUrl":"10.1007/s00280-025-04794-5","url":null,"abstract":"<p><strong>Background: </strong>Hand-foot syndrome (HFS) is the most common adverse effect of capecitabine.</p><p><strong>Objective: </strong>We aimed at evaluating the protective effect of celecoxib against capecitabine induced hand and foot syndrome in patients with colorectal cancer (CRC).</p><p><strong>Methods: </strong>In this randomized controlled parallel study, 44 newly diagnosed patients with stage II CRC were randomly allocated into two groups; Group 1(control group; n = 22) which received 6 cycles of capecitabine-based chemotherapy (cycle is every 3 weeks) and group 2 (celecoxib group; n = 22) which received 6 cycles of capecitabine-based chemotherapy (cycle is every 3 weeks) in addition to 200 mg of oral celecoxib twice daily for 14 days of the 3-week cycle. At baseline and after the 6th chemotherapy cycle the patients' quality of life (QOL) was assessed using hand and foot syndrome (HFS) specific QOL questionnaire (HFS-14). Moreover, blood samples were collected in order to evaluate the serum levels of cyclooxygenase-2 (COX-2), tumour necrosis factor-alpha (TNF-α) and malondialdehyde (MDA). Data was analysed using paired and un-paired t-tests.</p><p><strong>Results: </strong>At the end of the study and as compared to control group, celecoxib treated group showed significantly lower incidence of HFS (P = 0.015). Additionally, celecoxib treated group showed significant decline in the serum levels of TNF-α (P = 0.016) and MDA (P = 0.014) which was associated with non-significant difference in the serum level of COX-2 between the two groups (P = 0.476). Celecoxib was safe and well-tolerated throughout the study period.</p><p><strong>Conclusion: </strong>Celecoxib may represent a potential protective agent against capecitabine induced hand and foot syndrome in patients with colorectal cancer.</p>","PeriodicalId":9556,"journal":{"name":"Cancer Chemotherapy and Pharmacology","volume":"95 1","pages":"72"},"PeriodicalIF":2.7,"publicationDate":"2025-07-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144574889","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
Impact of altitude on hemoglobin dynamics and prognosis in patients with advanced hepatocellular carcinoma receiving antiangiogenic TKIs: A propensity score matched study. 海拔对接受抗血管生成TKIs治疗的晚期肝癌患者血红蛋白动态和预后的影响:一项倾向评分匹配研究
IF 2.7 4区 医学
Cancer Chemotherapy and Pharmacology Pub Date : 2025-07-05 DOI: 10.1007/s00280-025-04786-5
Mengyun Zhou, Xiang Zhao, Meng Zhang, Mao Peijing, Chilie Quncuo, Pubu Zhuoga, Bianba Qiongda, Meilang Chutso, Bian Ma Cuo, Bangchao Zhao, Guangfa Wang, Cheng Yuan
{"title":"Impact of altitude on hemoglobin dynamics and prognosis in patients with advanced hepatocellular carcinoma receiving antiangiogenic TKIs: A propensity score matched study.","authors":"Mengyun Zhou, Xiang Zhao, Meng Zhang, Mao Peijing, Chilie Quncuo, Pubu Zhuoga, Bianba Qiongda, Meilang Chutso, Bian Ma Cuo, Bangchao Zhao, Guangfa Wang, Cheng Yuan","doi":"10.1007/s00280-025-04786-5","DOIUrl":"10.1007/s00280-025-04786-5","url":null,"abstract":"<p><strong>Purpose: </strong>Antiangiogenic tyrosine kinase inhibitors (TKIs) are associated with elevated hemoglobin [Hb] levels, potentially influencing prognosis in advanced hepatocellular carcinoma (HCC) patients. However, the impact of altitude on Hb dynamics and its prognostic significance remains underexplored. This study aimed to assess altitude-related Hb changes and their relationship with treatment outcomes in patients following TKI treatment.</p><p><strong>Methods: </strong>In this retrospective cohort study, medical data from two institutions in Tibet and Beijing were analyzed. Between 2016 and 2022, 128 advanced HCC patients treated with antiangiogenic TKIs were divided into high- and low-altitude groups based on their city of residence. Hematological parameters were retrieved at baseline and every 3 months for 9 months post-treatment initiation. Propensity score matching (PSM) was used to adjust for demographic and baseline differences. Hb percentage changes from baseline (no increase, increase < 15%, increase ≥ 15%) were evaluated at each time point as predictors of time to treatment failure (TTTF) using the Cox proportional hazards model.</p><p><strong>Results: </strong>After PSM, Hb trajectories differed between the altitude groups. The high-altitude patients exhibited progressive increases, while the low-altitude patients experienced a transient rise followed by a decline. We found no significant TTTF differences between the matched altitude groups (P = 0.33). However, in the high-altitude unmatched cohort, a ≥ 15% increase in Hb at 9 months was linked to a significantly lower risk of treatment failure (HR = 0.22 [95% CI = 0.06-0.83]; P = 0.03). Patients with increases < 15% showed a numerical trend toward prolonged TTTF (HR = 0.30 [0.08-1.15]).</p><p><strong>Conclusion: </strong>Antiangiogenic TKIs induce altitude-dependent Hb changes, with sustained increases at high altitudes and transient reversibility at low altitudes. A ≥ 15% increase in Hb at 9 months after TKI therapy may serve as a potential biomarker for identifying high-altitude populations likely to benefit more from TKI therapy. Future studies should validate these findings in larger cohorts.</p>","PeriodicalId":9556,"journal":{"name":"Cancer Chemotherapy and Pharmacology","volume":"95 1","pages":"70"},"PeriodicalIF":2.7,"publicationDate":"2025-07-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144567139","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
Peptides derived from the POU domain of BRN2 show antitumor activity against murine melanoma model cells in vitro and in vivo. 来源于BRN2 POU结构域的肽在体内和体外均显示出对小鼠黑色素瘤模型细胞的抗肿瘤活性。
IF 2.7 4区 医学
Cancer Chemotherapy and Pharmacology Pub Date : 2025-07-02 DOI: 10.1007/s00280-025-04790-9
Maria Carolina Mariano Cesar, Agnes Kobayashi Calvo de Sant'ana, Renato Arruda Mortara, Victória Santos Souza, Thaysa Paschoalin, Marco Antônio Soufen, Juliana Machado Anastácio, Erenildo F Macedo, Fernanda Fernandes Miranda da Cunha, Dayane Batista Tada, Denise Costa Arruda
{"title":"Peptides derived from the POU domain of BRN2 show antitumor activity against murine melanoma model cells in vitro and in vivo.","authors":"Maria Carolina Mariano Cesar, Agnes Kobayashi Calvo de Sant'ana, Renato Arruda Mortara, Victória Santos Souza, Thaysa Paschoalin, Marco Antônio Soufen, Juliana Machado Anastácio, Erenildo F Macedo, Fernanda Fernandes Miranda da Cunha, Dayane Batista Tada, Denise Costa Arruda","doi":"10.1007/s00280-025-04790-9","DOIUrl":"https://doi.org/10.1007/s00280-025-04790-9","url":null,"abstract":"<p><p>The BRN2 transcription factor controls the protein expression involved in cell motility and is overexpressed in melanoma. Gene mutations involved in cell signaling pathways lead to BRN2 overexpression, tumor formation and metastasis. Peptides derived from the DNA binding domain of transcription factors can compete for the transcription binding and regulate protein expression. In this work, the antitumor activity in vitro and in vivo of the peptide E24G, derived from the DNA-binding POU domain of the BRN2 transcription factor was investigated. This peptide was fragmented into two smaller peptides E12F and A12G, their antitumor activities were characterized and compared with E24G. The E24G at 1 mM significantly reduced cell motility in vitro of B16F10-Nex2 melanoma cells. E12F peptide also inhibited cell motility at a concentration eight times smaller than E24G in murine and human melanoma cells. We observed that the antitumor activity of both E24G and E12F peptides depends on the macropinocytosis displayed by tumor cells. Also, the E24G and E12F peptides induced an increase of the CDH13 expression in 50%, however the treatment with E12F increased the expression already after 12 h by 100%. In vivo assays showed that both peptides reduced the development of metastatic lung nodules without presenting toxicity to normal organs. Our results indicate that E12F and E24G peptides can restore normal expression of BRN2 target genes at the molecular level, inhibiting the cell motility. In addition, we confirmed that the peptide binds to the DNA binding site of the BRN2 transcription factor. Further studies will elucidate their mechanisms of antitumor activity, so far our results pointed out the potential application of E12F and E24G peptides as innovative treatments for metastatic melanoma.</p>","PeriodicalId":9556,"journal":{"name":"Cancer Chemotherapy and Pharmacology","volume":"95 1","pages":"67"},"PeriodicalIF":2.7,"publicationDate":"2025-07-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144539086","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
ETV1 genetic polymorphisms as a candidate prognosis biomarker of Gastrointestinal stromal tumor. ETV1基因多态性作为胃肠道间质瘤的候选预后生物标志物。
IF 2.7 4区 医学
Cancer Chemotherapy and Pharmacology Pub Date : 2025-07-02 DOI: 10.1007/s00280-025-04789-2
Wei Zhuang, Minju Jo, Haibo Qiu, Wanlong Lin, Min Huang, Xueding Wang
{"title":"ETV1 genetic polymorphisms as a candidate prognosis biomarker of Gastrointestinal stromal tumor.","authors":"Wei Zhuang, Minju Jo, Haibo Qiu, Wanlong Lin, Min Huang, Xueding Wang","doi":"10.1007/s00280-025-04789-2","DOIUrl":"https://doi.org/10.1007/s00280-025-04789-2","url":null,"abstract":"<p><strong>Purpose: </strong>While imatinib is effective for treating Gastrointestinal Stromal Tumors (GISTs), significant variability in patient outcomes exists, highlighting the need for reliable prognostic biomarkers. ETV1, a key transcription factor involved in GIST progression, is implicated in disease biology, but the role of ETV1-related single nucleotide polymorphisms (SNPs) in predicting prognosis remains unclear.</p><p><strong>Methods: </strong>This study included 75 GIST patients. We focused on identifying tag SNPs in the ETV1 gene and examined their association with clinical outcomes. Patient characteristics, somatic mutations, and imatinib concentration were also analyzed in a multivariate model. ETV1 expression was assessed using immunohistochemistry, and miRNA interactions with ETV1 transcripts were investigated via the dual-luciferase reporter assay system.</p><p><strong>Results: </strong>We found that the rs3735343 SNP, located in the 3' untranslated region of ETV1, was significantly associated with progression-free survival (PFS) in GIST patients receiving imatinib (P = 0.008). Multivariate analysis identified tumor size (P = 0.032, Hazard Ratio [HR] = 4.173, 95% CI: 1.127-15.454) and rs3735343 (P = 0.009, HR = 8.995, 95% CI: 1.712-47.255) as independent predictors of PFS. The rs3735343 risk allele also correlated with elevated ETV1 expression in GIST tissue (P = 0.04). Additionally, miR-4311 was found to specifically and negatively regulate ETV1 mRNA levels associated with the rs3735343 risk allele in vitro.</p><p><strong>Conclusion: </strong>This study reported ETV1 rs3735343 as a novel prognostic candidate biomarker for GISTs treated with Imatinib, providing a potential biomarker for risk assessment of GIST. Additionally, our findings suggest that rs3735343 may act as a miRNA-regulated SNP, with miR-4311 playing a key role in its regulation.</p>","PeriodicalId":9556,"journal":{"name":"Cancer Chemotherapy and Pharmacology","volume":"95 1","pages":"68"},"PeriodicalIF":2.7,"publicationDate":"2025-07-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144539084","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}
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