Modulation of prostaglandin-endoperoxide synthase-2 (PTGS2) mediated VEGF-signalling pathway by oral metronomic chemotherapy in locally advanced oral squamous cell Carcinoma: A brief report.

IF 2.3 4区医学 Q3 ONCOLOGY

Cancer Chemotherapy and Pharmacology Pub Date : 2025-10-04 DOI:10.1007/s00280-025-04819-z

Mehta Vedant Kamal, Akhil Palod, Preetiparna Parida, Ananth Pai, Krishna Sharan, Vijetha Shenoy Belle, Rama Rao Damerla, Mahadev Rao, Naveena A N Kumar

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引用次数: 0

Abstract

Background: Locally advanced oral squamous cell carcinoma (OSCC) is associated with poor survival outcomes, particularly in resource-limited settings, where treatment delays are prevalent. Oral metronomic chemotherapy (OMCT) utilising methotrexate and celecoxib is a potentially low-toxicity, cost-effective alternative in the neoadjuvant setting.

Methods: Thirteen patients diagnosed with stage 3 or 4 resectable OSCC were enrolled in this study. Each participant received one month of OMCT prior to surgical intervention and continued OMCT as maintenance therapy following treatment. The expression levels of PTGS2, VEGFA, VEGFB, KDR, CXCR1, and CXCR2 were analysed both before and after OMCT administration. Additionally, organ function and patient survival were evaluated to determine the efficacy and toxicity of treatment.

Results: PTGS2, VEGFA, VEGFB, and KDR were significantly upregulated in the tumour tissues at baseline. Post-OMCT, VEGFA, VEGFB, and KDR were significantly downregulated, whereas PTGS2 expression increased. No significant changes were observed in CXCR1 and CXCR2 expression. Liver, renal, and thyroid functions remained within normal limits. No adverse events were reported. The median overall survival was 22.1 months, and the median disease-free survival was 20 months. Upregulation of PTGS2, VEGFA, and VEGFB was correlated with improved outcomes.

Conclusion: OMCT has the potential to manage disease progression in patients with OSCC awaiting surgical intervention. It is characterised by low toxicity and may exert anti-angiogenic effects through modulation of the VEGF pathway. Further large-scale trials are necessary to substantiate these findings and to establish optimal treatment strategies.

Trial registration: The study was also registered in the Clinical Trials Registry of India (registration number: CTRI/2021/01/030256).

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口服节律化疗对局部晚期口腔鳞状细胞癌中前列腺素内过氧化物合酶-2 （PTGS2）介导的vegf信号通路的调节：简要报告

背景：局部晚期口腔鳞状细胞癌（OSCC）与较差的生存结果相关，特别是在资源有限的环境中，治疗延误普遍存在。口服节律化疗（OMCT）利用甲氨蝶呤和塞来昔布是一个潜在的低毒性，成本效益的替代方案，在新辅助设置。方法：本研究纳入13例诊断为3期或4期可切除的OSCC患者。每位参与者在手术前接受一个月的OMCT，并在治疗后继续接受OMCT作为维持治疗。分析OMCT给药前后PTGS2、VEGFA、VEGFB、KDR、CXCR1、CXCR2的表达水平。此外，评估器官功能和患者生存以确定治疗的疗效和毒性。结果：PTGS2、VEGFA、VEGFB和KDR在基线时在肿瘤组织中显著上调。omct后，VEGFA、VEGFB和KDR显著下调，而PTGS2表达升高。CXCR1和CXCR2的表达未见明显变化。肝、肾和甲状腺功能均在正常范围内。无不良事件报告。中位总生存期为22.1个月，中位无病生存期为20个月。PTGS2、VEGFA和VEGFB的上调与预后改善相关。结论：OMCT有可能控制等待手术治疗的OSCC患者的疾病进展。它的特点是低毒性，并可能通过调节VEGF途径发挥抗血管生成作用。需要进一步的大规模试验来证实这些发现并建立最佳治疗策略。试验注册：该研究也在印度临床试验注册中心注册（注册号：CTRI/2021/01/030256）。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Cancer Chemotherapy and Pharmacology 医学-药学

CiteScore

6.10

自引率

3.30%

发文量

116

审稿时长

2.5 months

期刊介绍： Addressing a wide range of pharmacologic and oncologic concerns on both experimental and clinical levels, Cancer Chemotherapy and Pharmacology is an eminent journal in the field. The primary focus in this rapid publication medium is on new anticancer agents, their experimental screening, preclinical toxicology and pharmacology, single and combined drug administration modalities, and clinical phase I, II and III trials. It is essential reading for pharmacologists and oncologists giving results recorded in the following areas: clinical toxicology, pharmacokinetics, pharmacodynamics, drug interactions, and indications for chemotherapy in cancer treatment strategy.