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肿瘤乏氧调控对初诊弥漫性大 B 细胞淋巴瘤(DLBCL)患者化疗后可溶性白细胞介素 2 受体(sIL-2R)水平的影响:一项随机临床试验。

The Impact of Tumor Hypoxia Modulation on sIL-2R Levels in Newly Diagnosed Diffuse Large B Cell Lymphoma (DLBCL) Patients Undergoing Chemotherapy: A Randomized Clinical Trial.

机构信息

Division of Hematology and Medical Oncology, Department of Internal Medicine, Faculty of Medicine Diponegoro University, Dr. Kariadi General Hospital, Semarang, Indonesia.

Department of Hematology/Medical Oncology, A. M. Parikesit Hospital and A. W. Sjahranie Hospital, Mulawarman School of Medicine, Samarinda, East Kalimantan, Indonesia.

出版信息

Asian Pac J Cancer Prev. 2024 Apr 1;25(4):1315-1324. doi: 10.31557/APJCP.2024.25.4.1315.

Abstract

OBJECTIVE

Tumor hypoxia induces the production of Hypoxia-Inducible Factor (HIF)-1 alpha, which interacts with NF-kB, leading to cancer proliferation and metastasis. This study investigated the effect of tumor hypoxia modulation using carbogen (95% O2 and 5% CO2) and nicotinamide on reducing soluble interleukin-2 receptor (sIL-2R) levels in newly diagnosed DLBCL patients with tissue overexpression of HIF-1α ≥10%.

MATERIAL AND METHODS

A prospective randomized controlled clinical trial was conducted at Dr. Kariadi Hospital in Semarang, Indonesia, from 2021 to 2022. Newly diagnosed DLBCL patients with tissue HIF-1α ≥10% were randomized into an intervention group (nicotinamide 2,000 mg + carbogen 10 liters/min during R-CHOP) and a control group (R-CHOP alone) for one cycle. sIL-2R levels were measured in the blood before and after intervention.

RESULTS

The intervention group showed a significant reduction in sIL-2R levels after chemotherapy (p=0.026), with 85% of samples exhibiting a decrease. In contrast, only 45% of samples in the control group demonstrated a decrease in sIL-2R levels (p=0.184). The median sIL-2R level decreased from 139.50 pg/mL to 70.50 pg/mL in the intervention group, while the control group exhibited an increase from 182.50 pg/mL to 250.00 pg/mL following one cycle of chemotherapy.

CONCLUSION

Tumor hypoxia modulation led to a significant decrease in serum sIL-2R levels, potentially through improvements in the crosstalk between hypoxia and inflammation pathways.

摘要

目的

肿瘤缺氧诱导缺氧诱导因子(HIF)-1α的产生,其与 NF-kB 相互作用,导致癌症增殖和转移。本研究探讨了使用碳化氧(95%O2 和 5%CO2)和烟酰胺调节肿瘤缺氧对降低新诊断的弥漫性大 B 细胞淋巴瘤(DLBCL)患者组织中 HIF-1α过表达≥10%患者可溶性白细胞介素-2 受体(sIL-2R)水平的影响。

材料和方法

本前瞻性随机对照临床试验于 2021 年至 2022 年在印度尼西亚三宝垄卡里迪亚医院进行。组织 HIF-1α过表达≥10%的新诊断 DLBCL 患者被随机分为干预组(尼烟酸 2000mg+R-CHOP 期间每分 10 升碳化氧)和对照组(单独 R-CHOP)进行一个周期。在干预前后测量血液中的 sIL-2R 水平。

结果

化疗后干预组 sIL-2R 水平显著降低(p=0.026),85%的样本下降。相比之下,对照组仅有 45%的样本 sIL-2R 水平下降(p=0.184)。干预组 sIL-2R 中位数从 139.50pg/mL 降至 70.50pg/mL,而对照组化疗后从 182.50pg/mL 增至 250.00pg/mL。

结论

肿瘤缺氧调节导致血清 sIL-2R 水平显著降低,可能是通过改善缺氧和炎症途径的串扰。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8295/11162723/193f4106b2d2/APJCP-25-1315-g001.jpg

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