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2
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7
Bromelain and acetylcysteine (BromAc) alone and in combination with gemcitabine inhibit subcutaneous deposits of pancreatic cancer after intraperitoneal injection.菠萝蛋白酶和乙酰半胱氨酸(BromAc)单独使用以及与吉西他滨联合使用时,腹腔注射后可抑制胰腺癌的皮下沉积。
Am J Transl Res. 2021 Dec 15;13(12):13524-13539. eCollection 2021.

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1
Enhancing the potency of chemotherapeutic agents by combination with bromelain and N-acetylcysteine - an in vitro study with pancreatic and hepatic cancer cells.通过与菠萝蛋白酶和N-乙酰半胱氨酸联合使用提高化疗药物的效力——一项针对胰腺和肝癌细胞的体外研究
Am J Transl Res. 2020 Nov 15;12(11):7404-7419. eCollection 2020.
2
A novel treatment of bromelain and acetylcysteine (BromAc) in patients with peritoneal mucinous tumours: A phase I first in man study.新型菠萝蛋白酶和乙酰半胱氨酸(BromAc)治疗腹膜黏液性肿瘤患者的研究:I 期首次人体研究。
Eur J Surg Oncol. 2021 Jan;47(1):115-122. doi: 10.1016/j.ejso.2019.10.033. Epub 2019 Oct 31.
3
The role of necroptosis in cancer biology and therapy.细胞坏死性凋亡在癌症生物学和治疗中的作用。
Mol Cancer. 2019 May 23;18(1):100. doi: 10.1186/s12943-019-1029-8.
4
Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries.全球癌症统计数据 2018:GLOBOCAN 对全球 185 个国家/地区 36 种癌症的发病率和死亡率的估计。
CA Cancer J Clin. 2018 Nov;68(6):394-424. doi: 10.3322/caac.21492. Epub 2018 Sep 12.
5
N-Acetylcysteine as an antioxidant and disulphide breaking agent: the reasons why.N-乙酰半胱氨酸作为一种抗氧化剂和二硫键断裂剂:原因如下。
Free Radic Res. 2018 Jul;52(7):751-762. doi: 10.1080/10715762.2018.1468564. Epub 2018 May 9.
6
Relevance of copper transporter 1 and organic cation transporters 1-3 for oxaliplatin uptake and drug resistance in colorectal cancer cells.铜转运蛋白 1 和有机阳离子转运蛋白 1-3 对结直肠癌细胞奥沙利铂摄取和耐药性的相关性。
Metallomics. 2018 Mar 1;10(3):414-425. doi: 10.1039/c7mt00334j. Epub 2018 Feb 8.
7
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Oncotarget. 2017 Nov 6;8(63):106888-106900. doi: 10.18632/oncotarget.22455. eCollection 2017 Dec 5.
8
The American Society of Colon and Rectal Surgeons Clinical Practice Guidelines for the Treatment of Colon Cancer.美国结肠和直肠外科医师协会结肠癌治疗临床实践指南。
Dis Colon Rectum. 2017 Oct;60(10):999-1017. doi: 10.1097/DCR.0000000000000926.
9
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Mol Cancer. 2017 Jul 6;16(1):116. doi: 10.1186/s12943-017-0691-y.
10
Efficacy and Toxicity of Low-Dose versus Conventional-Dose Chemotherapy for Malignant Tumors: a Meta-Analysis of 6 Randomized Controlled Trials.低剂量与常规剂量化疗治疗恶性肿瘤的疗效与毒性:6项随机对照试验的Meta分析
Asian Pac J Cancer Prev. 2017 Feb 1;18(2):479-484. doi: 10.22034/APJCP.2017.18.2.479.

在吉西他滨中添加菠萝蛋白酶和乙酰半胱氨酸可增强对人结肠癌细胞系LS174T的肿瘤抑制作用。

Addition of bromelain and acetylcysteine to gemcitabine potentiates tumor inhibition in human colon cancer cell line LS174T.

作者信息

Mekkawy Ahmed H, Pillai Krishna, Badar Samina, Akhter Javed, Ke Kevin, Valle Sarah J, Morris David L

机构信息

Department of Surgery, St. George Hospital Kogarah, NSW 2217, Australia.

Mucpharm Pty Ltd Australia.

出版信息

Am J Cancer Res. 2021 May 15;11(5):2252-2263. eCollection 2021.

PMID:34094682
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8167695/
Abstract

The combinations of Bromelain and Acetylcysteine (BromAc) with cytotoxics such as Gemcitabine, 5-Fluorouracil or Oxaliplatin have shown a dramatic reduction in IC50 values in a variety of cancers, including colon cancer, suggesting the possibility of effective treatment without undesired side effects. In the current study, we investigated whether a similar effect is present using the colorectal cell line LS174T. Animals after acclimatization were randomized and allocated equally in the groups for the different studies (safety, dose-escalation, and efficacy). Drugs were delivered by the intraperitoneal route and animals were monitored for wellbeing. Separately, an efficacy study was conducted with intraperitoneal drug delivery after intraperitoneal tumor induction. At the termination of the experiment, tumors and other tissues were collected for evaluation. BromAc was safe when delivered intraperitoneally in a rat model at the concentrations used. Subsequent investigations of these adjuvants in combination with Gemcitabine, Oxaliplatin, and 5-Fluorouracil in mice were also proven to be safe. Preliminary efficacy studies with Oxaliplatin and 5-Fluorouracil on tumor growth (LS174T) were negative. Gemcitabine was assessed with BromAc showing an almost 71% tumor inhibition compared to controls. This study indicates that Gemcitabine at 2 mg/kg in combination with BromAc 3 mg/300 mg/Kg was effective and safe, supporting its potential for future clinical application.

摘要

菠萝蛋白酶与乙酰半胱氨酸(BromAc)的组合,与吉西他滨、5-氟尿嘧啶或奥沙利铂等细胞毒性药物联合使用时,在包括结肠癌在内的多种癌症中显示出IC50值显著降低,这表明有可能实现有效治疗且无不良副作用。在本研究中,我们使用结肠直肠癌细胞系LS174T研究是否存在类似效果。适应环境后的动物被随机分组,并平均分配到不同研究(安全性、剂量递增和疗效)的组中。药物通过腹腔内途径给药,并监测动物的健康状况。另外,在腹腔内诱导肿瘤后,通过腹腔内给药进行疗效研究。实验结束时,收集肿瘤和其他组织进行评估。在大鼠模型中,以所用浓度腹腔内给药时,BromAc是安全的。随后在小鼠中对这些佐剂与吉西他滨、奥沙利铂和5-氟尿嘧啶联合使用的研究也被证明是安全的。奥沙利铂和5-氟尿嘧啶对肿瘤生长(LS174T)的初步疗效研究结果为阴性。吉西他滨与BromAc联合使用时,与对照组相比显示出近71%的肿瘤抑制率。本研究表明,2mg/kg的吉西他滨与3mg/300mg/Kg的BromAc联合使用是有效且安全的,支持其未来临床应用的潜力。