Jefferson Pancreas, Biliary, and Related Cancer Center, Department of Surgery, Thomas Jefferson University, Philadelphia, PA.
Jefferson Pancreas, Biliary, and Related Cancer Center, Department of Surgery, Thomas Jefferson University, Philadelphia, PA.
J Am Coll Surg. 2020 Apr;230(4):659-667. doi: 10.1016/j.jamcollsurg.2019.12.033. Epub 2020 Feb 11.
Chronic obstructive respiratory disorders (ORDs) are linked to increased rates of cancer-related deaths. Little is known about the effects of hypercapnia (elevated CO) on development of pancreatic ductal adenocarcinoma (PDAC) and drug resistance.
Two PDAC cell lines were exposed to normocapnic (5% CO) and hypercapnic (continuous/intermittent 10% CO) conditions, physiologically similar to patients with active ORD. Cells were assessed for proliferation rate, colony formation, and chemo-/radiotherapeutic efficacy. In a retrospective clinical study design, patients with PDAC who had undergone pancreatic resection between 2002 and 2014 were reviewed. Active smokers were excluded to remove possible smoking-related protumorigenic influence. Clinical data, pathologic findings, and survival end points were recorded. Kaplan-Meier and Cox regression analyses were performed.
Exposure to hypercapnia resulted in increased colony formation and proliferation rates in vitro in both cell lines (MIA-PaCa-2: 111% increase and Panc-1: 114% increase; p < 0.05). Hypercapnia exposure induced a 2.5-fold increase in oxaliplatin resistance (p < 0.05) in both cell lines and increased resistance to ionizing radiation in MIA-PaCa-2 cells (p < 0.05). Five hundred and seventy-eight patients were included (52% were male, median age was 68.7 years [interquartile range 60.6 to 76.8 years]). Cox regression analysis, assessing TNM staging, age, sex, and ORD status, identified ORD as an independent risk factor for both overall survival (hazard ratio 1.64; 95% CI, 1.2 to 2.3; p < 0.05) and disease-free survival (hazard ratio 1.68; 95% CI, 1.06 to 2.67).
PDAC cells exposed to hypercapnic environments, which is common in patients with ORD, showed tumor proliferation, radioresistance, and chemoresistance. Patients with a history of ORD had a worse overall prognosis, suggesting that hypercapnic conditions play a role in the development and progression of PDAC and stressing the need for patient-tailored care.
慢性阻塞性呼吸道疾病（ORDs）与癌症相关死亡率的增加有关。人们对高碳酸血症（CO 升高）对胰腺导管腺癌（PDAC）发展和耐药性的影响知之甚少。
将两种 PDAC 细胞系暴露于常碳酸（5%CO）和高碳酸（连续/间歇 10%CO）条件下，这与患有活跃 ORD 的患者的生理情况相似。评估细胞的增殖率、集落形成和化疗/放疗效果。在回顾性临床研究设计中，回顾了 2002 年至 2014 年间接受胰腺切除术的 PDAC 患者。排除活跃吸烟者，以消除可能的与吸烟相关的促肿瘤影响。记录临床数据、病理发现和生存终点。进行 Kaplan-Meier 和 Cox 回归分析。
在两种细胞系中，暴露于高碳酸环境导致集落形成和增殖率增加（MIA-PaCa-2：增加 111%；Panc-1：增加 114%；p < 0.05）。高碳酸暴露导致奥沙利铂耐药性增加 2.5 倍（p < 0.05），并增加 MIA-PaCa-2 细胞对电离辐射的耐药性（p < 0.05）。纳入了 578 名患者（52%为男性，中位年龄为 68.7 岁[四分位距 60.6 至 76.8 岁]）。Cox 回归分析评估 TNM 分期、年龄、性别和 ORD 状态，确定 ORD 是总生存期（危险比 1.64；95%置信区间，1.2 至 2.3；p < 0.05）和无病生存期（危险比 1.68；95%置信区间，1.06 至 2.67）的独立危险因素。
暴露于高碳酸环境中的 PDAC 细胞，这在患有 ORD 的患者中很常见，表现出肿瘤增殖、放射抵抗和化疗耐药性。有 ORD 病史的患者总体预后较差，这表明高碳酸条件在 PDAC 的发展和进展中发挥作用，并强调需要针对患者的护理。
