EMR3738, Faculté de Médecine Lyon-Sud, Université Lyon 1, BP12 69921, Oullins Cedex, France.
Cell Stress Chaperones. 2013 Sep;18(5):623-30. doi: 10.1007/s12192-013-0415-1. Epub 2013 Mar 19.
Despite the strong rationale for combining cytoreductive surgery (CRS) with hyperthermic intraperitoneal chemotherapy (HIPEC) in patients with peritoneal carcinomatosis, thermotolerance and chemoresistance might result from heat shock protein overexpression. The aim of the present study was thus to determine whether the heat shock protein 27 (Hsp27), a potential factor in resistance to treatment, could have a higher level in serum from patients under this combined therapy. Patients receiving CRS plus HIPEC for peritoneal carcinomatosis (group 1), patients with cancer or a history of cancer undergoing abdominal surgery (group 2), and patients without malignancies undergoing abdominal surgery (group 3) were included. Hsp27 serum levels were determined before and at different times following CRS and HIPEC using enzyme-linked immunosorbent assay. In group 1 (n = 25), the high Hsp27 levels, observed at the end of surgery compared with before (p < 0.0001), decreased during HIPEC, but remained significantly higher than before surgery (p < 0.0005). In groups 2 (n = 11) and 3 (n = 15), surgery did not significantly increase Hsp27 levels. A targeted molecular strategy, inhibiting Hsp27 expression in tumor tissue, could significantly reduce resistance to the combined CRS plus HIPEC treatment. This approach should be further assessed in a clinical phase I trial.
尽管在患有腹膜癌病的患者中联合细胞减灭术 (CRS) 和腹腔内热化疗 (HIPEC) 具有很强的理论依据，但热休克蛋白过表达可能导致热耐受性和化疗耐药性。因此，本研究的目的是确定治疗抵抗的潜在因素热休克蛋白 27 (Hsp27) 是否在接受联合治疗的患者血清中具有更高水平。将接受 CRS 加 HIPEC 治疗腹膜癌病的患者（第 1 组）、患有癌症或有腹部手术史的患者（第 2 组）和无恶性肿瘤接受腹部手术的患者（第 3 组）纳入研究。使用酶联免疫吸附试验在 CRS 和 HIPEC 前后不同时间测定 Hsp27 血清水平。在第 1 组（n = 25）中，与术前相比，手术结束时 Hsp27 水平较高（p < 0.0001），在 HIPEC 过程中降低，但仍明显高于术前（p < 0.0005）。在第 2 组（n = 11）和第 3 组（n = 15）中，手术未显著增加 Hsp27 水平。靶向分子策略，抑制肿瘤组织中 Hsp27 的表达，可显著降低对联合 CRS 加 HIPEC 治疗的耐药性。应在 I 期临床试验中进一步评估该方法。
