结直肠癌患者血清类胰蛋白酶、类胰蛋白酶阳性肥大细胞与微血管密度之间的相关性：可能的生物学临床意义。
Correlation between serum tryptase, mast cells positive to tryptase and microvascular density in colo-rectal cancer patients: possible biological-clinical significance.
作者信息
Ammendola Michele, Sacco Rosario, Sammarco Giuseppe, Donato Giuseppe, Montemurro Severino, Ruggieri Eustachio, Patruno Rosa, Marech Ilaria, Cariello Marica, Vacca Angelo, Gadaleta Cosmo Damiano, Ranieri Girolamo
机构信息
Department of Medical and Surgery Science, Clinical Surgery Unit, University of Catanzaro "Magna Graecia" Medical School, Catanzaro, Italy; Surgery Unit, National Cancer Research Centre Istituto Tumori "Giovanni Paolo II", Bari, Italy.
Department of Medical and Surgery Science, Clinical Surgery Unit, University of Catanzaro "Magna Graecia" Medical School, Catanzaro, Italy.
出版信息
PLoS One. 2014 Jun 10;9(6):e99512. doi: 10.1371/journal.pone.0099512. eCollection 2014.
BACKGROUND
Tryptase is a serin protease stored and released from mast cells (MCs) that plays a role in tumour angiogenesis. In this study we aimed to evaluate serum tryptase levels in colo-rectal cancer (CRC) patients before (STLBS) and after (STLAS) radical surgical resection. We also evaluated mast cell density positive to tryptase (MCDPT) and microvascular density (MVD) in primary tumour tissue.
METHODS
A series of 61 patients with stage B and C CRC (according to the Astler and Coller staging system) were selected. Serum blood samples were collected from patients one day before and one day after surgery. Tryptase levels were measured using the UniCAP Tryptase Fluoroenzymeimmunoassay (Pharmacia, Uppsala, Sweden). Tumour sections were immunostained with a primary anti-tryptase antibody (clone AA1; Dako, Glostrup, Denmark) and an anti CD-34 antibody (QB-END 10; Bio-Optica Milan, Italy) by means of immunohistochemistry and then evaluated by image analysis methods.
RESULTS
The mean ± s.d. STLBS and STLAS was 5.63±2.61 µg/L, and 3.39±1.47 µg/L respectively and a significant difference between mean levels was found: p = 0.000 by t-test. The mean ± s.d. of MCDPT and MVD was 8.13±3.28 and 29.16±7.39 respectively. A strong correlation between STLBS and MVD (r = 0.83, p = 0.000); STLBS and MCDPT (r = 0.60, p = 0.003); and MCDPT and MVD (r = 0.73; p = 0.001) was found.
CONCLUSION
Results demonstrated higher STLBS in CRC patients, indicating an involvement of MC tryptase in CRC angiogenesis. Data also indicated lower STLAS, suggesting the release of tryptase from tumour-infiltrating MCs. Serum tryptase levels may therefore play a role as a novel bio-marker predictive of response to radical surgery. In this context tryptase inhibitors such as Gabexate and Nafamostat Mesilate might be evaluated in adjuvant clinical trials as a new anti-angiogenic approach.
背景
类胰蛋白酶是一种储存于肥大细胞（MCs）并由其释放的丝氨酸蛋白酶，在肿瘤血管生成中发挥作用。在本研究中，我们旨在评估结直肠癌（CRC）患者根治性手术切除前（STLBS）和后（STLAS）的血清类胰蛋白酶水平。我们还评估了原发性肿瘤组织中类胰蛋白酶阳性的肥大细胞密度（MCDPT）和微血管密度（MVD）。
方法
选取61例B期和C期CRC患者（根据阿斯特勒和科勒分期系统）。在手术前一天和手术后一天采集患者的血清血样。使用UniCAP类胰蛋白酶荧光酶免疫测定法（瑞典乌普萨拉法玛西亚公司）测量类胰蛋白酶水平。通过免疫组织化学用抗类胰蛋白酶一抗（克隆AA1；丹麦格罗斯楚普达科公司）和抗CD-34抗体（QB-END 10；意大利米兰生物光学公司）对肿瘤切片进行免疫染色，然后通过图像分析方法进行评估。
结果
STLBS和STLAS的均值±标准差分别为5.63±2.61μg/L和3.39±1.47μg/L，发现均值水平之间存在显著差异：经t检验，p = 0.000。MCDPT和MVD的均值±标准差分别为8.13±3.28和29.16±7.39。发现STLBS与MVD之间存在强相关性（r = 0.83，p = 0.000）；STLBS与MCDPT之间存在强相关性（r = 0.60，p = 0.003）；MCDPT与MVD之间存在强相关性（r = 0.73；p = 0.001）。
结论
结果表明CRC患者的STLBS较高，表明MC类胰蛋白酶参与了CRC血管生成。数据还表明STLAS较低，提示类胰蛋白酶从肿瘤浸润性MCs中释放。因此，血清类胰蛋白酶水平可能作为一种预测根治性手术反应的新型生物标志物发挥作用。在这种情况下，可在辅助临床试验中评估诸如加贝酯和甲磺酸萘莫司他等类胰蛋白酶抑制剂作为一种新的抗血管生成方法。
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