Meram Andrew T, Chen Jie, Patel Stavan, Kim Dongsoo D, Shirley Brett, Covello Paul, Coppola Domenico, Wei Eric X, Ghali Ghali, Kevil Christopher G, Shackelford Rodney E
Head & Neck Oncologic/Microvascular Reconstructive Surgery Department of Oral & Maxillofacial/Head & Neck Surgery, Louisiana State University Health Sciences Center, Shreveport, LA, U.S.A.
Department of Pathology and Translational Pathobiology Louisiana State University Health Sciences Center, Shreveport, LA, U.S.A.
Anticancer Res. 2018 Jul;38(7):3843-3852. doi: 10.21873/anticanres.12668.
BACKGROUND/AIM: Hydrogen sulfide (HS) and the enzymes that synthesize it, cystathionine-b-synthase, cystathionine γ-lyase, and 3-mercaptopyruvate, are increased in different human malignancies. Due to its short half-life, HS concentrations have not been directly measured in a human malignancy. Here we directly measured in vivo HS levels within oral squamous cell carcinoma (OSCC).
Punch biopsies of OSCC and benign mucosae from 15 patients were analyzed by HPLC, western blotting, and tissue microarray analyses.
HS concentrations were significantly higher in OSCC compared to adjacent benign oral mucosae. Western blot and tissue microarray studies revealed significantly increased cystathionine-b-synthase, cystathionine γ-lyase, and 3-mercaptopyruvate, phopho-Stat3, mitoNEET, hTERT, and MAPK protein levels in OSCC.
HS concentrations and the enzymes that synthesize it are significantly increased in OSCC. Here, for the first time HS concentrations within a living human malignancy were measured and compared to adjacent counterpart benign tissue.
背景/目的:硫化氢(HS)及其合成酶,如胱硫醚-β-合成酶、胱硫醚γ-裂解酶和3-巯基丙酮酸,在不同的人类恶性肿瘤中均有升高。由于其半衰期较短,尚未在人类恶性肿瘤中直接测量HS浓度。在此,我们直接测量了口腔鳞状细胞癌(OSCC)体内的HS水平。
对15例患者的OSCC和良性黏膜进行打孔活检,采用高效液相色谱法、蛋白质印迹法和组织芯片分析。
与相邻的良性口腔黏膜相比,OSCC中的HS浓度显著更高。蛋白质印迹和组织芯片研究显示,OSCC中胱硫醚-β-合成酶、胱硫醚γ-裂解酶、3-巯基丙酮酸、磷酸化信号转导和转录激活因子3、线粒体膜联蛋白、人端粒酶逆转录酶和丝裂原活化蛋白激酶的蛋白水平显著升高。
OSCC中HS浓度及其合成酶显著增加。在此,首次测量了人类活体恶性肿瘤中的HS浓度,并与相邻的对应良性组织进行了比较。