ABSTRACT
Objective To investigate the expression of vascular cell adhesion molecule-1 (VC.AM-1) in oxidative stress induced hypertrophic chondrocytes,in Kaschin-Beck disease (KBD) patients and in rat fed with T-2 toxin under selenium deficient conditions in order to analyze the relationship between VCAM-1 biological function and the dysregulation of chondrocyte differentiation in KBD.Methods The ATDC5 was cultured in 1％ ITS solution (10 mg/L insulin,5.5 mg/L transferrin,and 6.7 μg/L sodium selenite) for 21 days,and stimulated with 3-morpholino-sydnonimine (SIN-1,a nitric oxide [NO] donor) to obtain the oxidative stress induced hypertrophic chondrocytes.Real-time PCR was used to detect VCAM-1 mRNA in hypertrophic chondrocytes induced by different concentrations of SIN-1.The expressions of VCAM-I in articular cartilage of child and adult KBD patients and KBD animal model were determined via the immunohistochemical method,and KBD cartilage samples were obtained in KBD areas from KBD child who had died or from adults who had had surgery.Results After treatment of hypertrophic chondrocytes (ATCD5 cells) with SIN-1 (0,1,3,5 mmol/L),VCAM-1 mRNA levels (1.00 + 0.00,1.22 ± 0.20,0.71 ± 0.22,0.37 ± 0.16) were decreased in a dose-dependent manner when compared with the control group (F =27.788,P ＜ 0.05).The densities of VCAM-1 positive cells in superficial and middle zones of the articular cartilage of children KBD patients [(16.08 ± 5.20)％,(19.20 ± 9.71)％] were higher than those of control group [(0.00 ± 0.00)％,(0.00 ± 0.00)％],while that in the deep zone [(7.00 ± 4.40)％] in children KBD patients was significantly lower than that of control [(51.60 ± 20.58)％,tS/M/D=-10.972,-6.249,6.564,P ＜ 0.05].The positive cell density of VCAM-1 in the adult patients was significantly increased in the superficial zone [(7.92 ± 4.29)％ vs (3.12 ± 1.12)％] but significantly decreased in the middle zone [(17.54 ± 8.27)％ vs (31.75 ± 13.30)％] of articular cartilage when compared with that of control group (tS/D =-3.824,3.037,P ＜ 0.05).In articular cartilage of the four groups of KBD rats,the density of VCAM-1 positive cells in the superficial zone was significantly higher in low selenium diet group,T-2 toxin diet group and selenium deficient plus T-2 toxin diet group [(4.11 ± 1.90)％,(5.00 ±2.02)％,(2.78 ± 1.48)％ vs (1.89 ± 1.76)％,P ＜ 0.05].But the density of VCAM-1 positive cells in the deep zone was significantly lower in rat feed with selenium diet and selenium deficient plus T-2 toxin diet [(13.67 ± 2.45)％,(20.56 ± 7.42)％] than that of control group [(33.00 ± 12.57)％,P ＜ 0.05] in the epiphyseal cartilage of KBD rats.Conclusions The level of VCAM-1 is decreased both in the SIN-1 induced hypertrophic chondrocytes and in the deep zone of articular cartilage in KBD patients and in rat fed with T-2 toxin and selenium-deficient diets.VCAM-1 may be associated with the death of deep zone chondrocytes and differentiation disorder in cartilage.
ABSTRACT
Esophageal squamous-cell carcinoma (ESCC) is one of the most lethal malignancies in the world and occurs at particularly higher frequency in China. While several genome-wide association studies (GWAS) of germline variants and whole-genome or whole-exome sequencing studies of somatic mutations in ESCC have been published, there is no comprehensive database publically available for this cancer. Here, we developed the Chinese Cancer Genomic Database-Esophageal Squamous Cell Carcinoma (CCGD-ESCC) database, which contains the associations of 69,593 single nucleotide polymorphisms (SNPs) with ESCC risk in 2022 cases and 2039 controls, survival time of 1006 ESCC patients (survival GWAS) and gene expression (expression quantitative trait loci, eQTL) in 94 ESCC patients. Moreover, this database also provides the associations between 8833 somatic mutations and survival time in 675 ESCC patients. Our user-friendly database is a resource useful for biologists and oncologists not only in identifying the associations of genetic variants or somatic mutations with the development and progression of ESCC but also in studying the underlying mechanisms for tumorigenesis of the cancer. CCGD-ESCC is freely accessible at http://db.cbi.pku.edu.cn/ccgd/ESCCdb.
Subject(s)
Aged , Female , Humans , Male , Middle Aged , Asian People , Genetics , China , Epidemiology , Databases, Genetic , Esophageal Squamous Cell Carcinoma , Genetics , Genetic Predisposition to Disease , Genetic Variation , Genome-Wide Association Study , Internet , Polymorphism, Single Nucleotide , Genetics , User-Computer InterfaceABSTRACT
Objective To study the expression of tumor stem cell marker aldehyde dehydrogenase 1 (ALDH1)in invasive bladder cancer tissue and to clarify its relationship with the biological behavior of bladder cancer. Methods The ALDH1 expression in 109 cases of primary invasive carcinomas specimens (case group)and 20 cases of normal bladder tissue surrounding cancer (control group)was detected by immunohistochemistry. At the same time,the ALDH1 expression in 6 cases of metastatic pelvic lymph node tissue and 20 cases of non-metastatic pelvic lymph node tissue was detected. The relationship between the ALDH1 expression and the chinicopathological charateristics of invasive bladder cancer and its influence in the survival rate and disease-free survival were analyzed. Results The positive rates of ALDH1 expression in bladder cancer tissue and normal bladder tissue were 33.94%(37/109)and 5.00% (1/20),respectively,there was significant different between them (P<0.01);they were 19.05% (8/42)and 43.28% (29/67)in the cases with non muscle invasive and nmuscle invasive bladder cancer, respectively,there was significant difference (P<0.01);they were 13.04% (3/23)and 39.53% (34/86)in the cases of bladder cancer with low grade and high grade,respectively,there was significant difference (P<0.05);they were 50.00% (3/6)and 12.90% (4/31)in the tissue of bladder cancer with metastatic lymph nodes and non metastatic ones,respectively,there was significant difference (P<0.05);they were 50.00% (3/6)and 0.00%(0/20)in the metastatic lymph nodes and non metastatic ones,respectively,there was significant difference (P<0.01).The overall survival rate in the patients with positive ALDH1 expression was 64.9% while it was 84.7% in negative ones,there was significant difference (P<0.05);the disease-free Survival was 51.4% and 75% in the patients with positive and negative ALDH1 groups,respectively,there was significant difference (P<0.05). Conclusion The high expression of tumor stem cell marker ALDH1 is associated with staging, grading and prognosis of invasive bladder cancer.ALDH1 may play a role in the tumorigenesis,progression and metastasis of bladder cancer.