ABSTRACT
Objective:To investigate the predictive value of KAI1 expression in colon cancer tissues for tumor recurrence.Methods:Ninety-two pathological tissue samples were collected from patients undergoing radical operation for colon cancer in Tangshan People's Hospital from August 2010 to November 2011. According to the results of follow-up, the patients were divided into recurrent group (33 cases) and non-recurrent group (59 cases). KAI1 expression in tumor tissues was detected by immunohistochemistry. χ2 test was used to analyze the relationship between KAI1 expression in colon cancer tissues and clinicopathological characteristics of patients with colon cancer. Spearman correlation test was used to analyze the relationship between KAI1 expression in colon cancer tissues and the recurrence time of patients. Cox proportional hazards model was used to analyze the related factors affecting postoperative recurrence of colon cancer. Results:KAI1 expression in tumor tissues in the recurrent group was lower than that in the non-recurrent group [39.39% (13/33) vs. 62.71% (37/59), χ2 = 4.638, P = 0.031]. KAI1 expression was not associated with patients' gender, age and tumor maximum diameter (all P > 0.05), but related to the tumor differentiation and lymphatic metastasis [high and medium differentiation vs. low differentiation: 70.3% (26/37) vs. 43.6% (24/55), χ2 = 6.324, P =0.012; lymph node metastasis vs. non-lymph node metastasis: 43.2% (19/44) vs. 64.6% (31/48), χ2 = 4.238, P = 0.039]. KAI1 expression in tumor tissues was positively correlated with tumor recurrence time ( r = 0.845, P < 0.05). Cox multivariate analysis showed that the low differentiation of the tumor, lymph node metastasis and negative expression of KAI1 in colon cancer tissues were independent risk factors for recurrence of colon cancer after surgery ( HR = 1.736, 95% CI 1.598-5.391, P = 0.019; HR =1.526, 95% CI 1.175-3.029, P = 0.037; HR = 1.799,95% CI 1.756-5.825, P = 0.013). Conclusion:Low KAI1 expression in colon cancer tissues is closely related to colon cancer recurrence, and the detection of KAI1 expression in colon cancer tissues has certain predictive value for tumor recurrence.
ABSTRACT
Objective To study the effects of melatonin (MT) on mitochondrial autophagy in neonatal rats with hypoxic-ischemic brain damage (HIBD).Method Animal model of HIBD was established.Forty-five 7-day-old Sprague-Dawley (SD) rats were randomly assigned to sham operation group and HIBD group.Brain tissue were taken at 0,2,4,6,8,12,24 and 48 h after model preparation,and the expressions of mitochondrial autophagy-related protein Bnip3 and autophagy-related protein LC3-Ⅱ were detected.Seventy-two 7-day-old SD rats were randomly assigned to sham operation group,HIBD group and post-HIBD treatment group (3-MA,Mdivi-I,Rapa,MT,3-MA + MT,Mdivi-1 + MT,Rapa + MT).The sizes of cerebral infarction after different treatment were detected using triphenyltetrazolium chloride staining (TIC).Primary cortical cells of fetal SD rats (embryonic day:17 ～ 19 d) were cultured.JC-I staining was used to detect mitochondrial membrane potential and immunofluorescence method was used to observe mitochondrial autophagy.The Oxygen glucose deprivation/reperfusion/R (OGD) model was prepared.Autophagy inhibitor 3-MA,mitochondrial autophagy inhibitor Mdivi-1,autophagy activator Rapa,and MT were applied and Bnip3 and LC3-Ⅱ expressions and CCK8 (Cell Counting Kit CCK 8) for cell viability assay were examined.Result TTC staining results showed significant white infarcts in the tissue of HIBD group after hypoxia-ischemia,especially in the 3-MA and Mdivi-1 groups,and the infarcts were smaller in Rapa group and groups with MT treatment,the differences were statistical significant (P ＜ 0.05).Compared with the sham operation group,the expressions of Bnip3 and LC3-Ⅱ in the HIBD group were significantly increased (P ＜ 0.05).Compared with the normal group,the expressions of Bnip3 and LC3-Ⅱ in the OGD/R group were increased (P ＜0.05).The activities of 3-MA and Mdivi-1 cells decreased significantly,the mitochondrial membrane potential decreased,and mitochondrial autophagy were decreased (P ＜ 0.05).The cell activity,mitochondrial membrane potential,and mitochondrial autophagy of Rapa group were increased (P ＜ 0.05).The cell viability,Bnip3 and LC3-Ⅱ expressions were increased in groups with MT intervention (P ＜ 0.05).Conclusion MT may play an important protective role in the early stage of brain injury by enhancing mitochondrial autophagy of HIBD,which provide a theoretical basis for the study of specific related mechanisms.
ABSTRACT
Objective To study the expression of Ca-A/K channel-related molecules glutamate receptor 2 and 1(GluR2/1) in hippocampus tissues of neonatal rats with hypoxic-ischemic brain damage (HIBD). Methods A total of 60 7-day-old Sprague-Dawley rats were randomly divided into sham operation group and HIBD group. Hippocampal tissues were obtained at 0 h, 1 h, 6 h, 24 h, 48 h and 72 h after HIBD. The expression of GluR2, GluR1 and autophagy marker protein Beclin-1, LC3 were detected by Western blot assay. Results Edema and focal softening and necrosis were observed 6 h after HIBD in the brains of neonatal rats. Compared with Con group, at each time point, the expression levels of GluR2 were lower while the levels of GluR1, Beclin-1 and LC3 were higher significantly in HIBD group (P<0.05). The protein levels of LC3, Beclin-1, GluR1 and GluR2 in hippocampus tissues of HIBD group were significantly different among different time points after the estab-lishment of HIBD model (F=10.65~701.14, P<0.01). The protein level of GluR2 was decreased from 1 h to 24 h after HIBD and reached the lowest level at 24 h. The levels of GluR1, Beclin-1 and LC3 were increased at 6 h, plateaued at 24 h and remained there until 48 h. The levels of these proteins returned back to the initial level at 72 h. Conclusions Ca-A/K channel-related mol-ecules GluR2 and GluR1 play important roles in the autophagic cell death of hippocampus tissues in neonatal rats with hypoxic-ischemic brain damage.