胡桃醌通过p38/JNK MAPK信号通路调控口腔鳞癌Tac8113细胞增殖和凋亡

目的:探讨胡桃醌通过p38/c-Jun氨基末端激酶(JNK)丝裂原活化蛋白激酶(MAPK)信号通路调控口腔鳞癌Tac8113细胞增殖和凋亡。方法:体外培养口腔鳞癌Tac8113细胞,分别给予终浓度为0,5,10,20μmol·L^-1的胡桃醌,继续培养24 h,检测细胞增殖、细胞凋亡和活性氧(ROS)水平,同时检测Tac8113细胞中p38、p-p38、JNK、p-JNK和Caspase-3蛋白表达水平。结果:与空白对照组比较,给予胡桃醌处理后,Tac8113细胞增殖率降低,Tac8113细胞凋亡率和ROS水平增加(P<0.05),且随着胡桃醌剂量增加,细胞增殖率、凋亡率和ROS变化越显著(P<0.05)。与空白对照组比较,给予胡桃醌处理后,Tac8113细胞p38和JNK蛋白表达变化不显著(P>0.05);p-p38、p-JNK和Caspase-3蛋白表达增加(P<0.05),且随着胡桃醌剂量增加,增加越显著(P<0.05)。结论:胡桃醌可能通过激活p38/JNK MAPK信号通路来诱导Tac8113细胞凋亡,从而达到抑制Tac8113细胞的目的。     

Human papillomavirus‐related basaloid squamous cell carcinoma of the bladder associated with genital tract human papillomavirus infection

Basaloid squamous cell carcinoma is a biologically aggressive neoplasm mainly found in the head and neck region. Recently, four cases of basaloid squamous cell carcinoma of the bladder have been reported, and three of them occurred in patients with neurogenic bladder, repeated catheterizations and human papillomavirus infection of the urinary tract. To the best of our knowledge, none of the patients affected by basaloid squamous cell carcinoma of the bladder described in the literature had documented genital involvement by human papillomavirus. Herein, we describe the case of a woman with neurogenic bladder affected by basaloid squamous cell carcinoma of the bladder and by a concomitant genital tract human papillomavirus infection.     

Connecting the P300 to the diagnosis and prognosis of unconscious patients

The residual consciousness of unconscious patients can be detected by studying the P300, a wave among event-related potentials. Previous studies have applied tones, the subject's name and other names as stimuli. However, the results were not satisfactory. In this study, we changed the constituent order of subjects' two-character names to create derived names. The subject's derived names, together with tones and their own names, were used as auditory stimuli in event-related potential experiments. Healthy controls and unconscious patients were included in this study and made to listen to these auditory stimuli. In the two paradigms, a sine tone followed by the subject's own name and the subject's derived name followed by the subject's own name were used as standard and deviant stimuli, respectively. The results showed that all healthy controls had the P300 using both paradigms, and that the P300 in the second paradigm had a longer latency and two peaks. All minimally conscious state patients had the P300 in the first paradigm and the majority of them had the P300 in the second paradigm. Most vegetative state patients had no P300. Patients who showed the P300 in the two paradigms had more residual consciousness, and patients with the two-peak P300 had a higher probability of awakening within a short time. Our experimental findings suggest that the P300 event-related potential could reflect the conscious state of unconscious patients.     

Delayed hippocampal neuronal death in young gerbil following transient global cerebral ischemia is related to higher and longer-term expression of p63 in the ischemic hippocampus

The tumor suppressor p63 is one of p53 family members and plays a vital role as a regulator of neuronal apoptosis in the development of the nervous system. However, the role of p63 in mature neuronal death has not been addressed yet. In this study, we first compared ischemia-induced effects on p63 expression in the hippocampal regions (CA1–3) between the young and adult gerbils subjected to 5 minutes of transient global cerebral ischemia. Neuronal death in the hippocampal CA1 region of young gerbils was significantly slow compared with that in the adult gerbils after transient global cerebral ischemia. p63 immunoreactivity in the hippocampal CA1 pyramidal neurons in the sham-operated young group was significantly low compared with that in the sham-operated adult group. p63 immunoreactivity was apparently changed in ischemic hippocampal CA1 pyramidal neurons in both ischemia-operated young and adult groups. In the ischemia-operated adult groups, p63 immunoreactivity in the hippocampal CA1 pyramidal neurons was significantly decreased at 4 days post-ischemia; however, p63 immunoreactivity in the ischemia-operated young group was significantly higher than that in the ischemia-operated adult group. At 7 days post-ischemia, p63 immunoreactivity was decreased in the hippocampal CA1 pyramidal neurons in both ischemia-operated young and adult groups. Change patterns of p63 level in the hippocampal CA1 region of adult and young gerbils after ischemic damage were similar to those observed in the immunohistochemical results. These findings indicate that higher and longer-term expression of p63 in the hippocampal CA1 region of the young gerbils after ischemia/reperfusion may be related to more delayed neuronal death compared to that in the adults.     

p38MAPK信号通路在鞘内注射利多卡因诱发糖尿病神经病变大鼠脊髓神经元凋亡中的作用

目的探讨p38丝裂原活化蛋白激酶(p38MAPK)信号通路在鞘内注射利多卡因诱发糖尿病(DM)神经病变(DNP)大鼠脊髓神经元凋亡中的作用。方法健康成年雄性SD大鼠50只,随机取10只为对照组(C组),余40只大鼠高糖高脂饮食+小剂量链脲佐菌素(STZ)腹腔注射建立2型DM,之后继续喂养28d,得35只DNP大鼠。将C组大鼠和DNP大鼠均进行鞘内置管。将置管成功的25只DNP大鼠采用随机数字法分为三组:NS组8只,鞘内注射重比重利多卡因10μl 3d+0.9%NaCl 10μl 5d;DM组8只,鞘内注射重比重利多卡因10μl 3d+2%二甲亚砜(DMSO)10μl 5d;SB组9只,鞘内注射重比重利多卡因10μl 3d+SB203580(SB203580需溶解在DMSO溶剂中)10μg/10μl 5d。于腹腔注射STZ前(C组鞘内置管前28d,T1)、STZ后28d(C组鞘内置管前,T2)、STZ后34d(T3)、STZ后39d(T4)时测定大鼠后爪机械缩足反射阈值(MWT);测完MWT立即处死大鼠,取L4~5的脊髓组织,光镜下观察其病理学结果,采用TUNEL法检测脊髓神经元凋亡的情况,采用ELISA法检测p-p38MAPK水平。结果 T2、T3时NS、DM和SB组MWT均明显低于C组(P0.05)。T4时NS和DM组MWT明显低于C和SB组(P0.05)。NS和DM组脊髓神经元凋亡指数,脊髓p-p38MAPK水平明显高于C和SB组(P0.05)。HE染色光镜下见NS组及DM组大鼠脊髓组织结构模糊,出现轻度的水肿,同时神经元的细胞核间隙轻微增宽;C组脊髓组织无明显病理改变;SB组大鼠脊髓组织病理损伤较轻,几乎正常。结论鞘内注射重比重利多卡因诱发DNP大鼠脊髓神经元的凋亡可能与进一步激活p38MAPK信号通路有关,且应用p38MAPK抑制剂SB203580对其有保护作用。     

大肠小扁平腺瘤、息肉样腺瘤p53、p21表达的研究

目的:观察大肠小扁平腺瘤p53、p21基因的表达,探讨小扁平腺瘤与息肉样腺瘤生物学行为的不同及其与大肠癌的关系.方法:利用免疫组化法研究50例小扁平腺瘤(A组)和30例息肉样腺瘤(B组)以及20例正常大肠黏膜(C组)的p53、P21基因表达情况.结果:p53、p21 在A、B、C 三组中阳性率分别为58%、56%;33.3%、36.7%;5%、10%.P53阳性率三组间差异有显著性(P＜0.05).p21阳性率:A、B组分别与C组有差异显著性(P＜0.05);A组高于B组,但卡方检验P＞0.05,无统汁学差异;A组进一步与B组中直径＜1.0cm的腺瘤的p21阳性率(30%)比较,差异有显著性(P＜0.05).结论:大肠小扁平腺瘤p53、p21基因的异常表达提示小扁平腺瘤的生物学行为与息肉样腺瘤有差别,可能更易于恶变.     

Mutations of p53 Tumor Suppressor Gene, Apoptosis, and Proliferation in Intrahepatic Cholangiocellular Carcinoma of the Liver

This study was performed to examine the correlation between mutations of the p53 tumor suppressor gene, the occurrence of apoptosis, and proliferation in cholangiocellular carcinoma of the liver. The results obtained were compared with pathohistological stage (according to UICC) and grade and with disease related survival rate. In 41 curatively (R0–) resected intrahepatic cholangiocellular carcinomas, the status of the p53 gene was determined by direct sequencing of exons 4–9 and immunohistochemically. Apoptosis was assessed using the in situ end labeling (ISEL) technique in combination with morphological criteria. Proliferation was analyzed by immunohistochemistry of MIB-1 (Ki-67), Proliferating cell nuclear antigen (PCNA), and silver-stained nucleolar organizer regions (AgNOR). The results obtained were compared with pathohistological stage (according to UICC), grade, several other histopathological factors, and survival rate. Mutations of p53 were detected in 15/41 carcinomas examined (37%). The most common change was a GC and CT transition, changing the hot spot amino acid determined by exons 4–8. Of these 15 tumors, 14 were also p53-positive by immunohistochemistry. In each carcinoma examined, we could demonstrate MIB-1, PCNA, and AgNOR dots and also apoptotic cells in variable proportions. The proliferation markers showed a significant correlation among themselves. In univariate survival analysis, the extent of the primary tumor, lymph node status, grade, and p53 were significant factors influencing patient survival. Performing multivariate Cox regression survival analysis, however, only the extent of primary tumor and lymph node status had an independent prognostic impact. Apoptosis was not related to patient prognosis or to other parameters examined. In conclusion, these results indicated that p53 could serve as an additional prognostic parameter that could provide auxiliary information for patient outcome. However, tumor stage and lymph node involvement were the strongest prognostic factors. We failed to establish apoptosis or other pathological parameters as factors predicting the prognosis of patients with cholangiocellular carcinoma.