USP11通过去泛素化p53调控p53稳定性

研究目的：深入研究p53的泛素化及稳定性的调控。创新要点：发现一个新的调控p53去泛素化的酶USPll,它可以通过与p53的结合去泛素化并稳定p53,从而揭示了一个新的p53去泛素化调控的机制。研究方法：通过免疫共沉淀发现p53可以与USP11结合（图1a）,通过泛素化检测试验发现USPI1可以去泛素化p53（图3a和3b）,最后通过逆转录．聚合酶链式反应（RT—PCR）试验发现在DNA损伤后,USP11对p53转录活性的提高是非常重要的。     

p53基因蛋白在食道正常上皮及增生、癌变后表达的观察

目的 :探讨p5 3蛋白在食管癌组织发生中表达的意义。方法 :应用免疫组织化学技术检测 72例食管鳞状上皮癌 ,19例增生鳞状上皮及 17例正常食道鳞状上皮中 p5 3蛋白的表达。结果 :p5 3在食管癌组织中的阳性率为 4 7.95 % (35 / 72 ) ,在增生鳞状上皮中的阳性率为 36 .84 % (7/ 19) ,在正常食道鳞状上皮中的阳性率为 5 .88% (1/ 17) ,正常组与增生组和癌变组比较均有显著性差异 (P <0 .0 5 )。p5 3蛋白与癌的分化程度、淋巴结有无转移和浸润深度等指标均无明显关系。结论 :p5 3蛋白与食管癌的发生、发展有关。     

Association of p53 codon 72 polymorphism with liver metastases of colorectal cancers positive for p53 overexpression

Objective: To evaluate the association between p53 codon 72 polymorphism (R72P) and the risk of colorectal liver metastases. Methods: The p53 R72P genotype was identified by polymerase chain reaction-restriction fi'agment length poly-morphism (PCR-RFLP) method in 78 consecutive colorectal cancer patients with liver metastases and 214 age- and sex-matched cases with nonmetastatic colorectai cancer. Results: The R allele of the p53 R72P polymorphism was more frequently found in metastatic cases than in nonmetastatic cases (P=0.075). Carriers of the 72R allele had a 2.25-fold (95% CI (confidence inter-val)=1.05～4.83) increased risk of liver metastases. On the stratification analysis, 72R-carrying genotype conferred a 3.46-fold (95% CI=1.02～11.72) and a 1.05-fold (95% CI=0.36～3.08) increased risk of liver metastases for p53 overexpression-positive and negative colorectal cancers, respectively. Conclusion: These results demonstrate for the first time that the 72R allele of the p53 polymorphism has an increased risk for liver metastases in colorectal cancers positive for p53 overexpression.     

Prognostic significance of bcl-2 and p53 expression in colorectal carcinoma

INTRODUCTION Colorectal cancer is the most common cancer ofthe Western world and accounts for approx.Elevenpercent of all cancer deaths in the United States.Aswith other malignancies,colorectal adenocarcinomais thought to develop through the accumulation ofgenetic alterations that inhibit cell growth.Two of theoncogenes that have been implicated in this processare bcl-2and p53,the products of which are involvedin apoptosis,cell proliferation and tumor develop-ment(Garewal et al.,1996).S…     

Screen p53 mutations in hepatocellular carcinoma by FASAY: A novel splicing mutation

INTRODUCTION Hepatocellular carcinoma (HCC) is the sixth most common cancer in new cases per year (626 000) and the third most common cancer resulting in death (598 000) (Parkin et al., 2005). China is the country most seriously suffering from HCC, accounting for 55% of total cases and deaths worldwide per year. The clinical behavior of HCC is heterogeneous and difficult to predict, and in patients undergoing resec-tion, recurrence rates can be as high as 50% in two years and life ex…     

乳腺癌组织中c-erbB-2、p53和nm23蛋白表达及相互关系和意义

目的　探讨c erbB 2、p53和nm2 3蛋白在乳腺癌组织中的表达与乳腺癌临床病理参数、雌激素受体 (ER)、孕激素受体 (PR)的关系。方法　应用免疫组化ABC法对 5 5例乳腺癌组织中的c erbB 2、p53和nm2 3蛋白表达进行检测。结果　 5 5例乳腺癌中c erbB 2、p53及nm2 3的阳性率分别为 49 1 % (2 7/5 5 )、47 3 % (2 6 /5 5 )和 49 1 % (2 7/5 5 ) ,c erbB 2和p53蛋白在乳腺癌中的阳性率与肿瘤病理分级及淋巴结转移有显著意义 (P <0 0 5 ) ,与雌孕激素受体状况呈负相关 (P <0 0 1 )。nm2 3蛋白在乳腺癌中的阳性率与肿瘤病理分级、淋巴结转移有密切的关系 (p <0 0 5 ) ,与雌孕激素受体状呈正相关 (p <0 0 1 )。 70 9% (3 9/5 5 )肿瘤有上述蛋白的异常表达 ,其中 49 1 % (2 7/5 5 )的肿瘤同时有多个蛋白异常表达。结论　肿瘤的多因素分析比单因素分析更有价值 ,癌基因c erbB 2、nm2 3和抑癌基因p53蛋白的表达异常及协同作用在乳腺癌的发生发展中起重要使用     

大肠癌组织中p53基因的表达及意义

采用S-P免疫组织化学的方法,配对检测了37例大肠癌组织及同一病人的正常粘膜上皮中p53蛋白的表达情况。结果表明,p53蛋白表达阳性19例,阴性18例,阳性率为51.4％,而配对的大肠正常粘膜检测结果均呈p53阴性;p53蛋白表达与病人性别、年龄、Dukes分期等因素无明显相关性,而与淋巴结转移、浸润深度和不同分化程度等存在明显相关性。提示p53蛋白的检测可以作为大肠癌病人病情诊断和预后分析的辅助手段。     

新城疫病毒感染对小鼠肉瘤S180细胞p53蛋白的表达及细胞周期的影响

目的:研究新城疫病毒(NDV)感染对小鼠肉瘤S180细胞p53蛋白的表达及细胞周期的影响。方法:通过NDV体外感染小鼠肉瘤S180细胞,经倒置显微镜观察细胞形态变化,噻唑蓝(MTT)比色法检测小鼠肉瘤S180细胞的增殖状况;经流式细胞仪分析检测NDV体内感染后荷瘤鼠腹水中S180细胞分裂周期各时相的变化、细胞凋亡情况及细胞表面p53蛋白的表达情况。结果:NDV体内、外感染对小鼠肉瘤S180细胞的杀伤作用明显,NDV体内感染后荷瘤鼠腹水中S180细胞高表达p53蛋白,细胞凋亡率增加,G2/S期细胞减少,增殖指数(PI)降低,与阴性对照组比较有显著性差异(P<0.05)。结论:NDV感染可增强小鼠肉瘤S180细胞p53蛋白的表达,影响其细胞周期,诱导其凋亡且有较强的杀瘤作用。     

大肠癌P21、P53蛋白表达和K-ras基因、p53基因突变研究

采用免疫组化技术和PCR-SSCP技术对高、中、低分化大肠腺癌、癌旁粘膜、正常粘膜及大肠腺瘤型息肉的P21、P53蛋白表达和K-ras基因、p53基因突变进行了检测,检测结果高、中、低分化大肠腺癌、癌旁粘膜、正常粘膜和大肠腺瘤型息肉六组P21蛋白表达阳性率分别为57.5％、62.5％、75％、13.3％、6.7％、50％,p53蛋白表达阳性率分别为30％、37.5％、50％、4.4％、22％、33.3％,K-ras基因突变率分别为32.5％、37.5％、62.5％、2.2％、0％、16.7％,p53基因突变率分别为22.5％、25％、37.5％、0％、0％、0％.结果表明大肠腺癌P21、P53蛋白表达比大肠腺瘤增多,但增加不显著(P>0.05), 二组均比癌旁粘膜和正常粘膜P21、P53蛋白表达阳性率高(P<0.01);大肠腺癌K-ras基因和p53基因突变率比大肠腺瘤、癌旁粘膜和正常粘膜组显著增加(P<0.01);高、中、低分化大肠癌各组中,随恶性程度增加,P21、P53蛋白表达增加,K-ras基因和p53基因突变率增加,但均不显著(P>0.05).说明K-ras基因、p53基因突变及其蛋白表达产物P21、P53在细胞癌变、癌细胞恶性表型维持中起重要作用。     

Using an adaptation programme to introduce children to the early years of schooling in Slovakia

The article presents a new adaptation programme entitled ‘With a smile to school’ for pupils of the first year at primary schools. The adaptation programme comprises several methods and measures which are focused on the regulation of pupils’ adaptation process. The efficiency and effectiveness of the adaptation programme were verified through an experiment at selected primary schools in Slovakia in the school year 2016/2017. Based on the experiment results, a proposal for implementation of the adaptation programme to school practice was drawn up. The experiment results were evaluated by means of selected statistical methods.     

Emergent fields through adaptation and identity: overcoming social distance

We examine the inseparability of one’s environment with the elements of adaptation and identity. Specifically, we revisit the Project H.O.M.E. learning environment as we suggest that the entities of adaption and environment are not only binding, but also naturally in constant flux as they interact with each other. Contrary to nature, however, the social distance between the instructors and learners is the result of a human construct that often hinders adaptation and identity development. We address the factors that afforded participants overcoming social distance and ultimately cultivating a shift in the learning structure of Project H.O.M.E.

Organisational culture and values and the adaptation of academic units in Australian universities

This study explores connections between the organisational culture and values of academic units in Australian universities and their efforts to adapt to external environmental pressures. It integrates empirical findings from case studies with theories of organisational culture and values and adaptation. It identifies seven dimensions of academic unit’s organisational culture and values that influenced how case study academic units adapted. Then patterns of heterogeneity and homogeneity within these dimensions are noted and their associations with different modes of adaptation are discussed.     

Selecting learning tasks: Effects of adaptation and shared control on learning efficiency and task involvement

Complex skill acquisition by performing authentic learning tasks is constrained by limited working memory capacity [Baddeley, A. D. (1992). Working memory. Science, 255, 556–559]. To prevent cognitive overload, task difficulty and support of each newly selected learning task can be adapted to the learner’s competence level and perceived task load, either by some external agent, the learner herself, or both. Health sciences students (N = 55) participated in a study using a 2 × 2 factorial design with the factors adaptation (present or absent) and control over task-selection (program control or shared control). As hypothesized, adaptation led to more efficient learning; that is, higher learning outcomes combined with less effort invested in performing the learning tasks. Shared control over task-selection led to higher task involvement, that is, higher learning outcomes combined with more effort directly invested in learning. Adaptation also produced greater task involvement.     

口腔扁平苔藓上皮细胞凋亡和P53的表达及关系的研究

目的:目前,国内外对细胞凋亡与OLP、OLP与P53的关系有一定的研究,对OLP病变过程中凋亡与P53的关系暂未见报道。通过本研究,探讨OLP的可能发病机理。方法:采用甲基绿派诺宁法检测30例OLP患者及20例正常对照者口腔上皮细胞凋亡的阳性表达,用免疫组化SABC法检测P53,CyclinD1,ki67蛋白在两组上皮中的分布和表达。结果:(1)正常组与OLP组凋亡细胞阳性指数分别为0.69±0.25,1.98±1.07,t=5.28(P=0.03<0.05),有统计学意义;(2)正常组与OLP组P53蛋白阳性指数分别为5.15±3.12,20.73±10.56,t=6.35(P=0.001<0.05),有统计学意义;(2)P53阳性细胞指数与凋亡指数呈正相关。其相关系数分别为r=0.8209,P<0.01有统计学意义。结论:(1)细胞凋亡及凋亡相关因子P53蛋白的异常表达可能导致OLP的病变。(2)二者的平衡失调导致了OLP病变的反复发作。     

P53、C-myc蛋白在睾丸肿瘤中的表达及意义

目的:探讨P53、C-myc蛋白在睾丸肿瘤中的表达及其临床价值.方法:应用免疫组化技术法检测47例睾丸肿瘤P53、C-myc蛋白阳性表达水平.结果:发现P53、C-myc蛋白表达阳性率分别为44.7%(21/47)和51.1%(24/47),其阳性率与肿瘤临床分期呈显著正相关(P<0.05),P53蛋白阳性表达与C-myc蛋白阳性表达呈高度正相关(P<0.05).结论:联合检测P53、C-myc蛋白有助于判断睾丸肿瘤的恶性程度及患者的预后.     

基于小波神经网络的NLAR(p)过程的逼近

小波神经网络是近年来发展起来的一种逼近非线性函数的新型人工神经网络.特别是,正交尺度函数为基函数的小波神经网络更适合于函数逼近.本文在此基础上讨论了小波神经网络对非线性AR(p)过程的逼近.     

Adenovirus-mediated wild-type p53 gene transfer in combination with bronchial arterial infusion for treatment of advanced non-small-cell lung cancer, one year follow-up

Objective: In the present study, we have examined the safety and efficacy of recombinant adenovirus encoding human p53 tumor suppressor gene (rAd-p53) injection in patients with advanced non-small-cell lung cancer (NSCLC) in the combination with the therapy of bronchial arterial infusion (BAI). Methods: A total of 58 patients with advanced NSCLC were enrolled in a non-randomized, two-armed clinical trial. Of which, 19 received a combination treatment of BAI and rAd-p53 (the combo group), while the remaining 39 were treated with only BAI (the control group). Patients were followed up for 12 months, with safety and local response evaluated by the National Cancer Institute's Common Toxicity Criteria and response evaluation criteria in solid tumor (RECIST), respectively. Time to progression (TTP) and survival rates were also analyzed by Kaplan-Meier method. Results: In the combo group,19 patients received a total of 49 injections of rAd-p53 and 46 times of BAI, respectively, while 39 patients in the control group received a total of 113 times of BAI. The combination treatment was found to have less adverse events such as anorexia, nausea and emesis, pain, and leucopenia (P<0.05) but more arthralgia. fever, influenza-like symptom, and myalgia (P<0.05), compared with the control group. The overall response rates (complete response (CR)+partial response (PR)) were 47.3% and 38.4% for the combo group and the control group, respectively (P>0.05). Patients in the combo group had a longer TTP than those in the control group (a median 7.75 vs 5.5 months, P=0.018). However, the combination treatment did not lead to better survival, with survival rates at 3, 6, and 12 months in the combo group being 94.74%, 89.47%, and 52.63%, respectively, com-pared with 92.31%, 69.23%, and 38.83% in the control group (P=0.224). Conclusion: Our results show that the combination of rAd-p53 and BAI was well tolerated in patients with NSCLC and may have improved the quality of life and delayed the disease progression. A further study to better determine the efficacy of this combination therapy is warranted.     

P_(53)、Bcl-2在大肠癌中的表达及临床病理研究

目的:探讨P_(53)、Bcl-2基因蛋白在大肠癌中的表达及临床病理联系。方法:对88例大肠癌手术切除标本进行石蜡切片SP法免疫组织化学染色。结果:P_(53)、Bcl-2基因在大肠癌组织中表达率分别为55.68％(49/88)、63.63％(56/88),癌旁移行区粘膜上皮及腺体P_(53)、Bcl-2阳性表达率分别为3.12％(2/64)、31.25％(20/64),二者均有显著性差异(P<0.01)。P_(53)与大肠癌浸润深度有关(P<0.05),而与组织学类型、分化程度、有无淋巴结转移关系不显著(P>0.05)。Bcl-2的表达率在无淋巴结转移大肠原发癌中高于有淋巴结转移的大肠原发癌(P<0.01)。而在淋巴结转移癌组织中Bcl-2表达率高于原发癌组织Bcl-2表达率,差异有显著性(P<0.05)。结论:P_(53)、Bcl-2在大肠癌组织中均有高表达,可能与细胞恶变有密切关系,P_(53)与大肠癌浸润进展有关,与其它生物学行为关系不大;Bcl-2在大肠癌无淋巴结转移前有高表达,在淋巴结转移癌中的表达高于原发癌,提示Bcl-2的表达参与大肠癌转移的形成。     

E(p,q)与E_0(p,q)空间中解析函数的积分的代数性质

证明了E(p,q)和E0(p,q)中的函数的积分关于乘法构成一个代数