Tanshinone ⅡA improves Alzheimer’s disease via RNA nuclearenriched abundant transcript 1/microRNA-291a-3p/member RAS oncogene family Rab22a axis

BACKGROUND Alzheimer’s disease(AD)is a neurodegenerative condition characterized by oxidative stress and neuroinflammation.Tanshinone ⅡA(Tan-ⅡA),a bioactive compound isolated from Salvia miltiorrhiza plants,has shown potential neuroprotective effects;however,the mechanisms underlying such a function remain unclear.AIM To investigate potential Tan-ⅡA neuroprotective effects in AD and to elucidate their underlying mechanisms.METHODS Hematoxylin and eosin staining was utilized to analyze structural brain tissue morphology.To assess changes in oxidative stress and neuroinflammation,we performed enzyme-linked immunosorbent assay and western blotting.Additionally,the effect of Tan-ⅡA on AD cell models was evaluated in vitro using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay.Genetic changes related to the long non-coding RNA(lncRNA)nuclear-enriched abundant transcript 1(NEAT1)/microRNA(miRNA,miR)-291a-3p/member RAS oncogene family Rab22a axis were assessed through reverse transcription quantitative polymerase chain reaction.RESULTS In vivo,Tan-ⅡA treatment improved neuronal morphology and attenuated oxidative stress and neuroinflammation in the brain tissue of AD mice.In vitro experiments showed that Tan-ⅡA dose-dependently ameliorated the amyloid-beta 1-42-induced reduction of neural stem cell viability,apoptosis,oxidative stress,and neuroinflammation.In this process,the lncRNA NEAT1-a potential therapeutic target-is highly expressed in AD mice and downregulated via Tan-ⅡA treatment.Mechanistically,NEAT1 promotes the transcription and translation of Rab22a via miR-291a-3p,which activates nuclear factor kappa-B(NF-κB)signaling,leading to activation of the pro-apoptotic B-cell lymphoma 2-associated X protein and inhibition of the anti-apoptotic B-cell lymphoma 2 protein,which exacerbates AD.Tan-ⅡA intervention effectively blocked this process by inhibiting the NEAT1/miR-291a-3p/Rab22a axis and NF-κB signaling.CONCLUSION This study demonstrates that Tan-ⅡA exerts neuroprotective effects in AD by modulating the NEAT1/miR-291a-3p/Rab22a/NF-κB signaling pathway,serving as a foundation for the development of innovative approaches for AD therapy.

The role of tazarotene-induced gene 1 in carcinogenesis:is it a tumor suppressor gene or an oncogene?

Tazarotene-induced gene 1(TIG1)is induced by a derivative of vitamin A and is known to regulate many important biological processes and control the development of cancer.TIG1 is widely expressed in various tissues;yet in many cancer tissues,it is not expressed because of the methylation of its promoter.Additionally,the expression of TIG1 in cancer cells inhibits their growth and invasion,suggesting that TIG1 acts as a tumor suppressor gene.However,in some cancers,poor prognosis is associated with TIG1 expression,indicating its protumor growth characteristics,especially in promoting the invasion of inflammatory breast cancer cells.This review comprehensively summarizes the roles of the TIG1 gene in cancer development and details the mechanisms through which TIG1 regulates cancer development,with the aim of understanding its various roles in cancer development.

Concomitant epidermal growth factor receptor mutation/c-ros oncogene 1 rearrangement in non-small cell lung cancer: A case report

BACKGROUND Epidermal growth factor receptor(EGFR)mutation and c-ros oncogene 1(ROS1)rearrangement are key genetic alterations and predictive tumor markers for non-small cell lung cancer(NSCLC)and are typically considered to be mutually exc-lusive.EGFR/ROS1 co-mutation is a rare event,and the standard treatment appr-oach for such cases is still equivocal.CASE SUMMARY Herein,we report the case of a 64-year-old woman diagnosed with lung adenocar-cinoma,with concomitant EGFR L858R mutation and ROS1 rearrangement.The patient received two cycles of chemotherapy after surgery,but the disease prog-ressed.Following 1-month treatment with gefitinib,the disease progressed again.However,after switching to crizotinib,the lesion became stable.Currently,crizotinib has been administered for over 53 months with a remarkable treatment effect.CONCLUSION The efficacy of EGFR tyrosine kinase inhibitors and crizotinib was vastly different in this NSCLC patient with EGFR/ROS1 co-mutation.This report will aid future treatment of such patients.

子宫内膜息肉与子宫内膜癌中Ki-ras基因表达及临床意义

目的 探讨 Ki- ras基因激活与子宫内膜癌中的发生发展关系及子宫内膜息肉与子宫内膜癌的关系。方法 对子宫内膜癌及癌前病变组织进行 Ki- ras蛋白免疫组化测定 ,并利用 PCR技术检测 Ki- ras基因第一外显子 1 2密码子突变。结果 Ki- ras蛋白广泛存在于子宫内膜癌和癌前病变组织中 ,癌前病变 Ki- ras表达为 1 1 .9% ,癌组为 62 .96% ,P<0 .0 5。Ki- ras表达与细胞恶性程度呈正相关。 PCR- RFLP检测与免疫组化结果类似。结论 1 .Ki- ras基因激活可导致细胞周期增殖失控 ,是内膜癌发生发展的一个重要环节 ;2 .动态观测子宫内膜息肉中的 p2 1 ras表达阳性者 ,对子宫内膜癌的早期发现可能有积极意义。

杂色曲霉素致人胚肺细胞p53及Ki-ras基因突变研究

为探讨中国恶性肿瘤高发区粮食中优势污染霉菌毒素—杂色曲霉素 (Sterigmatocystin,ST)的致癌作用 ,运用银染 PCR- SSCP方法分析了不同浓度的 ST(1μg/ ml和 3μg/ m l)对体外培养的人胚肺细胞恶性转化过程中抑癌基因 p5 3第 5、6、7、8外显子及癌基因 Ki- ras的突变情况。结果显示 ST处理后第 2 2周 ,人胚肺成纤维细胞 p5 3基因的第 8外显子和 Ki- ras癌基因均出现异常泳动带型 ,表明 ST诱发了抑癌基因 p5 3及癌基因 Ki- ras突变 ,进一步证实了 ST对人肺组织的致癌作用。

非小细胞肺癌Ki-ras基因第12位密码子突变与吸烟的关系

目的探讨Ｋｉ－ｒａｓ基因突变在肺癌不同病理型中的分布及与吸烟的关系。方法采用聚合酶链反应－单链构象多态性分析（ＰＣＲ－ＳＳＣＰ）检测４０例肺癌病理标本Ｋｉ－ｒａｓ基因第１２位密码子点突变。结果检出６例突变者，突变率为１５％。腺癌和鳞癌的突变率分别为１７．４％（４／２３）和１３．３％（２／１５），无显著性差异（χ２＝１．４３，Ｐ＞０．０５）。有吸烟史的肺癌突变率为６．４５％（２／３１），非吸烟肺癌中突变率为４４．４％（４／９）。结论在非小细胞肺癌中未发现Ｋｉ－ｒａｓ基因突变与吸烟有关。

突变Ki-ras基因修饰的肺癌DC疫苗的体外抗癌活性

目的 探讨以Ki ras基因 12位密码子点突变为靶点 ,构建DC Ad Ki ras(V12 )肺癌疫苗及其抗肺癌免疫治疗的可能性。方法 应用重组腺病毒的方法将人Ki ras基因 12位密码子点突变 (由甘氨酸转变为缬氨酸 )的cDNA导入DC ,构建DC Ad Ki ras(V 12 )肺癌疫苗 ,以流式细胞术、PCR、MLR和CTL等方法检测其免疫活性。结果 ( 1)DC Ad Ki ras(V12 )肺癌疫苗不仅能表达人Ki ras(V12 )基因 ,且能明显刺激T细胞增殖及提高CTL的杀伤作用。 ( 2 )突变Ki ras基因修饰的DC免疫小鼠后 ,可产生针对表达Ki ras(V 12 )基因的Lewis肺癌的特异性杀伤作用 ,但对B16黑色素瘤细胞则无明显杀伤作用。结论 以人突变Ki ras基因修饰的肺癌DC疫苗可在体外特异性诱导抗可表达Ki ras(V 12 )基因的Lewis肺癌的活性。

子宫内膜息肉与子宫内膜癌中Ki-ras基因表达及临床意义

目的:探讨Ki-ras基因激活与子宫内膜癌中的发生发展关系及子宫内膜息肉与子宫内膜癌的关系。方法:对子宫内膜癌及癌前病变组织进行Ki-ras蛋白免疫组化测定。结果:Ki-ras蛋白广泛存在于子宫内膜癌和癌前病变组织中,癌前病变Ki-ras表达为11.9％,癌组为62.96％,P<0.05;。Ki-ras表达与细胞恶性程度呈正相关。结论:①Ki-ras基因激活可导致细胞周期增殖失控,是内膜癌发生发展的一个重要环节;②动态观测子宫内膜息肉中的P21^(ras)表达阳性者,对子宫内膜癌的早期发现可能有积极意义。

大肠肿瘤p53和ki-ras基因协同突变的研究

目的探讨大肠肿瘤p53和ki-ras基因协同突变的临床意义。方法采用免疫组化和PCR-SSCP方法,检测58例大肠肿瘤患者的良性病变、良性病变转为恶变、原发腺癌组织的p53基因、ki-ras基因的表达和突变情况。结果良性病变组与恶变组间的p53基因和Ki-ras基因的表达有显著差异,良性病变组与原发腺癌组的Ki-ras基因表达差异显著;良性病变组的p53基因与Ki-ras基因的表达呈负相关,而恶变组和原发腺癌组呈正相关。p53基因和ki-ras基因两种基因突变率无显著差异,而协同突变与淋巴结转移密切相关,相关系数r=0.335,P=0.017,P<0.05。结论 p53和ki-ras基因协同突变可以促进了大肠癌的发展。监测p53基因和Ki-ras基因的协同表达和突变,有助于大肠肿瘤的早期诊断和预后评价。

快速、高敏感度检测Ki-ras基因突变方法的建立及其在检测大肠癌中的应用

建立一种检测Ｋｉ－ｒａｓ基因突变的快速、高敏感度的方法，并将其应用于大肠癌的检测中。应用引物诱导限制富集突变等位基因检测法（ＰＣＲ－ＰＩＲＥＭＡ，ＰｒｉｍｅｒＩｎｔｒｏｄｕｃｅｄＲｅｓｔｒｉｃｔｉｏｎｗｉｔｈＥｎ－ｒｉｃｈｍｅｎｔｏｆＭｕｔａｎｔＡｌｅｌｅＡｓｓａｙ）的敏感度达１０－５～１０－６，并在３０例大肠癌样品中检测出了８例Ｋｉ－ｒａｓ基因１２密码子突变的样本，突变率达２６．７％。证明ＲＣＲ－ＰＩＲＥＭＡ法是一种快速、敏感度高的方法，适用于在大量野生型拷贝中检测稀有的突变。

大肠腺癌及其癌前病变中Ki-ras突变的检测

大肠腺癌及其癌前病变中Ｋｉ┐ｒａｓ突变的检测郑天郢１张尚忠２刘宇印３汪润山关键词Ｋｉ┐ｒａｓ突变腺瘤腺癌溃疡性结肠炎ＰＣＲ┐ＲＦＬＰ作者单位：１．山东医科大学附属医院肿瘤防治中心化疗组（济南２５００１２）２．山东医科大学附属医院消化内科３．山东医科大...

胰腺肿瘤和正常胰腺组织中c-Ki-ras第12密码子点突变

对2例正常人胰腺组织、7例人胰腺内分泌肿瘤、5例胰腺癌手术标本、3例胰腺癌细胞系、7例胰腺癌裸鼠移植瘤标本的DNA进行PCR扩增后，分别用斑点杂交和单链构象多态性技术对c－Ki-ras第12密码子．点突变进行检测。结果发现，仅胰腺癌标本存在高频率的c－Ki-ras第12密码子的突变（斑点杂交阳性率11／15，单链构象多态性为12／15）。单链构象多态性技术与斑点杂交技术相比具有方便快速的特点。

原癌基因Ki-ras在寻常性银屑病患者皮损表皮中的表达

运用细胞原位杂交的方法 ,对 16例寻常性银屑病患者及 10例正常人皮肤中原癌基因 Ki-ras的表达进行了观察。结果表明 ,Ki- ras在所有被检测的表皮中均有表达 ,而在银屑病皮损表皮中的表达高于正常人对照 ( P<0 .0 1)。提示原癌基因 Ki-

Ki-Ras反义寡核苷酸对人胃癌细胞及血管内皮细胞的作用

:目的 用Ki Ras的反义寡核苷酸 (ASODN)作用于人胃癌细胞和血管内皮细胞 ,为其抑制胃癌生长及其内血管生成进行前期基础研究。方法 MTT法观察Ki RasASODN对两种细胞增殖的影响 ,电镜下观察细胞的超微结构变化及有无凋亡发生。结果 Ki RasASODN可明显抑制人胃癌细胞和血管内皮细胞的增殖。在一定剂量下还可诱发细胞凋亡。结论 Ki RasP2 1在人胃癌细胞和血管内皮细胞的增殖与凋亡调控中具有重要作用。

人胃癌移植瘤裸小鼠Ki-ras基因突变的检测

目的 检测人胃癌裸小鼠移植瘤Ki ras基因的突变情况。方法 将人胃癌细胞SGC 790 1于裸小鼠脾包膜下移植 ,12周后处死 ,采用PCR DNA测序法检测Ki ras基因第 12、13密码子的突变情况。结果 共检测 2 9例裸鼠移植瘤 ,DNA经扩增后 2 0例为阳性 ,其中 12例进行DNA测序 ,未发现第 12、13密码子的突变。结论 人胃癌移植瘤裸小鼠Ki ras基因第 12。

Expressions of oncogenes c-fos and c-myc in skin lesion of cutaneous squamous cell carcinoma

Objective:To explore the expressions of c-fos and c-myc in skin lesion of cutaneous squamous cell carcinoma(CSCC).Methods:Using retrospective analysis.73 cases of CSCC were selected from Department of Dermatology,the Second Affiliated Hospital of Xi'an Jiaotong University.which were removed between January 2000 and January 2012.It was considered as experimental group.Meanwhile.11 cases of normal skin specimens of non tumor patients were selected as control group.The expression level of c-fos and c-myc was compared in the two groups.Results:The expressions of c-fos[72.60%(53/73)]and c-myc[83.56%(61/73)]in experimental group were statistically significant(P≤0.05)compared with control group(0%).Expression of c-myc protein was negatively related to differentiation of CSCC.The difference was statistically significant(X^2=7.26.P=0.001<0.05).While expression of c-fos protein was positively related to differentiation of CSCC.which was statistically significant(X^2=7.47,P=0.0012<0.025).Conclusions:The expression level of c-fos and c-myc can be used as an importan indicator of CSCC differentiation,and it has closely connection with the differentiated degree,which can guide clinical prognosis.

Study of differential polymerase chain reaction of C-erbB-2 oncogene amplification in gastric cancer

AIM To study the significance of C-erbB-2 oncogene amplification in gastric cancer.METHODS C-erbB-2 oncogene amplification was examined by using differential polymerase chain reaction (dPCR) in surgical and endoscopic specimens of 83 cases of gastric cancer and 101 metastatic lymph nodes.RESULTS C-erbB-2 amplification was found in 28.9% (24/ 83) surgical specimens and 20.5% (17/ 83) endoscopic ones of gastric cancer patients. The amplification was significant in both types of specimens of advanced cancer cases (P＜0.05) and surgical specimens with lymph node metastasis (P＜0.01). The incidence of C-erbB-2 amplification in lymph nodes with metastasis was higher than in primary sites (surgical specimens, P＜0.05). The patients with amplification tumors had poorer 5-year survival rates than those with unamplification ones in the early cancers and well to moderately differentiated adenocarcinomas (P＜0.05). The same surgical samples were tested again by Southern blot hybridization to ascertain C-erbB-2 amplification, and the positive rate of C-erbB-2 amplification (15.7%) was lower than that of dPCR (28.9%, P＜0.05).CONCLUSION Examining C-erbB-2 amplification by dPCR is a quick, simple, reliable and independent method, and is helpful in predicting prognosis and metastatic potential of gastric cancer.

ki-ras和野生型p53 mRNA在人胚胎多种组织中表达的研究

目的 探讨 ki- ras和 p5 3基因在胚胎形成和发育过程中的作用。方法 采用 RNA斑点杂交法研究 ki-ras和 p5 3基因在各胚胎组织中的表达情况。结果 斑点杂交显示 ki- ras和 p5 3基因在人胚胎多种组织中均有表达 ,但表达水平各不一致。ki- ras基因在胚胎发育第 4～ 5个月间为表达最低点 ,以后在各组织中的表达随胚龄增加而上升 ;p5 3基因则在胚胎发育第 4～ 5月间为表达最高点 ,以后随胚龄增加其表达水平下降。结论 提示 ki- ras和p5 3基因在人胚胎的形成和发育过程中可能起着较为重要的作用。

Dual fluorescence in situ hybridization in detection of HER-2 oncogene amplification in primary hepatocellular carcinoma

BACKGROUND: Molecular cytogenetics of oncogene HER-2 amplification in primary hepatocellular carcinoma (HCC) is still unknown. The aim of this study was to in vestigate the frequency of HER-2 oncogene amplification in primary HCC and its relations to clinicopathological pa rameters and prognosis. METHODS: Forty-two surgical samples from patients with primary HCC were detected for their HER-2 oncogene am plification. The number of chromosome 17 and their ratio were tested by dual fluorescence in situ hybridization (FISH) technique, and then the correlations between HER-2 amplification, clinicopathological characteristics and prog nosis were analyzed statistically. RESULTS: HER-2 oncogene amplification was detected in 9 (21.4%) of the 42 primary HCCs, including 4 patient with high copy (HC) (9.5%) and 5 patients with low copy (LC) (11.9%). HER-2 amplification was associated signifi cantly with tumor size and postoperative survival time o HCC patients (P<0.05), and the presence of HER-2 gene amplification was correlated with postoperative relapse (P— 0.257), but not related to sex, age, AFP level, HBV infec tion, histopathological grading and clinical staging of HCC patients (P>0.05). The HER-2 oncogene copy was exa mined in 31 (73.8%) of the 42 primary HCCs, consisting of 9 patients with HER-2 amplification (21.4%) and 22 pa tients with aneuploidy (52.4%). No significant relation were observed between the HER-2 oncogene copy, patien sex, tumor size, histopathological grading, clinical stag ing, postoperative relapse and survival time (P >0.05); bu the HER-2 oncogene copy was correlated significantly to age, AFP level and HBV infection (P <0.05). CONCLUSIONS: There are a lower frequency of HER-2 oncogene amplification and a higher frequency of chromo- some 17 aneuploidy in primary HCC. HER-2 oncogene amplification may be involved in the development and pro- gression of large HCC in some patients, and seems to be a valuably independent prognostic factor predicting the re- currence and poor survival in patients with large HCC.