Silent information regulator sirtuin 1 ameliorates acute liver failure via the p53/glutathione peroxidase 4/gasdermin D axis

BACKGROUND Acute liver failure(ALF)has a high mortality with widespread hepatocyte death involving ferroptosis and pyroptosis.The silent information regulator sirtuin 1(SIRT1)-mediated deacetylation affects multiple biological processes,including cellular senescence,apoptosis,sugar and lipid metabolism,oxidative stress,and inflammation.AIM To investigate the association between ferroptosis and pyroptosis and the upstream regulatory mechanisms.METHODS This study included 30 patients with ALF and 30 healthy individuals who underwent serum alanine aminotransferase(ALT)and aspartate aminotransferase(AST)testing.C57BL/6 mice were also intraperitoneally pretreated with SIRT1,p53,or glutathione peroxidase 4(GPX4)inducers and inhibitors and injected with lipopolysaccharide(LPS)/D-galactosamine(D-GalN)to induce ALF.Gasdermin D(GSDMD)^(-/-)mice were used as an experimental group.Histological changes in liver tissue were monitored by hematoxylin and eosin staining.ALT,AST,glutathione,reactive oxygen species,and iron levels were measured using commercial kits.Ferroptosis-and pyroptosis-related protein and mRNA expression was detected by western blot and quantitative real-time polymerase chain reaction.SIRT1,p53,and GSDMD were assessed by immunofluorescence analysis.RESULTS Serum AST and ALT levels were elevated in patients with ALF.SIRT1,solute carrier family 7a member 11(SLC7A11),and GPX4 protein expression was decreased and acetylated p5,p53,GSDMD,and acyl-CoA synthetase long-chain family member 4(ACSL4)protein levels were elevated in human ALF liver tissue.In the p53 and ferroptosis inhibitor-treated and GSDMD^(-/-)groups,serum interleukin(IL)-1β,tumour necrosis factor alpha,IL-6,IL-2 and C-C motif ligand 2 levels were decreased and hepatic impairment was mitigated.In mice with GSDMD knockout,p53 was reduced,GPX4 was increased,and ferroptotic events(depletion of SLC7A11,elevation of ACSL4,and iron accumulation)were detected.In vitro,knockdown of p53 and overexpression of GPX4 reduced AST and ALT levels,the cytostatic rate,and GSDMD expression,restoring SLC7A11 depletion.Moreover,SIRT1 agonist and overexpression of SIRT1 alleviated acute liver injury and decreased iron deposition compared with results in the model group,accompanied by reduced p53,GSDMD,and ACSL4,and increased SLC7A11 and GPX4.Inactivation of SIRT1 exacerbated ferroptotic and pyroptotic cell death and aggravated liver injury in LPS/D-GalNinduced in vitro and in vivo models.CONCLUSION SIRT1 activation attenuates LPS/D-GalN-induced ferroptosis and pyroptosis by inhibiting the p53/GPX4/GSDMD signaling pathway in ALF.

Exosome-Transmitted miR-224-5p Promotes Colorectal Cancer Cell Proliferation via Targeting ULK2 in p53-Dependent Manner

Objective To investigate the role and molecular mechanism of exosomal miR-224-5p in colorectal cancer(CRC).Methods The miR-224-5p expression in CRC patient tissues and cell-derived exosomes was measured by laser capture microdissection and qRT-PCR,respectively.Dual-luciferase reporter gene assay was used to determine the target gene of miR-224-5p.The protein expressions of p53 and unc-51 like kinase 2(ULK2)in CRC cells were detected by western blot.Flow cytometry was used to detect cell cycle and apoptosis.Cell proliferation was measured by CCK8 and EdU assay.Results The miR-224-5p expression was upregulated in CRC tissues and increased progressively with the rise of CRC stage.CRC cells secreted extracellular miR-224-5p mainly in an exosome-dependent manner,and then miR-224-5p could be transferred to surrounding tumor cells to regulate cell proliferation in the form of autocrine or paracrine.Moreover,ULK2 was characterized as a direct target of miR-224-5p and was downregulated in CRC tissues.Interestingly,ULK2 inhibited CRC cell proliferation in a p53-dependent manner.Furthermore,exosome-derived miR-224-5p partially reversed the proliferation regulation of ULK2 on CRC cells.Conclusion Our findings demonstrate that exosome-transmitted miR-224-5p promotes p53-dependent cell proliferation by targeting ULK2 in CRC,which may offer promising targets for CRC prevention and therapy.

Anticancer therapeutic strategies for targeting mutant p53-Y220C

The tumor suppressor p53 is a transcription factor with a powerful antitumor activity that is controlled by its negative regulator murine double minute 2(MDM2,also termed HDM2 in humans)through a feedback mechanism.At the same time,TP53 is the most frequently mutated gene in human cancers.Mutant p53 proteins lose wild-type p53 tumor suppression functions but acquire new oncogenic properties,among which are deregulating cell proliferation,increasing chemoresistance,disrupting tissue architecture,and promoting migration,invasion and metastasis as well as several other pro-oncogenic activities.The oncogenic p53 mutation Y220C creates an extended surface crevice in the DNA-binding domain destabilizing p53 and causing its denaturation and aggregation.This cavity accommodates stabilizing small molecules that have therapeutic values.The development of suitable small-molecule stabilizers is one of the therapeutic strategies for reactivating the Y220C mutant protein.In this review,we summarize approaches that target p53-Y220C,including reactivating this mutation with small molecules that bind Y220C to the hydrophobic pocket and developing immunotherapies as the goal for the near future,which target tumor cells that express the p53-Y220C neoantigen.

Celecoxib enhances the response of tumor cells to cisplatin through upregulating PUMA in non–small cell lung cancer carrying wild-type p53

Celecoxib,a cyclooxygenase-2 inhibitor,can enhance the efficacy of chemotherapy;however,its effect seems inconsistent.In this study,we investigated whether celecoxib would increase the antiproliferative effects of cisplatin in human lung cancer cells.Our data demonstrated the synergistic effects of celecoxib with cisplatin in wild-type p53 cells and their antagonistic effects inmutated or deleted p53 cells.Combination indices of 0.82 to 0.93 reflected a synergistic effect between celecoxib and cisplatin in lung cancer cells with wild-type p53.Combination indices of 1.63 to 3.00 reflected antagonism between celecoxib and cisplatin in lung cancer cells with mutated or deleted p53.Compared with that in cells with mutated or deleted p53,apoptosis significantly increased with the addition of celecoxib and cisplatin in wild-type p53 cells(P<0.05).Moreover,the results in vivo were similar to those in vitro:celecoxib combinedwith cisplatin slowed tumor growth in wild-type p53 groups and not in mutated or deleted p53 groups.In addition,celecoxib promoted p53 translocation into the nucleus and upregulated active p53 expression in wild-type p53 cells.Celecoxib combined with cisplatin upregulated PUMA(PUMA is a downstream gene of p53)after active p53 increased in wild-type p53 cells.In summary,the combination of celecoxib and cisplatin demonstrates clear synergistic effects in wild-type p53 cells and antagonistic effects inmutated or deleted p53 cells.The synergistic effect was achieved by apoptosis,induced by upregulating PUMA.Our results will provide a new treatment strategy for patients carrying wild-type p53,insensitive to cisplatin.

Ginger polysaccharide UGP1 suppressed human colon cancer growth via p53,Bax/Bcl-2,caspase-3 pathways and immunomodulation

In previous study,we got a purified ginger polysaccharide UGP1 and verified its significant antitumor activities on colon cancer HCT116 cells.In this article,we aimed to illustrate the underlying mechanism of UGP1 exerted antitumor activities on colon cancer by using in vitro cell models and in vivo animal models.The results demonstrated that UGP1 could induce S-phase cell cycle arrest,up-regulate the expression of Bax and p53,down-regulate the expression of Bcl-2,and activate the downstream protein caspase-9 and caspase-3,which was related to intrinsic apoptosis pathway on HCT116 cells.Moreover,UGP1 significantly stimulated RAW264.7 cell proliferation and secretion activity.Similarly,UGP1 inhibited tumor proliferation on tumor-bearing mice,increased the expression of p53 and the ratio of Bax/Bcl-2,enhanced the secretion of pro-inflammatory cytokines TNF-α,IL-2,IL-6 and decreased the secretion of pro-tumor cytokines TGF-βand b FGF in serum.In conclusion,it indicated that the UGP 1 could sup press human colon cancer growth by inducing apoptosis via the regulation of p53,caspase-3,and Bax/Bcl-2 ratio-dependent pathway and regulating immune system activity.Thi s investigation provided basic theoretical mechanism of ginger polysaccharideexerted antitumor activities,and contributed to develop a possible functional food or adjuvant agent for prevention or treatment of colon cancer.

Acetylated-PPARγexpression is regulated by different P53 genotypes associated with the adipogenic differentiation of polyploid giant cancer cells with daughter cells

Objective:Polyploid giant cancer cells(PGCCs)with daughter cells express epithelial–mesenchymal transition(EMT)-associated proteins.Highly malignant tumor cells with EMT properties can transdifferentiate into mature tumor cells.In this study,we elucidated the potential for,and underlying mechanism of,adipogenic differentiation of PGCCs with daughter cells(PDCs).Methods:Cobalt chloride was used to induce PGCC formation in HEY(wild-type P53)and MDA-MB-231(mutant P53)cells;these cells were then cultured in adipogenic differentiation medium.Oil red O staining was used to confirm adipogenic differentiation,and the cell cycle was detected with flow cytometry.The expression of adipogenic differentiation-associated proteins and P300 histone acetyltransferase activity were compared before and after adipogenic differentiation.Animal xenograft models were used to confirm the adipogenic differentiation of PDCs.Results:PDCs transdifferentiated into functional adipocytes.Two different cell cycle distributions were observed in PDCs after adipogenic differentiation.The expression levels of PPARγ,Ace-PPARγ,and Ace-P53 were higher in PDCs after adipogenic differentiation than in cells before adipogenic differentiation.Ace-PPARγand FABP4 expression increased in HEY cells and decreased in MDA-MB-231 PDCs after p53 knockdown.A485 treatment increased Ace-P53,Ace-PPARγ,and FABP4 expression in HEY PDCs by inhibiting SUMOylation of P53.In MDA-MB-231 PDCs,A485 treatment decreased Ace-P53,Ace-PPARγ,and FABP4 expression.Animal experiments also confirmed the adipogenic differentiation of PDCs.Conclusions:Acetylation of P53 and PPARγplays an important role in the adipogenic differentiation of PDCs.

Role of p53 suppression in the pathogenesis of hepatocellular carcinoma

In the world,hepatocellular carcinoma(HCC)is among the top 10 most prevalent malignancies.HCC formation has indeed been linked to numerous etiological factors,including alcohol usage,hepatitis viruses and liver cirrhosis.Among the most prevalent defects in a wide range of tumours,notably HCC,is the silencing of the p53 tumour suppressor gene.The control of the cell cycle and the preservation of gene function are both critically important functions of p53.In order to pinpoint the core mechanisms of HCC and find more efficient treatments,molecular research employing HCC tissues has been the main focus.Stimulated p53 triggers necessary reactions that achieve cell cycle arrest,genetic stability,DNA repair and the elimination of DNA-damaged cells’responses to biological stressors(like oncogenes or DNA damage).To the contrary hand,the oncogene protein of the murine double minute 2(MDM2)is a significant biological inhibitor of p53.MDM2 causes p53 protein degradation,which in turn adversely controls p53 function.Despite carrying wt-p53,the majority of HCCs show abnormalities in the p53-expressed apoptotic pathway.High p53 in-vivo expression might have two clinical impacts on HCC:(1)Increased levels of exogenous p53 protein cause tumour cells to undergo apoptosis by preventing cell growth through a number of biological pathways;and(2)Exogenous p53 makes HCC susceptible to various anticancer drugs.This review describes the functions and primary mechanisms of p53 in pathological mechanism,chemoresistance and therapeutic mechanisms of HCC.

乳腺癌组织COX-2蛋白c-erbB-2 P53 VEGF-C蛋白表达及其与临床病理参数和预后的关系

目的:分析乳腺癌组织环氧化酶-2(COX-2)蛋白、人表皮生长因子受体2(c-erbB-2)、突变型P53蛋白、血管内皮生长因子C(VEGF-C)蛋白表达及其与临床病理参数和预后的关系。方法:选取2017年3月至2019年5月到我院就诊103例乳腺癌患者的手术切除标本。免疫组化法测定患者入组时的COX-2、c-erbB-2、P53、VEGF-C蛋白阳性率;比较上述各指标水平与患者TNM分期、分化程度等病理参数的关系;随访患者术后3年生存资料,Kaplan-Meier分析COX-2、c-erbB-2、P53、VEGF-C蛋白水平对预后生存的影响。结果:患者TNM分期、分化程度与COX-2阳性相关(P<0.05);肿瘤直径≥3cm、淋巴结转移与c-erbB-2阳性相关(P<0.05);TNM分期、分化程度、淋巴结转移与P53阳性相关(P<0.05);淋巴结转移与VEGF-C阳性相关(P<0.05)。103例患者随访3年,随访率为100%,截止至2022年5月死亡20例(19.42%),存活83例(80.58%);根据死亡情况将阳性患者分为存活亚组及死亡亚组,死亡亚组患者入组时的组化评分均明显高于存活亚组(P<0.05)。Log-rank χ^(2)检验显示随访3年P53、VEGF-C阳性及阴性的累积存活率比较差异有统计学意义(χ^(2)=14.000、5.206,P均<0.05);COX-2、c-erbB-2阳性及阴性患者的累积存活率比较差异无统计学意义(χ^(2)=1.761、2.830,P=0.184、0.093)。结论:乳腺癌组织中COX-2、c-erbB-2、P53、VEGF-C蛋白阳性率与TNM分期、淋巴结转移、分化程度等病理参数相关,在患者预后评估中具有一定指导意义。

Evolution of p53 pathway-related genes provides insights into anticancer mechanisms of natural longevity in cetaceans

DEAR EDITOR,Despite the generally increased cancer risk in large,long-lived organisms,cetaceans,among the largest and longest-living mammals,appear to possess a counteracting mechanism.Nevertheless,the genetic basis underlying this mechanism remains poorly understood.The p53 pathway serves as an ideal target for studying the mechanisms behind cancer resistance,as most cancer types have evolved strategies to circumvent its suppressive functions.

KIF15, a key regulator of nasopharyngeal carcinoma development mediated by the P53 pathway

Background:Kinesin family member 15(KIF15)is a protein that regulates cell mitosis and plays an important role in the development and progression of several types of human cancers.However,the role of KIF15 in the development of nasopharyngeal cancer(NPC)is still unclear.Methods:The differential expression of KIF15 in NPC and para-carcinoma tissues was evaluated based on data collected from Gene Expression Omnibus(GEO)database and immunohistochemical analysis of clinical specimens collected from a patient cohort.Cell lines 5-8F and CNE-2Z were selected for the construction of KIF15‑knockdown cell models.CCK8 assay,flow cytometry,wound healing,Transwell and clone formation assays were used to detect the proliferation,apoptosis,migration,invasion and colony formation of NPC cells in vitro.A mouse xenograft model and the tail intravenous mouse distant transfer model were constructed for in vivo study.Furthermore,the potential molecular mechanisms underlying the effects of KIF15 were explored through western blot analysis,and several in vitro and in vivo functional assays were performed to explore its role in NPC.Results:The results revealed significantly higher expression of KIF15 in NPC tissues compared to para-carcinoma tissues.High levels of KIF15 expression were also associated with short overall survival(OS)and progression-free survival(PFS).Knockdown of the KIF15 gene led to a cell cycle arrest in the growth 2(G2)phase,inhibition of cell proliferation,migration,invasion,colony formation,and enhanced cell apoptosis.The in vivo murine xenograft experiments showed that down-regulation of the KIF15 gene could inhibit tumor growth and reduce the risk of liver and lung metastasis in NPC.Moreover,the evaluation of the molecular pathway showed that the mitogen-activated protein kinase/P53 pathways might be involved in the KIF15-induced regulation of NPC.Rescue assays indicated that Pifithrin-αcould counteract the pro-proliferative and pro-apoptotic effects mediated by KIF15.Conclusion:This work indicated that KIF15 overexpression accelerated the progression of NPC and promoted the development of distant metastases.Therefore,KIF15 may have an important role as a prognostic indicator and a potential drug target for the treatment of NPC.

The zinc figure protein ZNF575 impairs colorectal cancer growth via promoting p53 transcription

Zinc-finger proteins play different roles in cancer;however,the function of zinc-finger protein ZNF575 in cancer remains unclear.In the present study,we aimed to determine the function and expression of ZNF575 in colorectal cancer.Proliferation assay,colony formation assay,and tumor model in mice were used to investigate the function of ZNF575 after ectopic expression of ZNF575 in colorectal cancer(CRC)cells.RNA sequencing,ChIP,and luciferase assays were used to investigate the mechanism behind ZNF575 regulation of CRC cell growth.The expression of ZNF575 was determined by IHC staining in 150 pairs of malignant CRC tissues,followed by prognosis analysis.We indicated that ectopic expression of ZNF575 inhibited CRC cell proliferation,colony formation and promoted cell apoptosis in vitro.Tumor growth in CRC was also impaired by ZNF575 in mice.RNA sequencing,follow-up western blotting,and qPCR results demonstrated the increase of p53,BAK,and PUMA in ZNF575-expressing CRC cells.Further results indicated that ZNF575 directly targeted the p53 promoter and promoted the transcription of p53.Downregulation of ZNF575 was confirmed in malignant tissues,and ZNF575 expression was positively correlated with the prognosis of CRC patients.The present study demonstrated the function,underlying mechanism,expression,and the prognosis-predicting role of ZNF575 in CRC,which indicated that ZNF575 would be a potential prognostic predictor and therapeutic target for CRC and other cancers.

Promoter Region Analysis of STAMP1/STEAP2 Gene-Silencing of STAMP1/STEAP2 Gene Triggers P53 Upregulation

Prostate cancer is the most commonly diagnosed cancer and the second leading cause of cancer mortality in men in the Western World. In the initial stages, prostate cancer is dependent on androgens for growth which is the basis for androgen ablation therapy. The effects of androgens are mediated by the Androgen Receptor (AR). Therefore, studies focus on the identification of AR-regulated genes that are also highly expressed in the prostate. STAMP family genes STAMP1/STEAP2 and STAMP2/STEAP4 have only expressed in androgen receptor-positive cells, the role of AR in STAMP family gene expression is an important question. STEAP (Six Transmembrane Epithelial Antigen of Prostate) is the first characterized prostate of enriched six transmembrane gene, expressed in metastatic prostate cancer samples, it is tempting to speculate that STAMP/STEAP family genes may be involved in similar functions with a role for both the normal biology and pathophysiology of the prostate. Using siRNA technology in LNCaP cells expressing STAMP genes per se, an apoptosis panel including pro-apoptotic and/or apoptotic molecules was assayed by RT-PCR, By this research project, prostate-specific STAMP gene family and its regulatory effects on the p53- and caspase-related pathways were characterized.

浸润性乳腺癌患者组织P120ctn p53及CK5/6表达及意义分析

目的:探究浸润性乳腺癌(IBC)患者癌组织P120连环蛋白(catenin,P120ctn)、p53蛋白、细胞角蛋白5/6(CK5/6)表达及临床意义。方法:回顾性分析2018年10月至2021年10月120例IBC患者临床资料,采用免疫组织化学法检测癌组织、癌旁组织P120ctn、p53、CK5/6表达情况,并分析其与患者临床病理特征、术前新辅助化疗(NAC)疗效关系。结果:癌组织P120ctn、p53及CK5/6阳性表达率81.67%、75.83%、38.33%,显著高于癌旁组织的55.00%、15.00%、3.25%(P均<0.05);P120ctn表达与分子分型、淋巴结转移有关(P<0.05),p53与肿瘤直径、分子分型、组织学分级、淋巴结转移、临床分期有关(P<0.05),CK5/6与分子分型、组织学分级有关(P<0.05);Spearman秩相关分析显示,癌组织P120ctn、p53及CK5/6表达互呈正相关(r=0.384、0.406、0.581,P均<0.05);120例患者术前经2个周期NAC后,有效率为63.33%(76/120);单因素分析显示,肿瘤直径>2cm、组织学分级G3、淋巴结转移、P120ctn阳性表达、p53阳性表达、CK5/6阳性表达者有效率较低(P<0.05);多因素Logistic回归分析显示,淋巴结转移、P120ctn阳性表达、p53表达阳性是影响患者NAC疗效的危险因素(P<0.05)。结论:IBC患者癌组织P120ctn、p53、CK5/6表达明显升高,且与患者临床病理特征有关,其中P120ctn、p53阳性表达是患者术前NAC疗效的影响因素。

Low-Dose Gamma Radiation Fields Decrease Cell Viability, Damage DNA, and Increase the Expression of Hsp70 and p53 Proteins in Human Leukocytes

Ionizing radiations are tools in diagnosis and treatment of diseases. Leukopenia from exposure to ionizing radiation has been reported. Due to their radiosensitivity, leukocytes are a biological model to analyze cell damage. Therefore, cell viability, DNA damage, and Hsp70 and p53 expression in human leukocytes exposed to low-dose gamma radiation fields from a 137Cs source were evaluated. A decrease in cell viability, DNA damage and an increase in the expression of Hsp70 and p53 proportional to the radiation dose received was found, which was 0.2, 0.4, 0.6, 0.8 and 1.0 mGy.

卵巢肿瘤中癌基因 nm23Hl,c-erbB-2,ras 和 p53 的蛋白表达与腹膜后淋巴结转移关系的研究

目的本研究旨在结合腹膜后淋巴结切除术，探讨癌蛋白ｎｍ２３Ｈ１，ｐ１８５，ｐ２１，ｐ５３在卵巢癌中的表达与卵巢癌腹膜后淋巴转移（ＬＮＭ）的关系。方法采用免疫组化方法测定石腊包埋标本中ｎｍ２３Ｈ１，ｐ１８５，ｐ２１和ｐ５３的表达，单因素、多因素分析它们的表达与淋巴结转移关系。结果在３１例（３１．６％）患者中ｎｍ２３Ｈ１蛋白表达阳性；ｐ２１的表达与组织分化程度及残留癌相关。病理证实４９例（５５．１％）有淋巴结转移；ｎｍ２３Ｈ１蛋白表达阳性的ＬＮＭ率低（３５．７％ｖｓ６３．９％，Ｐ＝０．０１２）；ｐ２１表达与ＬＮＭ正相关（Ｐ＜０．００１）；ｐ１８５（～）病例ＬＮＭ率（６４．４％）高于ｐ１８５（＋）或ｐ１８５（－）的转移率（４５．９％），但差异无统计学意义；ｐ５３表达与ＬＮＭ无关。与ＬＮＭ相关的临床因素是伴有腹水、组织分化不良、残留灶和分期晚。经Ｌｏｇｉｓｔｉｃ回归多因素分析，影响淋巴结转移的独立危险因素是ｎｍ２３Ｈ１蛋白阴性表达，ｐ２１的阳性表达、有残留灶和分化差。结论在卵巢恶性肿瘤中，ｎｍ２３Ｈ１蛋白和ｐ２１的表达对腹膜后淋巴结转移有独立的联合作用，而ｐ１８５和ｐ５３的表达则无关。

VEGF p53和p21 ras在原发性肝细胞癌中的表达及其临床病理意义

目的：研究ＶＥＧＦ，ｐ５３和ｐ２１ｒａｓ在原发性肝细胞癌（ＨＣＣ）的表达和三者间的相关性及其与ＨＣＣ病理分级，转移行为的关系。方法：应用免疫组织化学Ｓ－Ｐ法对３４例ＨＣＣ的癌组织中的ＶＥＧＦ，ｐ２１ｒａｓ和ｐ５３的表达作了研究。结果：ＶＥＧＦ，ｐ２１ｒａｓ和ｐ５３三者在肝癌和癌旁组织的阳性率均有非常显著的差异（Ｐ＜０．０１），ＶＥＧＦ的表达与ｐ２１ｒａｓ和ｐ５３均呈显著的正相关（Ｐ＜０．０１）。三者间的协同表达亦与ＨＣＣ的病理分级和转移行为有关，而与肿瘤大小，ＡＦＰ水平，ＨＢｓＡｇ阳性无关。结论：ＶＥＧＦ可能在ＨＣＣ的形成，发展和转移中与ｐ５３和ｒａｓ基因协同作用，三者的协同作用可能与ＨＣＣ的病理分级和转移行为有关。

利用Tet-OnTM基因表达系统直接克隆 p53下游基因(英文)

目的 直接克隆 p5 3下游基因 ,并对其功能进行初步研究。方法 采用哺乳动物细胞诱导表达系统 -Tet-onTM基因表达系统 ,建立 p5 3基因诱导表达可调控的细胞系 ;通过mRNA差异显示技术直接克隆p5 3下游基因 ,并利用原位杂交技术检测其在小鼠胚胎发育过程中的表达。结果 克隆到一个新的p5 3下游基因侯选基因 ,并检测到它在小鼠胚胎发育过程中有特异性表达。结论 直接克隆 p5 3下游基因的成功 ,为进一步研究 p5 3基因的功能奠定了基础。

六味地黄汤对小鼠诱发性肺腺瘤 P53 基因表达的影响

六味地黄汤能够显著降低氨基甲酸乙酯所致小鼠肺腺瘤的诱发率，且这种抑制作用在甲状腺素“阴虚”小鼠中表现得更为明显。诱发肺腺瘤小鼠的肺组织中，肿瘤抑制基因Ｐ５３ｍＲＮＡ表达比正常肺组织明显下降，给予六味地黄汤后，Ｐ５３基因表达明显回升；在甲状腺素“阴虚”小鼠中，六味地黄汤也具有同样作用。

PTEN p53及hTERT在Ⅰ型子宫内膜癌中的表达

目的:探讨PTEN、p53及hTERT在Ⅰ型子宫内膜癌中的表达,为子宫内膜癌的早期诊断和治疗提供理论依据。方法:应用免疫组织化学SABC法同步检测49例子宫内膜癌中的p53、PTEN、hTERT的表达,取同期49例正常的子宫内膜组织做对照,数据采用SPSS13.0软件处理,计数资料进行X2检验,等级资料进行秩和检验。结果:PTEN蛋白在子宫内膜癌中阳性表达率为40.8%,低于正常子宫内膜组97.9%,且阳性表达与子宫内膜癌的组织分级、FIGO分期、淋巴转移、肌层浸润深度呈负相关;相反,hTERT和p53两种蛋白在子宫内膜癌组阳性表达率(67.3%、38.8%)均高于正常子宫内膜组,并子宫内膜癌恶性程度及FIGO分期呈正相关。结论:与正常子宫内膜相比,PTEN在子宫内膜癌中表达减少,而P53及hTERT呈表达升高,三者均可作为子宫内膜诊断及判定预后的标记物。

P16 P53在针刺乳腺增生模型大鼠乳腺组织的表达及意义

目的:通过观测乳腺增生大鼠及针刺治疗后乳腺组织中P16、P53蛋白表达的干预作用,探讨针刺对乳腺增生病的疗效与作用机理,为临床针刺治疗乳腺增生病,预防乳腺癌发生提供实验依据。方法:将48只健康雌性大白鼠随机分为4组,空白对照组、模型组、针刺治疗甲乙两组,每组12只。除空白对照组外,均采用贾氏造模方法建立乳腺增生模型。空白对照组、模型对照组的大鼠于第31天开始每日抓拿一次,不作任何治疗;针刺治疗的两组大鼠在第31天开始行穴位针刺治疗。治疗30天后处死大鼠,观测乳房形态大小,采集乳腺组织标本分别固定后,采用免疫组化法测定乳腺组织的P16、P53表达水平。结果:实验结果显示模型组造模成功,细胞结构中P16、P53表达明显;而针刺治疗组乳腺组织中P16、P53明显轻于模型组,两者比较有显著性差异。结论:针刺对乳腺增生大鼠乳腺组织P16、P53表达有干预作用,说明针刺对乳腺增生病有治疗作用,对乳腺癌发生有预防作用。