Science Letters:IGFBP7 plays a potential tumor suppressor role against colorectal carcinogenesis with its expression associated with DNA hypomethylation of exon 1

Insulin-like growth factor binding-protein-7 (IGFBP7) was obtained from our previous colonic adenocarcinoma (CRC) and normal mucosa suppression subtraction hybridization (SSH) cDNA libraries. By RT-PCR and immunohistochemistry, we found that IGFBP7 was overexpressed in CRC tissue compared to normal tissue. However, our in vitro experiments performed in 10 CRC cell lines showed that IGFBP7 expressed only in SW480 and Caco2 cell lines, which implied an underlying reversible regulatory mechanism. Using methylation-specific PCR (MSP) and bisulfite sodium PCR (BSP), we found that its expression was associated with DNA hypomethylation of exon1. This was further supported by the in vitro study which showed restored IGFBP7 expression after demethylation agent 5-aza-2’-deoxycytidine treatment. Correlation analysis between IGFBP7 expression and prognosis indicated that overexpression of IGFBP7 in CRC tissue correlated with favourable survival. Investigation of the func-tional role of IGFBP7 through transfection studies showed that IGFBP7 protein could inhibit growth rate, decrease colony for-mation activity, and induce apoptosis in RKO and SW620 cells, suggesting it a potential tumor suppressor protein in colorectal carcinogenesis. In conclusion, our study clearly demonstrated that IGFBP7 plays a potential tumor suppressor role against colo-rectal carcinogenesis and its expression is associated with DNA hypomethylation of exon 1.

Alteration of tumor suppressor gene p16 and Rb in gastric cancinogesis

Ａｌｔｅｒａｔｉｏｎｏｆｔｕｍｏｒｓｕｐｐｒｅｓｓｏｒｇｅｎｅｐ１６ａｎｄＲｂｉｎｇａｓｔｒｉｃｃａｎｃｉｎｏｇｅｓｉｓＺＨＯＵＱｉ１，ＺＯＵＪｉａｎＸｉａｎｇ２，ＣＨＥＮＹｕＬｏｎｇ２，ＹＵＨｕｉＺｈｅｎ３，ＷＡＮＧＬｉＤｏｎｇ１，ＬＩＹｏ...

Prokaryotic expression, purification of a novel candidate tumor suppressor gene FUS1 and characterization of its polyclonal antibodies

FUS1 is a novel candidate tumor suppressor gene identified in human chromosome 3p21.3. Its expression showed significantly reduction or even loss in lung cancer and other types of cancers. In order to further investigate the biological function of FUS1 protein, FUS1 cDNA from MRC-5 cells was amplified by RT-PCR and cloned into prokaryotic expression vector pQE-30. The recombinant expression plasmids were transformed into M15 strain and grown at 20℃ or 37℃. SDS–PAGE analysis revealed that the accumulation of the recombinant protein FUS1 (rFUS1) in inclusion body forms reached maxium amount when induced with 0.5 mM IPTG for 5 h at 37℃. The inclusion bodies were solubilized in 2M urea and purified by a 6 ×His tagged affinity column under denaturing condition. The purified rFUS1 was identified by electrospray ionization-mass spectrometry (ESI-MS) and tested for purity by HPLC chromatography. The purified rFUS1 proteins were then used to immunize rabbits to obtain anti-human FUS1 polyclonal antibodies, which were suitable to detect both the recombinant exogenous FUS1 and the endogenous FUS1 from tissues and cells by western blot and immunohistochemistry, Available purified rFUS1 proteins and self-prepared polyclonal antibodies against FUS1 may provide effective tools for further studies on biological function and application of FUS1.

虎杖苷调节Akt/MDM2/p53信号通路对胆囊癌细胞增殖、迁移和细胞周期的影响

目的探讨虎杖苷(PD)调节蛋白激酶B/原癌基因MDM2/抑癌基因p53信号通路对胆囊癌细胞增殖、迁移和细胞周期的影响。方法以人胆囊癌细胞株(GBC-SD)为研究对象,体外培养人胆囊癌细胞株(GBC-SD),使用浓度为10~160 mmol/L的虎杖苷处理细胞24、48、72 h,采用CCK-8法检测细胞的增殖能力,确定最佳实验浓度。将GBC-SD细胞分为对照组(Control组)、虎杖苷低、中、高浓度组(PD-L组、PD-M组、PD-H组)、虎杖苷+Akt激活剂组(PD+SC79组),Transwell小室法评价细胞的迁移能力,Hoechst染色观察细胞的凋亡,流式细胞术检测细胞周期与细胞凋亡,Western blot检测Akt、MDM2、p53磷酸化水平,建立荷瘤小鼠模型评价虎杖苷对胆囊癌肿瘤生长的影响。结果浓度为10~160 mmol/L的虎杖苷处理细胞24 h,可显著抑制GBC-SD细胞的增殖活性,选择10、20、40 mmol/L的虎杖苷进行后续实验;与Control组比较,PD-L组、PD-M组、PD-H组GBC-SD细胞的迁移数、细胞凋亡率、G2/M期细胞比例及S期细胞比例、P-Akt、P-MDM2蛋白表达显著降低,G0/G1期细胞比例、P-p53蛋白表达显著升高,且呈浓度依赖性(P<0.05);与PD-H组比较,PD+SC79组GBC-SD细胞的迁移数、细胞凋亡率、G2/M期细胞比例及S期细胞比例、P-Akt、P-MDM2蛋白表达显著升高,G0/G1期细胞比例、P-p53蛋白表达显著降低(P<0.05);虎杖苷干预治疗后,小鼠移植瘤的生长速度显著降低(P<0.05)。结论虎杖苷可以通过调节Akt/MDM2/p53信号通路使细胞周期阻滞,抑制胆囊癌细胞增殖、迁移。

CTNNB1、TP53蛋白在儿童肝母细胞瘤组织中的表达及与病理特征、预后的关系

目的 探讨钙黏蛋白相关蛋白(cadherin associated protein beta 1,CTNNB1)、肿瘤抑制因子P53(tumor suppressor factor P53,TP53)蛋白在儿童肝母细胞瘤(hepatoblastoma, HB)组织中的表达及与病理特征、预后的关系。方法 选取2017-06/2020-06月作者医院收治的72例HB患儿为研究对象,手术留取癌组织标本及对应的癌旁组织。连续随访3年,记录患儿的预后生存情况,并计算总生存率(overall survival, OS)。采用免疫组织化学法检测CTNNB1、TP53蛋白在HB患儿癌组织及癌旁组织中的表达情况;采用χ~2检验分析CTNNB1、TP53蛋白表达与HB患儿临床病理特征的关系;采用多因素Cox回归分析探讨HB患儿预后的影响因素。结果 HB患儿癌组织中CTNNB1阳性表达率(76.39%)高于对照组(43.06%),TP53阴性表达率(70.83%)高于对照组(38.89%)(P均<0.05)。初诊甲胎蛋白浓度≥100μg/L、POST-TEXT分期Ⅲ~Ⅳ期、肿瘤直径≥3 cm、有肿瘤侵袭或转移HB患儿的CTNNB1阳性表达率、TP53阴性表达率高于初诊甲胎蛋白<100μg/L、POST-TEXT分期Ⅰ~Ⅱ期、肿瘤直径<3 cm、无肿瘤侵袭或转移HB患儿(P均<0.05)。初诊甲胎蛋白≥100μg/L、POST-TEXT分期Ⅲ~Ⅳ期、有肿瘤侵袭或转移、CTNNB1阳性表达、TP53阴性表达的HB患儿3年OS低于初诊甲胎蛋白<100μg/L、POST-TEXT分期Ⅰ~Ⅱ期、无肿瘤侵袭或转移、CTNNB1阴性表达、TP53阳性表达的HB患儿(P均<0.05)。多因素Cox回归分析结果显示,POST-TEXT分期Ⅲ~Ⅳ期(HR=2.077,95%CI:1.423~3.032)、有肿瘤侵袭或转移(HR=2.291,95%CI:1.536~3.417)、CTNNB1阳性表达(HR=2.757,95%CI:1.781~4.268)、TP53阴性表达(HR=2.477,95%CI:1.635~3.753)是HB患儿预后的独立危险因素(P<0.05)。结论 HB患儿癌组织中CTNNB1主要呈阳性表达,而TP53主要呈阴性表达,二者与初诊甲胎蛋白、POST-TEXT分期、肿瘤直径、有肿瘤侵袭或转移密切相关,有望作为评估HB患儿预后的生物学指标。

铁死亡抑制蛋白1在肿瘤中的作用

铁死亡抑制蛋白1(FSP1)是铁死亡过程中的关键抑制因子,能够阻止细胞死亡,具有重要的生物学功能和潜在的临床应用价值。本研究详细探讨了FSP1的发现背景、基因定位与结构特性,以及其在抑制铁死亡和促进细胞凋亡中的双重作用。临床研究已经开发出针对FSP1的抑制剂,如铁死亡抑制蛋白1抑制剂(iFSP1)和相分离诱导型铁死亡抑制蛋白1抑制剂(icFSP1),未来的研究将进一步探讨FSP1的表达调控机制、与肿瘤免疫逃逸的关联以及其作为肿瘤预后和治疗反应监测指标的潜力。

组蛋白H2A去泛素化酶BAP1对恶性胶质瘤细胞发生发展的作用及临床应用价值研究

目的探索乳腺癌/卵巢癌易感基因1相关蛋白1(breast/ovarian cancer susceptibility gene 1 associated protein 1,BAP1)对人源恶性胶质瘤发生、发展的作用与BAP1作为恶性胶质瘤临床诊断标志物的可行性。方法基于基因表达综合数据库(gene expression omnibus,GEO)的子数据集GSE4290,GSE90598,分析BAP1在正常组织及胶质瘤组织中的差异性表达情况;受试者工作特征(receiver operating characteristic,ROC)曲线分析BAP1对恶性胶质瘤的早期诊断价值;选取自主收集的非配对28例恶性胶质瘤患者的原发灶组织、5例颅脑外伤患者内减压术切除的非瘤脑组织,采用实时荧光定量PCR(quantitative real-time polymerase chain reaction,qRT-PCR)检测BAP1的表达水平;利用靶向BAP1的特异性小干扰RNAs(small interfering RNAs,siRNAs)瞬时转染U251细胞系,进一步检测其干涉效率;基于流式细胞仪分析BAP1下调的U251细胞系,其细胞周期、凋亡的变化情况。结果生物信息学结果显示,BAP1在恶性胶质瘤组织中的表达水平均低于正常脑组织(GSE4290:1209±18.49 vs 1476±53.90;GSE90598:5.19±0.10 vs 5.65±0.21),差异具有统计学意义(t=5.115,2.267,均P<0.05)。ROC曲线显示,BAP1可高效区分恶性胶质瘤组织与正常脑组织(GSE4290:AUC=0.78;GSE90598:AUC=0.75,均P<0.05)。临床标本结果显示,BAP1在恶性胶质瘤原发灶组织中的表达水平显著低于非瘤脑组织(0.27±0.04 vs 1.06±0.07),差异具有统计学意义(t=10.22,P<0.001)。在U251细胞系中下调BAP1的表达,其细胞周期中S期细胞比例明显增多,由17.59%分别增至27.21%(siBAP1-1)和25.79%(siBAP1-2),差异具有统计学意义(t=6.576,6.642,均P<0.01),而细胞凋亡水平则有所下降,由10.17%分别降至2.70%(siBAP-1)和3.00%(siBAP-2),差异具有统计学意义(t=10.31,9.428,均P<0.01)。结论组蛋白H2A去泛素化酶BAP1能够通过抑制恶性胶质瘤细胞周期快速进展并促进其凋亡,进而发挥肿瘤抑癌基因的功能,可作为潜在的恶性胶质瘤临床诊断标志物。

Function of apoptosis and expression of the proteins Bcl-2,p53 and C-myc in the development of gastric cancer

INTRODUCTIONIn China ,the incidence and mortality of gastric cancer rank the second among all cancers. Recent development of cancer [1-20].The aim of this study was investigat the insight of apoptosis and bcl-2, p53 and C-myc protein expression in the development of gastric cancer .

Altered expression of nuclear matrix proteins in etoposide induced apoptosis in HL-60 cells

The events of cell death and the expression of nuclear matrix protein (NMP) have been investigated in a promyelocytic leukemic cell line HL-60 induced with etoposide. By means of TUNEL assay, the nuclei displayed a characteristic morphology change, and the amount of apoptotic cells increased early and reached maximun about 39% after treatment with etoposide for 2 h. Nucleosomal DNA fragmentation was observed after treatment for 4 h. The morphological change of HL-60 cells, thus, occurred earlier than the appearance of DNA ladder. Total nuclear matrix proteins were analyzed by 2-dimensional gel electrophoresis. Differential expression of 59 nuclear matrix proteins was found in 4 h etoposide treated cells. Western blotting was then performed on three nuclear matrix acssociated proteins, PML, HSC70 and NuMA. The expression of the suppressor PML protein and heat shock protein HSC70 were significantly upregulated after etoposide treatment, while NuMA, a nuclear mitotic apparatus protein, was down regulated. These results demonstrate that significant biochemical alterations in nuclear matrix proteins take place during the apoptotic process.

AU-rich element-binding proteins in colorectal cancer

Trans-acting factors controlling mRNA fate are critical for the post-transcriptional regulation of inflammation-related genes, as well as for oncogene and tumor suppressor expression in human cancers. Among them, a group of RNA-binding proteins called "Adenylate-Uridylate-rich elements binding proteins"(AUBPs)control mRNA stability or translation through their binding to AU-rich elements enriched in the 3'UTRs of inflammation-and cancer-associated mRNA transcripts. AUBPs play a central role in the recruitment of target mRNAs into small cytoplasmic foci called Processing-bodies and stress granules(also known as P-body/SG). Alterations in the expression and activities of AUBPs and Pbody/SG assembly have been observed to occur with colorectal cancer(CRC)progression, indicating the significant role AUBP-dependent post-transcriptional regulation plays in controlling gene expression during CRC tumorigenesis.Accordingly, these alterations contribute to the pathological expression of many early-response genes involved in prostaglandin biosynthesis and inflammation,along with key oncogenic pathways. In this review, we summarize the current role of these proteins in CRC development. CRC remains a major cause of cancer mortality worldwide and, therefore, targeting these AUBPs to restore efficient post-transcriptional regulation of gene expression may represent an appealing therapeutic strategy.

Aberrant expression of genes and proteins in pterygium and their implications in the pathogenesis

Pterygium is a common ocular surface disease induced by a variety of factors. The exact pathogenesis of pterygium remains unclear. Numbers of genes and proteins are discovered in pterygium and they function differently in the occurrence and development of this disease. We searched the Web of Science and PubMed throughout history for literatures about the subject. The keywords we used contain pterygium, gene, protein, angiogenesis, fibrosis, proliferation, inflammation, pathogenesis and therapy. In this review, we summarize the aberrant expression of a range of genes and proteins in pterygium compared with normal conjunctiva or cornea, including growth factors, matrix metalloproteinases and tissue inhibitors of mefalloproteinases, interleukins, tumor suppressor genes, proliferation related proteins, apoptosis related proteins, cell adhesion molecules, extracellular matrix proteins, heat shock proteins and tight junction proteins. We illustrate their possible mechanisms in the pathogenesis of pterygium as well as the related intervention based on them for pterygium therapy.

Potential effect of hepatitis C Virus non-structural protein 4B on liver carcinogenesis

Objective：To investigate the effect of hepatitis C virus non-structural protein 4B（HCV NS4B） on c-Myc, P53, ras gene expression＂ and apoptosis in hepatic cells and study the possible role that NS4B played in the carcinogenesis of heparoma. Methods： The recombinant plasmid（PCXN2-NS4B, PCXN2-P53） and the empty, vector were transfected or co-transfected into Chang liver cells with liposome. Screening was performed with G418. Plasmid mRNA was detected by RT-PCR. The pro rein expressions of c-Myc and ras genes were analyzed by immunocytochemistry. The expressions of wild-type P53 （wtp53） gene were detected by in situ hybridization. TUNEL（flow cytometry） was used for assessing the rate of apoptosis. Results：No expression of c-Myc gene was found in PCXN2 group. The expression of c-Myc gene in NS4B group was 21.3% ＋ 1.2%. The ex pression of ras gene in PCXN2 group was lower than that in NS4B group. Compared with PCXN2 group, the expression of P53 mRNA was not promoted or inhibited in NS4B group. But the expression of P53 mRNA in NS4B-P53 group was lower than that in P53 group. In PCXN2, NS4B, P53 and NS4B-P53 group, the rates of apoptosis were 17.02% ± 1.24%, 11.94% ± 2.24%, 25.84% ± 3.49% and 18.34% ± 1.55% respectively. Conclusion ：HCV NS4B induces the expression of c-Myc and ras gene. HCV NS4B may play a role in the inhibition of cell death through P53-dependent manner. Results from this study suggested that HCV NS4B might contribute to the viral carcinogenesis.

牛磺酸对胰腺癌细胞系BxPC-3和PANC-1细胞增殖、凋亡和迁移的影响

目的探讨牛磺酸(Tau)对胰腺癌导管细胞增殖、凋亡和迁移的影响。方法体外培养胰腺癌BxPC-3和PANC-1细胞,采用不同浓度Tau(0、10、20、40、80、160 mmol/L)进行预处理。采用CCK-8、细胞划痕实验、TUNEL法观察Tau对BxPC-3和PANC-1细胞增殖、迁移和凋亡的影响;实时荧光定量聚合酶链反应(qPCR)和蛋白质免疫印迹法检测Tau影响BxPC-3和PANC-1细胞中相关细胞凋亡及细胞周期分子mRNA和蛋白表达的情况。结果Tau可抑制BxPC-3和PANC-1的细胞增殖和迁移活性;同时,Tau能够促进BxPC-3和PANC-1细胞凋亡。与对照组相比,Tau处理后的BxPC-3细胞中相关凋亡因子P53、P21、Bcl-2关联X蛋白(BAX)表达水平呈上升趋势,而增殖细胞核抗原(PCNA)的表达降低;Tau处理后的PANC-1细胞中B淋巴细胞瘤-2蛋白(Bcl-2)、PCNA、细胞周期蛋白CyclinA2、CyclinB1、CyclinE、周期蛋白依赖性激酶CDK1、CDK2、CDK4、CDK6等的表达较对照组均下降,而相关凋亡蛋白P53、P21的表达水平升高。结论Tau可抑制胰腺癌细胞BxPC-3和PANC-1的增殖和迁移活性,并促进细胞凋亡,可能是通过影响相关细胞凋亡基因和细胞周期蛋白来抑制胰腺癌细胞的活性。

柴胡三参胶囊对心肌缺血再灌注损伤大鼠心脏的保护作用及铁死亡机制研究

目的 研究柴胡三参胶囊对心肌缺血再灌注损伤(myocardial ischemia reperfusion injury, MIRI)大鼠心脏的保护作用。方法 取84只SPF级大鼠随机分为假手术组、模型组、地尔硫艹卓组和柴胡三参胶囊低、中、高剂量组,每组14只。术前对大鼠进行灌胃,假手术组及模型组大鼠灌胃等溶剂生理盐水。假手术组只穿线不结扎,其余各组均用无菌缝合线结扎大鼠冠状动脉左前降支30 min并松线90 min构建心肌缺血再灌注模型,再灌注结束后立即取血,剥离心脏。比较各组心律失常积分,运用TTC染色法计算心肌梗死面积,运用HE染色法镜下观察心肌组织病理改变,Western blot法检测心肌组织中铁死亡相关蛋白表达水平。结果 与假手术组相比,模型组大鼠心律失常积分升高(P<0.05),心肌细胞排列紊乱,细胞核大小参差不齐,大量细胞肥大、水肿、变性,心肌梗死区域显著增加(P<0.05),铁死亡相关蛋白混合谱系激酶3(mixed lineage kinase 3, MLK3)、c-Jun氨基末端激酶(c-Jun N-terminal kinase, JNK)、肿瘤抑制蛋白p53(tumor suppressor protein p53, p53)的表达显著升高(P<0.01)。与模型组相比,柴胡三参胶囊低剂量组大鼠在心律失常积分、心肌细胞损伤改善、心肌梗死面积和铁死亡相关蛋白MLK3、JNK、p53的表达上差异无统计学意义(P>0.05);柴胡三参胶囊中、高剂量组和地尔硫艹卓组大鼠心律失常积分明显降低(P<0.05),心肌细胞损伤改善,细胞排列较整齐,水肿程度减轻,心肌梗死面积减少(P<0.05),铁死亡相关蛋白MLK3、JNK、p53的表达显著降低(P<0.01)。结论 柴胡三参胶囊中、高剂量可减轻MIRI大鼠心律失常,减少心肌梗死面积,减轻心肌病理损伤,降低铁死亡相关蛋白表达水平,其机制可能与抑制心肌铁死亡有关。

p53信号通路调控铁死亡在肝细胞癌中的作用机制

肝细胞癌(HCC)在我国是最常见的肝癌类型,其发生发展是一个复杂的病理过程。铁死亡作为一种新的细胞死亡方式,在治疗HCC方面有巨大的潜在作用。本文介绍了抑癌因子p53在调控铁死亡中的作用机制,简述其在HCC发生、发展中的作用。抑癌因子p53可以通过影响溶质载体家族7成员11、亚精胺/精胺N1-乙酰转移酶1、谷氨酰胺酶2、二肽基肽酶4和细胞周期蛋白依赖性激酶抑制剂1A来促进或抑制铁死亡,进而影响HCC的进展,通过调控铁死亡通路治疗HCC具有很大的应用前景。

体外靶向TP53BP2基因shRNA慢病毒载体的构建及功能鉴定

目的 本研究旨在构建靶向肿瘤蛋白p53结合蛋白2(TP53BP2)基因的短发夹RNA(shRNA)慢病毒载体,以抑制肝癌细胞TP53BP2的表达。方法 设计了2对针对TP53BP2基因的RNA干扰序列,并合成相应的shRNA序列。shRNA退火形成双链oligo序列后,应用基因重组技术构建重组质粒,经菌落PCR和测序鉴定,将重组正确的质粒进行慢病毒包装和滴度测定,并采用Western Blot、qRT-PCR和激光共聚焦技术观察慢病毒Lenti-shTP53BP2对HepG2细胞TP53BP2基因的干扰效果。结果 测序比对结果显示,各重组慢病毒载体与设计参考序列一致,提示各重组慢病毒体构建成功;重组慢病毒载体经慢病毒包装后,显示pHS-ASR-LW429、pHS-ASR-LW512和pHS-ASR-LW513的滴度分别为9.7×108TU/mL、6.1×108TU/mL和6.4×108TU/mL;用慢病毒Lenti-shTP53BP2(pHS-ASR-LW512和pHS-ASR-LW513)感染HepG2细胞后,与对照慢病毒(pHS-ASR-LW429)比,经Western Blot、qRT-PCR和激光共聚焦结果显示两个Lenti-shTP53BP2均能显著下调HepG2细胞TP53BP2基因水平和蛋白表达量。结论 本研究成功构建了靶向TP53BP2基因shRNA慢病毒载体,其能有效下调HepG2细胞TP53BP2的表达,为进一步研究TP53BP2在肝癌发生发展过程中的机制研究奠定了基础。

TP53、NLRP3、miR-551b在胆囊癌组织中的表达及与临床病理特征和预后的关系

目的 探究肿瘤抑制蛋白(tumor protein p53,Tp53)、核苷酸结合寡聚化结构域样受体蛋白3(nucleotide-binding oligomerization domain-like receptor protein 3,NLRP3)、微小核糖核酸551b(miR-551b)在胆囊癌组织中的表达及与临床病理特征和预后的关系。方法 选取在我院进行胆囊切除术的50例胆囊癌患者切除的胆囊癌组织为胆囊癌组,以及50例癌旁组织标本为对照组,同时期在我院接受胆囊炎治疗的50例为胆囊炎组。采用荧光定量聚合酶链反应测定miR-551b、TP53、NLRP3表达。观察P53、NLRP3、miR-551b表达在各组之间的表达,分析三者与临床病理和预后的关系,三者的相关性。结果 胆囊癌组TP53、NLRP3均高于对照组、胆囊炎组,miR-551b低于对照组(P<0.05)。对照组TP53、NLRP3低于胆囊炎组,miR-551b高于胆囊炎组(P<0.05)。随临床分期程度加重、分化程度越低、直径越大TP53、NLRP3表达不断升高,miR-551b表达不断降低(P<0.05)。有淋巴结转移患者TP53、NLRP3表达高于无淋巴结转移,miR-551b低于无淋巴结转移(P<0.05)。预后不良TP53、NLRP3表达高于预后良好,miR-551b低于预后良好(P<0.05)。TP53与NLRP3呈正相关,miR-551b与NLRP3、TP53呈负相关(P<0.05)。结论 P53、NLRP3在胆囊癌组织中高表达,miR-551b低表达,三者与临床特征、预后具有一定的相关性,三者之间具有相关性,高表达TP53、NLRP3以及低表达miR-551b是胆囊癌发病的风险预测因子。

p53与线粒体动力学的相互作用及其在癌症治疗中的应用

p53蛋白是癌细胞代谢过程和代谢重编程的关键调节因子,在细胞死亡和存活之间保持平衡。线粒体动力学与细胞周期、免疫、凋亡和线粒体质量控制等许多细胞过程密切相关。p53和线粒体动力学之间存在复杂的相互作用,二者相互调节和相互影响,在细胞生理和病理过程中具有重要意义。本研究综述p53和线粒体动力学之间的相互作用机制及其在癌症中的作用,探讨相关调控机制的治疗策略。通过揭示细胞代谢和癌症发生机制,旨在为癌症治疗提供新的思路和方法。

血清sST2联合MELD评分等多指标在ALSS治疗前预测乙型肝炎病毒相关慢加急性肝衰竭患者治疗结局

目的探讨人工肝支持系统(ALSS)治疗前血清可溶性致瘤抑制蛋白2(sST2)与乙型肝炎病毒相关慢加急性肝衰竭(HBV-ACLF)患者治疗结局的关系。方法选取2017年10月至2021年7月苏州大学附属传染病医院收治并经过ALSS治疗的HBV-ACLF患者30例为HBV-ACLF组,乙型肝炎病毒相关肝硬化(HBV-LC)患者20例为HBV-LC组,另选取该院体检健康者25例作为对照组。采用酶联免疫吸附试验检测血清sST2、白细胞介素(IL)-2、IL-12、IL-17、干扰素(IFN)-γ水平,收集相关临床数据并采用受试者工作特征(ROC)曲线、Kaplan-Meier生存曲线分析各指标和患者治疗结局的关系。结果血清sST2水平在HBV-ACLF组中升高,明显高于对照组和HBV-LC组(P<0.05)。利用ROC曲线获得sST2最佳临界值,并根据其将30例HBV-ACLF患者分为高值组和低值组,结果发现低值组患者30 d生存率明显高于高值组(P<0.05)。sST2联合终末期肝病模型(MELD)评分和炎症相关指标IL-12具有较高的预测价值,其曲线下面积为0.775,明显高于其他指标联合检测结果。结论外周血sST2水平可以预测ALSS疗效,sST2联合MELD评分和IL-12可以有效预测ALSS治疗效果,提示sST2可作为一种新型生物标志物协助临床预测ACLF患者治疗结局。

三阴性乳腺癌组织中雄激素受体、肿瘤抑制蛋白P53的表达及与预后的关系

目的 探讨雄激素受体(AR)、肿瘤抑制蛋白p53(P53)在三阴性乳腺癌(TNBC)组织中的表达及与患者预后的关系。方法 将52例女性TNBC患者纳入观察组,同期收治的50例女性非三阴性乳腺癌(NTNBC)患者纳入对照组,所有患者均经手术病理检查确诊。运用免疫组织化学法检测2组癌组织内的AR、P53表达情况;同时分析AR、P53的表达与TNBC患者临床病理特征的关系。随访3年,以Kaplan-Meier法分析AR、P53表达与TNBC患者预后的关系。结果 观察组的AR阳性表达率低于对照组,P53阳性表达率高于对照组,有统计学差异(P<0.05)。AR、P53的表达与TNBC患者的组织学分级、TNM分期、淋巴结转移有关(P<0.05),与年龄、绝经状态、肿瘤直径无关(P>0.05)。Kaplan-Meier结果显示:AR阴性表达患者的3年生存率[40.63%(13/32)]低于AR阳性表达[75.00%(15/20)],P53阳性表达患者的3年生存率[40.00%(16/40)]低于P53阴性表达[75.00%(9/12)],有统计学差异(P<0.05)。结论 TNBC患者的癌组织内的AR呈阴性表达,P53呈阳性表达,AR、P53的表达与患者的组织学分级、TNM分期、淋巴结转移联系紧密,且AR阴性表达、P53阳性表达患者生存率更低,预后更差。