TOX介导T细胞耗竭的机制及其逆转研究

胸腺细胞选择相关的高迁移率族蛋白(TOX)是一种与DNA结合的转录因子,参与免疫细胞的发育过程。TOX是促进T细胞耗竭的关键转录因子,并与肿瘤的发生发展密切相关,提示TOX可能是潜在的免疫生物标志物和恶性肿瘤免疫治疗的靶点。本文就TOX介导T细胞耗竭的分子机制及其逆转研究的最新进展做一综述,为设计基于TOX更为精准的肿瘤免疫治疗策略提供依据。

Ligustrazine facilitates hair cell regeneration in the cochlea following gentamicin ototoxicity

BACKGROUND： Ligustrazine （tetramethylpyrazine） decreases ototoxicity induced by gentamicin and facilitates hair cell regeneration and repair, but the precise mechanisms remain controversial.OBJECTIVE： To explore the protective effects of ligustrazine on gentamicin ototoxicity by determining heat shock protein 70 mRNA and protein expression in the cochlear stria vascularis of guinea pigs at different time points.DESIGN, TIME AND SETTING： The randomized, controlled study was performed at the Laboratory of Physiology, Shenyang Medical College of China in 2007.MATERIALS： Ligustrazine parenteral solution （Qiqihar Pharmaceutical Factory, China） and gentamicin sulfate （Shenyang First Pharmaceutical Factory, China） were used in this experiment.METHODS： White guinea pigs with red eyes were randomly intraperitoneally administered gentamicin sulfate injection ＋ saline, gentamicin sulfate injection ＋ ligustrazine, and ligustrazine ＋ saline, respectively.MAIN OUTCOME MEASURES： Auditory brains tern response threshold was measured. Immunohistochemistry, in situ hybridization, and image analyzing techniques were utilized to determine heat shock protein 70 mRNA and protein expression in cochlear stria vascularis of guinea pigs.RESULTS： Following gentamicin ototoxicity, the auditory brainstem response threshold increased, peaked on day 3, and then decreased with increased time after drug withdrawal. The auditory brainstem response threshold was significantly diminished following ligustrazine intervention, but recovered to normal on day 30 （P〉0.05）. Heat shock protein 70 expression also increased, peaked on day 3, and then decreased in the cochlear stria vascularis of guinea pigs following gentamicin ototoxicity. Ligustrazine intervention resulted in decreased heat shock protein 70 expression in the cochlear stria vascularis, which recovered to normal on day 14. Heat shock protein 70 mRNA expression increased in the cochlear stria vascularis following gentamicin ototoxicity, but ligustrazine intervention resulted in decreased levels. CONCLUSION： Ligustrazine significantly ameliorated gentamicin ototoxicity by reducing heat shock protein 70 mRNA and protein expression in the cochlear stria vascularis.

Nephroprotective activity of Solanum xanthocarpum fruit extract against gentamicin-induced nephrotoxicity and renal dysfunction in experimental rodents

Objective:To evaluate nephroprotective potential of Solarium xanthocarpum(S.xanthocarpum) fruit extract(SXE) against gentamicin(GM) induced nephrotoxicity) and renal dysfunction. Methods:Twenty-four Wistar rats were divided into four groups(n=6).Control rats that received normal saline(i.p.) and 0.5%carboxymethyl cellulose(p.o.) per day lor 8 d.Nephrotoxicity was induced in rats by intraperitoneal administration of GM(100 mg/kg/d for 8 d) and were treated with SXE(200 and 400 mg/kg/d(p.o.) for 8 d).Plasma and urine urea and creatinine,kidney weight,urine output,blood urea nitrogen,renal enzymatic and non-enzymatic antioxidants and lipid peroxidation was evaluated along with histopathological investigation in various experimental groupsof rats.Results:It was observed that the GM treatment induced significant elevation(P【0.001) in plasma and urine urea,creatinine,kidney weight,blood urea nitrogen, renal lipid peroxidation along with significant decrement(P【0.001) in urine output,renal enzymatic and non-enzymatic antioxidants.SXE 200 and 400 mg/kg treatment to GM treated rats recorded significant decrement(up to P【0.001) in plasma and mine urea and creatinine, renal lipid peroxidation along with significanl increment(up to P【0.001) in renal enzymatic and non-enzvmatic antioxidants.Histological obsenatioiis of kidney tissues too correlated with the biochemical obsenatioiis.Conclusions:These finding powerfully supports that S,xanthocarpum fruit extract acts in the kidney as a potent scavenger of free radicals to prevent the toxic effects of GM both in the biochemical and histopathological parameters and thus validates its elhnomedicinal use.

Anti-inflammatory, anti-oxidative and anti-apoptotic effects of Heracleum persicum L. extract on rats with gentamicin-induced nephrotoxicity

Objective:To evaluate the effect of Heracleum persicum L.against gentamicin-induced nephrotoxicity in rats.Methods:Thirty-six Wistar rats were divided into 6 groups including control(normal saline),gentamicin(80 mg/kg/d for 10 d),Heracleum persicum(750 mg/kg/d),and gentamicin(10 d)+Heracleum persicum extract at three different doses(250,500,and 750 mg/kg/d for 40 d).Urine creatinine,urea,protein,and albumin levels were determined.In addition,serum urea,creatinine,sodium,potassium,cytokines(TNF-α,IL-1β,IL-6,and IL-10),glutathione peroxidase activity,total antioxidant capacity,kidney malondialdehyde,stereological parameters,and expressions of apoptosis-related genes(p53,Bax,Bcl-2,and caspase-3)were measured.The LD50 of Heracleum persicum extract was determined based on Lorke’s method.Histopathological evaluation was also performed.Results:In addition to decreased urine protein and albumin,and increased creatinine and urea,co-treatment with gentamicin and Heracleum persicum significantly reduced levels of creatinine and urea,and increased sodium and potassium in serum.Heracleum persicum treatment also improved stereological parameters and serum inflammatory cytokines.There was a significant increase in serum glutathione peroxidase activity and total antioxidant capacity as well as a reduction in malondialdehyde level.Furthermore,treatment with Heracleum persicum extracts downregulated p53,caspase-3,and Bax and upregulated Bcl-2 expressions.In histopathological evaluation,Heracleum persicum extracts showed protection against gentamicin-induced renal damages.Conclusions:Heracleum persicum exhibits protective effects against gentamicin-induced structural and functional renal impairments.

尼罗罗非鱼高迁移率族蛋白4(TOX4)基因克隆及其在细菌感染过程中的表达特征

为了解析与胸腺细胞选择相关的高迁移率族蛋白4(tox high mobility group box family member 4,TOX4)在尼罗罗非鱼(Oreochromis niloticus)响应无乳链球菌(Streptococcus agalactiae)感染过程中的功能,利用聚合酶链式反应(PCR)克隆和鉴定尼罗罗非鱼TOX4基因(GenBank登录号:XP003458812)的开放阅读框(open reading frame,ORF)序列,对推导的TOX4氨基酸序列进行生物信息学分析,分析其亚细胞定位特征,以及在尼罗罗非鱼头肾淋巴细胞亚群的分布特征,并利用荧光定量PCR(qRT-PCR)技术分析TOX4基因在健康鱼各组织及响应无乳链球菌感染过程中的表达模式。结果表明:尼罗罗非鱼TOX4基因的ORF全长为2004 bp,编码667个氨基酸,预测TOX4蛋白的相对分子质量为69060,理论等电点为4.69,无信号肽序列及跨膜结构,具有一个HMG保守结构域;亚细胞定位结果显示,TOX4蛋白主要表达于细胞核中;多序列比对及系统进化分析均显示,尼罗罗非鱼与斑马拟丽鱼(Maylandia zebra)TOX4氨基酸序列的同源性最高;qRT-PCR分析显示,TOX4基因在健康尼罗罗非鱼各组织中均有表达,且在血液中表达量最高;单细胞转录组数据分析显示,TOX4基因主要在尼罗罗非鱼非特异性细胞毒性细胞(nonspecific cytotoxic cell,NCC)和巨噬细胞(macrophage,Mφ)中表达;经无乳链球菌感染后,尼罗罗非鱼脑、头肾、肠道和脾脏中TOX4基因的表达量显著上调,并在感染后12 h(脑、头肾、肠道)和48 h(脾脏)达到峰值。研究表明,TOX4可能参与尼罗罗非鱼响应细菌感染的免疫应答过程。

Floral extract of Tecoma stans:A potent inhibitor of gentamicin-induced nephrotoxicity in vivo

Objective:To highlight the nephroprotective activity of ethyl acetate extract of dried flowers of Tecomu stans for its protective effects on genlamicin-induced nephrotoxicity in albino rats. Methods:For studying acute toxicity study,single oral dose of 5（KM） mg ethyl acetate floral extract/kg hodv weight was administered to albino rats（five females,five males）.Nephrotoxicity was induced in albino rats by intraperitoneal administration of gentamicin 80 mg/kg/day for eight days.Effect of concurrent administration of ethyl acetate floral extract of Tecoma stans at a dose of 100.200 and 300 mg/kg/day given by oral mute was determined using serum creatinine,serum uric acid,blood urea nitrogen and serum urea as indicators of kidney damage.The study groups contained six rats in each group.As nephrotoxicity of gentamicin is known to involve induction of oxidative stress,in vitro antioxidant aclivity and free radical-scavenging activity of this extract was also evaluated.Results:For acute toxicity testing both female and male rats administered with the extract at a dose of 5 000 mg/kg.The results showed no toxicity in terms of general behavior change,mortality,or change in gross appearance of internal organs(LD50】5 000 mg/kg). It was observed that the ethyl acetate floral extract of Tecoma stans significantly protected rat kidneys from gentamicin-induced histopathological changes.Gentamicin-induced glomerular congestion,peritubular and blood vessel congestion,epithelial desquamation,accumulation ol inflamnialoiy cells and necrosis of the kidney cells were found to be reduced in the groups receiving the ethyl acetate floral extract of Tecoma starts along with gentamicin in a dose dependent manner.The floral extract also reduced the gentamicin-induced increase in serum creatinine,serum uric acid,blood urea nitrogen and serum urea levels（P】0.01）.Conclusions: The present study indicates a verv important role of reactive oxygen species（BOS） and the relation to renal dysfunction and point to the therapeutic potential of Tecoma stans in gentamicin induced nephrotoxicity.

Toxicological evaluation and protective effect of ethanolic leaf extract of Launaea taraxacifolia on gentamicin induced rat kidney injury

Objective: To evaluate the toxic potential of Launaea taraxacifolia leaf extract(LTE) in rats within 14 d of oral administration and also assess the potential of LTE in protecting against kidney injury induced by gentamicin using rat model.Methods: The protective ability of LTE was done after sub-acute toxicity evaluation has been carried out. Acute Kidney Injury(AKI) was induced by gentamicin at a dose of 160 mg/kg intraperitoneal i.p. Parameters and indicators considered include mortality,clinical signs, body and organ weights, haematological and clinical chemistry parameters.Gross examination and histopathological assessment was also done on selected internal organs.Results: There were no treatment-related deaths or changes in clinical signs, haematological and clinical chemistry indices during sub-acute toxicity studies with the exception of creatinine levels. This was confirmed by micrographs obtained from histopathological analysis. Co-administration of LTE with 160 mg/kg of gentamicin(i.p) markedly decreased the levels of urea and creatinine when compared to negative control group.Histological studies of kidney tissues showed an insignificant change in tubular epithelium in LTE plus gentamicin treated group compared to LTE treated only.Conclusions: Data obtained show that ethanolic leaf extract of Launaea taraxacifolia is non-toxic within a 14 d administration at a maximum dose of 1 000 mg/kg bwt and also possesses the ability to protect against gentamicin-induced kidney damage in rats at a dose of 300 mg/kg bwt.

Effect of nettle(Urtica dioica) extract on gentamicin induced nephrotoxicity in male rabbits

Objective:To investigate the antioxidant ef ect of an orally administered ethanol extract of nettle(Urtica dioica) and its protective role in preventing or ameliorating oxidative stress as a major factor in gentamicin-induced nephrotoxicity in male rabbits. Methods: Twenty rabbits were divided into 4 equal groups:(G1) control group,(G2) gentamicin treated group(100 mg/kg),(G3) nettle treated group(100 mg/kg),(G4) combination treated group with both gentamicin(100 mg/kg) and nettle(100 mg/kg) for 10 days. The antioxidant properties of nettle were evaluated using dif erent antioxidant tests, such as determination of glutathione and malondialdehyde levels and total phenolic content analysis. Results: Biochemical and histopathological study revealed that gentamicin caused nephrotoxicity observed clearly in the histopathological section of the kidney in the gentamicin treated group. Serum creatinine and blood urea nitrogen were biochemical indicators for nephrotoxicity which increased signii cantly in gentamicin treated group; other groups have no signii cant change in these two parameters. Nettle extract protected the rabbits from alteration in the level of blood urea nitrogen and serum creatinine when given after inducing of gentamicin nephrotoxicity. The nettle treated group showed a great ef ect as an antioxidant factor by increasing the glutathione level and reducing malondialdehyde level. No signii cant changes in biochemical parameters and no renal histopathological changes observed in the groups treated with nettle extract, which meant nettle had powerful antioxidant activity. Conclusions: Therefore, it can be assumed that the nephroprotective ef ect shown by nettle in gentamicin-induced nephrotoxicity can reserve intracellular levels of biological pathways and supportively enhance excretion of toxic levels of gentamicin.

Novel genomic biomarkers for acute gentamicin nephrotoxicity in dog

Objectives: Novel biomarkers indicative of drug-induced kidney injury (DIKI) in dogs would have significant application in preclinical drug development. We conducted a feasibility study to identify genomic expression profiles for monitoring progressive, acute DIKI in dogs. Materials and Methods: Animals were intramuscularly administered either 0.9% physiological saline or gentamicin (40 mg/kg/day) for 10 consecutive days and euthanized on day 11. Serum and urine samples were collected at various time points and kidney samples were collected at necropsy for biomarker measurements. Results: Acute gentamicin-induced renal histopathology changes were localized to the proximal convoluted tubules and characterized as slight-to-marked, diffuse cortical-medullary tubular epithelial degeneration/necrosis. Serum creatinine (sCr) and blood urea nitrogen (BUN) elevations suggestive of mild renal dysfunction were first observed on days 7 to 8. Gentamicin-induced increased urinary kidney injury molecule-1 (KIM-1) mRNA was observed on day 6 preceding detectable elevations of sCr and/or BUN. Increased urinary KIM-1 mRNA correlated with multifocal KIM-1 immunostaining in the corticomedullary tubular epithelial cells. Microarray analysis revealed changes in additional mRNA expression products detected in urine and/or kidney that should be further investigated for use as potential biomarkers for acute gentamicin related nephrotoxicity in dogs. Conclusion: These findings suggested the utility of non-invasive urinary genomic parameters for monitoring acute DIKI in dogs.

Allolobophora caliginosa coelomic fluid ameliorates gentamicin-induced hepatorenal toxicity in rats

Objective:To explore the efficacy of earthworm’s coelomic fluid against gentamicin-induced hepatic and renal toxicity in rats.Methods:The animals were divided randomly into three groups(n=6 per group):control,gentamicin,and Allolobophora caliginosa coelomic fluid-treated groups.Toxicity was established after injection of gentamicin daily for 8 days at a dose of 100 mg/kg.Aspartate aminotransferase,alanine aminotransferase,alkaline phosphatase,total proteins,albumin,creatinine,urea,uric acid,malondialdehyde,glutathione,catalase and histopathology of tissues were investigated in the study.Results:Allolobophora caliginosa coelomic fluid significantly decreased urea,creatinine,uric acid,alanine aminotransferase,aspartate aminotransferase,alkaline phosphatase,and malondialdehyde levels while significantly increasing levels of total proteins,albumin,glutathione and catalase.The histopathological investigation showed partial restoration of renal and hepatic architecture.Conclusions:This study shows the potency of Allolobophora caliginosa coelomic fluid in improving the biochemical and histopathological changes induced by gentamicin in the liver and kidney of the rats.

Gentamicin Renal Excretion in Rats: Probing Strategies to Mitigate Drug-Induced Nephrotoxicity

The renal excretion of gentamicin, an aminoglycoside antibiotic, was studied in the isolated perfused rat kidney (IPRK) model. Dose-linearity experiments were carried out at four doses (400, 800, 1600, 3200 μg), targeting initial perfusate levels of 5, 10, 20 and 40 μg/ml. Additionally, gentamicin was co-perfused with sodium bicarbonate (0.25 mM) and/or cimetidine (2 mM) to evaluate the effect of urinary alkalization and secretory inhibition on gentamicin excretion and kidney accumulation. Gentamicin displayed net reabsorption in the IPRK, consistent with extensive luminal uptake. Kinetic analysis indicated that luminal transport of gentamicin (kidney ? urine) is the rate-determining step for gentamicin urinary excretion. Clearance and cumulative excretion decreased with increased gentamicin dose. Gentamicin kidney accumulation, estimated by mass balance, ranged from ~20% - 30%. Urinary alkalization significantly increased gentamicin excretion, with no effect on kidney accumulation. Conversely, cimetidine co-administration did not affect gentamicin clearance in the IPRK, but kidney accumulation was significantly reduced. When both sodium bicarbonate and cimetidine were administered together, gentamicin kidney accumulation decreased ~80% with corresponding increases in clearance and excretion ratio (XR) compared to gentamicin alone. A main strategy to reduce the incidence of nephrotoxicity with gentamicin therapy (up to ~25%) involves reducing kidney accumulation of the compound. The results of this research suggest that the combination of urinary alkalization and inhibition of basolateral secretion (blood → kidney) may be a viable approach to mitigate aminoglycoside toxicity, and warrants further investigation.

Predicting ADME/Tox properties of hydroxytyrosol in the leaves of Olea europaea L.

In order to study the possibility of hydroxytyrosol(HT)as a drug,we used SwissADME system to predict ADME of HT and pkCSM system to predict Tox of HT.The results show that hydroxytyrosol meets the Lipinski’s five principles of drug-like properties.With strong efficacy and pharmacological activity,HT has high drug-likeness degree.With good bioavailability,it can be easily absorbed by the gastrointestinal tract,though not absorbed by skin.Hydroxytyrosol has not only a strong potency and pharmacological activity,but also no liver toxicity and skin allergy.Tox data predicts that it has mutagenic potential,which may be the result of overreduction.

尿路感染细胞实验中庆大霉素对尿路致病大肠杆菌的杀伤作用及细胞毒性研究

目的在尿路感染体外细胞实验中,比较不同浓度庆大霉素(0、10、20、50、100、200μg/mL)对尿路致病大肠杆菌(UPEC)的杀伤作用,对尿路上皮细胞及炎性细胞如巨噬细胞的毒性作用。方法比较不同浓度庆大霉素对不同量UPEC J96菌株(10^(8)、10^(7)、10^(6))的杀伤情况;CCK-8实验检测不同浓度庆大霉素在不同时间内(2 h或24 h)对原代培养的C57BL/6雄鼠肾小管上皮细胞、腹腔巨噬细胞、人膀胱上皮细胞系J82的毒性作用;根据实验选择合适的庆大霉素浓度和作用时间,检测J96对小鼠肾小管上皮细胞的黏附、入侵以及小鼠巨噬细胞对J96的吞噬、清除作用。结果庆大霉素(≥10μg/mL)对J96的杀伤作用均强于1%的青霉素/链霉素双抗(P<0.0001),高浓度庆大霉素(≥100μg/mL)可在30 min内完全杀伤高达10^(8)的J96。50μg/mL庆大霉素作用2 h可对人膀胱上皮细胞系J82产生毒性作用(P<0.05)。结论本文明确了不同细胞体外实验时适宜的庆大霉素处理浓度及时间,人膀胱上皮细胞系J82对庆大霉素更为敏感。

BPQDs@TNTs药物载体的构建及其缓释性能研究

目的在骨科钛板表面构建能负载阿仑膦酸钠及硫酸庆大霉素的双载药复合药物载体。方法通过阳极氧化法在TiO_(2)表面制备纳米管阵列(TNTs),动态吸附阿伦磷酸钠后再填充载有硫酸庆大霉素的载药黑磷量子点(BPQDs),管口采用肉豆蔻醇进行封装,并利用X射线衍射、透射电镜进行表征,最后通过液相色谱法测定其上负载的阿仑膦酸钠及硫酸庆大霉素的缓释速率。结果X射线衍射表明构建的BPQDs@TNTs药物载体具备BP和TNTs的特征衍射峰,透射电镜扫描表明,肉豆蔻醇成功地对TNTs进行了封口,TiO_(2)纳米管中的阿仑膦酸钠及BPQDs载体的硫酸庆大霉素在72 h内已基本释放完毕,BPQDs@TNTs药物载体上阿仑膦酸钠及硫酸庆大霉素则在96 h内才基本释放完毕。结论BPQDs@TNTs药物载体能成功搭载阿仑膦酸钠及硫酸庆大霉素,且在体液中具有更好的缓释效能。

稳定过表达TOX3的乳腺癌MDA-MB-231细胞系的建立

目的构建人TOX高迁移率蛋白家族成员3(TOX3)基因慢病毒表达载体并建立稳定过表达TOX3的MDA-MB-231人乳腺癌细胞系。方法通过全基因合成法合成TOX3基因序列片段,并进行PCR扩增。将TOX3基因克隆到pLVEF-1a/GFP-Puro载体中,构建pLVEF-1a/GFP-Puro-TOX3慢病毒载体。经酶切和测序鉴定后,将构建好的慢病毒载体进行病毒包装和病毒滴度检测。用获得的慢病毒液转染MDA-MB-231人乳腺癌细胞系,通过嘌呤霉素选择性培养,用荧光显微镜观察绿色荧光蛋白(GFP)的表达,采用实时定量PCR(qRT-PCR)检测MDA-MB-231细胞中TOX3 mRNA的表达,Western blot法检测MDA-MB-231细胞中TOX3蛋白的表达。结果经酶切和测序鉴定,成功构建了pLVEF-1a/GFP-Puro和pLVEF-1a/GFP-Puro-TOX3慢病毒表达载体,病毒包装后检测病毒滴度分别为2×108TU/mL和1×108TU/mL,转染MDA-MB-231细胞后,GFP表达的细胞达95%以上。与阴性对照组相比,qRT-PCR和Western blot结果显示,MDA-MB-231-TOX3细胞中TOX3的mRNA和蛋白表达水平均明显升高。结论成功构建了TOX3慢病毒表达载体并建立了稳定过表达TOX3的MDA-MB-231细胞系。

无机物的ADME/Tox研究

无机物的吸收、分配、代谢和排除以及毒性 ( ADME/Tox)研究在药物和毒物研究中非常重要。近年来发展的在细胞层次上应用高通量和计算机等技术系统探索药物先导化合物的 ADME/Tox发展迅速。金属和其它无机化合物的 ADME/Tox研究在国内外都还是一个新兴的、具有广阔发展前途的跨学科研究领域。本文综述了国内外对于铁和铜以及稀土等金属的化合物的 ADME/Tox研究结果 。

肠出血性大肠杆菌O157∶H7toxB基因的分片段克隆和表达

根据Gen Bank已有tox B基因全长序列,分别设计6对引物扩增tox B基因,克隆到质粒p GEX-4T-1,构建重组菌BL21(plys)(p GEX-4T-1-tox B),IPTG诱导表达重组蛋白质,用Western blot鉴定重组蛋白质免疫原性。tox B基因片段大小分别为1 531 bp、1 590 bp、1 609 bp、1 603 bp、1 525 bp和1 690 bp,重组蛋白质分子量分别为8.1×104、8.3×104、8.4×104、8.3×104、8.0×104和8.7×104。以兔源EHEC O157∶H7抗血清为一抗,Western blot分析结果显示6个重组蛋白质均具有良好的免疫原性。

细胞壁缺陷对白喉棒状杆菌Tox基因影响

目的探讨细胞壁缺陷对白喉棒状杆菌毒力基因及其表达的影响。方法以非高渗分离培养法诱导并获得产毒性白喉棒状杆菌稳定L型纯培养物,提取白喉棒状杆菌稳定L型的染色体DNA,用Tox基因特异性引物进行PCR扩增,并进行序列测定和分析。分别采用对流免疫电泳(CIEP)和十二烷基磺酸钠-不连续聚丙烯酰胺凝胶电泳(SDS-PAGE)检测白喉棒状杆菌稳定L型可溶性代谢产物中的白喉毒素蛋白质。结果白喉棒状杆菌在氨苄青霉素作用下可发生细胞壁缺陷而成为L型,该稳定L型的传代培养物可仍然保留同其亲代细菌型一致的Tox基因及其核苷酸序列;但在其可溶性代谢产物中并未检测到白喉毒素蛋白质。结论白喉棒状杆菌稳定L型虽然保留了Tox基因但并不能表达白喉毒素蛋白质,提示细胞壁缺陷可影响Tox基因在宿主菌细胞内的表达。

TOX3基因rs3803662位点基因型与乳腺癌病理、临床特征的关系

目的 探讨TOX3基因rs3803662位点基因型与病理、临床特征的关系.方法 采用TaqMan 单核苷酸多态性（SNP）法检测TOX3基因rs3803662位点基因型,分析不同病理特征和临床特征与基因型分布的关系.结果 病理类型、组织分级、淋巴结转移、ER状态等病理特征与rs3803662位点基因型分布无关（P＞0.05）;IDC型和SBR3级变异型基因携带率分别显著高于DCIS型和SBR2级（P＜0.05）.诊断时年龄、临床分期、月经持续时间（年）及月经状态等临床特征与rs3803662基因型分布有关（P＜0.05）,纯合突变携带率随月经持续年限增加而显著增加（PTrend=0.034）.结论 TOX3基因rs3803662位点变异型基因与病理类型和组织分级有关,与临床分期、月经持续时间等临床特征有关.