热休克蛋白70-甲胎蛋白重组复合物抗瘤免疫的实验研究

目的:构建含有分子伴侣热休克蛋白70(HSP70)和甲胎蛋白(AFP)分子的蛋白复合物,研究此蛋白复合物是否具有针对AFP肿瘤诱导产生特异性CTL反应和保护性效应的能力.方法:戊二醛交联HSP70和AFP构建HSP70-AFP复合物.皮下注射免疫Balb/c纯系小鼠,同时设立单独AFP和HSP70免疫小鼠组作为对照.酶联免疫斑点实验(ELISPOT)和酶联免疫实验(ELISA)分别检测免疫后小鼠脾产生细胞因子IFN-γ的细胞数目和抗AFP抗体的水平.采用小鼠体内肿瘤负荷实验评价重组蛋白复合物的免疫效应.结果:经重组蛋白复合物免疫,ELISPOT和ELISA实验结果表明HSP70-AFP复合物免疫组分泌IFN-γ细胞因子的脾细胞数目和产生AFP的抗体水平显著高于AFP和HSP70免疫组(P<0.01).HSP70-AFP复合物免疫组瘤体积也明显小于AFP和HSP70免疫组(P<0.01).结论:研究证实了HSP70的免疫佐剂效应.实验结果表明重组HSP70-AFP复合物的连续免疫可以在小鼠体内产生有效的抗瘤免疫,HSP70-AFP重组蛋白复合物对于今后肿瘤疫苗的研究可能具有一定的意义.     

负载人AFP肽段的树突细胞在体内外对小鼠肝癌的抑制作用

背景与目的:甲胎蛋白(alpha-fetoprotein,AFP)是原发性肝细胞癌(hepatocellular carcinoma,HCC)免疫治疗的一个良好的靶分子,如何克服对自身抗原的免疫耐受状态是诱导有效抗肿瘤免疫反应的关键.本研究探讨异种同源蛋白疫苗负载人AFP肽段的树突细胞(human AFP-derived peptide-pulsed dendritic cells,hAFP-DCs)对小鼠肝癌的体外杀伤作用和体内抑瘤效应.方法:传统方法制备骨髓来源的DCs.MTT法检测hAFP-DCs诱导的CTL对小鼠肝癌细胞Hepal-6的体外杀伤活性.建立Hepal-6细胞C57BL/6小鼠移植瘤模型,分别瘤内注射hAFP-DCs、DCs和PBS(每周两次),观察小鼠肿瘤体积和荷瘤存活时间.结果:成功制备小鼠骨髓来源的DCs.体外杀伤实验显示,hAFP-DCs刺激组和单纯DCs刺激组CTL对Hepal-6细胞的杀伤作用强于PBS组,但组间差异无统计学意义(P>0.05).体内实验表明.每个C57BL/6小鼠接种7×106个Hepal-6细胞31 d后,hAFP-DCs、DCs和PBS组小鼠平均移植瘤体积分别为(195.04±155.22)mm3、(360.65±209.02)mm3和(756.19±503.24)mm3,组间比较差异有显著性(P<0.001).在40 d的观察期内,小鼠的累积存活率分别为100%、90%和50%(P=0.008).结论:负载人AFP抗原肽的DEs疫苗在体外和体内均能有效抑制小鼠肝癌的生长.     

自体肿瘤瘤苗对荷瘤鼠Th1、Th2型细胞因子及细胞毒作用的影响

目的研究经处理的H22肝癌细胞肿瘤瘤苗作为全细胞瘤苗对H22荷瘤小鼠体内Th1/Th2细胞比例和细胞因子的影响以及CTL的杀伤活性.方法用加重组白细胞介素2、重组粒细胞单核细胞集落刺激因子及福氏不完全佐剂制成疫苗,建立荷瘤小鼠模型,用51Cr释放法测定瘤苗免疫组、荷瘤组、正常组小鼠脾细胞对亲本H22肝癌细胞的杀伤活性;流式细胞仪检测单个核细胞中的Th1和Th2细胞,并取血检测血清中IL-10、IFN-γ水平.结果效靶比为200:1时,免疫小鼠脾细胞体外杀伤亲本H22肝癌细胞的杀伤率为38.3%,显著高于荷瘤组的13.6%,正常组的7.5%,以及对S180细胞的9.1%(P均＜0.05).瘤苗免疫组Th1细胞及Th1/Th2细胞的比值显著升高(P＜0.01),血清IFN-γ较对照组明显升高(P＜0.01);血清IL-10较对照组明显降低(P＜0.01).结论肿瘤细胞加小剂量IL-2和GM-CSF及佐剂组成的肿瘤细胞瘤苗可激发特异性细胞介导的免疫反应,改善抗肿瘤免疫反应.     

共表达基因疫苗MAGE-1/IL-18的抗肿瘤免疫治疗作用

目的观察已构建的共表达基因疫苗pcIL-18-MAGE诱导特异性免疫应答的能力和抗肿瘤免疫治疗作用。方法共表达疫苗肌注小鼠,间隔十天加强免疫一次,共免疫三次,以pcMAGE-1、 pcIL-18、pcDNA3和PBS为对照,检测小鼠脾细胞上清液IL-12和IFN-γ的浓度、脾细胞CTL杀伤活性及小鼠T细胞亚群情况;观察基因疫苗免疫MAGE (+)小鼠的成瘤时间和生存时间。结果pcIL-18-MAGE质粒免疫的小鼠,其脾细胞对SMMC-7721的杀伤率最高,与各对照组相比,差异有统计学意义;脾细胞CD3⁺、CD4⁺、CD8⁺ T细胞和上清液中细胞因子IL-12和IFN-γ均明显升高。共表达疫苗免疫MAGE (+)小鼠后,小鼠成瘤时间明显延迟,生存时间明显延长。结论共表达基因疫苗pcIL-18-MAGE在实验动物体内有显著的诱导特异性抗肿瘤免疫作用,且对肿瘤的生成有一定的抑制作用。     

fat-1基因对乳腺癌细胞的增殖抑制作用

目的: 以胃癌特异性多肽抗原MG7为靶点研制胃癌特异性纳米疫苗,并观察其对小鼠的免疫效能.方法: 人工合成胃癌MG7-Ag的模拟表位多肽,用磁力超声法将其包封于纳米乳剂中,通过透析纯化,HPLC检测其包封效率.用包封有MG7抗原肽的纳米疫苗免疫健康Balb/c小鼠,以空白纳米疫苗和PBS作为对照,测定其免疫活性,通过ELISA测定血清中抗MG7抗体的效价;ELISPOT测定小鼠脾CTL活性.同时,用表达MG7-Ag的小鼠艾氏腹水瘤细胞进行肿瘤攻击2周,观察疫苗对小鼠的保护作用.结果: 成功制备了胃癌MG7-Ag的纳米疫苗,并具有较好的包封率和较好的稳定性,小鼠产生MG7抗体, ELISPOT检测包封组与对照组相比分泌IFN-γ的活性淋巴细胞数量明显增高.疫苗免疫组8只小鼠中有2只未见肿瘤形成, 而对照组8只小鼠则全部成瘤.结论: 胃癌MG7-Ag表位纳米疫苗具有免疫原性,可以诱导小鼠产生抗肿瘤免疫.     

gp96-肽复合物体外诱导CTL反应及其抗肿瘤效应研究

目的研究小鼠肝癌腹水瘤H22细胞来源的gp96-肽复合物体外诱导小鼠脾淋巴细胞特异性细胞毒T细胞的产生及其抗肿瘤效应.方法利用蛋白提取纯化技术、Western-blot法、细胞培养技术、流式细胞术、CCK-8法、RT-PCR法等研究gp96-肽复合物体外诱导扩增CTL及其抗肿瘤效应.结果流式细胞仪检测表明,经gp96-肽复合物诱导后的CD8 T细胞比例达到近70%,远远高于对照组的35%、26%.该活化的CTL细胞在效靶比为50:1时的肿瘤杀伤率达72%与对照组相比具有统计学意义;将活化的CTL细胞回输小鼠体内能产生对该肿瘤细胞良好的过继性免疫保护,延长荷瘤小鼠的生存时间;RT-PCR法检测该活化的脾细胞较正常脾淋巴细胞高表达IFN-γ mRNA.结论肿瘤来源的热休克蛋白gp96-肽复合物能诱导小鼠脾淋巴细胞的CTL反应,并增强脾细胞 IFN-γ mRNA的表达,该CTL具有特异性抗H22肿瘤细胞的免疫保护作用.     

Ad介导人AFP和IFN-у协同诱发抗小鼠肝癌免疫效应

背景与目的:原发性肝癌(hepatocellular carcinoma,HCC)是常见的恶性肿瘤之一,目前对HCC的治疗尚无行之有效的手段。本研究探讨腺病毒(Adenovirus,Ad)载体介导异种甲胎蛋白(Alpha-fetoprotein,AFP)和酌干扰素(Interferon-gamma,IFN-γ酌)的协同抗肝癌效应。方法:用RT-PCR(reverse transcri-ptase-polymerase chain reaction)方法克隆小鼠IFN-γ酌基因并构建复制缺损型腺病毒编码人AFP和小鼠IFN-γ酌联合表达载体(Ad-hAFP/IFN-γ酌)。皮内免疫C57BL/6小鼠7d后,取脾细胞行51Cr释放实验检测特异性细胞毒T淋巴细胞(Cytotoxic Tlymphocytes,CTLs)杀伤活性;或给免疫小鼠皮下接种Hepa1-6肝癌细胞,观察荷瘤小鼠成活情况。结果:51Cr释放实验显示,Ad-hAFP/IFN-γ酌免疫小鼠1周后其诱导产生的特异性CTL杀伤活性明显强于Ad-hAFP或Ad-IFN-γ酌单独免疫,在效∶靶比(E∶T)为10∶1时,Ad-hAFP/IFN-γ酌、Ad-hAFP和Ad-IFN-γ酌诱发的CTL杀伤率分别(43.8±5.5)%、(28.2±3.2)%和(12.8±1.9)%;30∶1时,为(79.6±6.4)%、(51.9±4.3)%和(15.6±2.3)%以及90∶1时(88.2±6.3)%、(62.5±4.8)%和(26.5±2.4)%。荷瘤试验表明,Ad-hAFP或Ad-IFN-γ酌单独免疫小鼠后1周接种5×106Hepa1-6肝瘤细胞,观察2个月,Ad-hAFP免疫组80%的小鼠荷瘤,Ad-IFN-γ酌免疫组小鼠则100%荷瘤;而Ad-hAFP/IFN-γ酌免疫小鼠在接种同样数量的Hepa1-6细胞,2个月无小鼠荷瘤,小鼠100%存活。结论:腺病毒载体介导异种AFP能有效地诱发针对小鼠AFP的特异性细胞免疫反应,IFN-γ酌能明显增强这种效应。     

修饰的肿瘤抗原肽CEA_（610D）疫苗的体外抗肿瘤作用

目的:评价修饰的CEA610D抗原肽疫苗体外抗肿瘤免疫的有效性,为其临床应用提供依据.方法:多肽固相合成法合成HLA-A2 CEA修饰肽(CEA610D)、HLA-A2天然肽CEA605-613(天然肽)和HLA-A2无关肽MAGE-3(无关肽),采用同种异体混合淋巴细胞与肽共孵育的方法,诱导肽特异性细胞毒性T淋巴细胞(CTL),利用MTT法检测CTL的增殖和杀伤活性;流式细胞术观察细胞表型;RT-PCR检测细胞穿孔素的表达;ELISA法检测CTL上清中IFN-γ的水平.结果:CEA610D疫苗产生肽特异性CTL的能力最强(P<0.05),其CD8+T细胞数也高于天然肽组和无关肽组;在效靶比为40∶1时,CEA610D和天然肽所诱导的CTL对CEA+HLA-A2限制性人结肠癌细胞T84的杀伤活性可达(56.7±3.73)%和(51.2±1.86)%,而3种肽特异性CTL细胞对CEA+HLA-A2人结肠癌lovo细胞杀伤活性维持在本底水平;CEA610D组的CTL所释放的杀伤相关介质穿孔素和上清中IFN-γ的水平也显著高于其余两组(P<0.01).结论:与天然肽相比,CEA610D疫苗可打破自身表位的免疫耐受,在体外抗肿瘤免疫中更具优势.     

ehCGβ肿瘤基因疫苗诱生的效应脾细胞过继免疫抗肿瘤作用的研究

目的:探讨ehCGβ肿瘤基因疫苗诱生的效应脾细胞过继免疫在抗肿瘤中的作用.方法:通过转染建立稳定表达ehCGβ和HBV-preS2/S的细胞株Sp2/0-ehCGβ和Sp2/0-preS2/S.以TR421-hCGβ质粒实施基因免疫,免疫后检测小鼠脾细胞,特异性细胞毒活性;同期将脾细胞过继免疫给正常小鼠,以过继TR421-hCGβ质粒免疫小鼠脾细胞为实验组、过继TR421质粒免疫小鼠脾细胞为对照组,检测脾细胞杀伤效应.结果:效应脾细胞对SP2/0-ehCGβ的杀伤率明显高于Sp2/0-preS2/S(P＜0.05).Sp2/0-ehCGβ在实验组小鼠仅2只形成实体瘤,TR421-hcGβ质粒基因免疫抗肿瘤任用有肿瘤特异性,两组有显著性差异(P＜0.05),而在对照组小鼠均形成实体瘤.Sp2/0-preS2/S在所有的小鼠均形成了实体瘤,其瘤重无显著性差异.结论:ehCGβ肿瘤基因疫苗诱生的效应细胞可特异性杀伤肿瘤,过继免疫效应细胞能使正常小鼠获得明显的特异性抗肿瘤能力.     

HIFU治疗后肿瘤抗原对树突状细胞的活化及其抗肿瘤效应

目的：探讨HIFU治疗小鼠H22抑制性肝癌后产生的肿瘤抗原对机体抗肿瘤免疫功能增强的机制。方法：正常小鼠骨髓中提取骨髓细胞,在rmIL-4、rmGM-CSF奈件下培养7d,制备小鼠骨髓树突状细胞,用HIFU治疗小鼠移植性肝癌后产生的肿瘤抗原活化树突状细胞,再用活化后的树突状细胞激活T淋巴细胞为细胞毒性T细胞,用MTT法检测CTL在体外特异性杀伤肿瘤靶细胞的能力。结果：B16肿瘤HSP70-肽复合物组和H22肿瘤HSP70-肽复合物组的脾淋巴细胞的增殖率均高于阴性对照组、H22肿瘤粗提物组和HIFU后H22肿瘤粗提物组,P〈0．001;但两组之间差异无统计学意义,P〉0．05。H22肿瘤HSP70-肽复合物组CTL对H22肿瘤细胞的杀伤率为70．0％,明显高于阴性对照组、H22肿瘤粗提物组和HIFU后H22肿瘤粗提物组（P〈0．001）,但对非靶细胞B16肿瘤的杀伤率与上述各组的差异无统计学意义;B16肿瘤HSP70-肽复合物组CTL对B16肿瘤细胞的杀伤率为78．5％,对H22细胞的杀伤率为21．4％,表明CTL对肿瘤细胞的杀伤作用具有特异性。结论：HIFU治疗后坏死肿瘤组织中的HSP70-肽复合物作为肿瘤疫苗,通过活化DC和刺激T淋巴细胞增殖为CTL,发挥特异性抗肿瘤免疫功能。     

人食管鳞癌组织中热休克蛋白72和糖蛋白96的表达及其意义

目的：探讨热休克蛋白72（HSP72）和糖蛋白96（gp96）在人食管鳞癌组织中的表达及其意义。方法：利用EnVision免疫组织化学和图像分析方法检测人食管鳞癌组织及其癌旁组织中HSP72和gp96的表达与临床病理的关系。结果：90例食管鳞癌中85例（94．4％）HSP72呈现阳性，主要定位于细胞核，而gp96主要表达于胞浆，其阳性率为80．0％（72／90）。HSP72和gp96在食管鳞癌和癌旁组织中的表达存在明显的差异（P〈0．01）。与癌旁组织相比，HSP72的表达与肿瘤的分化程度具有一定的相关性。结论：食管鳞癌组织存在HSP72和sp96的高表达。HSP72和gp96在人食管鳞癌细胞中的表达对于研究食管鳞癌的进展和预后具有一定的意义。     

Application of serum pepsinogen and carbohydrate antigen 72-4 (CA72-4) combined with gastrin-17 (G-17) detection in the screening,diagnosis, and evaluation of early gastric cancer

BackgroundGastric cancer is a common malignant tumor. The aim of the present study was to analyze the application value of serum pepsinogen (PG), carbohydrate antigen 72-4 (CA72-4), and gastrin-17 (G-17) detection in the screening, diagnosis, and evaluation of early gastric cancer.MethodsIn total, 122 patients with gastric cancer treated in our hospital from January 2018 to January 2021 were selected as the gastric cancer group and subdivided into the early gastric cancer (group A) and advanced gastric cancer (group B) groups. Sixty-five patients with benign gastric disease treated in the same hospital during the same period were selected as the control group, and 122 healthy people who underwent physical examination during the same period were allocated to the control group. The differences in the levels of G-17, PGI, PGII, PGI/PGII, and CA72-4 were compared; receiver-operating characteristic curves were drawn; and the efficacy of different factors in the diagnosis of early gastric cancer was calculated.ResultsG-17, PGI, and PGI/PGII levels in the gastric cancer group were significantly lower than those in the healthy group, and CA72-4 was significantly higher than that in the healthy group (P<0.05), but there was no significant difference in PGII between the 2 groups (P>0.05). G-17, PGI, and PGI/PGII levels in groups A and B were significantly lower than those in the control group. CA72-4 in groups A and B was significantly higher than that of the control group, and was highest in group B (P<0.05). The areas under the curve (AUC) of G-17, PGI, PGI/PGII, and CA72-4 were 0.671, 0.726, 0.769, and 0.602, respectively, and the AUC of combined detection was 0.883, which was significantly higher than that of single detection.ConclusionsSerum PG, CA72-4 combined with G-17 detection has high sensitivity and specificity in the screening and diagnosis of early gastric cancer, and has high clinical application value.     

血清ＣＡ７２-４预测胃癌根治术后复发的临床研究

目的　探讨血清糖链抗原７２-４（ＣＡ７２-４）水平在胃癌根治术后复发患者中的临床价值。方法　动态监测７１例胃癌患者根治术术前、术后至复发的血清ＣＡ７２-４水平,分别记录复发前血清ＣＡ７２-４高于正常组（Ａ组）首次出现ＣＡ７２-４升高值及其距手术时间和距复发时间,以及Ａ组与复发前血清ＣＡ７２-４正常组（Ｂ组）的无病生存期（ＤFＳ）;采用受试者工作特征曲线（ＲＯＣ）计算Ａ组患者６个月内复发的血清ＣＡ７２-４阈值。结果　７１例复发患者中Ａ组为４３例,Ｂ组为２８例,两组的中位ＤＦＳ分别为１８.４个月和２６.９个月（Ｐ＝０.０００）。Ａ组患者首次出现ＣＡ７２-４升高值及其距手术时间和距复发时间分别为（５７.７±２６.８）Ｕ／ｍｌ、１２.４个月和５.２个月。在Ａ组中,首次出现ＣＡ７２ ４升高的６个月内复发者为２６例,中位距复发时间为４.５个月;６个月以上复发者１７例,中位距复发时间为９.５个月,经ＲＯＣ计算６个月内复发的血清ＣＡ７２-４阈值为５６.８Ｕ／ｍｌ（Ａｚ＝０.９４１）。７１例患者复发前首次出现血清ＣＡ７２-４≥５６.８Ｕ／ｍｌ组的中位ＤＦＳ为１７.０个月,低于复发前首次出现血清ＣＡ７２.４升高且<５６.８Ｕ／ｍｌ组的２１.１个月和Ｂ组的２６.９个月（Ｐ＝０.０００）。结论　动态监测血清ＣＡ７２-４水平对胃癌根治术后复发具有早期预测作用,尤其当首次检测血清ＣＡ７２-４升高且≥５６.８Ｕ／ｍｌ时能够较好地预测胃癌的复发。     

Correlation of TP53 and MDM2 genotypes with response to therapy in sarcoma

BACKGROUND:

Relatively few sarcomas harbor TP53 (tumor protein p53) mutations, but in many cases, amplification of MDM2 (murine double minute 2) effectively inactivate p53. The p53 pathway activity can also be affected by normal genetic variation.

METHODS:

The mutation status of TP53 and expression of MDM2, TP53, and their genetic variants SNP309 and R72P (Arg72Pro) were investigated in 125 sarcoma patient samples and 18 sarcoma cell lines. Association of the different genotypes and gene aberrations with chemotherapy response and survival, as well as response to MDM2 antagonists in vitro was evaluated.

RESULTS:

Twenty‐two percent of the tumors had mutant TP53 and 20% MDM2 gene amplification. Patients with wild‐type TP53 (TP53^Wt) tumors had improved survival (P < .001) and TP53^Wt was an independent prognostic factor (hazard ratio = 0.41; 95% confidence interval = 0.23‐0.74; P = .03). Interestingly, there was a trend toward longer time to progression after chemotherapy for tumors with the apoptosis‐prone p53 variant R72 (P = .07), which was strongest with doxorubicin/ifosfamide‐based regimens (P = .01). Liposarcomas had low R72 frequency (33% versus 56%), but increased levels of MDM2 and MDM4 (51% and 11%, P < .001). MDM2 overexpression on a TP53^Wt background predicted better response to MDM2 antagonist Nutlin‐3a, irrespective of R72P or SNP309 status.

CONCLUSIONS:

Improved survival after chemotherapy was found in patients with TP53^Wt tumors harboring the R72 variant. MDM2 overexpression in TP53^Wt tumors predicted good response to MDM2 antagonists, irrespective of R72P or SNP309 status. Thus, detailed TP53 and MDM2 genotype analyses prior to systemic therapy are recommended. Cancer 2013. © 2012 American Cancer Society.     

MDM2 and TP53 Polymorphisms as Predictive Markers for Head and Neck Cancer in Northeast Indian Population: Effect of Gene-Gene and Gene-Environment Interactions

Background: Polymorphisms in the MDM2 309 (T>G) and TP53 72 (G>C) genes are reported to increasethe susceptibility to head and neck cancer (HNC) in various populations. The risk for HNC is also stronglyassociated with etiologic habits such as smoking, alcohol consumption and/or chewing of betel quid (BQ). In acase-control study, we investigated the significance of the above polymorphisms alone, and upon interaction withone another as well as with various etiologic habits in determining HNC risk in a Northeast Indian population.Materials and Methods: Genotyping at 309 MDM2 and 72 TP53 in 122 HNC patients and 86 cancer free healthycontrols was performed by PCR using allele specific primers, and the results were confirmed by DNA sequencing.Results: Individuals with the GG mutant allele of MDM2 showed a higher risk for HNC in comparison to thosewith the TT wild type allele (OR=1.9, 95%CI: 1.1-3.3) (p=0.022). The risk was further increased in femalesby ~4-fold (OR=4.6, 95% CI: 1.1-19.4) (P=0.04). TP53 polymorphism did not contribute to HNC risk alone;however, interaction between the TP53 GC and MDM2 GG genotypes resulted in significant risk (OR=4.9, 95%CI: 0.2-105.1) (p=0.04). Smokers, BQ- chewers and alcohol consumers showed statistically significant and dosedependentincrease in HNC risk, irrespective of the MDM2 genotype. Conclusions: MDM2 genotype could serveas an important predictive biomarker for HNC risk in the population of Northeast India.     

TGFβ1 (Leu10Pro), p53 (Arg72Pro) can predict for increased risk for breast cancer in south Indian women and TGFβ1 Pro (Leu10Pro) allele predicts response to neo-adjuvant chemo-radiotherapy

The breast cancer incidence has been increasing in the south Indian women. A case (n = 250)–control (n = 500) study was undertaken to investigate the role of Single Nucleotide Polymorphisms (SNP’s) in GSTM1 (Present/Null); GSTP1 (Ile105Val), p53 (Arg72Pro), TGFβ1 (Leu10Pro), c-erbB2 (Ile655Val), and GSTT1 (Null/Present) in breast cancer. In addition, the value of the SNP’s in predicting primary tumor’s pathologic response following neo-adjuvant chemo-radiotherapy was assessed. Genotyping was done using PCR (GSTM1, GSTT1), Taqman Allelic discrimination assay (GSTP1, c-erbB2) and PCR-CTPP (p53 and TGFβ1). None of the gene SNP’s studied were associated with a statistically significant increased risk for the breast cancer. However, combined analysis of the SNP’s showed that p53 (Arg/Arg and Arg/Pro) with TGFβ1 (Pro/Pro and Leu/Pro) were associated with greater than 2 fold increased risk for breast cancer in Univariate (P = 0.01) and Multivariate (P = 0.003) analysis. There was no statistically significant association for the GST family members with the breast cancer risk. TGFβ1 (Pro/Pro) allele was found to predict complete pathologic response in the primary tumour following neo-adjuvant chemo-radiotherapy (OR = 6.53 and 10.53 in Univariate and Multivariate analysis respectively) (P = 0.004) and was independent of stage. This study suggests that SNP’s can help predict breast cancer risk in south Indian women and that TGFβ1 (Pro/Pro) allele is associated with a better pCR in the primary tumour.     

No association between the TP53 codon 72 polymorphism and risk or prognosis of Hodgkin and non-Hodgkin lymphoma

The role of the TP53 gene's R72P polymorphism in non-Hodgkin lymphoma (NHL) has been analyzed in several studies but it has not been studied in Hodgkin lymphoma (HL). We have evaluated the role of R72P in 340 NHL and 298 HL patients. There was no difference in the R72P frequency between analyzed lymphoma cases and 749 controls. We found no association of R72P with the risk of NHL and HL development [OR_{ArgPro/ProPro} = 0.9 (95% CI 0.7-1.2) and 1.2 (95% CI 0.9-1.5), respectively] or with survival. Our results support the evidence that R72P is not a prognostic factor in Caucasian NHL patients, and they indicate its irrelevance for HL development or prognosis.     

新型肿瘤标志物CK18-3A9血清水平对胃癌诊断的价值

 目的　观察和探讨新型肿瘤标志物细胞角蛋白18片段（CK18-3A9）血清水平对胃癌的诊断价值。方法　采用化学发光法检测并比较350例胃癌、150例胃炎和500名健康体检者空腹血清中CK18-3A9水平,对比血清CK18-3A9与CA72-4水平对胃癌的诊断效果。结果　CK18-3A9诊断胃癌灵敏度为46.29 %,特异度为96.92 %;CA72-4灵敏度为26.00 %,特异度为93.23 %。CK18-3A9灵敏度和特异度明显高于CA72-4 （P＜0.001）。结论　新型肿瘤标志物CK18-3A9血清水平检测对胃癌能起到临床辅助诊断的作用。     

CA72-4在10种恶性肿瘤患者血清中检测的临床价值

近年来,人们一直致力于发现和应用血清肿瘤标志物,糖类抗原72-4(Carbohydrate Antigen72-4,CA72-4)作为一种较新的标志物应用于胃癌和卵巢癌的辅助诊断及病情监测的报道国内陆续可见,但在其他肿瘤的应用相关报道尚少.本文对CA72-4在10种常见恶性肿瘤中的表达进行探讨,为合理选择和应用标志物提供依据.     

p53codon72多态性在乳腺癌发生发展中的作用

乳腺癌仍是女性发病率和死亡率最高的肿瘤之一,约占全世界女性肿瘤的1/3。其发生率因种族和地理环境而异,其中欧美国家为高发地区,亚洲发病率则明显降低。乳腺癌发病率近年来呈明显上升趋势,但其确切的发病机制尚未阐明。大约50%