胃癌组织中PTEN与COX-2基因表达及临床意义

目的检测PTEN、COX-2在胃癌组织中的表达情况,探讨其与胃癌发生发展的关系及作用机理。方法用免疫组化S-P法检测胃癌组织与非胃癌黏膜中PTEN与COX-2表达情况。结果 80例胃癌组织中42例PTEN蛋白表达明显下降或缺失,且与胃癌TNM分期、淋巴结转移相关(P<0.05)。COX-2在胃癌组织中的阳性率为67.5%,显著高于非胃癌黏膜组织(P<0.05),并相关于胃癌淋巴结转移、TNM分期。结论抑癌基因PTEN与凋亡抑制基因COX-2可能存在相互作用,共同参与了胃癌的发展、转移及浸润。     

胃癌相关基因p53与COX-2表达及其相关性

目的:观察环氧化酶-2(COX-2)与抑癌基因p53在胃癌组织中的表达,并探讨这两个分子与胃癌发展的相关性。方法:使用免疫组织化学的方法检测61例胃癌组织及33例非胃癌组织中p53和COX-2的表达,并分析这两个分子的表达与患者的年龄、性别及其胃癌组织分化程度、浸润深度和淋巴结转移情况之间的关系。结果:p53在胃癌组织中的阳性率72.1%显著高于非胃癌组织的45.5%,COX-2在胃癌组织中的阳性率86.9%显著高于非胃癌组织48.5%,而这两个分子其在胃癌组织中的表达与患者的年龄、性别、胃癌的分化程度和浸润深度无显著关系,然而在淋巴结转移的胃癌组织中发现,p53阳性率显著低于没有淋巴结转移的胃癌组织(P<0.05),COX-2阳性率显著高于没有淋巴结转移的胃癌组织(P<0.05),且这两个分子在胃癌组织中的表达具有明显的相关性(r=0.364,P<0.05)。结论:p53可能通过调控COX-2的表达来改变胃癌组织的耐药性,COX-2也有可能通过调控p53在胃癌组织中的活性影响下游基因的表达情况。     

COX-2在胃癌组织中的表达及其与幽门螺杆菌感染的关系

目的探讨胃癌组织中环氧化酶-2(COX-2)的表达特征及其与幽门螺杆菌(Hp)感染的关系。方法采用免疫组化S-P法,检测68例胃癌组织中COX-2蛋白的表达情况,并并采用快速尿素酶试验及Warthin-starry银染色法检测Hp。结果 68例胃癌组织中COX-2蛋白的阳性率为51.5%;低分化、TNM分期Ⅲ-Ⅳ期和有淋巴结转移的胃癌组织COX-2的阳性率明显高于高分化、TNM分期Ⅰ-Ⅱ期和无淋巴结转移的胃癌组织,差异均有统计学意义(P<0.05);Hp阳性组胃癌组织中COX-2的阳性表达率高于Hp阴性组(P<0.05)。结论 COX-2的表达与胃癌的发展、生物学行为和预后可能有关,可作为重要的生物学标志。     

舌鳞状细胞癌组织中COX-2、VEGF、MMP-9和Bcl-2表达水平及临床意义

目的 观察舌鳞状细胞癌患者癌组织中环氧化酶-2(C OX-2)、血管内皮生长因子(VEGF)、基质金属蛋白酶-9(MMP-9)和B淋巴细胞瘤-2(Bcl-2)的表达水平,并探讨其临床意义.方法 选取2014年2月-2016年2月手术切除的40例舌鳞状细胞癌标本作为观察组,另选取同期40例正常舌黏膜组织标本作为对照组.检测2组COX-2、VEGF、MMP-9和Bcl-2表达水平,分析其与舌鳞状细胞癌临床病理参数的关系以及4种蛋白表达的相关性.结果 观察组COX-2、VEGF、MMP-9和Bcl-2蛋白阳性表达率高于对照组(P＜0.01).COX-2在有淋巴结转移组织中的阳性表达率高于无淋巴结转移组织(P＜0.05);VEGF、MMP-9与Bcl-2在有淋巴结转移与临床分期Ⅲ+Ⅳ期组织中的阳性表达率高于无淋巴结转移与临床分期Ⅰ+Ⅱ期的组织(P＜0.05).COX-2、VEGF、MMP-9、Bcl-2表达水平均呈正相关(P ＜0.05,P＜0.01).结论 COX-2、VEGF、MMP-9和Bcl-2蛋白参与舌鳞状细胞癌的生长、转移与侵袭,且四者间可能存在相互协同的作用.     

MMP-9在胃腺癌中的表达意义

目的 探讨MMP-9在胃腺癌中的表达意义.方法 采用免疫组化S-P法检测10例正常胃黏膜上皮、20例癌旁组织、60例胃腺癌组织中MMP-9的表达,并分析其表达意义及与胃癌临床病理特征的关系.结果 在正常胃黏膜上皮、癌旁组织、胃腺癌组织中,MMP-9的表达阳性率在胃腺癌组织中显著高于正常胃黏膜上皮及癌旁组织中(P＜0.01),在癌旁组织中显著较高于正常组织中(P＜0.05).MMP-9的表达阳性率在低分化癌组显著高于中分化癌组(P＜0.05),在浸润肌层及浸润浆膜层组显著高于浸润黏膜下层组(P＜0.05),在淋巴结转移组显著高于无淋巴结转移组(P＜0.05).MMP-9的表达阳性率与患者性别、年龄、肿瘤体积等无关(P>0.05).结论 MMP-9的表达增强可能与胃癌的转移侵袭有关;MMP-9可能促进了胃癌的发生发展.     

PTEN和VEGFPCNAbcl-2在胃癌组织中的表达及相关性研究

目的通过对PTEN和血管内皮生长因子(vascularendothelialgrowthfactor,VEGF)、增生细胞核抗原(proliferatingcellnuclearantigen,PCNA)、bcl-2在胃癌中表达的研究,结合临床病理特征,探讨PTEN和VEGF、PCNA、bcl-2的相关性。方法应用免疫组织化学S-P法检测68例胃癌组织及20名正常胃黏膜中PTEN、VEGF、PCNA和bcl-2的表达。结果胃癌组织中PTEN蛋白表达率为47%(33/68),显著低于正常胃黏膜的表达100%(20/20)(P<0.01),与组织分化程度呈正相关(P<0.01),与淋巴结转移呈负相关(P<0.05)。VEGF在胃癌中的表达率为75%(51/68),显著高于正常胃黏膜的表达10%(2/20)(P<0.01),与癌组织浸润深度呈正相关(P<0.01),与淋巴结转移也呈正相关(P<0.05),与组织分化程度无关。PCNA在胃癌中的表达率为74%(50/68),显著高于正常胃黏膜的表达20%(4/20),与癌组织浸润深度呈正相关(P<0.01),与淋巴结转移呈正相关(P<0.05),与组织分化程度呈负相关(P<0.05)。bcl-2在胃癌中的表达率为54%(37/68),显著高于正常胃黏膜的表达5%(1/20)(P<0.01),与癌组织浸润深度、淋巴结转移及组织分化程度无关。PTEN在胃癌中的表达与VEGF、PCNA呈负相关(P<0.01)。结论PTEN失活或蛋白表达降低与胃癌的组织分化程度及淋巴结转移密切相关,且与VEGF、PCNA呈显著负相?     

MMP-9 的表达与胃癌浸润转移的相关性研究

目的探讨MMP-9的表达与胃癌浸润转移的关系。方法采用原位杂交法和免疫组化法,检测80例胃癌组织与60例癌旁正常胃粘膜组织中MMP-9mRNA及其蛋白的表达,根据组织学类型、浸润深度和有无淋巴结转移分类分析其与MMP-9表达水平的相关性。结果胃癌组织中MMP-9mRNA的阳性表达率为75%,MMP-9蛋白的阳性表达率为71.25%,而癌旁正常胃粘膜组织中MMP-9mRNA的阳性表达率为43.33%,MMP-9蛋白的阳性表达率为41.67%。胃癌组织中MMP-9mRNA及蛋白的阳性表达率均明显高于癌旁正常胃黏膜组织(P<0.05)。未侵及浆膜层的胃癌组织中MMP-9的mRNA和蛋白的阳性表达率分别为63.2%和57.9%;而侵及浆膜层的胃癌组织中MMP-9的mRNA和蛋白的阳性表达率分别为85.7%和83.3%,分别明显高于未侵及浆膜层的胃癌组织(P<0.05)。无淋巴结转移的胃癌组织中MMP-9的mRNA和蛋白的阳性表达率分别为64.4%和60.0%;而有淋巴结转移的胃癌组织中MMP-9的mRNA和蛋白的阳性表达率分别为88.6%和85.7%,分别明显高于无淋巴结转移的胃癌组织(P<0.05)。结论胃癌组织中MMP-9的mRNA和蛋白表达明显高于癌旁正常胃粘膜,MMP-9的阳性表达与胃癌的浸润和淋巴结转移均存在明显的相关性,可作为胃癌的诊断和预后评估的备选指标。     

环氧化酶-2和P53蛋白在非小细胞肺癌中的表达及意义

目的研究环氧化酶-2（COX-2）和P53蛋白在非小细胞肺癌（NSCLC）组织和癌旁组织中表达情况,探讨其在NSCLC的发生、发展中的作用。方法应用免疫组化SP方法,检测NSCLC组织（40例）和癌旁组织（40例）中COX-2及P53蛋白表达情况。结果COX-2及P53蛋白在NSCLC组织中的表达显著高于癌旁组织。COX-2在NSCLC组织中的表达与组织类型、分化程度、肿瘤大小、临床分期及淋巴结转移密切相关;在腺癌中的表达明显高于鳞癌,且随着肿瘤分化程度越低、肿瘤体积增大、分期越高及淋巴结转移增多,COX-2表达阳性率越高。P53蛋白在NSCLC组织中的表达与淋巴结转移密切相关,随着肿瘤淋巴结转移增多,P53蛋白表达阳性率越高。P53的表达与COX-2正相关,P〈0．01。结论COX-2及P53蛋白在NSCLC组织中呈高表达,它们在非小细胞肺癌的发生、发展过程中起重要作用,有助于判断NSCLC的发展、淋巴结转移及其预后。     

Eph受体酪氨酸激酶A2和金属蛋白酶2在大肠癌组织的表达及其与大肠癌发生发展的关系

目的 探讨Eph受体酪氨酸激酶A2(EphA2)和金属蛋白酶2(MMP-2)在大肠癌组织中的表达及其与临床病理特征和预后关系.方法 采用免疫组织化学法检测76例大肠癌患者手术标本中癌组织和癌旁组织的EphA2蛋白和MMP-2蛋白表达情况.结果 EphA2蛋白在大肠癌组织中的表达概率明显高于癌旁组织(92.10%比26.31%,P<0.05),MMP-2蛋白在大肠癌组织中的表达概率同样明显高于癌旁组织(80.20%比15.90%,P<0.05);EphA2蛋白表达水平与组织分化程度大肠癌、Dukes分期、淋巴结转移、年龄密切关联;MMP-2蛋白表达水平与大肠癌组织学分化程度、Dukes分期、淋巴结转移、年龄密切关联.结论 EphA2蛋白和MMP-2蛋白在大肠癌组织中的高表达可能在大肠癌的发生、发展过程中发挥重要作用.     

喉癌组织中Survivin、MMP-2的表达、临床意义及相关性研究

目的探讨喉癌组织中存活素(Survivin)和基质金属蛋白酶-2(MMP-2)的表达及其相关性。方法采用免疫组织化学链酶卵白素-生物素复合体(SABC)法检测Survivin、MMP-2蛋白在92例喉鳞状细胞癌及相距10 mm的癌旁组织和25例喉正常黏膜中的表达。结果 Survivin在喉癌组织中的阳性率(76.09%)明显高于癌旁(13.04%)及喉正常黏膜组织(8.00%),差异有统计学意义(P<0.05),与临床分期有关,与年龄、淋巴结转移、分化程度无关。MMP-2在喉癌组织中的阳性率(78.26%)明显高于癌旁(18.48%)及喉正常黏膜组织(12.00%),差异有统计学意义(P<0.05),与分化程度和临床分期有关,与年龄、淋巴结转移无关。两者呈正相关。结论 Survivin、MMP-2的异常表达可能对喉癌的发生、发展起重要作用,联合检测可能对喉癌的早期诊断、进一步治疗和判断预后有一定参考价值。     

2-吡啶甲醇及2-吡啶甲醛的合成

以 2 -甲基吡啶为原料、过氧化氢为氧化剂制备 2 -吡啶甲醇和 2 -吡啶甲醛,工艺方法经济、安全     

Synthesis and immunosuppressive activity of 2-substituted 2-aminopropane-1,3-diols and 2-aminoethanols

A series of 2-substituted 2-aminopropane-1,3-diols was synthesized and evaluated for their lymphocyte-decreasing effect and immunosuppressive effect on rat skin allograft. A phenyl ring was introduced into the alkyl chain of the lead compound 3, which is an immunosuppressive agent structurally simplified from myriocin (1, ISP-I) via compound 2. The potency of the various compounds was dependent upon the position of the phenyl ring within the alkyl side chain. The most suitable length between the quaternary carbon atom and the phenyl ring was two carbon atoms. 2-Substituted 2-aminoethanols were successively synthesized and evaluated for their T-cell-decreasing effect and immunosuppressive effect using a popliteal lymph node gain assay in rats. The absolute configuration at the quaternary carbon affected the activity, and the (pro-S)-hydroxymethyl group of compound 6 was essential for potent immunosuppressive activity. Favorable substituents for the (pro-R)-hydroxymethyl group of 6 were hydroxyalkyl (hydroxyethyl and hydroxypropyl) or lower alkyl (methyl and ethyl) groups. 2-Amino-2-[2-(4-octylphenyl)ethyl]propane-1,3-diol hydrochloride (6, FTY720) was found to possess considerable activity and is expected to be useful as an immunosuppressive drug for organ transplantation.     

2-苯基-1-丁醇与2-二甲氨基-2-苯基丁腈的合成

目的为马来酸曲美布汀的重要中间体2-二甲氨基-2-苯基-1-丁醇的合成奠定基础。方法苯乙腈与溴乙烷进行烃化反应得2-苯基-1-丁腈,所得产物经水解得2-苯基-1-丁酸,然后通过硼氢化钠-碘体系还原得2-苯基-1-丁醇;苯乙腈与N-溴代丁二酰亚胺进行卤代反应得溴代苯乙腈,所得产物与二甲胺进行烃化反应得2-二甲氨基苯乙腈,然后与溴乙烷进行烃化反应得2-二甲氨基-2-苯基丁腈。结果合成了2-苯基-1-丁醇和2-二甲氨基-2-苯基丁腈,总收率为分别为51%和59.4%。目标产物的结构经核磁共振氢谱、质谱确证。结论本合成方法原料易得,操作简单,收率较高,适合于工业化生产。     

Metabolism and metabolic effects of 2-azahypoxanthine and 2-azaadenosine

The metabolism and metabolic effects of 2-azahypoxanthine and 2-azaadenosine were studied to elucidate the biochemical basis for their known cytotoxicities. 2-Azaadenosine is a known substrate for adenosine kinase. That 2-azahypoxanthine is a substrate for hypoxanthine (guanine) phosphoribosyltransferase is shown by the observations that, in cell-free fractions from HEp-2 cells supplemented with 5-phosphoribosyl-1-pyrophosphate, 2-azahypoxanthine inhibited the conversion of hypoxanthine to IMP but not the conversion of adenine to AMP, and hypoxanthine, but not adenine, inhibited the conversion of 2-azahypoxanthine to 2-azaIMP. [8-14C]2-Azahypoxanthine was synthesized from [8-14C]hypoxanthine via [2-14C]-4-amino-5-imidazolecarboxamide. In HEp-2 cells in culture, the principal metabolite of [8-14C]-2-azahypoxanthine was 2-azaATP; there was no detectable 14C in deoxynucleotides or in DNA or RNA fractions. 2-Azaadenosine was much more toxic than 2-azahypoxanthine, and, when used in the presence of an adenosine deaminase inhibitor, 2'-deoxycoformycin, was converted in HEp-2 cells to 2-azaATP in amounts that exceeded those of ATP in control cells. The pool of ATP was reduced by as much as 75% as 2-azaATP accumulated. In a short-term experiment (4 hr), 2-azaadenosine selectively reduced the pools of adenine nucleotides, whereas 2-azahypoxanthine reduced the pools of guanine nucleotides selectively. Both 2-azahypoxanthine and 2-azaadenosine inhibited the incorporation of formate into purine nucleotides and were without effect on the conversion of thymidine and uridine to nucleotides. 2-Azahypoxanthine inhibited the incorporation of thymidine into macro-molecules but not that of uridine or leucine; 2-azaadenosine inhibited the incorporation of all three of these precursors non-selectively. 2-AzaIMP inhibited IMP dehydrogenase competitively with IMP (Ki = 66 microM). The difference in effects of 2-azahypoxanthine and 2-azaadenosine perhaps may be due to the production, from 2-azahypoxanthine but not from 2-azaadenosine + 2'-deoxycoformycin, of 2-azaIMP, which inhibits synthesis of guanine nucleotides and thereby results in inhibition of DNA synthesis. Specific sites of action for 2-azaadenosine are yet undefined.     

Molecular modeling of 2-alkyloxy- and 2-aralkyloxy-adenosine A1- and A2-agonists

The C2-region of adenosine A1- and A2-receptors by a molecular modeling technique has been extended and applied to a series of 2-substituted adenosines reported by Olsson, et al. The similarity and dissimilarity of the structure maps obtained by molecular modeling have been used as a basis for the mapping of the analysed receptor domain. The proposed model of the C2-region of the A1-receptor consists of a narrow and sterically limited area that interacts well electrostatically with small and electron rich moieties. Olsson's provisional model of the C2-region of the A2-receptor has been extended with two subsites, as well as with a forbidden area near the C2-position of the purine ring. The conformational analysis performed in the study does not support the hypothesis of Olsson et al. that adenosine C2 substituents may partly occupy the same receptor domain as the N6 substituents of the A1-receptor. The occupation of the cycloalkyl subsite increases the receptor selectivity while the occupation of the other subsite by aryl rings, fixed at a parallel position to the purine system, highly enhances the receptor affinity.     

Synthesis and antiviral evaluation of carbocyclic analogues of 2'-azido- and 2'-amino-2'-deoxycytidine

Carbocyclic analogues of 2'-azido- and 2'-amino-2'-deoxycytidine, compounds 8 and 9, were synthesized by an eight-step synthesis from (+/-)-(1 alpha,2 alpha,3 beta,5 beta)-3-amino-5-(hydroxymethyl)-1,2- cyclopentanediol (1), which was prepared from cyclopentadiene via an eight-step route. These compounds were tested in vitro against herpes simplex virus type 1 (HSV-1). The 2'-amino analogue was found to show moderate antiviral activity, with an ED50 of 50 microM. However, the 2'-azido analogue was not active at a concentration up to 400 microM.     

2-Fluoroformycin and 2-aminoformycin. Synthesis and biological activity

Syntheses of 2-fluoroformycin [7-amino-5-fluoro-3-(beta-D-ribofuranosyl)pyrazolo[4,3-d]pyrimidine] (2b) and 2-aminoformycin [5,7-diamino-3-(beta-D-ribofuranosyl)pyrazolo[4,3-d]pyrimidine] (2c) are described. Cytotoxicity data are given for 2b and 2c alone as well as with added pentostatin. Kinetic parameters for adenosine deaminase are also provided. 2-Fluoroformycin, although a much poorer substrate for adenosine deaminase than formycin A, is not nearly as cytotoxic to cells in culture.