PTEN、VEGF、Bcl-2在大肠癌中的表达及相关性研究

目的研究PTEN、VEGF、Bcl-2在大肠癌中的表达、相互关系及它们在大肠癌发生、发展和转移过程中的作用。方法应用免疫组化SP法检测58例大肠癌中PTEN、VEGF、Bcl-2的表达,分析PTEN与VEGF、Bcl-2的相关性及与大肠癌生物学行为的关系。结果大肠癌组织中,PTEN表达率为46．6％（27／58）显著低于正常大肠组织（P〈0．01）．VEGF、Bcl-2表达率分别为84．5％（49／58）、63．8％（37／58）,显著高于正常大肠组织（P〈0．01）,PTEN表达与淋巴结转移显著相关（P〈0．05）．与患者年龄、性别、肿块大小、分化程度及浸润深度无统计学意义。大肠癌组织中PTEN的表达与VEGF表达之间呈负相关（P〈0．05）。结论PTEN与VEGF、Bcl-2在大肠癌的发生、发展中起着不同的作用,PTEN表达的缺失可能引起VEGF的表达率增加,促进肿瘤血管生成,从而促进大肠癌的转移,联合检测VEGF、PTEN可作为判断大肠癌预后的生物学指标。     

HLA-G蛋白及基因在子宫内膜异位症在位和异位内膜中的表达

目的 探讨人类白细胞抗原G（HLA-G）基因及蛋白在子宫内膜异位症（EM）在位和异位内膜组织中的表达及其生物学意义。方法 应用免疫组化法和原位杂交法检测38例子宫腺肌症、30例卵巢子宫内膜异位症异位内膜及在位内膜、20例子宫肌瘤患者（对照组）在位子宫内膜中HLA-G蛋白和基因的表达。结果 HLA-G蛋白和基因在子宫内膜异位症患者异位和在位内膜组织中的表达均明显高于对照组（P〈0．01）,但在异位内膜和在位内膜的表达无明显差异（P〉0．05）。HLA-G蛋白在EM不同临床分期的表达无明显差异（P〉0．05）,在增生期和分泌期子宫内膜的表达无差异（P〉0．05）。结论 HLA-G的表达可能与子宫内膜异位症的发病有关。     

大肠癌组织Fas抗原和p53蛋白的表达及临床意义

目的　探讨大肠癌组织Fas抗原及 p5 3蛋白的表达及临床意义。 方法　采用免疫组织化学方法对 32例大肠癌组织的Fas抗原 ,16例正常大肠组织及 p5 3蛋白表达进行检测和比较。 结果　Fas抗原在正常大肠组织中表达阳性 ,p5 3蛋白在正常大肠组织中表达阴性 ,Fas抗原在大肠癌组织中表达阳性率为 4 0 .6 2 %(13/ 32 ) ,p5 3蛋白在大肠癌组织中的表达阳性率为 5 3.13%。Fas抗原及 p5 3蛋白在大肠癌组织中的表达与患者性别、年龄、肿瘤大小、部位、大体分型、浸润深度、Ducks及局部淋巴结转移等无明显关系 (P >0 .0 5 ) ,Fas抗原在大肠癌组织明显下降 ,Fas抗原表达与大肠癌组织学类型及肝转移相关 (P <0 .0 5 )。p5 3蛋白表达与大肠癌肝转移相关 (P <0 .0 5 )。结论　Fas抗原在大肠癌组织中表达明显下降。随着肿瘤恶性程度的提高 ,Fas抗原表达减少。在肝转移患者中未见表达。p5 3蛋白在大肠癌组织中表达阳性 ,尤以发生肝转移者为著。Fas抗原表达下降或缺乏及 p5 3蛋白过度表达均提示预后不良     

大肠癌APE1的表达特点及临床意义

目的 探讨脱嘌呤／脱嘧啶核酸内切酶（APE1）在大肠癌发生、发展中的作用。方法 应用免疫组化SP法检测125例大肠癌、72例大肠腺瘤、60例癌旁大肠黏膜和40例正常大肠黏膜中APE1的表达情况,并分析APE1与大肠癌临床病理之间的关系。结果 正常大肠黏膜APE1呈胞核表达,大肠腺瘤和大肠癌组织APE1表达特征发生改变,呈胞核表达、单纯胞质表达或核浆共同表达。APE1胞质异位表达率大肠癌组织为73．6％,大肠腺瘤组织为83．3％,二者无显著性差异（P〉0．05）,但均显著高于癌旁大肠黏膜（10％）和正常大肠黏膜（0％,P〈0．01）。APE1胞质异位表达与大肠癌临床分期和淋巴结转移有关（P〈0．01,P〈0．05）。结论 APE1胞质异位表达可能在大肠癌的发生、发展中起重要作用。     

宫颈癌中MTSS1基因的表达及其临床意义

目的：检测宫颈正常组织以及不同临床分期宫颈癌组织中转移抑制基因1（ metastasis suppressor 1, MTSS1）的表达,分析该基因在各组织中的变化与临床病理因素的关系,并初步探讨该基因在宫颈癌发生发展及转移过程中的作用及分子机制。方法取2011年12月至2014年12月期间采集的103例宫颈组织,病理切片诊断患者宫颈组织类型,判断分化程度,应用实时荧光定量PCR（ q-PCR）和Western印迹法检测不同宫颈组织中MTSS1基因及其蛋白的表达水平。结果 q-PCR结果提示,ⅡB-Ⅳ期宫颈癌组MTSS1基因表达量明显高于正常宫颈组及Ⅰ-ⅡA期宫颈癌组,3组间均有明显差异（P＝0．000）;Western印迹检测MTSS1蛋白在正常宫颈组织中的阳性表达率为23．3％,在宫颈癌组织中为53．3％,两组间差异明显（ P＝0．002）;MTSS1在宫颈癌组织中的表达与年龄、分化以及有无淋巴结转移均无明显相关性（P＞0．05）,而在临床分期中,ⅡB-Ⅳ期MTSS1蛋白表达率明显高于Ⅰ-ⅡA期的宫颈癌组织（P＝0．005）。结论 MTSS1的表达与宫颈癌的临床分期呈正相关趋势,该基因可能在宫颈癌的发生发展中起着重要的作用。     

Survivin、caspase-3、AKT1基因蛋白在大肠癌伴血吸虫病中的表达及意义

目的探讨大肠癌伴血吸虫病中Survivin、Caspase-3AKT1蛋白的表达及其意义。方法采用免疫组化技术检测40例大肠癌伴血吸虫病中Survivin、Caspase-3、AKT1蛋白的表达,并与35例不伴血吸虫病的大肠癌及40例正常结肠粘膜作对照。结果AKT1在大肠腺癌中的表达与正常大肠粘膜相比有显著意义（P〈0．01）,在大肠腺癌中Survivin的阳性率与正常大肠粘膜相比,差异具有显著性意义（P〈0．01）,caspase-3在大肠腺癌中的阳性表达率与对照组相比差异无统计学意义（P〉0．05）。AKT1在大肠腺癌不伴血吸虫病、伴血吸虫病中阳性表达率分别为85．7％和82．5％,差异无统计学意义（P〉0．05）。Sur-vivin在大肠腺癌不伴血吸虫病、伴血吸虫病中表达率分别为91．4％,90．0％,差异无统计学意义（P〉0．05）。Caspase-3在大肠腺癌不伴血吸虫病、伴血吸虫病中表达率分别为57．1％,62．5％;差异无统计学意义（P〉0．05）。结论在大肠癌变过程中起重要作用的三种基因（AKT1、Survivin、caspase）的改变与血吸虫病无明确关系,因此血吸虫病与大肠癌之间的关系还需进-步探讨。     

大肠癌组织血管内皮生长因子及其受体的表达与肿瘤血管生成的关系

为探讨血管内皮生长因子（VEGF）及其受体（KDR）的表达与人大肠癌组织血管生成的关系，采用免疫组织化学SABC法观察了68例人大肠癌组织中的VEGF及KDR的定位与分布，并对血管进行染色及计数。结果显示，68例大肠癌组织中VEGF表达阳性率为55．9％（38／68），阳性物质阳性物质主要位于肿瘤细胞胞膜及胞浆；KDR表达阳性率为45．6％（31／68），既可位于癌组织及癌组织旁的血管内皮细胞，又可位于肿瘤细胞胞膜及胞浆。VEGF表达与大肠癌Dukes分期密切相关。VEGF表达阳性大肠癌组织的微血管密度（MVD）显著高于VEGF表达阴性者（P＜0．01），而且随着VEGF表达强度的增强，癌组织内微血管密度明显增加（P＜0．01）。结果提示，大肠癌细胞分泌的VEGF既可以旁分泌的形式促进肿瘤血管的生成，也可能存在着自分泌形式；VEGF与大肠癌的生长、浸润和转移密切相关，是大肠癌主要的血管新生诱导因子之一，可促进大肠癌的血管生成。     

Fas/APO-1基因表达与食管鳞状细胞癌分级的相关性及意义

目的：探讨Fas/APO-1基因蛋白的表达与食管鳞状细胞癌发生发展的关系。方法：应用免疫组织化学方法，对78例人食管鳞状细胞癌及20例癌旁组织标本的Fas/APO-1蛋白的表达分别进行了检测。结果：在78例食管鳞癌组织中，Fas/APO-1基因蛋白阳性表达率为47．4％（37／78），与癌旁正常组织（阳性表达率为5％）相差显著（P＜0．05）。其中I、Ⅱ、Ⅲ期阳性率分别为18．2％、48．3％及55．3％，Fas/APO-1的表达同食管癌TNM分期存在相关趋势（P＜0．05）。结论：Fas/APO-1基因可能在食管癌的发生发展中起重要作用，对判断食管癌的预后有一定的价值。     

Livin和survivin在胃癌组织中的表达及其临床意义

目的探讨胃癌组织中凋亡抑制蛋白Livin和survivin表达情况及其与各临床病理因素的关系，以及两者在胃癌组织中表达的相关性。方法采用免疫组化S-P方法检测正常胃黏膜及胃癌组织中Livin和survivin的蛋白表达。结果胃癌组织中Livin和survivin的蛋白表达阳性率分别为48．3％、63．8％，分别与正常胃黏膜蛋白表达阳性率比较差异有统计学意义（P〈0．05）；在组织分化差、淋巴结转移者、临床分期高者Livin表达率增高，与对应组比较差异有统计学意义（P〈0．05）；在胃癌组织中Livin表达和survivin表达呈正相关性（rs=0．530，P〈0．01）。结论Livin和survivin在胃癌组织中表达增高，提示参与胃癌的发生、发展，Livin可作为胃癌的生物学标志物，可能成为胃癌治疗的新分子靶点。     

Grp-94在子宫内膜癌中的表达及其临床意义

目的研究葡萄糖调节蛋白94（Grp-94）在子宫内膜癌组织中的表达及其临床病理学意义。方法应用免疫组化S—P法检测50例子宫内膜癌组织中Grp-94表达,同时回顾性研究了表达与子宫内膜癌发生、浸润及转移等临床病理学参数的关系。结果在50例子宫内膜癌组织中,Grp-94的阳性表达率为68．0％（34／50）,对照组织中Grp-94的阳性表达率为6．0％（3／50）,子宫内膜癌组织中的阳性表达率高于对照组织的阳性表达率,两组间比较,差异有统计学意义（P〈0．05）。不同分化程度高分化、中分化、低分化Grp-94的阳性表达检出率分别为56．5％、70．0％和82.4％。三者比较,r=6．0．P〈0．05．统计学差异有显著性,随着分化程度的恶化,Grp-94的阳性表达增高。无淋巴结和有淋巴结转移Grp-94的阳性表达检出率分别为40．0％和86．7％,统计学检验显示,χ^2=24．0,P〈0．05,Grp-94的阳性表达在子宫内膜癌组织的表达升高与淋巴结转移明显相关。临床分期T Ⅰ～Ⅱ和TⅢ～ⅣGrp-94的阳性表达率分别为69．4％、64.3％,两者比较,χ^2=0．4,P〉0．05,统计差异无显著性。结论Grp-94与子宫内膜癌的发生发展关系密切,可成为子宫内膜癌转移及预后的标志物,与临床分期关系不密切。     

Radiotherapeutic efficacy of (153)Sm-CMDTPA-Tyr(3)-octreotate in tumor-bearing rats

A number of radiolabeled somatostatin analogs have been evaluated in animal tumor models for radiotherapeutic efficacy. The majority of the agents tested have used either high-energy beta-emitters, such as Y-90 or Re-188, or the Auger electron-emitting radionuclide, In-111. Because a medium-energy beta-emitter might have equivalent efficacy compared to high-energy emitters, and lower toxicity to non-target tissues, we have evaluated the therapeutic potential of the beta-emitting nuclide, Sm-153, chelated to the somatostatin analog, CMDTPA-Tyr(3)-octreotate. Using an in vitro binding assay, this octreotate derivative was shown to have high affinity for the somatostatin subtype-2 receptor (IC(50) = 2.7 nM). Biodistribution studies in CA20948 tumor-bearing Lewis rats demonstrate that the Sm-153 labeled compound has high uptake and retention in tumor tissue (1.7% injected dose/g tissue, 4 hrs post injection) and has rapid overall clearance properties from non-target tissue. Radiotherapy studies were carried out using (153)Sm-CMDTPA-Tyr(3)-octreotate and CA20948 tumor bearing Lewis rats at 7 days post implant. Dose regimens consisting of single and multiple i.v. injections of 5.0 mCi/rat (185 MBq) were employed over a time span of 7 days. Suppression of tumor growth rate was observed in all treated animals compared to untreated controls. Greater inhibition of tumor growth was observed in animals that received multiple doses. These studies indicate that medium-energy beta-emitting isotopes have considerable potential for the treatment of somatostatin receptor-positive tumors.     

3D-Ultraschall (3D-US) in der Diagnostik von Mammaherdbefunden

ZusammenfassungHintergrund Untersucht wurde, ob der 3D-US die Beurteilung von Mammaherdbefunden verbessern kann.Material und Methoden 60 Patientinnen wurden mit 2D- und 3D-US (Logiq 9 der Fa. GE, 14 MHz, multiplanare Rekonstruktionen in 3 Ebenen) untersucht. Die Herdläsionen wurden sonographisch nach BIRADS klassifiziert. Als Referenzmethode stand in allen Fällen das Ergebnis der histopathologischen Untersuchung zur Verfügung.Ergebnisse Bei den 38 malignen und 22 benignen Läsionen ergab sich mit der 2D-US eine Sensitivität/Spezifität von 92/81%, mit der 3D-US von 97/72% und bei der Kombination von 2D- und 3D-US von 97/81%. Bei malignen Tumoren zeigt sich im 3D-US eine sternförmige echoarme Formation mit Retraktion des umgebenden Gewebes.Schlussfolgerung Der 3D-US ermöglicht die mehrdimensionale Darstellung von Mammaherdbefunden, in der als Malignitätskriterium die Retraktion des umgebenden Gewebes eindrucksvoll zur Darstellung kommt.     

Peptide receptor radionuclide therapy (PRRT) in European Neuroendocrine Tumour Society (ENETS) grade 3 (G3) neuroendocrine neoplasia (NEN) - a single-institution retrospective analysis

Purpose

Grade 3 NENs are aggressive tumours with poor prognosis. PRRT+/? radiosensitising chemotherapy is a potential treatment for disease with high somatostatin receptor (SSTR) expression without spatially discordant FDG-avid disease. We retrospectively evaluated the efficacy of PRRT in G3 NEN.

Methods

Kaplan–Meier estimation was used to determine progression-free survival (PFS) and overall survival (OS) defined from start of PRRT. Subgroup analysis was performed for patients with Ki-67 ≤ 55% and >55%. Anatomical response (RECIST 1.1) and toxicity 3 months after PRRT was determined. Disease control rate (DCR) was defined as complete response (CR), partial response (PR) and stable disease (SD) of those with prior progression.

Results

28 patients (M = 17; age 16–78 years; Ki-67 ≤ 55% = 22) were reviewed. 17 patients had pancreatic, 5 small bowel, 3 large bowel, 2 bronchial and 1 unknown primary disease. 25/28 had significant FDG-avid disease prior to treatment. Most had ¹⁷⁷Lu-DOTA-octreotate (median cumulative activity 24.4 GBq, median 4 cycles). Twenty patients had radiosensitising chemotherapy. 89% were treated for disease progression; 79% after prior chemotherapy. Median follow-up was 29 months. The median PFS was 9 months for all patients. 16 patients died (Ki-67 ≤ 55% = 11; Ki-67 > 55% = 5) with median OS of 19 months. For Ki-67 ≤ 55% (N = 22), the median PFS was 12 months and median OS 46 months. For Ki-67 > 55% (N = 6), the median PFS was 4 months and median OS 7 months. On CT imaging, DCR at 3 months post-PRRT was 74%, 35% (8/23) PR and 39% (9/23) SD. Eleven patients received further PRRT due to recrudescent disease after response. Five patients developed progression of discordant FDG-avid disease and were referred for targeted therapy/chemotherapy. Grade 3 and 4 lymphopenia and thrombocytopenia occurred in five and five patients, respectively. No renal or liver toxicity related to treatment was seen.

Conclusions

PRRT achieves clinically relevant disease control with acceptable toxicity in G3 NENs.

     

(3)He-particle-induced reactions on (nat)Sb for production of (124)I.

Excitation functions of the reactions (nat)Sb((3)He,xn)(124,123,121)I were measured from their respective thresholds up to 35 MeV, with particular emphasis on data for the production of the medically important radionuclide (124)I. The conventional stacked-foil technique was used. From the experimental data the theoretical yields of the three investigated radionuclides were calculated. The yield of (124)I over the energy range E9(30He) = 35 --> 13 MeV amounts to 0.95 MBq/microA h. The radionuclidic impurities are discussed. A comparison of (3)He- and alpha-particle-induced reactions on antimony for production of (124)I is given. The alpha-particle-induced reaction on enriched (121)Sb and the (3)He-particle-induced reaction on enriched (123)Sb would lead to comparable (124)I yields, but the level of impurities in the latter case would be somewhat higher.     

Sodium/proton exchanger 3 (NHE3) and sudden infant death syndrome (SIDS)

The sodium/proton exchanger protein 3 (NHE3) is located in chemosensitive areas of the medulla oblongata and plays an important role in the central control of respiration. Overexpression of NHE3 is correlated with lower respiration and might therefore contribute to the vulnerability of infants dying suddenly and unexpected (sudden infant death syndrome, SIDS). Our aim in this study was to verify already reported genetic variations in the NHE3 gene in an independent SIDS cohort from Switzerland. Two single nucleotide polymorphisms (SNPs) in the promoter region (G1131A and C1197T) and one variation in the coding sequence of exon 16 (C2405T) in the NHE3 gene were analyzed in 160 Caucasian SIDS infants and 192 Swiss adult controls by using a single base extension method (SNaPshot multiplex). No significant differences were detected in the allelic frequencies of the three NHE3 polymorphisms between SIDS cases and controls. We conclude that the three investigated NHE3 SNPs are unlikely to play a major role in the pathogenesis of SIDS in Caucasian infants. However, further genetic investigations in different ethnicities are required to determine whether variations in NHE3 are associated with an increased SIDS risk.     

(R)-N-Methyl-3-(3-(125)I-pyridin-2-yloxy)-3-phenylpropan-1-amine: a novel probe for norepinephrine transporters

Alterations in serotonin and norepinephrine neuronal functions have been observed in patients with major depression. Several antidepressants bind to both serotonin transporters and norepinephrine transporters (NET). The ability to image NET in the human brain would be a useful step toward understanding how alterations in NET relate to disease. In this study, we report the synthesis and characterization of a new series of derivatives of iodonisoxetine, a known radioiodinated probe. The most promising, (R)-N-methyl-3-(3-iodopyridin-2-yloxy)-3-phenylpropylamine (PYINXT), displayed a high and saturable binding to NET, with a K(d) value of 0.53+/-0.03 nM. Biodistribution studies of (R)-N-methyl-3-(3-(125)I-pyridin-2-yloxy)-3-phenylpropan-1-amine in rats showed moderate initial brain uptake (0.54% dose/organ at 2 min) with a relatively fast washout from the brain (0.16% dose/organ at 2 h) as compared to [(125)I]INXT. The hypothalamus (a NET-rich region)-to-striatum (a region devoid of NET) ratio was found to be 2.14 at 4 h after intravenous injection. Preliminary results suggest that this improved iodinated ligand, when labeled with (123)I, may be useful for mapping NET-binding sites with single photon emission computed tomography in the living human brain.     

[188Re(CO)3(H2O)3]+间接标记免疫磁性纳米微粒的实验研究

目的探讨标记单克隆抗体磁性纳米微粒的实验条件。方法以[二（2-吡啶甲基）-氨基]-乙酸（PADA）作为双功能螯合剂，将[^188Re（CO）3（H2O）3]^＋间接标记到耦联了单克隆抗体的磁性纳米微粒。结果[^188Re（CO）3（H2O）3]^＋间接标记免疫磁性纳米微粒的标记率大于80％，在小牛血清和生理盐水中48h后稳定性仍能保持在90％以上。结论使用PADA作为双功能螯合剂，[^188Re（CO）3（H2O）3]^＋间接标记免疫磁性纳米微粒的标记率高，稳定性好，适于进一步体内研究。