TβRⅡ,MMP-7,TIMP-2表达及在HNPCC侵袭转移中的作用

目的:通过观察TβRⅡ,MMP-7及TIMP-2在HNPCC和散发性大肠癌中的表达,探讨其在HNPCC侵袭转移的生物学行为中的作用.方法:选取1980-05/2005-06空军总医院收治的HNPCC和散发性大肠癌各30例,应用免疫组化SP染色法检测其肿瘤组织中TβRⅡ,MMP-7,TIMP-2的表达情况.结合其相应临床病理资料进行分析TβRⅡ,MMP-7,TIMP-2表达在HNPCC侵袭转移中的作用.结果:TβRⅡ,MMP-7,TIMP-2在HNPCC组的阳性表达率分别为4 0.0%,46.7%,63.3%;而在散发性大肠癌组的阳性表达率为73.3%,86.7%,20.0%.散发性大肠癌组中MMP-7( ～ )/TIMP-2(-)比例明显高于HNPCC组.而其MMP-7(-)/TIMP-2( ～ )者则明显少于HNPCC组.TβRⅡ,MMP-7,TIMP-2的阳性表达率与肿瘤的大小和部位无关.而与肿瘤的侵犯深度和转移与否密切相关.侵犯浆膜外组织和有转移者的MMP-7的阳性表达率明显增高,而TβRⅡ,TIMP-2的阳性表达率则明显降低(P＜0.05).在两组大肠癌中TβRⅡ与MMP-7呈正相关(r=0.735,P=0.000;r=0.792,P=0.000),TIMP-2与TβRⅡ(r=-0.582,P=0.001;r=-0.394,P=0.031)和MMP-7 (r=-0.473,P=0.008;r=-0.388,P=0.034)的表达均呈负相关.结论:TβRⅡ,MMP-7,TIMP-2在散发性大肠癌和HNPCC中的表达差异显著.TβRⅡ,MMP-7在散发性大肠癌中的表达率和表达强度明显高于HNPCC,而TIMP-2的表达结果则相反.因此,散发性大肠癌中MMP-7/TIMP-2的比例失衡明显高于HNPCC组.     

大肠癌E-cadherin,β-catenin,MMP-7表达及其临床意义

目的:探讨大肠癌(CRC)中上皮钙黏附蛋白(E-cad)、β-连接素(β-cat)和基质金属蛋白酶-7(MMP-7)的表达水平,并分析三者的相互关系.方法:应用免疫组化方法检测60例CRC肿瘤组织标本和8例正常大肠组织标本中E-cad,β-cat和MMP-7的表达水平,分析E-cad,β-cat和MMP-7在二者中表达的差异,并结合其临床病理资料进行综合分析.结果:E-cad、正常β-cat、异常β-cat和MMP-7在CRC中的阳性表达率分别为73.3%(44/60),66.7%(40/60),63.3%(38/60)和73.3%(44/60).E-cad,β-cat和MMP-7的阳性表达率与患者的年龄、性别和肿瘤的大小、部位及分化类型均无关.而与肿瘤的侵犯深度和转移与否密切相关.E-cad和β-cat正常表达之间呈明显正相关(r=0.359,P=0.005).β-cat正常表达和β-cat异常表达之间呈明显负相关(r=-0.324,P=0.012).β-cat异常表达和MMP-7之间呈明显正相关(r=0.487,P=0.000).结论:E-cad,β-cat和MMP-7的表达与CRC的侵袭转移和预后密切相关,可作为判定CRC预后的有效指标.     

Mixed Adenoneuroendocrine Carcinoma of the Gallbladder

Mixed adenoneuroendocrine carcinoma rarely occurs in the gallbladder. Most cases of cholecystic mixed adenoneuroendocrine carcinoma have been reported from Asia, North American, and Europe; however, there is scarce literature available on this tumor in other populations. Here, we report a case of mixed adenoneuroendocrine carcinoma in a Melanoderm woman who was initially suspected to have gallbladder cancer. No specific symptoms or abnormal blood test results were observed preoperatively. Magnetic resonance imaging revealed a 7-cm hypointense mass in the gallbladder fossa, which invaded the surrounding liver segments. Radical cholecystectomy, partial liver resection, and regional lymphadenectomy were performed. Finally, she was diagnosed as mixed adenoneuroendocrine carcinoma of the gallbladder upon postoperative pathological examination and immunohistochemical staining. She received six cycles of systemic chemotherapy and somatostatin treatment and survived 21 months after surgery. Our case highlights the fact that mixed adenoneuroendocrine carcinoma of the gallbladder can occur in African populations as well. Surgical approach combined with adjuvant chemotherapy and somatostatin treatment may contribute a relatively good survival outcome.     

The CD4 Lymphocyte Count is a Better Predictor of Overall Infection Than the Total Lymphocyte Count in ANCA-Associated Vasculitis Under a Corticosteroid and Cyclophosphamide Regimen: A Retrospective Cohort

Patients with antineutrophil cytoplasmic autoantibody associated vasculitis (AAV) have a high prevalence of infection during immunosuppressive therapy, and the total lymphocyte count (TLC) has been demonstrated to be an independent predictor of infection. The current study investigated the value of the TLC and its subsets, particularly the CD4 count, for predicting infections of AAV in a single Chinese cohort.A total of 124 AAV patients were retrospectively recruited in our department from December 1997 to October 2013. Multivariate Cox models with the CD4 count or TLC measured at three typical time points, that is, at baseline, at the beginning of immunosuppressant dose reduction, and at the last visit before infection or censoring, or with the measurements included as time-varying covariates, were compared to select the most predictive time point for infection. A time-dependent area under the receiver operating characteristic curve (AUC(t)) for the TLC (AUC(t)_TLC) and the CD4 count (AUC(t)_CD4count) measured at the most predictive time point were calculated and compared.During an average follow-up of 11.5 (range 0.5–142) months, 55 of the 124 patients (44.3%) experienced a microbiologically confirmed infection. Independent predictors of overall infection were initial creatinine clearance (P = 0.02 and 0.04), pulmonary interstitial fibrosis (P = .04 and .05), pulmonary nodule or cavity (P = 0.002 and .002), CD4 count (P < 0.001) or TLC (P = 0.05) from the last visit. The comparison of Cox models fitted at different time points confirmed the last visit to be the most predictive one for overall infection. The predictive value of the CD4 count or TLC from the last visit measured by AUC showed that the AUC(t)_CD4count (62.8–70.2%) was almost always higher than AUC(t)_TLC (55.2–58.1%) during the first 2 years of immunosuppressive therapy (P = 0.01–0.2). In terms of different pathogens, both the CD4 count and TLC performed well for non-bacterial infection (AUC(t) 69.2–82.7%), and the difference between them was not significant (P > 0.1).The TLC and CD4 count were both independent risk factors of overall infection and non-bacterial infection in AAV patients. The CD4 count had a higher predictive value than the TLC for overall infections, particularly during the first 2 years of immunosuppressive therapy.     

遗传性非息肉病性大肠癌组织E-cad,β-cat和MMP-7表达在侵袭转移中的作用

目的:探讨上皮钙黏附蛋白(E-cad)、β-连接素(β-cat)和基质金属蛋白酶-7(MMP-7)在遗传性非息肉病性大肠癌(HNPCC)和散发性大肠癌(sporadic CRC)的表达及与遗传性非息肉病性大肠癌(HNPCC)侵袭转移间的关系.方法:应用免疫组化SP法检测HNPCC(n= 30)、散发性大肠癌(sporadic CRC)(n=30)和正常大肠黏膜(n=8)中E-cad,β-cat和MMP-7的表达情况.结果:E-cad和胞膜表达β-cat在HNPCC中的阳性表达率高于其在sporadic CRC中的表达率(E-cad:86.7% vs 60.0%:胞膜β-cat:83-3% vs 50.0%,均P<0.05).而胞质表达β-cat和MMP-7则相反(胞质β-cat:46.7% vs 80.0%;MMP-7:46.7% vs 86.7%;均P>0.05).两组中E-cad,胞膜表达β-cat,胞质表达β-cat,MMP-7的阳性表达率与患者的性别和肿瘤的大小、部位及分化类型均无关:而与肿瘤的侵犯深度和转移与否密切相关(r=0.732、P<0.05).E-cad与胞膜表达β-cat呈正相关(r=0.477,P<0.05),胞膜表达β-cat与胞质表达β-cat呈负相关(r=-0.419,P<0.05),而胞质表达β-cat与MMP-7呈正相关(r=0.380,P<0.05).结论:E-cad,β-cat和MMP-7在HNPCC和sporadicc CRC中的阳性表达率差异显著.可能是HNPCC在获得诊断时侵袭弱、转移少和预后较好的原因之一.     

1—（9H—咔唑—4—氧）—3—取代氨基—2—丙醇类化合物的合成及生物活性（Ⅱ）

目的 寻找有β-受体阻滞活性，且高效低毒的化合物。方法 以β-受体阻滞剂咔唑洛尔为先导化合物，根据药物设计中的结构拼合原理，对其丙醇胺侧链进行结构修饰。设计并合成了3个1-（9H-咔唑-4-氧）-3-取代氨基-2-丙醇类化合物V11-V13及其6个相应的酯化物VI1-VI6。结果和讨论 所合成的目的物均未见文献报道，结构经红外光谱，核磁共振氢谱，质谱，元素分析或高分辨质谱确证，初步药理筛选结果显示，9个化合物均能够不同程度地拮抗异丙肾上腺素引起的心动过速，其中化合物V12，Ⅵ3,Ⅵ4的活性与先导化合物相当。     

2,4-Toluene diisocyanate suppressed the calcium signaling of ligand gated ion channel receptors

Toluene diisocyanate (TDI) is widely used as a chemical intermediate in the production of polyurethane. TDI-induced asthma is related to its disturbance of acetylcholine activity in most affected workers, but the relevant mechanisms are unclear. Toluene diamine (TDA) is the main metabolite of TDI. TDI and TDA have in common the basic toluene structure. Toluene is an abused solvent affecting neuronal signal transduction by influencing the function of ligand gated ion channel receptors, including nicotinic acetylcholine receptors (nAChR), P2X purinoceptors, [gamma]-aminobutyric acid type A (GABAA) receptors, etc. To understand the actions of TDI and TDA on ligand gated ion channels, we investigated their effects on the changes of cytosolic calcium concentration ([Ca2+]c) while stimulating nAChR in human neuroblastoma SH-SY5Y cells, P2 purinoceptors in PC12 cells, and GABAA receptors in bovine adrenal chromaffin cells. Our results showed that both TDI and TDA suppressed the [Ca2+]c rise induced by the potent nicotinic ligand, epibatidine, in human SH-SY5Y cells. Similar but stronger suppression of ATP-induced [Ca2+]c rise occurred in PC12 cells. TDI and TDA also partially suppressed the [Ca2+] c rise induced by GABA in bovine adrenal chromaffin cells. We conclude that TDI and TDA can act on ligand gated ion channel receptors. Our findings suggest that TDI and TDA might have some neurotoxicity that will need to be investigated.