HOX D13 expression across 79 tumor tissue types

HOX genes control normal development, primary cellular processes and are characterized by a unique genomic network organization. Locus D HOX genes play an important role in limb generation and mesenchymal condensation. Dysregulated HOXD13 expression has been detected in breast cancer, melanoma, cervical cancer and astrocytomas. We have investigated the epidemiology of HOXD13 expression in human tissues and its potential deregulation in the carcinogenesis of specific tumors. HOXD13 homeoprotein expression has been detected using microarray technology comprising more than 4,000 normal and neoplastic tissue samples including 79 different tumor categories. Validation of HOXD13 expression has been performed, at mRNA level, for selected tumor types. Significant differences are detectable between specific normal tissues and corresponding tumor types with the majority of cancers showing an increase in HOXD13 expression (16.1% normal vs. 57.7% cancers). In contrast, pancreas and stomach tumor subtypes display the opposite trend. Interestingly, detection of the HOXD13 homeoprotein in pancreas‐tissue microarrays shows that its negative expression has a significant and adverse effect on the prognosis of patients with pancreatic cancer independent of the T or N stage at the time of diagnosis. Our study provides, for the first time, an overview of a HOX protein expression in a large series of normal and neoplastic tissue types, identifies pancreatic cancer as one of the most affected by the HOXD13 hoemoprotein and underlines the way homeoproteins can be associated to human cancerogenesis. © 2009 UICC     

胎儿胰腺S100蛋白表达的发育

目的：探索人胚胎发育过程中胰腺S100蛋白表达的发生和分布。方法：采用免疫组织化学EnVision法,选用S100蛋白抗体对30例人胚胎胰腺进行标记。结果：S100蛋白免疫反应性纤维沿腺泡、导管和血管分布。胎龄14周胰腺内开始出现S100蛋白免疫反应性纤维样结构,并随胎龄逐渐增加,至胚胎发育后期（胎龄24-28周）达到高峰,至35周后开始减少。结论：胰腺神经系统的发育有明显的阶段性。     

高脂饮食诱发肥胖大鼠胰腺结构变化及其与糖尿病的关系

目的：观察高脂饮食诱发肥胖大鼠胰腺的结构变化,并探讨其与糖尿病的关系。方法：选用出生21 d雄性SD大鼠,经高脂饲料喂养,衡量其肥胖程度,检测血糖、胰岛素和C-肽水平,光镜和透射电镜观察胰组织等变化。结果：经高脂饮食诱发的肥胖大鼠,血糖、胰岛素光子数均高于对照组,血C-肽光子数与对照组差别不显著;肥胖大鼠的胰腺腺泡间或小叶间,出现脂肪细胞堆积,淋巴细胞浸润和结缔组织纤维增生;某些腺泡和胰岛细胞出现脂肪或空泡样变性。结论：高脂饮食可诱发大鼠肥胖,并出现血糖、胰岛素水平和胰组织结构的变化;该变化可能与胰组织通道阻塞、胰淋巴回流障碍、胰岛素等多肽激素转运异常有关。     

Thrombocytopenia in association with a wandering spleen

An ectopic, so-called wandering spleen is an uncommon occurrence. We present the case of a young woman who presented with abdominal pain and was found to have an enlarged spleen, located in the lower abdomen and pelvis. The possibility of lymphoma was entertained because of concomitant findings of thrombocytopenia and a possible mesenteric mass. The mass was subsequently found at laparotomy to be the tail of the malpositioned pancreas, and the thrombocytopenia resolved with splenectomy. Review of the literature indicates that lymphoma is an uncommon finding in wandering spleens, that wandering spleens are enlarged in most cases, and that thrombocytopenia, while uncommon, can be seen, in particular when associated with torsion of an elongated splenic pedicle. © 1996 Wiley-Liss, Inc.     

EXPRESSION OF MUC APOMUCINS IN NORMAL PANCREAS AND PANCREATIC TUMOURS

The epithelial expression of apomucins MUC1, MUC2, MUC3, and MUC5/6 was examined in normal pancreas and in pancreatic lesions, using immunohistochemical methods. In normal pancreas ( n =5), MUC1 apomucin was expressed in ducts and some acini, but there was no expression of MUC2, MUC3, or MUC5/6. In chronic pancreatitis ( n =5), MUC1 apomucin was expressed, but expression of the other apomucins was not noted. However, mucous hyperplastic foci of pancreatic ducts expressed MUC5/6 apomucin in 2/5 cases (40 per cent). In intraductal papillary-mucinous neoplasm (IPMN) of the pancreas ( n =9), MUC1, MUC2, MUC3, and MUC5/6 apomucins were expressed in 8/9 (89 per cent), 0/9 (0 per cent), 4/9 (44 per cent), and 9/9 (100 per cent) cases, respectively. In pancreatic mucinous cystadenoma ( n =8), MUC1, MUC2, MUC3, and MUC5/6 apomucins were expressed in 7/8 (88 per cent), 0/8 (0 per cent), (25 per cent), and 3/8 (38 per cent) cases, respectively. In invasive ductal adenocarcinoma of the pancreas ( n =25), expression of MUC1, MUC2, MUC3, and MUC5/6 apomucins was found in 25/25 (100 per cent), 1/25 (4 per cent), 20/25 (80 per cent), and 24/25 (96 per cent) cases, respectively. Atypical mucous duct hyperplasia near cancer cells consistently expressed MUC1 apomucin and occasionally expressed MUC3 and MUC5/6. In positive cases, MUC1 apomucin expression was noted in the cell membrane facing the ductal or neoplastic lumina, while expression of MUC2, MUC3, and MUC5/6 apomucins was found in the cytoplasm. These results suggest that MUC3 and MUC5/6 apomucins newly emerge during the neoplastic transformation of pancreatic mucinous cystadenoma and IPMN and during pancreatic ductal carcinogenesis, while MUC1 apomucin remains positive and MUC2 apomucin remains almost negative during neoplastic transformation.     

Papillary-cystic tumor of the pancreas

A case of papillary cystic tumor (PCT) of the pancreas in a 40-yr-old woman is reported. This rare neoplasm was discovered fortuitously by a CT-scan examination for a palpable abdominal uterine leiomyoma. Percutaneous fine-needle aspiration (FNA) of the pancreatic mass was performed under CT-scan guidance. Cytologic examination of the material gave the diagnosis of PCT, which was confirmed by histologic examination of the resected tumor. Immunohistochemical staining showed a high degree of positivity to wide-spectrum anticytokeratin and anticytokeratin 20, and a weak positivity to anti-NSE antibody. In addition, the tumor cells were highly reactive for progesterone antibody, while they were negative for estrogen. These findings suggest a ductal origin for PCT, and also suggest that sex hormones may play a role in its growth, but not in its genesis. We emphasize the value of FNA cytologic features in the diagnosis of these rare tumors. Diagn Cytopathol 1996;15:398–402. © 1996 Wiley-Liss, Inc.     

Efficient Closed Loop Simulation of Do-It-Yourself Artificial Pancreas Systems

Background:Numerical simulations, also referred to as in silico trials, are nowadays the first step toward approval of new artificial pancreas (AP) systems. One suitable tool to run such simulations is the UVA/Padova Type 1 Diabetes Metabolic Simulator (T1DMS). It was used by Toffanin et al. to provide data about safety and efficacy of AndroidAPS, one of the most wide-spread do-it-yourself AP systems. However, the setup suffered from slow simulation speed. The objective of this work is to speed up simulation by implementing the algorithm directly in MATLAB^®/Simulink^®.Method:Firstly, AndroidAPS is re-implemented in MATLAB^® and verified. Then, the function is incorporated into T1DMS. To evaluate the new setup, a scenario covering 2 days in real time is run for 30 virtual patients. The results are compared to those presented in the literature.Results:Unit tests and integration tests proved the equivalence of the new implementation and the original AndroidAPS code. Simulation of the scenario required approximately 15 minutes, corresponding to a speed-up factor of roughly 1000 with respect to real time. The results closely resemble those presented by Toffanin et al. Discrepancies were to be expected because a different virtual population was considered. Also, some parameters could not be extracted from and harmonized with the original setup.Conclusions:The new implementation facilitates extensive in silico trials of AndroidAPS due to the significant reduction of runtime. This provides a cheap and fast means to test new versions of the algorithm before they are shared with the community.     

猪胰肾联合移植动物模型的建立

目的:建立胰肾联合移植(SPKT)大动物模型.方法:选用杂种猪作SPKT的供受体,经猪腹主动脉原位灌注,多器官联合整块切取,胰、节段十二指肠、双肾、脾脏.切除受体胰腺,制作1型糖尿病模型, 切除受体双肾,供体门静脉远端与左肾静脉吻合, 门静脉近端及带有腹腔干、肠系膜上动脉和左肾动脉的腹主动脉段分别与受体下腔静脉及肾以下腹主动脉端侧吻合,供体十二指肠侧壁与受体上段空肠行侧侧吻合, 输尿管置管外引流,未作预防及抗排斥处理.结果:10头动物移植后,2头受体因术后内环境紊乱死亡,8头受体顺利完成胰肾联合移植术,术后移植肾、胰均迅速恢复功能, 存活期胰肾功能基本正常.术后3～5 d因排斥反应及体内代谢紊乱8头受体死亡.结论:建立猪SPKT模型是可行的,良好的外科技术是胰肾联合移植成功的基础.     

不同病理分级的胰腺神经内分泌肿瘤的MRI征象对比分析及“主胰管绕道征”的诊断价值探讨

目的:对比分析G1、G2级胰腺神经内分泌肿瘤（pNEN）的MRI征象,探讨“主胰管绕道征”的诊断价值。方法:收集32例pNEN患者的临床资料,以术后病理学检查为金标准,定量分析G1、G2级临床指标及影像学指标的差异,并着重分析pNEN与主胰管的关系。结果:32例患者中,病理分级G1、G2、G3级的患者分别有12例、16例、4例,分别以胰尾、胰头、胰颈为主要发生部位。与G1级神经内分泌瘤（NET）相比,G2级NET肿瘤直径显著增大,不规则形态的病灶增多,边缘模糊,生物学行为出现明显恶性倾向,主胰管扩张、胰腺外侵犯及淋巴结/肝转移的发生率升高。G1级NET的MRI平扫信号均质程度高于G2级（P＜0.05）,但二者在增强MRI扫描的各个期象信号强度均无明显差异（P＞0.05）。28例NET患者中,22例（78.6%）出现主胰管绕道征;神经内分泌癌（NEC）患者无一例出现此征象。术前,28例NET的诊断准确率为78.6%（22/28）,存在6例误诊,其中,3例误诊为胰腺癌,2例误诊为囊腺瘤（癌）,1例误诊为胰腺假性囊肿。在原MRI诊断依据的基础上纳入“主胰管绕道征”,诊断准确率提高至89.3%（25/28）,但仍存在3例误诊,其中2例误诊为囊腺瘤（癌）,1例误诊为胰腺假性囊肿,排除了胰腺癌的误诊。结论:MRI对鉴别诊断良恶性pNEN有较高的准确性,但对部分G1与G2级NET仍存在一定的误诊率,主胰管绕道征可帮助减少出现胰腺癌误诊。