Chronic diarrhea and facial dysmorphism in children--a clue to men 2B syndrome: a case report

Medullary thyroid cancer (MTC) is a highly malignant tumor of the thyroid gland in children, rarely diagnosed and treated by pediatric oncologists. The authors describe a 9-year-old male who presented with facial dysmorphism and history of chronic diarrhea before being diagnosed with advanced MTC. Familiarity with its clinical variants, associated RET protooncogene mutation and its clinical implication, can lead to early identification of this aggressive tumor. To date, surgery remains the only definitive therapy, with continuing dismal prognosis in metastatic disease. However, evolving newer therapeutic strategies like tyrosine kinase inhibitors and pretargeted radioimmunotherapy (pRAIT) may provide hope to children with this aggressive tumor.     

C-mer在增生性瘢痕中表达与意义

目的　原癌基因C mer与增生性病变关系密切。本研究探讨它在增生性瘢痕中所起的作用及意义。方法　收集瘢痕作为研究对象 ,利用原癌基因C mer的基因特异片段制成寡核苷酸探针 ,与瘢痕组织切片和成纤维细胞爬片原位杂交 ,统计学处理后分析其变化规律。结果　早期增生性瘢痕中C mer基因的探针在组织细胞中有较强阳性的反应 ,而非增生瘢痕则阳性反应较低 ,正常皮肤则更少。将增生性瘢痕与非增生瘢痕对比 ,二者差别特别显著。成纤维细胞爬片杂交结果存在相同的结果。结论　原癌基因C mer与瘢痕增生之间存在密切关系。同时 ,抑制该基因的表达 ,有望实现减轻瘢痕增生。     

热损伤诱导创面组织C-myc、C-myb、C-sis和C-jun原癌基因的表达

目的:研究创面组织部分原癌基因的表达。方法：雄性Wistar大鼠背部制作Ⅱ度烧伤模型，在不同时相点取创面组织及正常皮肤组织标本，应用mRNA点杂交，放射自显影及密度扫描方法分析原癌基因的表达水平。结果：热损伤诱导C－myc、C－myb，C－jun和C－sismRNA的表达。但这4种原癌基因的表达模式不尽相同。C－myc和C－jun的表达在伤后第1天就增加，分别于伤后1，3d达峰值。C－myB和C－sis的表达分别于伤后第3，5天开始增加，于第10天达峰值。结论：热损伤能诱导创面组织原癌基因的表达，其表达的有序性与受控性表明上述4种原癌基因作为调节因子参与了创面修复的过程。     

人肺癌中原癌基因的活化表达分析

以临床肺癌病人的手术切除标本提取癌组织细胞DNA和RNA,用Southern blotting和Northern blotting方法分析了细胞癌基因ras和myc的激活状态。在检测的10个病例标本中发现,ras和myc基因都有不同程度的基因扩增放大和激活表达;限制性酶切分析表明,对于ras和myc基因限制性片段长度多态性似乎与肺癌的病理分型没有严格的相关性。提示尽管肺癌发生的细胞类型不同,但其早期的细胞内基因的突变机制可能是相近的。     

Medullary thyroid carcinoma and multiple endocrine neoplasia type 2

Medullary thyroid carcinoma (MTC) occurs as both a sporadic and an inherited disease. MTC is a consistent feature of multiple endocrine neoplasia (MEN) 2A, MEN 2B, and familial non-MEN MTC (FMTC). Plasma calcitonin is a sensitive and specific marker for the presence of MTC. Genetic testing can identify mutant gene carriers, and prophylactic total thyroidectomy should be carried out in patients with the mutant gene. The outcome of MTC is progressively worse in FMTC, MEN 2A, sporadic MTC, and MEN 2B, and MEN 2B has been found to have the worst prognosis. There is a significant genotype-phenotype correlation, which allows a more sensitive individualized approach to the timing and extent of prophylactic thyroidectomy.     

甲状旁腺素氨基端1-34片段不同作用方式对人成骨样细胞SaoS-2的影响

目的观察人甲状旁腺素氨基端1-34片段(hPTH1-34)不同作用方式对人成骨样细胞(SaoS-2细胞)功能的影响,探讨hPTH1-34促进骨合成代谢的分子生物学机制.方法以48 h为一个周期,每个周期分别采用50 ng/ml的hPTH1-34进行连续刺激(刺激48 h/周期)或间歇刺激(分别刺激1、3、6、12、24 h/周期)SaoS-2细胞.采用"金氏"化学法、放射免疫法和竞争蛋白结合法测定碱性磷酸酶(ALP)、骨钙素(BGP)和环磷酸腺苷(cAMP)浓度;c-fos基因表达水平采用逆转录-聚合酶链反应技术(RT-PCR)进行半定量分析.结果hPTH1-34每周期间歇刺激3、6 h呈时间依赖性显著增加ALP产生(与对照比,P＜0.01;与连续刺激比,P＜0.05或P＜0.01)和cAMP浓度(与对照和连续刺激比,均P＜0.05),并迅速促进c-fos基因表达.未观察到BGP对hPTH1-34刺激的明显反应.结论hPTH1-34对骨合成代谢的促进作用取决于间歇刺激方式,以每48小时间歇刺激3、6 h作用最显著.蛋白激酶A信号途径是hPTH1-34发挥作用的主要途径,c-fos基因可能是重要的细胞内第三信使.     

大黄素对肾小管细胞增殖的影响及其分子机制探讨

观察大黄素对体外培养肾小管细胞增殖的影响。将２０ｍｇ·Ｌ－１大黄素加入肾小管细胞培养液后１２ｈ，肾小管细胞增殖明显受抑，（３Ｈ－ＴｄＲ掺入值２９４５．３３±１５１６．２４ｃｐｍ·ｗｅｌｌ－１Ｖｓ对照６３６８．１７±２０２５．９９ｃｐｍ·ｗｅｌｌ－１，Ｐ＜０．０５）。大黄素抑制肾小管细胞增殖与ｃ－ｍｙｃ原癌基因和ＴＧＦ－β基因ｍＲ－ＮＡ表达无明显联系。提示，大黄素抑制肾小管增殖可能通过其它调节机制起作用。     

Wnt/β-catenin signaling is a key downstream mediator of MET signaling in glioblastoma stem cells

Background

Glioblastoma (GBM) is the most lethal and common type of primary brain tumor. Recent evidence suggests that a subpopulation of GBM cells (glioblastoma stem cells [GSCs]) is critical for tumor progression, invasion, and therapeutic resistance. We and others have demonstrated that MET, a receptor tyrosine kinase, positively regulates the stemness phenotype and radioresistance of GSCs. Here, we interrogated the downstream effector pathways of MET signaling in GSCs.

Methods

We have established a series of GSCs and xenograft tumors derived from freshly dissociated specimens from patients with GBM and characterized a subpopulation enriched with MET activation (MET^high/+). Through global expression profiling and subsequent pathways analysis, we identified signaling pathways that are enriched in MET^high/+ populations, one of which is Wnt/β-catenin signaling pathway. To determine molecular interaction and the biological consequences of MET and Wnt/β-catenin signaling, we used pharmacological and shRNA-mediated genetic inhibition and performed various molecular and cellular analyses, including flow cytometry, immunohistochemistry, and clonogenicity assays.

Results

We found that Wnt/β-catenin signaling is highly active in MET^high/+ cells, compared with bulk tumor cells. We also showed that Wnt/β-catenin signaling activities in GBM are directly modulated by the addition of ligand-mediated MET activation or MET inhibition. Furthermore, the ectopic expression of active-β-catenin (S37A and S45Y) rescued the phenotypic effects caused by MET inhibition.

Conclusion

These data suggest that Wnt/β-catenin signaling is a key downstream effector of MET signaling and contributes to the maintenance of GSC and GBM malignancy.     

培养人视网膜色素上皮细胞在PVR患者视网膜下液作用下c-fos和c-jun的表达

目的 观察培养的人视网膜色素上皮细胞(human retinal pigment epithelium，hRPE)在不同程度增生性玻璃体视网膜病变(proliferative vitreoretinopathy，PVR)患者视网膜下液(subretinal fluid，SRF)作用下细胞增生与c—fos和c—jun的表达。方法 不同程度PVR患者SRF作用于培养的hRPE细胞后利用细胞计数和MTT比色实验观察SRF对培养hRPE细胞的作用，同时采用SP法在不同时间点作兔抗人c—fos多抗和兔抗人c—jun多抗的免疫组织化学染色。结果 PVR患者SRF作用组与对照组相比可明显促进培养hRPE细胞的增殖，同时实验组hRPE细胞c—fos和c—jun均表达增高，视网膜下液作用lh后，Fos蛋白抗体染色阳性，细胞核呈明显棕黄色染色；3h表达达高峰，持续约12h；视网膜下液作用lh后，Jun蛋白抗体染色阳性，细胞核呈明显棕黄色染色；6h表达达高峰，持续约48h，对照组hRPE细胞(未经SRF作用仅加入等量PBS)Fos蛋白抗体和Jun蛋白抗体染色均为阴性。结论 PVR患者SRF中含有能诱导c—fos和c—jun等“立早基因”转录的细胞外生长或分化因子；c—fos和c—jun的表达是SRF促进RPE细胞的增殖过程中一个非常重要的早期分子事件。