Glucocorticoid and Estrogen Receptors Have Elevated Activity in Human Endometrial and Ovarian Tumors as Compared to the Adjacent Normal Tissues and Recognize Sequence Elements of the H-ras Proto-oncogene

We examined the level of receptor binding in H- ras elements, using nuclear extracts derived from human endometrial and ovarian lesions and from adjacent normal tissue in gel retardation assays. We found increased binding of the glucocorticoid receptor (GR) to the H- ras GR element in more than 90% of endometrial tumors and in all ovarian tumors tested, as compared to the corresponding adjacent normal tissue. Additionally, we found elevated binding of the estrogen receptor (ER) in H- ras ER element in all pairs of ovarian tumor/normal tissue tested, whereas in ER-negative control breast tumor/normal tissue pairs, no differences in ER DNA-binding levels were observed. These results suggest that steroid hormone receptor binding could directly activate the H- ras oncogenic potency in human endometrial and ovarian lesions, providing additional evidence for the role of H- ras expression in hormonally responsive human cancers.     

17-β-雌二醇诱发大鼠腺垂体催乳素瘤的形成及原癌基因c-myc的高表达

给SD大鼠皮下埋植17-β-雌二醇,60天后,其垂体重量显著增加;垂体前叶细胞明显增生,分化受抑制;用放射免疫法测定血浆催乳素含量显著增加;斑点杂交显示垂体细胞原癌基因c-myc的转录水平也显著增加。     

人参皂苷Rg_1对大鼠海马c-fos基因表达和cAMP含量的影响(英文)

目的:探讨Rg_1对神经系统作用的机制。方法:采用Northern和Western印迹分析法,检测了Rg_1处理前后大鼠海马组织的c-fos基因和蛋白的表达。结果:老年鼠c-fos基因和蛋白的表达明显低于青年鼠,但给Rg_1后老年鼠和青年鼠均呈现显著性增强效应。此外,Rg_1还明显增加青年鼠和老年鼠海马组织的cAMP含量。结论:Rg_1升高cAMP水平及促进c-fos基因和蛋白的表达有助于阐明其促智和抗衰老作用的机制。     

多发性内分泌腺瘤病2A家系的RET原癌基因突变研究

目的 检测一个多发性内分泌腺瘤病2A(MEN 2A)型家系的RET原癌基因突变情况。方法 提取16名家系成员外周血基因组DNA，对RET原癌基因第ll外显子进行聚合酶链反应(PCR)，PCR产物进行直接基因测序。结果 家系中l例病理确诊嗜铬细胞瘤的患者存在RET原癌基因第ll外显子634密码子错义突变；另外筛查出2名家系成员为该突变基因携带者，其中l例经B超发现甲状腺结节性病灶伴血清降钙素升高。结论 MEN2A的诊断达到了基因水平，对家系基因筛查可以早期诊断该疾病。     

Long-term induction of c-jun mRNA and jun protein in rabbit retinal ganglion cells following axotomy or colchicine treatment

The expression of the c-jun, c-fos, and NGFI-A genes was studied in the rabbit retina after optic nerve crush (ONC) or an intravitreal injection of colchicine. By Northern blotting, the basal expression of c-fos and NGFI-A mRNAs were undetectable, whereas c-jun mRNA showed a low basal expression in shamoperated control retinas. Very few or no Jun- or Fosimmunoreactive nuclei were seen in control retinas. From 1 to 95 days after ONC a marked induction of JUN- but not FOS-immunoreactive neurons was seen in the ganglion cell layer peaking at 3 and 7 days. Jun-positive neurons also accumulated immunoreactive phosphorylated neurofilaments, indicating that they were ganglion cells. Northern blots demonstrated that retinal levels of c-jun mRNA, but not of c-fos or NGFI-A mRNAs, were increased 3 and 7 days after ONC. An intravitreal injection of colchicine also induced Jun-immunoreactivity within 24 hr in most of the neurons in the ganglion cell layer, but not in the inner nuclear and outer nuclear layers. The results indicate that axonal damage induces a specific pattern of IEG expression including a long-term induction of the c-jun gene in CNS neurons. © 1993 Wiley-Liss, Inc.     

The GDNF/Neurturin-Ret multicomponent receptor system

Glial cell line-derived neurotrophic factor (GDNF) and neurturin (NTN) are structurally related neurotrophic factors that play crucial roles in the survival of peripheral sensory, sympathetic and dopaminergic neurons as well as motoneurons. Glial cell line-derived neurotrophic factordeficient mice showed lack of enteric neurons and renal agenesis or dysgenesis. Surprisingly, this phenotype was strikingly similar to that of ret proto-oncogene-deficient mice, suggesting that Ret tyrosine kinase might be a functional receptor for GDNF. Recent studies demonstrated that both GDNF and NTN were able to induce Ret tyrosine phosphorylation although they did not bind to Ret with high affinity, but novel glycosyl-phosphatidylinositol (GPI)-linked cell-surface proteins as ligand-binding components were required for Ret activation. Since GDNF and NTN are expected as therapeutic agents in neurodegenerative disorders such as Parkinson's disease and amyotrophic lateral sclerosis, the studies on the mechanisms of their biological actions through Ret would contribute to the development of new therapeutic strategies for these diseases.     

Expression of ETS proto-oncogenes in astrocytes in human cortex

In order to investigate a possible function of ETS proto-oncogenes in human brain, we incubated a polyclonal antibody raised against the viral region of E26 homologous to ETS1 and ETS2 with human brain frontal cortex sections. Our results show that this antibody decorates astrocytes but not neurons. By using astrocytomas of different grades as a source of astrocytes, we demonstrate the presence of ETS1 and ETS2 messenger RNAs and proteins. This leads to the idea that ETS genes are expressed in cells with dividing potentialities in human cortex and that they could provide a new marker for glial cells. Recently, a microduplication on chromosome 21 including ETS2 locus was described in karyotypically ‘normal’ Down's syndrome and suspected in Alzheimer's disease; when testing Alzheimer's disease-affected brain cortex sections, no obvious difference was observed with the technique used.     

FDG PET imaging in hereditary thyroid cancer

AIM: To report the role of different imaging methods in staging individuals with multiple endocrine neoplasia 2A (MEN2A) or familial medullary thyroid carcinoma (FMTC). MATERIAL AND METHODS: Fourteen newly diagnosed gene carriers underwent cervical ultrasound scanning (US), cervical and mediastinal CT, MRI and whole-body meta-[131I]iodobenzylguanidine (MIBG) scintigraphy and [18F]fluorodeoxyglucose (FDG) PET scanning. RESULTS: US identified seven true primary cancer. CT and MRI located only tumors > or =5 mm in diameter. MIBG scintigraphy and FDG PET could not identify MTC foci within the thyroid. Whole-body FDG PET identified two true-positive and one false-positive lymph node metastases. MIBG scintigraphy did not identify lymph node metastases. Total thyroidectomy was performed in 12 cases, and subtotal thyroidectomy in two subjects. CONCLUSIONS: Whole-body FDG PET and cervical US help stage individuals carrying mutant genes verifying MEN2A or FMTC.     

酪氨酸激酶类受体C-Met抑制剂研究进展

酪氨酸激酶类受体C-Met及其配体肝细胞生长因子(HGF)与肿瘤的发生、发展及预后密切相关,是肿瘤治疗的重要靶标.寻找高效C-Met抑制剂是目前抗肿瘤药物研究的热点之一.本文综述了这一领域的最新研究进展.     

Chronic renal failure rats are highly sensitive to aristolochic acids, which are nephrotoxic and carcinogenic agents

Aristolochic acid (AA), a component of some Chinese herbal medicines, may cause Chinese Herbs Nephropathy (CHN) and multi-systemic tumors by the formation of AA-DNA adducts. In this study, we established an animal model to further characterize the mechanisms of AA-induced diseases. Our results indicated that AA significantly inhibited rat growth in terms of weight gain. By measuring the serum creatinine levels, AA resulted in considerable damage to the rat renal system, not only for those in which chronic renal failure (CRF) was induced but also for normal healthy rats. Mutation-specific polymerase chain reaction (PCR) and XbaI restriction fragment length polymorphism (RFLP) revealed the CAA-->CTA transversion mutation at codon 61 of the H-ras proto-oncogene from the stomach tissues of CRF rats fed with AA, but not from other tissues of rats in the same experimental group. In addition, no such mutations were found in the tissues of CRF rats without AA treatment or healthy rats fed with AA. Our results strongly demonstrated that AA was in fact nephrotoxic and carcinogenic, especially to those CRF rats.