OSCC中ER-α、RAR-β、MGMT。及P16INK4a基因启动子甲基化的临床研究

目的：探讨肿瘤相关基因ER-α、RAR-β、MGMT及P16INK4a启动子在口腔鳞状细胞癌（OSCC）组织中的甲基化状态。方法：20例病理确诊为OSCC的组织切片,经酶消化法提取组织DNA后双硫法检测ER-αL、RAR-β、MGMT及P16INK4a基因启动子的甲基化状态,比较分析4种基因启动子甲基化状态和临床病理参数的相关性。结果：20例中,P16INK4a、MGMT启动子甲基化发生率均为10％,RAR-B启动子甲基化发生率为40％,ER-d启动子甲基化发生率为55％,两株OSCC细胞系中,ER-α、RAR-β启动子均出现甲基化,而MGMT及P16INK4a启动子均未见甲基化。结论：RAR-β、ER-α基因启动子的甲基化较P16INK4a、MGMT＇g更为常见,提示前两者可能在OSCC的发生中具有更重要的作用。     

Deoxycytidine kinase promotes the migration and invasion of fibroblast-like synoviocytes from rheumatoid arthritis patients

Rheumatoid arthritis (RA) is a complex, multi-system disease whose primary site of inflammatory tissue damage is the joint. The increasing evidences indicate that activated RA fibroblast-like synoviocytes (FLS) play a critical role in the development of pannus by migrating into cartilage and bone. Furthermore FLS and T cells can activate each other in vitro and in vivo, which is crucial for the progress of RA. Deoxycytidine kinase (DCK) has been linked to peripheral T cell homeostatic proliferation and survival, which is very important for RA. Yet, the function of DCK in FLS is still unknown. Here, we present a story that DCK could regulate the migration and invasion of FLS through AKT pathway in RA patients. Moreover, DCK seems to be the upstream of AKT and FAK, and AKT inhibitor exerted the similar effect on FLS motility. In summary, our study characterized the new role of DCK in human primary FLS cells, and figured out the possible pathway DCK involved in, and these findings might propose DCK as a novel target for controlling joint destruction of RA.     

Somatostatin receptors: From signaling to clinical practice

Somatostatin is a peptide with a potent and broad antisecretory action, which makes it an invaluable drug target for the pharmacological management of pituitary adenomas and neuroendocrine tumors. Somatostatin receptors (SSTR1, 2A and B, 3, 4 and 5) belong to the G protein coupled receptor family and have a wide expression pattern in both normal tissues and solid tumors. Investigating the function of each SSTR in several tumor types has provided a wealth of information about the common but also distinct signaling cascades that suppress tumor cell proliferation, survival and angiogenesis. This provided the rationale for developing multireceptor-targeted somatostatin analogs and combination therapies with signaling-targeted agents such as inhibitors of the mammalian (or mechanistic) target of rapamycin (mTOR). The ability of SSTR to internalize and the development of rabiolabeled somatostatin analogs have improved the diagnosis and treatment of neuroendocrine tumors.     

Mutations in transmembrane domain of c-erbB-2 gene in human malignant tumours of the central nervous system

Abstract

Point mutations in the transmembrane domain of c-erbB-2 gene in human brain tumours were studied by DNA amplification with the polymerase chain reaction method. Amplified gene fragments in M13 phage vector were cloned, and subsequent nucleotide sequences were determined. Studied specimens were 10 human malignant and 3 human benign tumours of the central nervous system, and a normal human placenta. In malignant tissues, Val-to-Glu mutation that induces transforming activity of c-erbB-2 did not appear at codon 659 of c-erbB-2. In malignant tissues, many other types of mutations appeared in low frequency, either at codon 659 or other positions of the transmembrane domain of c-erbB-2. The ratio of mutated genes to normal genes was very low in all specimens of malignant tumours. The point mutations were not observed in benign brain tumour or normal human placental tissues. The transmembrane domain of c-erbB-2 may have several highly mutable hot spotswhere brain tumour tissues show a predilection for point mutation.     

Increased expression in human astrocytomas of a 100 kDa protein with sequence homology to the ros tyrosine kinase domain

Abstract

A monoclonal antibody against the v-ros synthetic peptide VWETLTLGQQPYPCLSN IEVL (amino acid residues 455-475 of v-ros), which is in the conserved region of the c-ros tyrosine kinase domain, was used for Western blotting of human astrocytoma specimens. High levels of a 100 kDa protein were detected in many of these primary brain tumours. In contrast, low levels of this 100 kDa protein were consistently found in the nontumour brain control samples. This 100 kDa protein is however, probably not the c-ros protein, but may be a novel cytosolic protein-tyrosine kinase and a marker for early transformation of astrocytomas. [Neurol Res 1993; 15: 316-320].     

Maternal obesity induced by a ‘cafeteria’ diet in the rat does not increase inflammation in maternal,placental or fetal tissues in late gestation

IntroductionObesity during pregnancy can cause serious complications for maternal and infant health. While this has often been attributed to increased inflammation during obese pregnancy, human and animal studies exhibit variable results with respect to the inflammatory status of the mother, placenta and fetus. Cafeteria (CAF) feeding induces more inflammation than standard high-fat feeding in non-pregnant animal models. This study investigated whether maternal obesity induced by a CAF diet increases maternal, fetal or placental inflammation.MethodsMaternal obesity was established in rats by 8 weeks of pre-pregnancy CAF feeding. Maternal plasma inflammatory markers (IL-1β, IL-6, IL-10, IL-12p40, MCP1, GRO/KC, MIP-2 and TNFα) and expression of inflammatory genes (Tnfα, Il-6, Il-1β, Tlr2, Tlr4, Cox2 and Emr1) in maternal, placental and fetal tissues were measured at day 21 of gestation.ResultsDespite CAF animals having 63% more central body fat than controls at day 21 of gestation, plasma inflammatory markers were not increased; indeed, levels of IL-6, IL-12p40 and MIP2 were reduced slightly. Similarly, inflammatory gene expression remained largely unaffected by CAF feeding, except for slight reductions to Tlr4 and Emr1 expression in CAF maternal adipose tissue, and reduced Tlr4 expression in male labyrinth zone (LZ). The junctional zone (JZ) displayed increased Il-6 expression in CAF animals when fetal sexes were combined, but no inflammatory genes were affected by the CAF diet in fetal liver.ConclusionsMaternal obesity induced by a CAF diet before and during pregnancy does not increase the inflammatory status of the mother, placenta or fetus in late gestation.     

癌基因 c-fos、c-m yc 蛋白在皮肤鳞状细胞癌皮损中的表达及意义

目的：研究关于c-fos、c-myc两个癌基因在皮肤鳞癌发生和发展过程中的表达情况。方法选择79例皮肤鳞癌病例,应用免疫组织化学的方法检测c-fos、c-myc的表达情况,并比较与正常皮肤组织的表达情况进。结果在正常皮肤组织中c-fos、c-myc两个癌基因不表达,而在皮肤鳞癌中两者分别有70＃．9％和78．5％阳性表达,癌组织的分化程度与两者表达水平密切相关（ P ＜0．05）,分化程度越高的肿瘤c-fos表达水平越高,而在分化程度越高的肿瘤中c-myc表达水平越低。结论可用c-fos、c-myc的表达水平判定皮肤鳞癌及分化程度及指导临床预后。