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11.
Ackland ML Newgreen DF Fridman M Waltham MC Arvanitis A Minichiello J Price JT Thompson EW 《Laboratory investigation; a journal of technical methods and pathology》2003,83(3):435-448
PMC42-LA cells display an epithelial phenotype: the cells congregate into pavement epithelial sheets in which E-cadherin and beta-catenin are localized at cell-cell borders. They abundantly express cytokeratins, although 5% to 10% of the cells also express the mesenchymal marker vimentin. Stimulation of PMC42-LA cells with epidermal growth factor (EGF) leads to epithelio-mesenchymal transition-like changes including up-regulation of vimentin and down-regulation of E-cadherin. Vimentin expression is seen in virtually all cells, and this increase is abrogated by treatment of cells with an EGF receptor antagonist. The expression of the mesenchyme-associated extracellular matrix molecules fibronectin and chondroitin sulfate proteoglycan also increase in the presence of EGF. PMC42-LA cells adhere rapidly to collagen I, collagen IV, and laminin-1 substrates and markedly more slowly to fibronectin and vitronectin. EGF increases the speed of cell adhesion to most of these extracellular matrix molecules without altering the order of adhesive preference. EGF also caused a time-dependent increase in the motility of PMC42-LA cells, commensurate with the degree of vimentin staining. The increase in motility was at least partly chemokinetic, because it was evident both with and without chemoattractive stimuli. Although E-cadherin staining at cell-cell junctions disappeared in response to EGF, beta-catenin persisted at the cell periphery. Further analysis revealed that N-cadherin was present at the cell-cell junctions of untreated cells and that expression was increased after EGF treatment. N- and E-cadherin are not usually coexpressed in human carcinoma cell lines but can be coexpressed in embryonic tissues, and this may signify an epithelial cell population prone to epithelio-mesenchymal-like responses. 相似文献
12.
13.
Elastin point mutations cause an obstructive vascular disease, supravalvular aortic stenosis 总被引:7,自引:2,他引:7
Li DY; Toland AE; Boak BB; Atkinson DL; Ensing GJ; Morris CA; Keating MT 《Human molecular genetics》1997,6(7):1021-1028
Supravalvular aortic stenosis (SVAS) is an inherited obstructive vascular
disease that affects the aorta, carotid, coronary and pulmonary arteries.
Previous molecular genetic data have led to the hypothesis that SVAS
results from mutations in the elastin gene, ELN. In these studies, the
disease phenotype was linked to gross DNA rearrangements (35 and 85 kb
deletions and a translocation) in three SVAS families. However, gross
rearrangements of ELN have not been identified in most cases of autosomal
dominant SVAS. To define the spectrum of ELN mutations responsible for this
disorder, we refined the genomic structure of human ELN and used this
information in mutational analyses. ELN point mutations co-segregate with
the disease in four familial cases and are associated with SVAS in three
sporadic cases. Two of the mutations are nonsense, one is a single base
pair deletion and four are splice site mutations. In one sporadic case, the
mutation arose de novo. These data demonstrate that point mutations of ELN
cause autosomal dominant SVAS.
相似文献
14.
Zelinski-Wooten MB; Slayden OD; Chwalisz K; Hess DL; Brenner RM; Stouffer RL 《Human reproduction (Oxford, England)》1998,13(2):259-267
Large doses of antiprogestin typically disrupt menstrual cyclicity. A
chronic low-dose regimen of the potent new antiprogestin ZK 137 316, which
permits continued menstrual cyclicity but alters gonadal- reproductive
tract activity, was established. Rhesus monkeys received vehicle (n = 6) or
0.01 (n = 8), 0.03 (n = 8) or 0.1 (n = 5) mg ZK 137 316/kg body weight
daily for five menstrual cycles (C-1 to C-5). Oestradiol, progesterone and
gonadotrophin profiles were normal during cycles involving vehicle and 0.01
and 0.03 mg ZK 137 316/kg body weight. In the 0.1 mg/kg group, mid-cycle
oestradiol and gonadotrophin surges, and subsequent progesterone
production, were absent in C-3 and C-5. Ovarian cyclicity was accompanied
by timely menstruation in the vehicle and 0.01 mg/kg groups. By C-3, half
the animals in the 0.03 mg/kg group and all animals in the 0.1 mg/kg group
were amenorrhoeic. A corpus luteum was noted during the mid-luteal phase of
C-5 in the vehicle, 0.01 mg/kg and 0.03 mg/kg groups. Large antral and
cystic follicles were evident in the 0.1 mg/kg group. Thus, a daily
treatment with 0.01 mg/kg ZK 136317 permitted normal menstrual cyclicity in
macaques. While the daily administration of 0.03 mg/kg ZK 136 317 allowed
ovarian cyclicity, menstruation was disrupted in some animals. Increasing
the dose to 0.1 mg/kg antagonized pituitary function and resulted in
anovulation and amenorrhoea. A chronic low-dose regimen of the
antiprogestin ZK 137 316, which permits normal ovarian/menstrual cyclicity,
has potential as a contraceptive in women.
相似文献
15.
Interchromosomal duplications of the adrenoleukodystrophy locus: a phenomenon of pericentromeric plasticity 总被引:13,自引:5,他引:13
Eichler EE; Budarf ML; Rocchi M; Deaven LL; Doggett NA; Baldini A; Nelson DL; Mohrenweiser HW 《Human molecular genetics》1997,6(7):991-1002
A 9.7 kb segment encompassing exons 7-10 of the adrenoleukodystrophy (ALD)
locus of the X chromosome has duplicated to specific locations near the
pericentromeric regions of human chromosomes 2p11,10p11, 16p11 and 22q11.
Comparative sequence analysis reveals 92-96% nucleotide identity,
indicating that the autosomal ALD paralogs arose relatively recently during
the course of higher primate evolution (5-10 million years ago). Analysis
of sequences flanking the duplication region identifies the presence of an
unusual GCTTTTTGC repeat which may be a sequence-specific integration site
for the process of pericentromeric- directed transposition. The breakpoint
sequence and phylogenetic analysis predict a two-step transposition model,
in which a duplication from Xq28 to pericentromeric 2p11 occurred once,
followed by a rapid distribution of a larger duplicon cassette among the
pericentromeric regions. In addition to facilitating more effective
mutation detection among ALD patients, these findings provide further
insight into the molecular basis underlying a pericentromeric-directed
mechanism for non- homologous interchromosomal exchange.
相似文献
16.
DL?MagerEmail author AD?Haffajee PM?Devlin CM?Norris MR?Posner JM?Goodson 《Journal of translational medicine》2005,3(1):27
Background
The purpose of the present investigation was to determine if the salivary counts of 40 common oral bacteria in subjects with an oral squamous cell carcinoma (OSCC) lesion would differ from those found in cancer-free (OSCC-free) controls. 相似文献17.
Arvanitis DA Angelakis E Koumantakis EE Spandidos DA 《International journal of molecular medicine》2002,10(1):55-63
Effectiveness of radiotherapy is influenced by several genetic properties of the targeted cells. The aim of this study was the identification of prognostic indicators of tumor response to radiation in cervical and endometrial cancer. Using microsatellite DNA analysis, we investigated 31 markers, located on 1p, 2p, 2q, 3p, 9p, 9q, 13q, 17p and 17q for genomic alterations in 37 cervical and 21 endometrial cancer cases, with complete follow-up data. Genetic alterations of the initial tumor genotypes were observed after radiation in 86.5% of cervical and 81.0% of endometrial cases. Reversions to the original normal genotype were observed in 40.5 and 28.6% respectively, predominantly in cured patients rather than in recurred cases. Survival curves by the Kaplan-Meier method showed a worse prognosis for cervical cancer patients whose tumors harbor allelic imbalance (AI) on 3p or 13q, and for endometrial cancer patients whose tumors harbor AI on 13q. Our data suggest a possible association of the hMLH1 or BRCA2 genes, implicated in distinct DNA repair pathways and located on 3p and 13q respectively, with response of cervical and endometrial cancer to radiotherapy. Moreover, microsatellite DNA analysis before and after radiation treatment could be used as a marker of the clinical outcome of patients. 相似文献
18.
0 引言 我科 1996 / 1998分别应用消痔灵与强的松龙混合液、消痔灵液、强的松龙液行鼻息肉内 ,鼻息肉蒂部注射治疗鼻息肉各 5 0例 ,并设对照组为鼻腔滴入及口服类固醇激素 5 0例 ,合计 2 0 0例 ,观察并对比其疗效 .1 对象和方法1.1 对象 男 12 8例 ,女 72例 ,年龄 8~ 78(平均 38)岁 ,病程 32 a~ 45 (平均 4.5 ) a.其中在本次治疗前做过一次鼻息肉摘除术后复发的 2 7例 ,做过 2次或 2次以上手术的 12例 .主要症状为鼻塞、流脓涕、头痛及嗅觉减退 .全部病例治疗前均行鼻窦 X线拍片 ,其中上颌窦炎 12 5例、筛窦炎 5 8例、蝶窦炎 2例、… 相似文献
19.
The presence of activating ras mutations in a cardiac leiomyosarcoma which occurred in the right atrium of the heart of a female patient was examined. The tumor had the appearance of leiomyosarcoma in rutine histopathological examination and the definite diagnosis was confirmed by a positive immunohistochemical reaction to smooth muscle actin. Molecular analysis by polymerase chain reaction (PCR) restriction fragment length polymorphism (RFLP) technique showed a point mutation of H-ras gene at codon 12. To the best of our knowledge, this is the first report describing ras gene mutation in a cardiac leiomyosarcoma implying a role for the ras oncogenes in the development of this tumor. 相似文献
20.
Chorvat RJ Bakthavatchalam R Beck JP Gilligan PJ Wilde RG Cocuzza AJ Hobbs FW Cheeseman RS Curry M Rescinito JP Krenitsky P Chidester D Yarem JA Klaczkiewicz JD Hodge CN Aldrich PE Wasserman ZR Fernandez CH Zaczek R Fitzgerald LW Huang SM Shen HL Wong YN Chien BM Arvanitis A 《Journal of medicinal chemistry》1999,42(5):833-848
The synthesis and CRF receptor binding affinities of several new series of N-aryltriazolo- and -imidazopyrimidines and -pyridines are described. These cyclized systems were prepared from appropriately substituted diaminopyrimidines or -pyridines by nitrous acid, orthoester, or acyl halide treatment. Variations of amino (ether) pendants and aromatic substituents have defined the structure-activity relationships of these series and resulted in the identification of a variety of high-affinity agents (Ki's < 10 nM). On the basis of this property and lipophilicity differences, six of these compounds (4d,i,n,x, 8k, 9a) were initially chosen for rat pharmacokinetic (PK) studies. Good oral bioavailability, high plasma levels, and duration of four of these compounds (4d,i,n,x) prompted further PK studies in the dog following both iv and oral routes of administration. Results from this work indicated 4i,x had properties we believe necessary for a potential therapeutic agent, and 4i1 has been selected for further pharmacological studies that will be reported in due course. 相似文献