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41.
Brooks TD Slomp J Quax PH De Bart AC Spencer MT Verheijen JH Charlton PA 《Clinical & experimental metastasis》2000,18(6):445-453
Recent reports suggest that elevated levels of plasminogen activator inhibitor-1 (PAI-1) may contribute to tumour progression.
The studies reported here were designed to help elucidate PAI-1's contribution to the invasive and migratory phenotype. Antibodies
to PAI-1 dose-dependently, and significantly, inhibited the invasive and migratory potential of human HT1080 fibrosarcoma
cells, as did an antibody to uPA and the plasmin inhibitor aprotinin. Invasion of the human melanoma cell line, BLM, was also
attenuated by the anti-PAI-1 monoclonal antibody MAI-12. The non-invasive human melanoma cell line, IF6, which does not express
uPA, provided further confirmation of PAI-1 and uPA's role as, upon transfection with uPA, this cell line attained an invasive
phenotype, which was again attenuated by MAI- 12. Although antibodies to PAI-1 did not affect the adhesion of HT1080 cells
to vitronectin, the antibody to uPA reduced their attachment. Addition of exogenous PAI-1, however, prevented HT1080 cell
adhesion (IC50 180nM) and promoted cell detachment from vitronectin. Furthermore melanoma cells transfected with a uPA variant, which had
an impaired interaction with PAI-1, were not invasive and had impaired binding to vitronectin. These data highlight the importance
of a balanced proteolysis and suggest an additional role for PAI-1 distinct from its role in proteolysis. These data also
suggest that uPA and PAI-1 may co-operate in the migratory process by respectively facilitating the attachment to, and subsequent
detachment from, vitronectin in the extracellular matrix. These results support the clinical findings and indicate that modulation
of PAI-1 activity may be of therapeutic benefit for the treatment of cancer.
This revised version was published online in July 2006 with corrections to the Cover Date. 相似文献
42.
43.
Erik W. Thompson Jeffrey Torri Marybeth Sabol Connie L. Sommers Stephen Byers Eva M. Valverius George R. Martin Marc E. Lippman Martha R. Stampfer Robert B. Dickson 《Clinical & experimental metastasis》1994,12(3):181-194
Expression of the intermediate filament protein vimentin, and loss of the cellular adhesion protein uvomorulin (E-cadherin) have been associated with increased invasiveness of established human breast cancer cell linesin vitro andin vivo. In the current study, we have further examined these relationships in oncogenically transformed human mammary epithelial cells. A normal human mammary epithelial strain, termed 184, was previously immortalized with benzo[a]pyrene, and two distinct sublines were derived (A1N4 and 184B5). These sublines were infected with retroviral vectors containing a single or two oncogenes of the nuclear, cytoplasmic, and plasma membrane-associated type (v-ras
H, v-ras
Ki, v -mos, SV40T and c -myc). All infectants have been previously shown to exhibit some aspects of phenotypic transformation. In the current study, cellular invasiveness was determinedin vitro using Matrigel, a reconstituted basement membrane extract. Lineage-specific differences were observed with respect to low constitutive invasiveness and invasive changes after infection withras, despite similarras-induced transformation of each line. Major effects on cellular invasiveness were observed after infection of the cells with two different oncogenes (v-ras
H + SV40T and v -ras
H + v -mos). In contrast, the effects of single oncogenes were only modest or negligible. All oncogenic infectants demonstrated increased attachment to laminin, but altered secretion of the 72 kDa and 92 kDa gelatinases was not associated with any aspect of malignant progression. Each of the two highly invasive double oncogene transformants were vimentinpositive and uvomorulin-negative, a phenotype indicative of the epithelial-mesenchymal transition (EMT) previously associated with invasiveness of established human breast cancer cell lines. Weakly invasive untransformed mammary epithelial cells in this study were positive for both vimentin and uvomorulin, suggesting that uvomorulin may over-ride the otherwise vimentin-associated invasiveness. 相似文献
44.
目的评价植入镍钛记忆合金微创融合器(NiTi-TFC/C)的颈椎节段的稳定性及压缩力学性能。方法采集24只羊颈椎标本随机分为4组,每组6份,四组处理分别为:单取髓核组、自体髂骨植骨组、微创融合器组和钛制融合器组(InterFix)。所有标本进行前路减压,并对后3组进行椎间融合术。分别对各组标本进行生物力学测试并进行比较。结果微创融合器组与钛制融合器组在强度、刚度及扭转力学等方面无显著性差异(P>0.05)。而微创融合器组与自体髂骨植骨组具有显著性差异(P<0.05)。最大承载力为12050N。结论该微创融合器强度大、刚度高、抗扭转能力强,具有良好的抗压能力,为颈椎融合提供新型的融合装置。 相似文献
45.
Biological properties and gene expression associated with metastatic potential of human osteosarcoma 总被引:4,自引:0,他引:4
Nakano T Tani M Ishibashi Y Kimura K Park YB Imaizumi N Tsuda H Aoyagi K Sasaki H Ohwada S Yokota J 《Clinical & experimental metastasis》2003,20(7):665-674
Lung metastasis has a great influence on the prognosis of patients with osteosarcoma. We previously established two high-metastatic
sublines, M112 and M132, from the HuO9 human osteosarcoma cell line by in vivo selection. In this study, we newly isolated a high-metastatic subline, H3, and three low-metastatic sublines, L6, L12 and
L13, from HuO9 by the dilution plating method. Three high-metastatic sublines produced more than 200 metastatic nodules in
the lung, while three low-metastatic sublines produced no or few nodules after injection of 2 × 106 cells into the tail vein of nude mice. There were significant differences in the motility and invasiveness between high-
and low-metastatic sublines, whereas the growth rates in vitro and the tumorigenicity in vivo showed no correlation with their metastatic abilities. Early adherence to culture plates was significantly lower in two of
three low-metastatic sublines, which occupied smaller surface areas on the culture plates than other sublines did. Comparison
of the expression of 637 cancer-related genes by cDNA microarray revealed that seven genes were differentially expressed between
high- and low-metastatic sublines. Among them, five genes (AXL, TGFA, COLL7A1, WNT5A, and MKK6) were associated with adherence, motility, and/or invasiveness. These results suggest that the differences in motility/invasiveness
and adhesive abilities are key determinants of lung metastasis in osteosarcoma.
This revised version was published online in July 2006 with corrections to the Cover Date. 相似文献
46.
Honecker F Kersemaekers AM Molier M Van Weeren PC Stoop H De Krijger RR Wolffenbuttel KP Oosterhuis W Bokemeyer C Looijenga LH 《The Journal of pathology》2004,204(2):167-174
Intercellular contacts, mediated by E-cadherin, are essential for germ cell migration and maturation. Furthermore, it has been suggested that decrease or loss of E-cadherin correlates with tumour progression and invasive behaviour. beta-catenin is involved in a number of different processes, including cell--cell interaction when bound to cadherins, and determination of cell fate in pluripotent cells when activated via the Wnt signal-transduction pathway. To shed more light on the role of these factors in normal fetal germ cell development and the pathogenesis of germ cell tumours (GCTs), the present study investigated the presence and localization of E-cadherin and beta-catenin by immunohistochemistry. E-cadherin was only weakly expressed in or absent from fetal germ cells of the second and third trimesters, and was not expressed in carcinoma in situ/intratubular germ cell neoplasia unclassified (CIS/ITGCNU) and gonadoblastoma, the precursor of an invasive GCT in dysgenetic gonads. In GCTs, it was generally not expressed in seminoma and dysgerminoma, but was found in the vast majority of non-seminoma cells. beta-catenin was found in the cytoplasm of fetal germ cells at all gestational ages and in spermatogenesis in post-pubertal testes. It was also present in CIS/ITGCNU and gonadoblastoma. Whereas seminomas and dysgerminoma were negative, non-seminoma cells were frequently found to express beta-catenin. Expression of both factors therefore reflects the degree of differentiation of these tumours. No differences for either E-cadherin or beta-catenin were observed between samples of tumours resistant or sensitive to chemotherapy, and E-cadherin expression did not correlate with vascular invasion. E-cadherin and beta-catenin therefore play a role in both normal and malignant germ cell development and differentiation that warrants further investigation, but they seem to be of limited value as predictive or prognostic factors in GCTs. 相似文献
47.
Expression of vascular endothelial growth factor receptor 3 in blood and lymphatic vessels of lung adenocarcinoma 总被引:6,自引:0,他引:6
Vascular endothelial growth factor receptor 3 (VEGFR-3) has been proposed as a marker for lymphatic endothelial cells. This study investigated the expression of VEGFR-3 in the tumour vessels of lung adenocarcinoma and evaluated whether VEGFR-3 staining was useful for identifying lymphatic vessels within the tumour stroma. It also explored whether active growth of lymphatic vessels occurred in lung adenocarcinoma. Formalin-fixed, paraffin-embedded specimens obtained from 60 cases of lung adenocarcinoma, including five cases of pure bronchiolo-alveolar carcinoma (BAC) without stromal, vascular, and pleural invasion, were examined. No VEGFR-3-positive vessels were observed in pure BAC, but varying numbers of VEGFR-3-positive vessels were found in 39 of 55 (70.9%) invasive adenocarcinomas. A comparison of serial sections stained for VEGFR-3, CD31, and laminin-1 showed that most of the VEGFR-3-positive vessels appeared to be blood vessels (CD31-positive, laminin-1-positive), but some had the characteristics of lymphatic vessels (variable staining for CD31, little or no staining for laminin-1). VEGFR-3 staining highlighted lymphatic invasion by cancer cells; this invasion could not be detected by CD31 or haematoxylin and eosin (H&E) staining. Active growth of lymphatic vessels (as indicated by nuclear Ki-67 labelling of the endothelium) was observed in five tumours, four of which showed a high level of lymphatic invasion by cancer cells. It was concluded that VEGFR-3 immunostaining did not discriminate clearly between vascular and lymphatic endothelial cells, since expression of VEGFR-3 can be up-regulated in tumour blood vessels. However, VEGFR-3 staining combined with laminin-1 and CD31 staining would be useful for identifying lymphatic vessels and their invasion by tumour cells in a more objective way. Finally, proliferation of lymphatic endothelial cells may occur in association with lymphatic invasion by cancer cells. 相似文献
48.
Krueger S Kalinski T Hundertmark T Wex T Küster D Peitz U Ebert M Nägler DK Kellner U Malfertheiner P Naumann M Röcken C Roessner A 《The Journal of pathology》2005,207(1):32-42
Recently, we identified increased cathepsin X expression in H. pylori-infected gastric mucosa. Here, we describe further up-regulation in gastric cancer and report on the role of inflammatory cytokines required for cathepsin X up-regulation in H. pylori-infected gastric mucosa, as well as on consequences for cellular invasion. Biopsy specimens were taken from the antrum, corpus and cardia of H. pylori-infected and non-infected patients. Gastric cancer samples were obtained from patients undergoing gastric surgery. Cathepsin X was detected in gastric mucosa by quantitative real-time RT-PCR, western blotting and immunohistochemistry. Induction of cathepsin X expression in epithelial and inflammatory cells caused by H. pylori infection was tested in in vitro contact and non-contact co-cultures of AGS cells and monocytic cells. Patients with H. pylori gastritis showed significantly higher cathepsin X mRNA (2.5-fold) and protein (1.6-fold) expression than H. pylori-negative patients. Cathepsin X was also up-regulated in gastric cancer (3-12-fold) compared to non-neoplastic mucosa. Cathepsin X was predominantly expressed by macrophages in the mucosal stroma and in glands of the antral mucosa. In addition, tumour cells stained for cathepsin X in 26 (68%) patients with gastric carcinoma. In general, staining was significantly more common (20 vs. 6 patients) and more intense (3.55 vs. 0.83) in intestinal type gastric cancer than in the diffuse type. In vitro cell culture experiments revealed that intercellular signalling between pathogenicity island (PAI)-positive H. pylori-infected epithelial cells and macrophages via soluble factors in the culture medium seems to be responsible for increased expression of cathepsin X in monocytes. Using antisense oligonucleotides, cathepsin X up-regulation was directly associated with higher invasiveness in vitro. Although no correlation of cathepsin X expression and TNM stage was found, our study demonstrates that cathepsin X plays a role not only in the chronic inflammation of gastric mucosa but also in the tumourigenesis of gastric cancer. 相似文献
49.
Cassio V. Penteado 《Surgical and radiologic anatomy : SRA》1983,5(2):125-127
Summary An anatomical study of the superficial and deep circumflex iliac arteries in 43 formalin-fixed cadavers is presented. The origin, calibre, course, branches, symmetry and variations of the vessels are pointed out as well as their special features related to surgical applications.
Etude anatomochirurgicale des artères circonflexes iliaques superficielle et profonde: bases anatomiques de la confection du lambeau libre iliaque composé cutanéo-osseux
Résumé Une étude anatomique des artères circonflexes iliaque superficielle et profonde est effectuée sur 43 cadavres formulés. L'origine, le calibre, le trajet, les branches, la symétrie et les variations des vaisseaux sont mis en évidence ainsi que leurs caractères particuliers en vue d'une application chirurgicale.相似文献
50.
Clinical stage I seminomas are effectively treated with surgery raising concerns as to when to give adjuvant radiation therapy given the risk of secondary malignancies. A recent randomized trial found tumor size and rete testis invasion to be the strongest predictors of relapse in clinical stage I seminomas. These 2 parameters may be surrogate measures of tumor volume. Intertubular seminoma (ITS) of the testis describes the presence of neoplastic germ cells within the interstitium of the testis. These cells are detected away from the main macroscopic mass. Because ITS can infiltrate in a 3-dimensional fashion, it may also represent a measure of tumor volume not usually noted in standard pathology reporting. The goal of this study was to determine the incidence of ITS in pure seminomas and its association with other prognostic parameters. One hundred twenty consecutive pure seminomas surgically removed between 1998 and 2003 were evaluated. ITS was defined as the presence of an interstitial or intertubular growth pattern of tumor cells, which was noncontiguous with the main tumor and present at least 3 high-power fields away from the tumor mass. The average tumor size was 3.4 cm. Of the entire cohort of patients, which included pathological stages T1 through T3, 11% had invasion through the tunica albuginea, 51% had rete testis invasion, 51% had lymphovascular invasion, 93% had associated intratubular germ-cell neoplasia, and 36% had ITS. ITS was significantly associated with rete testis invasion ( P = .001). Logistic regression analysis looking at ITS, tumor size, patient age, and lymphovascular invasion revealed that only ITS was associated with rete testis invasion (RR, 4.1, P < .0001). ITS is present in a significant proportion of pure seminomas and has a significant association with rete testis invasion. The presence of ITS may therefore be an important prognostic factor, not only because it alters the calculated size of the tumor but also because it has an association with rete testis invasion. 相似文献