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61.
The influence of cadmium (up to 10?4 M), fluoride (up to 10?4 M), and X-rays (up to 18.8 Gy) on different variables of preimplantation mouse embryos in vitro has been examined. The agents were applied either singly or in combination (0.94 Gy X-rays +3×10?7 M CdSO4 or CdF2; 0.94 Gy X-rays +3×10?6 M CdSO4 or CdF2). The following variables were determined:
- the microscopic visible development until 144 h post conceptionem (=144 h p.c.),
- the average cell numbers (48 h p.c., 56 h p.c., 72 h p.c., 96 h p.c., 120 h p.c., 144 h p.c.),
- the number of micronuclei (72 h p.c.),
- the distribution of cell nuclei within the cell cycle (72 h p.c.).
62.
Barbara Seliger Derek Atkins Michaela Bock Ulrike Ritz Soldano Ferrone Christoph Huber Stefan St?rkel 《Clinical cancer research》2003,9(5):1721-1727
The HLA class I antigen-processing machinery (APM) plays a crucial role in the generation of peptides from endogenously synthesized proteins and in their presentation to cytotoxic T lymphocytes. The potential role of defects of APM components in immune escape mechanisms used by malignant cells has prompted us to analyze their expression in renal cell carcinoma (RCC) lesions with special emphasis on TAP because of its critical role in the loading of HLA class I antigens with peptides. Immunohistochemical staining of 51 formalin-fixed RCC lesions and autologous normal renal epithelium detected transporter associated with antigen processing (TAP)1 and tapasin deficiencies in 63 and 80% of the tumor lesions. Impaired low molecular weight protein (LMP)2 and LMP7 expression was found in 73 and 33% of the RCC lesions analyzed, respectively. In contrast to the high frequency of APM component down-regulation, HLA class I heavy chain and beta(2)-microglobulin defects were detected in only 12 and 10% of the lesions, respectively. Concomitant TAP1 and LMP2 deficiencies were found in approximately 57% of RCC lesions, whereas a coordinated down-regulation of all APM components occurred only in 5% of the tumor specimens analyzed. The presence of APM defects was independent of tumor stage and grade but varied significantly among the RCC subtypes. TAP abnormalities do not appear to be attributable to structural alterations because no mutations in TAP1 were detected in TAP1-deficient RCC lesions. These data suggest that TAP defects in RCC lesions are caused by regulatory abnormalities. Therefore, T-cell-based immunotherapy may benefit from the administration of cytokines that up-regulate TAP expression. 相似文献
63.
Primary metastatic osteosarcoma: presentation and outcome of patients treated on neoadjuvant Cooperative Osteosarcoma Study Group protocols. 总被引:4,自引:0,他引:4
Leo Kager Andreas Zoubek Ulrike P?tschger Ulrike Kastner Silke Flege Beate Kempf-Bielack Detlev Branscheid Rainer Kotz Mechthild Salzer-Kuntschik Winfried Winkelmann Gernot Jundt Hartmut Kabisch Peter Reichardt Heribert Jürgens Helmut Gadner Stefan S Bielack 《Journal of clinical oncology》2003,21(10):2011-2018
PURPOSE: To determine demographic data and define prognostic factors for long-term outcome in patients presenting with high-grade osteosarcoma of bone with clinically detectable metastases at initial presentation. PATIENTS AND METHODS: Of 1,765 patients with newly diagnosed, previously untreated high-grade osteosarcomas of bone registered in the neoadjuvant Cooperative Osteosarcoma Study Group studies before 1999, 202 patients (11.4%) had proven metastases at diagnosis and therefore were enrolled onto an analysis of demographic-, tumor-, and treatment-related variables, response, and survival. The intended therapeutic strategy included pre- and postoperative multiagent chemotherapy as well as aggressive surgery of all resectable lesions. RESULTS: With a median follow-up of 1.9 years (5.5 years for survivors), 60 patients were alive, 37 of whom were in continuously complete surgical remission. Actuarial overall survival rates at 5 and 10 (same value for 15) years were 29% (SE = 3%) and 24% (SE = 4%), respectively. In univariate analysis, survival was significantly correlated with patient age, site of the primary tumor, number and location of metastases, number of involved organ systems, histologic response of the primary tumor to preoperative chemotherapy, and completeness and time point of surgical resection of all tumor sites. However, after multivariate Cox regression analysis, only multiple metastases at diagnosis (relative hazard rate [RHR] = 2.3) and macroscopically incomplete surgical resection (RHR = 2.4) remained significantly associated with inferior outcomes. CONCLUSION: The number of metastases at diagnosis and the completeness of surgical resection of all clinically detected tumor sites are of independent prognostic value in patients with proven primary metastatic osteosarcoma. 相似文献
64.
Katrin Lamszus Ulrike Ulbricht Jakob Matschke Marc A Brockmann Regina Fillbrandt Manfred Westphal 《Clinical cancer research》2003,9(4):1399-1405
PURPOSE: Vascular endothelial growth factor (VEGF)-A isa key mediator of angiogenesis in malignant gliomas. Soluble VEGF receptor 1 (sVEGFR-1) can complex VEGF-A and reduce its bioavailability. In several animal models sVEGFR-1 inhibited angiogenesis and tumor growth. We analyzed the levels of endogenous sVEGFR-1 in gliomas of different malignancy grades in relation to tumor vascularity and VEGF-A. EXPERIMENTAL DESIGN: The concentration of sVEGFR-1 was determined by ELISA in 104 gliomas and normal brain. Levels of sVEGFR-1 were compared with malignancy grade, microvessel density, and VEGF-A concentration. Effects of sVEGFR-1 on glioma extract-induced endothelial cell chemotaxis were analyzed in vitro. RESULTS: The concentration of sVEGFR-1 correlated with the malignancy grade and was 12-fold higher in glioblastomas than in diffuse astrocytomas (P < 0.001), with intermediate levels for anaplastic astrocytomas. VEGF-A levels were 30-fold higher (P < 0.001) in glioblastomas than in diffuse astrocytomas. The sVEGFR-1:VEGF-A ratio was 0.27 in glioblastomas and 0.70 in diffuse astrocytomas. Both sVEGFR-1 and VEGF-A correlated with microvessel density (P < 0.001) and with each other (P < 0.001); sVEGFR-1 and VEGF-A also correlated with each other when only glioblastomas were analyzed (P = 0.001). In vitro, recombinant sVEGFR-1 inhibited endothelial cell chemotaxis induced by tumor extracts. CONCLUSIONS: Although absolute levels of sVEGFR-1 are increased in the more malignant gliomas, the sVEGFR-1:VEGF-A ratio is decreased 2.6-fold in glioblastomas compared with diffuse astrocytomas, suggesting that the ensuing increased bioavailability of VEGF-A favors angiogenesis. The inhibition of tumor extract-induced endothelial chemotaxis by sVEGFR-1 suggests that sVEGFR-1 could be useful as an angiogenesis inhibitor in the specific context of human gliomas. 相似文献
65.
Ulrike Heider Corinna Langelotz Christian Jakob Ivana Zavrski Claudia Fleissner Jan Eucker Kurt Possinger Lorenz C Hofbauer Orhan Sezer 《Clinical cancer research》2003,9(4):1436-1440
PURPOSE: Increased bone resorption is a hallmark of multiple myeloma and is attributable to osteoclast activation. Recent studies showed that the receptor activator of nuclear factor kappaB ligand (RANKL) is the key mediator of osteoclastogenesis and plays a crucial role in bone destruction in malignant bone disease. We found that human myeloma cells express RANKL and analyzed the association of the RANKL expression with the presence of osteolytic bone disease in patients with multiple myeloma. EXPERIMENTAL DESIGN: Flow cytometry was performed on bone marrow samples derived from controls and multiple myeloma patients with or without osteolytic bone lesions on conventional radiography. Plasma cells were identified as CD38++/CD138+ cells. The level of RANKL expression on the surface of bone marrow plasma cells was correlated with the bone status of the patients. RESULTS: The bone marrow plasma cells from controls showed no or only a weak surface expression of RANKL, and the median mean fluorescence index (MFI) was 6. In contrast, expression of RANKL could be detected on bone marrow plasma cells from all of the patients with multiple myeloma, and median MFI was 47. The difference in MFI for RANKL expression of bone marrow plasma cells from controls and myeloma patients was highly significant (P < 0.0005). Myeloma patients with osteolytic bone lesions showed a significantly higher expression of RANKL (median MFI = 60; range, 16-2494) compared with patients without osteolysis (median MFI = 16; range, 6-229; P < 0.0005). CONCLUSIONS: These results show for the first time that the level of RANKL expression by myeloma cells correlates significantly with osteolytic bone disease. 相似文献
66.
Hans-Peter Gschwind Ulrike Pfaar Felix Waldmeier Markus Zollinger Claudia Sayer Peter Zbinden Michael Hayes Rolf Pokorny Michael Seiberling Monique Ben-Am Bin Peng Gerhard Gross 《Drug metabolism and disposition》2005,33(10):1503-1512
Imatinib mesylate (GLEEVEC, GLIVEC, formerly STI571) has demonstrated unprecedented efficacy as first-line therapy for treatment for all phases of chronic myelogenous leukemia and metastatic and unresectable malignant gastrointestinal stromal tumors. Disposition and biotransformation of imatinib were studied in four male healthy volunteers after a single oral dose of 239 mg of (14)C-labeled imatinib mesylate. Biological fluids were analyzed for total radioactivity, imatinib, and its main metabolite CGP74588. Metabolite patterns were determined by radio-high-performance liquid chromatography with off-line microplate solid scintillation counting and characterized by liquid chromatography-mass spectrometry. Imatinib treatment was well tolerated without serious adverse events. Absorption was rapid (t(max) 1-2 h) and complete with imatinib as the major radioactive compound in plasma. Maximum plasma concentrations were 0.921 +/- 0.095 mug/ml (mean +/- S.D., n = 4) for imatinib and 0.115 +/- 0.026 mug/ml for the pharmacologically active N-desmethyl metabolite (CGP74588). Mean plasma terminal elimination half-lives were 13.5 +/- 0.9 h for imatinib, 20.6 +/- 1.7 h for CGP74588, and 57.3 +/- 12.5 h for (14)C radioactivity. Imatinib was predominantly cleared through oxidative metabolism. Approximately 65 and 9% of total systemic exposure [AUC(0-24 h) (area under the concentration time curve) of radioactivity] corresponded to imatinib and CGP74588, respectively. The remaining proportion corresponded mainly to oxidized derivatives of imatinib and CGP74588. Imatinib and its metabolites were excreted predominantly via the biliary-fecal route. Excretion of radioactivity was slow with a mean radiocarbon recovery of 80% within 7 days (67% in feces, 13% in urine). Approximately 28 and 13% of the dose in the excreta corresponded to imatinib and CGP74588, respectively. 相似文献
67.
68.
OBJECTIVE: Many new stool tests intended to detect neoplastic cells or cell products are developed at present for colorectal cancer (CRC) screening. The aim of this study was to simulate a population-based screening setting to assess and compare the potential for early detection and prevention of CRC of screening based on stool tests with different sensitivity and specificity and of screening with colonoscopy as a primary screening tool. METHOD: A Markov model was developed aimed to estimate the proportion of CRC cases which are early detected or prevented due to screening as well as the number of equired stool tests and colonoscopies per early detected or prevented CRC case. Model outcomes were calculated for the offer of annual stool testing from age 55 to 74 in combination with colonoscopic follow-up of positive test results and for the offer of screening colonoscopy as a primary screening tool at ages 55 and 65. The long-lasting risk reduction of colonoscopy allowing the removal of precancerous lesions was taken into account quantitatively. RESULTS: For a variety of stool tests with different performance characteristics, the proportion of CRC cases early detected or prevented was estimated to be higher for stool testing in combination with colonoscopic follow-up of positive test results compared with screening colonoscopy assuming levels of compliance to be expected for the respective screening scheme. Optimizing performance characteristics of stool tests in terms of detecting precancerous lesions, in addition to those in terms of detecting CRC, seemed to be crucial for maximizing effectiveness of CRC screening with stool tests. CONCLUSION: Screening based on new stool tests with colonoscopic follow-up of positive test results might offer a high potential for early detection or prevention of CRC. 相似文献
69.
70.
Viral load,gene expression and mapping of viral integration sites in HPV16‐associated HNSCC cell lines 下载免费PDF全文
Jutta Kolligs Mieke Henfling Frans C.S. Ramaekers Iris Cornet Josefa A. van Lent‐Albrechts Alexander P.A. Stegmann Steffi Silling Ulrike Wieland Thomas E. Carey Heather M. Walline Susanne M. Gollin Thomas K. Hoffmann Johan de Winter Bernd Kremer Ernst‐Jan M. Speel 《International journal of cancer. Journal international du cancer》2015,136(5):E207-E218