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41.
Steven J Skates Nora Horick Yinhua Yu Feng-Ji Xu Andrew Berchuck Laura J Havrilesky Henk W A de Bruijn Ate G J van der Zee Robert P Woolas Ian J Jacobs Zhen Zhang Robert C Bast 《Journal of clinical oncology》2004,22(20):4059-4066
PURPOSE: In CA-125-based ovarian cancer screening trials, overall specificity and screening sensitivity of ultrasound after an elevated CA-125 exceeded 99.6% and 70%, respectively, thereby yielding a positive predictive value (PPV) exceeding 10%. However, sensitivity for early-stage disease was only 40%. This study aims to increase preoperative sensitivity for early-stage ovarian cancer while maintaining the annual referral rate to ultrasound at 2% by combining information across CA-125II, CA 15-3, CA 72-4, and macrophage colony-stimulating factor (M-CSF). For direct comparisons between marker panels, all sensitivity results correspond to a 98% fixed first-line specificity (referral rate 2%). PATIENTS AND METHODS: Logistic regression, classification tree, and mixture discriminant analysis (MDA) models were fit to a training data set of preoperative serum measurements (63 patients, 126 healthy controls) from one center. Estimates from the training set applied to an independent validation set (60 stage I to II patients, 98 healthy controls) from two other centers provided unbiased estimates of sensitivity. RESULTS: Preoperative sensitivities for early-stage disease of the optimal panels were 45% for CA-125II; 67% for CA-125II and CA 72-4; 70% for CA-125II, CA 72-4, and M-CSF; and 68% for all four markers (latter two results using MDA). CONCLUSION: Efficiently combining information on CA-125II, CA 72-4, and M-CSF significantly increased preoperative early-stage sensitivity from 45% with CA-125II alone to 70%, while maintaining 98% first-line specificity. Screening trials with these markers using MDA followed by referral to ultrasound may maintain previously high levels of specificity and PPV, while significantly increasing early-stage screening sensitivity. MDA is a useful, biologically justified method for combining biomarkers. 相似文献
42.
Velraeds MM van de Belt-Gritter B Busscher HJ Reid G van der Mei HC 《World journal of urology》2000,18(6):422-426
The ability of three Lactobacillus strains to inhibit the adhesion and growth of naturally occurring uropathogens on silicone rubber was investigated in human
urine. The importance of biosurfactant production by Lactobacillus in discouraging uropathogen growth was determined in relation to the binding affinities of the lactobacilli for silicone
rubber. L. fermentum B54 markedly inhibited uropathogen growth on the silicone rubber disks after 8 days for all five men included in the study,
albeit to various extents ranging from 77% to 100%. In urine from women, however, this inhibition was less clear, as it was
absent for two of the four women participating in this study. L. casei rhamnosus 36 completely discouraged uropathogen growth on the disks after 8 days for three of the four women, whereas its effect in
urine from men was less pronounced (inhibition ranged from 48% to 100% and was absent for one man). L. casei rhamnosus ATCC 7469T was the least inhibitory Lactobacillus strain tested and inhibition was absent for a number of both male and female participants, possibly as a result of the low
binding affinity of this strain for silicone rubber and of its inability to release biosurfactants. We conclude that the inhibition
of uropathogen growth is dependent on the Lactobacillus strain involved, and for L. fermentum B54 it was demonstrated to be sex-related. Hence, inhibition must be considered a multifactorial process. 相似文献
43.
Human kallikrein 6 (hK6): a new potential serum biomarker for diagnosis and prognosis of ovarian carcinoma. 总被引:12,自引:0,他引:12
Eleftherios P Diamandis Andreas Scorilas Stefano Fracchioli Marleen Van Gramberen Henk De Bruijn Alfthan Henrik Antoninus Soosaipillai Linda Grass George M Yousef Ulf-Hakan Stenman Marco Massobrio Ate G J Van Der Zee Ignace Vergote Dionyssios Katsaros 《Journal of clinical oncology》2003,21(6):1035-1043
PURPOSE: The discovery of new ovarian cancer biomarkers that are suitable for early disease diagnosis and prognosis may ultimately lead to improved patient management and outcomes. PATIENTS AND METHODS: We measured, by immunoassay, human kallikrein 6 (hK6) concentration in serum of 97 apparently healthy women, 141 women with benign abdominal diseases, and 146 women with histologically proven primary ovarian carcinoma. We then calculated the diagnostic sensitivity and specificity of this test and examined the association of serum hK6 concentration with various clinicopathologic variables and patient survival. RESULTS: Serum hK6 concentration between normal and benign disease patients was not different (mean, 2.9 and 3.1 micro g/L, respectively). However, hK6 in presurgical serum of ovarian cancer patients was highly elevated (mean, 6.8 micro g/L; P <.001). Serum hK6 decreased after surgery (to a mean of 3.9 micro g/L) in 68% of patients. The diagnostic sensitivity of serum hK6 at 90% and 95% specificity is 52% and 47%, respectively, in the whole patient population. For early stage disease (stage I or II), sensitivity is approximately 21% to 26%. When combined with CA-125, at 90% specificity, sensitivity increases to 72% (for all patients) and to 42% in stage I or II disease. Serum hK6 concentration correlates moderately with CA-125 and is higher in patients with late-stage, higher-grade disease and in patients with serous histotype. Preoperative serum hK6 concentration is a powerful predictor of disease-free and overall survival in both univariate and multivariate analyses. CONCLUSIONS: Serum hK6 concentration seems to be a new biomarker for ovarian carcinoma and may have value for disease diagnosis and prognosis. 相似文献
44.
Els M J J Berns Jan G M Klijn Maxime P Look Nicolai Grebenchtchikov Rolf Vossen Harry Peters Anneke Geurts-Moespot Henk Portengen Iris L van Staveren Marion E Meijer-van Gelder Bert Bakker Fred C G J Sweep John A Foekens 《Clinical cancer research》2003,9(4):1253-1258
PURPOSE: In recent studies, we showed that TP53 gene mutation or high levels of cytosolic vascular endothelial growth factor (VEGF) in estrogen receptor (ER)-alpha-positive primary breast tumors predict a poor disease outcome for patients treated with first-line tamoxifen for advanced disease. Mutant TP53 may up-regulate VEGF, whereas, on the other hand, wild-type TP53 may decrease VEGF production. EXPERIMENTAL DESIGN: In the present study, we aimed to assess the combined predictive value of TP53 gene mutation and VEGF status of 160 advanced breast cancer patients with ER-positive tumors who were treated with tamoxifen (median follow-up from start of tamoxifen treatment, 64 months). To assess TP53 gene mutation status, the entire open reading frame was sequenced; for VEGF status, an ELISA was used. RESULTS: In univariate analysis, both TP53 gene mutation (28% of the tumors) and a VEGF level above the median value were significantly associated with a short progression-free survival, post-relapse overall survival, and a poor rate of response to tamoxifen. In Cox multivariate regression analysis including the traditional predictive factors, the addition of TP53 gene mutation and VEGF status, alone or in combination, significantly predicted a poor efficacy of tamoxifen treatment. When the two factors were combined, a significantly decreased odds ratio was seen for the rate of response (odds ratio, 0.27). Similarly, an increased hazard ratio (HR) was seen for progression-free survival (HR, 2.32) and post-relapse overall survival (HR, 1.68) in the group with mutant TP53 and high VEGF compared with the group with both risk factors absent. CONCLUSIONS: Combined TP53 gene mutation status and high VEGF levels of ER-positive primary breast tumors independently predict a poor course of the disease of patients with advanced breast cancer treated with tamoxifen. These patients, having unfavorable tumor characteristics, might benefit more from other types of (individualized) treatment protocols. 相似文献
45.
Ilona Kryspin S rensen Eva Kristiansen Alicja Mortensen Gert M. Nicolaisen Jolanda A. H. Wijnands Henk J. van Kranen Coen F. van Kreijl 《Cancer letters》1998,130(1-2):217-225
Data from epidemiological studies suggest that isoflavones in soy may have a protective effect on the development of colon cancer in humans. Therefore, we have investigated whether soy isoflavones will inhibit intestinal tumour development in ApcMin mice. The mice were fed a Western-type high risk diet (high fat, low fibre and calcium) containing two different isolates of soy protein as a protein source. For the control and test groups this resulted in the administration of about 16 and 475 mg of total isoflavones per kg diet, respectively. As a positive control, a third group of mice was administered a low isoflavone diet supplemented with 300 ppm sulindac. No significant differences in the incidence, multiplicity, size and distribution of intestinal tumours were observed between Min mice fed low and high isoflavone-containing diets. However, a clear reduction in the number of small intestinal tumours was observed for the sulindac diet. Thus, in contrast to epidemiological studies, our results demonstrate that high amounts of soy isoflavones present in a Western-type high risk diet do not protect against intestinal tumour development in a relevant animal model such as the Min mice. 相似文献
46.
The aim of this study was to depict and characterize inflammatory soft tissue proliferations caused by rheumatoid arthritis
(RA) in the craniocervical region by unenhanced and contrast-enhanced CT. Computed tomography of the craniocervical region
was performed in 35 patients in the axial plane before and after the i. v. administration of contrast material. According
to the densities and contrast enhancement of the inflammatory soft tissue proliferations, four groups were classified. Ancillary
findings, such as a compression of the dural sac or spinal cord, erosions of the bony structures, and atlantoaxial subluxation,
were also evaluated. Inflammatory soft tissue proliferations were depicted in 28 of 35 patients and could be differentiated
by unenhanced and contrast-enhanced CT according to the above defined criteria: effusion in 6 patients (17 %); hypervascular
pannus in 8 (23 %); hypovascular pannus in 5 (14 %); and fibrous tissue in 9 patients (26 %). A compression of the dural sac
was seen in 11 (31 %) patients; 3 of these had neurological symptoms. Erosions of the odontoid process were found in 20 (57
%) patients; 16 (80 %) of these also showed erosions of the atlas. Atlantoaxial subluxation was seen in 11 (31 %) patients.
Inflammatory soft tissue proliferations in the craniocervical region caused by RA can be reliably demonstrated and classified
by unenhanced and contrast-enhanced CT, which can differentiate between joint effusion and various forms of pannus and depict
ancillary findings. Computed tomography is an alternative method for patients unable to undergo an MRI examination.
Received: 4 October 1999; Revised: 7 March 2000; Accepted: 14 March 2000 相似文献
47.
Induction of p53 up-regulated modulator of apoptosis messenger RNA by chemotherapeutic treatment of locally advanced breast cancer. 总被引:1,自引:0,他引:1
Rutger Middelburg Richard R de Haas Henk Dekker Ron M Kerkhoven Paula R Pohlmann Adolfo Fuentes-Alburo Alejandro Mohar Herbert M Pinedo Jan Lankelma 《Clinical cancer research》2005,11(5):1863-1869
PURPOSE: In biopsies of patients with locally advanced breast cancer, we investigated the in vivo changes of the gene expression pattern induced by chemotherapy to find genes that are potentially responsible for the efficacy of the drug. EXPERIMENTAL DESIGN: Early cellular responses to chemotherapy-induced damage, both in vivo and in vitro, were investigated by analyzing chemotherapy-induced changes in gene expression profiles. Core biopsies were taken from nine patients with locally advanced breast cancer, before and at 6 hours after initiation of doxorubicin-based chemotherapy. Both samples were cohybridized on the same microarray containing 18,000 cDNA spots. RESULTS: The analysis revealed marked differences in gene expression profile between treated and untreated samples. The gene which was most frequently found to be differentially expressed was p53 up-regulated modulator of apoptosis (PUMA). This gene was up-regulated in eight of nine patients with an average factor of 1.80 (range, 1.36-2.73). In vitro MCF-7 breast cancer cells exposed to clinically achievable doxorubicin concentrations for 6 hours revealed marked induction of PUMA mRNA, as well. CONCLUSIONS: This is the first report describing PUMA mRNA to be up-regulated as a response to chemotherapy in patients. Because PUMA is a known member of the family of BH3-only proapoptotic proteins, this finding suggests PUMA's potential importance for the response to anticancer drugs. 相似文献
48.
49.
50.
Jantine Posthuma De Boer Pim W. van Egmond Marco N. Helder Renée X. de Menezes Anne-Marie Cleton-Jansen Jeroen A.M. Beli?n Henk M. W. Verheul Barend J. van Royen Gert-Jan J.L. Kaspers Victor W. van Beusechem 《Oncotarget》2012,3(10):1169-1181
Osteosarcoma (OS) is the most common primary malignant bone tumour in children and adolescents. Despite aggressive therapy, survival outcomes remain unsatisfactory, especially for patients with metastatic disease or patients with a poor chemotherapy response. Chemoresistance contributes to treatment failure. To increase the efficacy of conventional chemotherapy, essential survival pathways should be targeted concomitantly. Here, we performed a loss-of-function siRNA screen of the human kinome in SaOS-2 cells to identify critical survival kinases after doxorubicin treatment. Gene silencing of JNK-interacting-protein-1 (JIP1) elicited the most potent sensitisation to doxorubicin. This candidate was further explored as potential target for chemosensitisation in OS. A panel of OS cell lines and human primary osteoblasts was examined for sensitisation to doxorubicin using small molecule JIP1-inhibitor BI-78D3. JIP1 expression and JIP1-inhibitor effects on JNK-signalling were investigated by Western blot analysis. JIP1 expression in human OS tumours was assessed by immunohistochemistry on tissue micro arrays. BI-78D3 blocked JNK-signalling and sensitised three out of four tested OS cell lines, but not healthy osteoblasts, to treatment with doxorubicin. Combination treatment increased the induction of apoptosis. JIP1 was found to be expressed in two-thirds of human primary OS tissue samples. Patients with JIP1 positive tumours showed a trend to inferior overall survival. Collectively, JIP1 appears a clinically relevant novel target in OS to enhance the efficacy of doxorubicin treatment by means of RNA interference or pharmacological inhibition. 相似文献