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Sökning: WFRF:(de la Torre Manuel)

  • Resultat 11-20 av 35
  • Föregående 1[2]34Nästa
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  • Gårdmark, Truls, et al. (författare)
  • Analysis of HER2 expression in primary urinary bladder carcinoma and corresponding metastases
  • 2005
  • Ingår i: BJU International. - 1464-4096 .- 1464-410X. ; 95:7, s. 982-986
  • Tidskriftsartikel (refereegranskat)abstract
    • <p>OBJECTIVE: To evaluate the expression of HER2 receptors (previously reported to be over-expressed in malignant urothelium) in both primary tumours and metastases of transitional cell cancer, using two different staining methods and two different scoring techniques, considering the potential use of these receptors as targets for planned systemic anti-HER2 nuclide-based treatment. MATERIALS AND METHODS: HER2 expression was evaluated with two different immunohistochemical methods in 90 patients with primary urinary bladder cancer tumours and corresponding metastases. Sections were first stained with the commercially available breast cancer test kit (HercepTest, Dako, Glostrup, Denmark). Parallel sections were then stained with a modified HercepTest procedure. Two different evaluation criteria were compared; the HercepTest score that requires &gt; or = 10% stained tumour cells (as for breast cancer) and a proposed 'Target score' that requires &gt; 67% stained tumour cells. The latter score is assumed to be preferable for HER2-targeted radionuclide therapy. RESULTS: Using the HercepTest kit, the Target score gave lower fractions of positive primary tumours and metastases than the HercepTest score. The modified HercepTest staining procedure and Target score gave high HER2 values in 80% of primary tumours and 62% of metastases, which is considerably more than that obtained with the HercepTest staining and score. There was a significant decrease in HER2 positivity with increasing distance from the primary tumour. In nine sentinel-node metastases assessed, all but one were HER2-positive. Considering all regional metastases, 74% were positive, and of distant metastases, 47%; 72% of the patients with positive primary tumours also expressed HER2 in their metastases. CONCLUSIONS: When combining the modified HercepTest with customised evaluation criteria, more HER2-positive tumours were diagnosed. The degree of HER2 down-regulation was significantly higher in distant than in regional metastases. HER2-targeted therapy may be an alternative or complementary to other methods in the future treatment of metastatic urinary bladder carcinoma.</p>
  • Hassan, Saadia Bashir, et al. (författare)
  • A hollow fiber model for in vitro studies of cytotoxic compounds : Activity of the cyanoguanidine CHS 828
  • 2001
  • Ingår i: Anti-Cancer Drugs. - 0959-4973 .- 1473-5741. ; 12:1, s. 33-42
  • Tidskriftsartikel (refereegranskat)abstract
    • <p>The hollow fiber assay is currently used as an in vivo model for anticancer drug screening in nude mice, but it can also be used as an in vitro model. In the current study, an in vitro hollow fiber model was used to study the effect and mode of induced cell death of a new cyanoguanidine, CHS 828. Human leukemia, adenocarcinoma and lymphoma cell lines as well as primary cultures of human tumor cells from patients with chronic lymphocytic leukemia (CLL) and ovarian cancer (OC) and normal human lymphocytes were cultured in semipermeable hollow fibers. The fibers were incubated for 3 or 14 days prior to CHS 828 exposure for 72 h, followed by determination of living cell density by MTT staining. For cell morphology, using harvested cultures on cytospin slides had technical advantages compared to using paraffin sections of the formalin-fixed fibers. CHS 828 showed higher antitumor activity on CLL and normal human lymphocyte cultures compared to OC cultures, and cell lines cultured 3 days were more sensitive than those cultured 14 days. Morphological examination of CHS 828-treated cultures revealed a mixture of apoptosis and necrosis.</p>
  • Hemdan, Tammer, et al. (författare)
  • Stathmin-1 is a promising prognostic factor and potential therapeutic target in urinary bladder cancer
  • ????
  • Annan publikation (övrigt vetenskapligt)abstract
    • <p><strong>Aim:</strong> The oncoprotein 18/stathmin 1 (STMN1), involved in cell cycle progression and cell migration, has been reported to be expressed in several types of cancer, and is associated with clinical outcome in e.g. breast and liver cancer. The aims in this study were to investigate the clinical significance of STMN1 and to examine if STMN1 might be a possible therapeutic target in urinary bladder cancer.</p><p><strong>Experimental design</strong>: Immunohistochemical analyses of STMN1 protein expression were performed in a wide-range tissue microarray (115 Ta-, 115 T1-, 112 T2-4-tumors) and in a metastatic primary tumor/matched metastasis-material (90 patients). In the T24 cell line, the effect of STMN1 on cell proliferation was evaluated by inhibiting the cellular expression of STMN using STMN1-siRNA.</p><p><strong>Results: </strong>Patients with T1- or muscle-invasive disease exhibiting high expression<strong> </strong>of the STMN1 protein had a poorer overall survival (OS) and disease specific survival (DSS). In a multivariate analysis adjusting for stage, age and gender the results were for T2-T4 patients: OS (HR=1.77 95% CI 1.02-3.07; p=0.04) and DSS (HR=2.04 95% CI 1.13-3.68; p=0.02); for T1-4 patients: DSS (HR=1.83 95% CI 1.09-3.08; p=0.02). In the metastatic bladder cancer material, the majority of the patients with one metastasis (69%) and with several matched metastases (70%) were STMN1-positive in both the primary tumor and the matched metastases. Moreover, the ability of the urinary bladder cancer cell line to grow was significantly reduced after 72 hours (p&lt;0.0001) when transfecting the cells with a siRNA targeting STMN1.</p><p><strong>Conclusion</strong>: Our results suggest that STMN1 protein-expression has a potential both as a prognostic marker and a novel treatment target in urinary bladder cancer.</p>
  • Kloos, Jacob L., et al. (författare)
  • The First Martian Year of Cloud Activity from Mars Science Laboratory (Sol 0 - 800)
  • 2016
  • Ingår i: Advances in Space Research. - 0273-1177 .- 1879-1948. ; 57:5, s. 1223-1240
  • Tidskriftsartikel (refereegranskat)abstract
    • <p>Using images from the Navigation Cameras onboard the Mars Science Laboratory rover Curiosity, atmospheric movies were created to monitor the cloud activity over Gale Crater. Over the course of the first 800 sols of the mission, 133 Zenith Movies and 152 Supra-Horizon Movies were acquired which use a mean frame subtraction technique to observe tenuous cloud movement. Moores et al. (2015a) reported on the first 360 sols of observations, representing LS = 150° to 5°, and found that movies up to LS = 184° showed visible cloud features with good contrast while subsequent movies were relatively featureless. With the extension of the observations to a full Martian year, more pronounced seasonal changes were observed. Within the Zenith Movie data set, clouds are observed primarily during LS = 3° - 170°, when the solar flux is diminished and the aphelion cloud belt is present at equatorial latitudes. Clouds observed in the Supra-Horizon Movie data set also exhibit seasonality, with clouds predominantly observed during LS = 72° - 108°. The seasonal occurrence of clouds detected in the atmospheric movies is well correlated with orbital observations of water-ice clouds at similar times from the MCS and MARCI instruments on the MRO spacecraft. The observed clouds are tenuous and on average only make up a few-hundredths of an optical depth, although more opaque clouds are observed in some of the movies. Additionally, estimates of the phase function calculated using water-ice opacity retrievals from MCS are provided to show how Martian clouds scatter sunlight, and thus provide insight into the types of ice crystals that comprise the clouds.</p>
  • Koliadi, Anthoula, et al. (författare)
  • Cyclin B is an immunohistochemical proliferation marker which can predict for breast cancer death in low-risk node negative breast cancer
  • 2010
  • Ingår i: Acta Oncologica. - 0284-186X .- 1651-226X. ; 49:6, s. 816-820
  • Tidskriftsartikel (refereegranskat)abstract
    • <p>Patients with low-risk node negative breast cancer have an excellent prognosis with 5% breast cancer mortality at 10 years. However, prognostic factors are needed to identify poor prognostic patients who might benefit from adjuvant systemic therapy. Proliferation has been identified as the most important component of gene expression profiles. Cyclin B is a proliferative marker easily assessed by immunohistochemistry. We wanted to examine cyclin B as a prognostic factor in low-risk breast cancer patients. Patients and methods. Using an experimental study design, we compared women dying early from their breast cancer (n=17) with women free from relapse more than eight years after initial diagnosis (n=24). All women had stage I, node negative and hormone receptor positive disease. None had received adjuvant chemotherapy. Tumor samples were immunostained for cyclin B using commercial antibodies. Results. The mean percentage of cyclin B (12%) was significantly higher (p=0.001) in women dying from their breast cancer compared with women free from relapse ( 5%). High cyclin B (&gt;= 9%) identified 11/17 patients dying from breast cancer and low cyclin B identified 22/24 patients free from relapse. The sensitivity and specificity of cyclin B was 65% and 92%, respectively. Discussion. We found that low-risk node negative patients with high expression of cylin B had a significantly worse outcome than patients with low expression of cyclin B. Cyclin B could separate patients with poor survival from those with good survival with 80% accuracy. We suggest that cyclin B might be a potent prognostic factor in this low-risk patient group.</p>
  • Lindén, Mårten, et al. (författare)
  • Galectin-1, a potential therapeutic target, in primary tumors and metastases of urinary bladder carcinomas
  • 2013
  • Annan publikation (övrigt vetenskapligt)abstract
    • <p>Urinary bladder cancer would gain from new protein biomarkers due to the heterogeneity of disease. The beta-galactoside-binding protein (GAL1) is one such candidate and in present study its prognostic value and expression at protein level in metastatic bladder cancer-disease, have been evaluated. The protein expression of GAL1 was investigated by immunohistochemistry in two tumor cohorts, one with primary tumors of different stage and grade (n=344) and another with primary tumors matched with metastases (n=90). The expression in the actual cancer cells as well as in stroma and blood vessels were considered since the presence of GAL1 in different tissue compartments has shown cancer relevance. The cellular expression increased with increased tumor stage and grade (p&lt;0.001). For the majority of the patients, cells from both primary tumor and metastasis showed a positive immunoreactivity for GAL1 (91% (n=64) for primary tumors with single metastasis (n=70) and 100% (n=20) for primary tumors with multiple metastasis (n=20). Further, strong immunoreactivity in T1 tumor cells correlated with lower risk of recurrence (p&lt;0.05). Both tumors and metastasis exhibited strong stromal-GAL1 staining that could not be correlated with clinical parameters. The expression in vessels showed that T1 tumors surrounded by GAL1 negative blood vessels had a higher risk of progression (p&lt;0.0001) into muscle invasive T2-4 stages. The results show that GAL1 is an important bladder cancer-protein from several aspects. Further, GAL1 is a promising therapeutic target in bladder cancer due to the general expression in advanced disease.</p>
  • Loskog, Angelica, et al. (författare)
  • Human bladder carcinoma is dominated by T-regulatory cells and Th1 inhibitory cytokines
  • 2007
  • Ingår i: Journal of Urology. - 0022-5347 .- 1527-3792. ; 177:1, s. 353-358
  • Tidskriftsartikel (refereegranskat)abstract
    • <p>Purpose: Immunotherapy has faced limited success, although many solutions have been proposed. Recently regulatory T cells have made a comeback in the immunological arena and the role of these cells in patients with cancer is in focus. It is under evaluation whether the immunological status of patients with cancer may affect their sensitivity to immunotherapy. We are developing immunostimulating gene therapy for treating bladder cancer. In this study we constructed an immunological profile of patients with bladder carcinoma to understand which obstacles must be circumvented. Materials and Methods: Biopsies and blood were used to identify immune cell populations by FACS®, histochemistry and proliferation assays, and cytokine production by polymerase chain reaction. Results: Results indicate that bladder carcinoma is a Tri dominated tumor, as shown by the infiltration of T-regulatory cells expressing FOXP3, and the presence of tumor necrosis factor-β and interleukin-10 mRNA copies. We further noted that circulating patient T cells were unresponsive to polyclonal T-cell activation compared to healthy donor cells. Moreover, CD4+CD25+ T cells were increased in patient blood and could suppress the expansion of allogeneic T cells from healthy donors. Conclusions: Patients with bladder carcinoma show an immunosuppressive regulatory profile, including nonresponsive T cells. Clinical protocols able to effectively counteract these mechanisms are warranted.</p>
  • Loskog, Angelica, et al. (författare)
  • Human urinary bladder carcinomas express adenovirus attachment and internalization receptors
  • 2002
  • Ingår i: Gene Therapy. - 0969-7128 .- 1476-5462. ; 9:9, s. 547-553
  • Tidskriftsartikel (refereegranskat)abstract
    • <p>The use of adenoviral vectors as potent gene delivery systems requires expression of the Coxsackievirus/adenovirus receptor (CVADR) on the target cell surface. This receptor is important for virus attachment to the cell surface. For effective internalization of the vector into the target cell the integrins alpha(v)beta(3) and/or alpha(v)beta(5) are needed. Since there have been reports of loss of CVADR in bladder cancer cell lines, we wanted to investigate the expression of this receptor in bladder carcinoma biopsies. Surgical biopsies, as well as five human bladder cancer cell lines, were analyzed for expression of CVADR, the integrins alpha(v)beta(3) and alpha(v)beta(5) and MHC class I. Further, we studied the ability to transduce these cell lines using adenoviral vectors. Immunohistochemistry revealed that all biopsies (27/27) were positive for CVADR. Some variation in expression was evident, and superficially growing tumors stained more strongly than invasive ones. Most human tumors expressed the integrin alpha(v)beta(5) (14/24), whereas integrin alpha(v)beta(3) was less frequently seen (3/20). The established cell lines were efficiently transduced with adenoviral vectors, and transduction could be reduced with anti-CVADR antibodies. The abundance of appropriate viral receptors on tumor biopsy cells is a further argument for using adenoviral vectors in gene therapy of bladder cancer.</p>
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  • Resultat 11-20 av 35
  • Föregående 1[2]34Nästa
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