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  • 1
    Keywords: IN-VIVO ; CHRONIC LYMPHOCYTIC-LEUKEMIA ; MEMORY T-CELLS ; TGF-BETA ; MESENCHYMAL STEM-CELLS ; HORMONE-RELATED PROTEIN ; zoledronic acid ; METASTATIC BREAST-CANCER ; TARGETED THERAPY ; DORMANT TUMOR-CELLS
    Abstract: The bone marrow (BM) of cancer patients is considered an essential secondary lymphoid organ with substantial impact on tumor cell dissemination and tumor-immune responses. Recent advances in the understanding of BM/primary tumor crosstalk, homing processes, premetastatic niche formation, tumor cell dormancy, and ultimately, identification of the BM micromilieu cytokines, chemokines, and growth factors may provide the basis for the development of targeted therapeutic strategies potentially rendering primary cancers and cancer bone metastases more susceptible to chemotherapy. The present review aims to dissect the individual components of the BM microenvironment in cancer patients, compare it to the healthy BM, and discuss its impact on interactions between the tumor and the immune system.
    Type of Publication: Journal article published
    PubMed ID: 23081701
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  • 2
    Abstract: PURPOSE: While intact circulating tumor cells (iCTC) have independent negative prognostic impact on patients with metastatic breast cancer (MBC), the prognostic relevance of apoptotic CTC (aCTC) has not been validated in larger patient cohorts. This study assessed aCTC and iCTC statuses at baseline (CTCBL) and CTC kinetics (CTCKIN) as changes from CTCBL to one completed treatment cycle for their utility in predicting response, progression-free survival (PFS), and overall survival (OS) in MBC. METHODS: Status of iCTC and aCTC was prospectively assessed in 442 patients using the CellSearch system. Different cutoffs were analyzed both for iCTC and aCTC (〉/=5, 〉/=10, 〉/=25 and 〉/=50 CTC/7.5 ml). CTCKIN were characterized by 〉/=25 % changes in CTC counts. RESULTS: Numbers of iCTC and aCTC at baseline correlated strongly (r = 0.7). For iCTCBL positive patients, additional detection of aCTCBL had a significant prognostic impact on OS (aCTCBL positive 10.3 vs. aCTCBL negative 16.4 months, p = 0.012). Worst prognosis for OS was observed in patients with 〉/=50 iCTC/7.5 ml and simultaneously detected aCTC. Determination of aCTCKIN showed stronger discriminating power than iCTCKIN, with higher PFS and OS for the group with decreasing CTCs (PFS 7.7 vs. 6.1; OS 22.2 vs. 16.4). CONCLUSIONS: Intact and aCTC are predictive of outcome in MBC. Apoptotic CTC counts 〉/= 5/7.5 ml in conjunction with iCTC at baseline have an independent unfavorable prognostic impact on OS. Decreasing aCTCKIN at 〉/= 5/7.5 ml in serial enumeration is associated with favorable outcome. Therefore, separate enumeration of iCTC and aCTC is useful in tailoring systemic treatment.
    Type of Publication: Journal article published
    PubMed ID: 27696083
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  • 3
    Keywords: IMMUNE-RESPONSES ; tumor-infiltrating lymphocytes ; MELANOMA PATIENTS ; ANTITUMOR IMMUNITY ; REGULATORY T-CELLS ; CLINICAL-RESPONSES ; EFFECTOR FUNCTIONS ; BONE-MARROW MICROENVIRONMENT ; PREDICT RESPONSE ; IMMUNOLOGICAL ASPECTS
    Abstract: Breast cancer is a systemic disease with a primarily local component. Besides surgical resection and irradiation of the locoregional tumor setting, central therapeutic aim is the elimination of disseminated micrometastatic tumor cells using cytostatic and/or hormonal treatment. Nevertheless, in the course of time a majority of patients suffer from systemic recurrence in the form of distant metastases. Intriguingly, in this connection, intratumoral cytotoxic T lymphocytes might serve as independent predictors of treatment efficacy and clinical outcome. Loss of immune balance (tumor dormancy) during intensive cross talk between T cells and tumor cells in the bone marrow microenvironment is suggested one reason for distant metastatic relapse. In this clinical context, further supportive therapies become increasingly attractive, taking immunological features of breast cancer cells into special account. The present review aims to dissect bone marrow-derived cellular antitumor immune responses and translational immunologic treatment options regarding their actual relevance to patients' clinical benefit and their future directions in breast cancer management.
    Type of Publication: Journal article published
    PubMed ID: 24337953
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  • 4
    Abstract: Considering the diverse functions of B cells, responses to tumor-associated antigens (TAA) have been thought to be the main source of B cell-mediated antitumor immunity. Polymorphic epithelial mucin (MUC1) is considered one of the most specific TAA in patients with breast cancer. The present study aims to dissect the level and subclasses of naturally occurring anti-MUC1 antibodies in regard to tumor biologic parameters, clinical characteristics and overall survival. In 288 primary, non-metastatic breast cancer patients, pretreatment serum levels of anti-MUC1 immunoglobulin G (IgG) and its subclasses G1-4 as well as immunoglobulin M (IgM) were analyzed via ELISA. With respect to overall survival (Kaplan-Meier analysis), tumor biologic parameters as hormone receptor status, human epidermal growth factor receptor 2 (Her2), Ki-67 expression and tumor grading have been correlated as well as clinical characteristics as nodal involvement, tumor stage and patients' age at the time of diagnosis. Median follow-up time was 148 mo (IQR: 73.1-158.5 mo). A significant increase in IgG antibody titers was correlated highly significantly with an improved overall survival of patients. In multivariate analysis, total IgG proved to be an independent prognostic marker for overall survival (p = 0.002). IgG subclass analysis did not reveal any correlation of IgG1, IgG3 and IgG4 levels with overall survival, while increased immunoglobulin G2 (IgG2) values, although statistically not significant, tended to correlate with prolonged patient survival. MUC1-specific IgM antibodies were shown not to be predictive of overall survival. Altogether, humoral immune responses appear to play a crucial part in the tumor immunity of breast cancer patients. The present data confirms the positive impact of tumor-specific IgG on prolonged overall survival in breast cancer patients. MUC1-antibody testing might be a useful tool to identify high-risk patients who may need adjuvant therapy and potentially might benefit from MUC1-directed immunotherapy.
    Type of Publication: Journal article published
    PubMed ID: 26942066
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  • 5
    ISSN: 1365-2958
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Biology , Medicine
    Notes: The gene encoding monophosphatidylinositol inositol phosphohydrolase (PI-specific phospholipase C, PI-PLC) of Bacillus thuringiensis was cloned in Staphylococcus carnosus TM300. The complete coding region comprises 987 base pairs corresponding to a precursor protein of 329 amino acids (molecular weight, 38095). The NH2-terminal sequence of the purified enzyme from Escherichia coli indicated that the mature PI-PLC consists of 299 amino acid residues with a molecular weight of 34586. Polyacrylamide gel electrophoresis revealed the same molecular weight for the purified enzyme isolated from the DNA-donor strain of B. thuringiensis and from the E. coli clone. By computer analysis, the secondary structure was predicted. The enzyme from the E. coli recombinant shows no activity on other phospholipids and sphingo-myelin. The cleaving specifity of PI-PLC was examined by thin layer chromatography.
    Type of Medium: Electronic Resource
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  • 6
    ISSN: 1612-1112
    Keywords: TLC ; Cu and Fe determination ; Cotton materials
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Summary A TLC method for the separation of quantitative determination of copper and iron in cotton material is described. The optimal solvent system is 9:2:1 (v/v), ethanol-nitric acid-hydrochloric acid and the locating reagent is Na-diethyldithiocarbamate. Regression analysis shows that the most precise results can be obtained for the concentration range of 0.0400–0.0800 mg/ml of iron and copper.
    Type of Medium: Electronic Resource
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  • 7
    ISSN: 1612-1112
    Keywords: Thin-layer chromatography ; Active carbon ; Phenol and cresol
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Summary The effect of the acidity of the media on the adsorption of phenol and creasols was investigated using TLC and using the RF-values as a measure of the adsorption ability of active carbon. Three types of chromatographic layers were employed: silica gel, silica gel containing 3% of active carbon and silica gel containing 6% of active carbon. Standard solutions of phenol, m-cresol and o-cresol were used as the samples. The acetic acid content of the solvent mixture significantly influences the adsorption of phenol and cresols on the active carbon layer. An increase in the acetic acid content results in a decrease of the adsorption of phenols. However, under specific conditions [81∶5∶7 hexane-diethyl ether-acetic acid, and 48∶2∶8 benzene-acetone-acetic acid developers] the competitive adsorption of phenols and acetic acid may take place, which has been observed by a steep increase in the adsorption of phenol and cresols.
    Type of Medium: Electronic Resource
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  • 8
    ISSN: 1612-1112
    Keywords: Aluminum ; TLC ; Zirconium
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Summary A simple thin-layer chromatographic method for the complete separation of Zr from aluminum is described. The optimum solvent composition is evaluated by means of the simplex method of optimization. Quantitative determination and regression analysis is carried out.
    Type of Medium: Electronic Resource
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  • 9
    ISSN: 1612-1112
    Keywords: TLC ; Cu, Fe, Mn detection ; Cotton materials
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Summary A TLC method for the fast detection of copper, iron and managanese ions in cotton materials is described. The optimal solvent system is 8∶1∶2 (v/v), acetone: HCl:H2O and the locating reagent is rubeanic acid followed by exposure to ammonia vapour. It was found that in cotton materials, metal ions can be detected at a lower limit of 20 μg per gram of material.
    Type of Medium: Electronic Resource
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  • 10
    ISSN: 1618-2650
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Summary Waste waters of film processing plants are rich with silver. Part of the silver is regenerated electrochemically, but the rest (0.5 g) remains in waste waters and is sent to sewers. This is a bad politic from both the environmental (toxic waste waters) and the economical point of view (a waste of silver). In this work, the silver was isolated by ion-exchange resins and then concentrated by microorganisms. For exchange of silver, Ionenaustauscher I, II and IV were used. The batch method was used to obtain a static equilibrium. Silver elution from exchangers is based on silver transformation to a stable cation or anion complex. By varying the ligands, pH and eluent concentrations, optimum elution is found at 1 mol/l Na2S2O3, 1 mol/l NH3, 2 mol/l HNO3 and 1 mol/l (NH2)2CO. The concentration of silver in the eluent is about 50 mg/l. The silver ion uptake from solutions after ion exchange by mixed bacterial culture isolated from photographic waste water drain and pure bacterial cultures Escherichia coli 3009 and Bacillus subtilis 3053. was studied. Experiments were carried out in submerse culture at pH 7 with different Ag+ concentrations (4, 8 and 40 mg/l) on a rotary shaker (100 rpm) at 37°C. At the lower Ag+ concentrations a good growth and simultaneous removal of Ag+ from the solutions was achieved. At Ag+ concentration of 40 mg/l growth and removal of Ag+ by mixed and pure culture differed significantly. Thus mixed bacterial culture grew well and at the same time removed efficiently Ag+ (approximately 90%) from medium. Pure bacterial cultures on the contrary were unable to grow at 40 mg/l Ag+, though their biomass showed to be an effective biosorbent for Ag+ (approximately 80% of Ag+ removal).
    Type of Medium: Electronic Resource
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