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  • 1
    ISSN: 1546-170X
    Source: Nature Archives 1869 - 2009
    Topics: Biology , Medicine
    Notes: [Auszug] Regulatory T (Treg) cells mediate homeostatic peripheral tolerance by suppressing autoreactive T cells. Failure of host antitumor immunity may be caused by exaggerated suppression of tumor-associated antigen–reactive lymphocytes mediated by Treg cells; however, definitive evidence that Treg ...
    Type of Medium: Electronic Resource
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  • 2
    ISSN: 1546-170X
    Source: Nature Archives 1869 - 2009
    Topics: Biology , Medicine
    Notes: [Auszug] Suppression of dendritic cell function in cancer patients is thought to contribute to the inhibition of immune responses and disease progression. Molecular mechanisms of this suppression remain elusive, however. Here, we show that a fraction of blood monocyte-derived myeloid dendritic cells (MDCs) ...
    Type of Medium: Electronic Resource
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  • 3
    Electronic Resource
    Electronic Resource
    Springer
    Journal of mammary gland biology and neoplasia 4 (1999), S. 353-365 
    ISSN: 1573-7039
    Keywords: BREAST CANCER ; IMMUNOTHERAPY ; T CELL ; VACCINES ; CYTOKINES ; ADOPTIVE T CELL THERAPY
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The application of immunotherapeutic principlesto the treatment and prevention of breast cancer is arelatively new undertaking. Although cytokine infusions,cancer vaccines, and T cell therapy have been extensively studied in solid tumors such asmelanoma and renal cell carcinoma, the therapeuticefficacy of these approaches is not well explored inbreast cancer. The recent definition of tumor-specific immunity in breast cancer patients and theidentification of several breast cancer antigens hasgenerated enthusiasm for the application of immune-basedtherapies to the treatment of breast malignancies. In general, immunotherapies can be consideredeither non-specific, such as a general immunomodulator(e.g., a cytokine), or tumor-specific (e.g., a vaccinethat targets breast cancer tumor antigens). This review describes three major immunotherapeuticstrategies that have the potential to enhance orgenerate an anti-breast cancer T cell immune response:(i) cytokine therapy; (ii) cancer vaccines; and (iii) T cell therapy, and explores how each strategyhas been applied to the treatment of breastcancer.
    Type of Medium: Electronic Resource
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  • 4
    ISSN: 1573-7217
    Keywords: antibody ; breast cancer ; HER-2/neu ; immunity ; ovarian cancer ; T-cell
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Immunomodulatory strategies, such as antibody therapy and cancer vaccines, are increasingly being considered as potential adjuvant therapies in patients with advanced stage breast cancer to either treat minimal residual disease or prevent relapse. However, little is known concerning the incidence and magnitude of the pre-existent breast cancer specific immune response in this patient population. Using the HER-2/neu oncogenic protein as a model, a well-defined tumor antigen in breast cancer, we questioned whether patients with advanced stage HER-2/neu overexpressing breast and ovarian cancers (III/IV) had evidence of pre-existent immunity to HER-2/neu. Forty-five patients with stage III or IV HER-2/neu overexpressing breast or ovarian cancer were evaluated for HER-2/neu specific T cell and antibody immunity. Patients enrolled had not received immunosuppressive chemotherapy for at least 30 days (median 5 months, range 1–75 months). All patients were documented to be immune competent prior to entry by DTH testing using a skin test anergy battery. Five of 45 patients (11%) were found to have a significant HER-2/neu specific T cell response as defined by a stimulation index ≥ 2.0 (range 2.0–7.9). None of eight patients who were HLA-A2 had a detectable IFNγ secreting T-cell precursor frequency to a well-defined HER-2/neu HLA-A2 T cell epitope, p369-377. Three of 45 patients (7%) had detectable HER-2/neu specific IgG antibodies, range 1.2–8.9 μg/ml. These findings suggest that patients with advanced stage HER-2/neu overexpressing breast and ovarian cancer can mount a T cell and/or antibody immune response to their tumor. However, in the case of the HER-2/neu antigen, the pre-existent tumor specific immune response is found only in a minority of patients.
    Type of Medium: Electronic Resource
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  • 5
    Electronic Resource
    Electronic Resource
    New York, N.Y. : Wiley-Blackwell
    Journal of Cellular Biochemistry 60 (1996), S. 130-138 
    ISSN: 0730-2312
    Keywords: islets ; oleic acid ; cytoskeleton ; insulin ; free fatty acids ; Life and Medical Sciences ; Cell & Developmental Biology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Chemistry and Pharmacology , Medicine
    Notes: Previous studies from our laboratory have demonstrated the presence of several isoforms of protein kinase C (PKC), Ca2+-independent and Ca2+-dependent, in both whole islets and tumor-derived beta cells. In the basal state, a major proportion of the isoform was found in the crude membrane fraction with smaller amounts found in both the cytosolic and cytoskeletal fractions. Whole islets showed a similar distribution of the isoform. These studies were done to analyze the effects of insulin secretagogues on the distribution of PKC δ to different cellular pools in isolated insulinoma beta cells. The phorbol ester, phorbol 12-myristate 13-acetate (PMA), produced a transient association of PKC δ with the beta cell cytoskeleton along with sustained decreases in cytosolic enzyme and transient increases in membrane enzyme. Neither glucose nor carbachol could acutely affect the subcellular distribution of PKC δ. Oleic acid decreased the amount of the enzyme associated with the cytoskeleton and led to a sustained decrease of cytosolic enzyme and a transient increase in membrane enzyme. Oleic acid was also able to prevent the increase in cytoskeletal enzyme induced by PMA. Both oleic acid and PMA potentiated glucose-induced insulin release but oleic acid, in contrast to PMA, was unable to initiate insulin release in the presence of substimulatory concentrations of glucose. These data demonstrate that different activators of PKC may have different effects on localization of the enzyme within the cells and suggest that there are at least three apparently distinct pools of PKC δ within the beta cell which may be important in insulin secretion or other aspects of beta cell function. © 1996 Wiley-Liss, Inc.
    Additional Material: 7 Ill.
    Type of Medium: Electronic Resource
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  • 6
    Electronic Resource
    Electronic Resource
    New York, N.Y. : Wiley-Blackwell
    Journal of Cellular Biochemistry 62 (1996), S. 543-552 
    ISSN: 0730-2312
    Keywords: islets ; free fatty acids ; indomethacin ; PKC ; arachidonic acid ; Life and Medical Sciences ; Cell & Developmental Biology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Chemistry and Pharmacology , Medicine
    Notes: We have previously identified expression of multiple protein kinase C (PKC) isoforms in insulinoma-derived beta-cells and whole islets. Both PKC γ and PKC α appear to be the more abundantly expressed isoforms. In this report we studied the effects of arachidonic acid (AA) on the subcellular distribution of PKC α and PKC γ. AA has been reported to activate both PKC α and PKC γ and it is thought to be an important second messenger in beta-cells. Here we report that AA interacted with and altered beta-cell pools of PKC γ preferentially over PKC α. AA (100 μM) over the course of 45 min reduced cytosolic levels of PKC γ (to 40 ± 15%, compared to time zero control) leaving membrane-and cytoskeleton-associated levels near control levels. Analysis of whole cell homogenates showed a slight down-regulation of PKC γ indicating proteolysis. The down-regulation of cytosolic PKC γ appeared to be isoform specific since cytosolic PKC α remained at control levels over the time course. The response was dose-dependent and negligible at concentrations below 30 μM and occurred, at least partially, in the cytosolic compartment of the cell. Indomethacin also down-regulated cytosolic PKC γ preferentially over PKC α possibly through accumulation of AA. These findings suggest that cytosolic PKC γ may be a downstream target of this beta-cell second messenger. © 1996 Wiley-Liss, Inc.
    Type of Medium: Electronic Resource
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