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Berlin Brandenburg

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  • 1
    In: PLoS ONE, 2014, Vol.9(7)
    Description: Secreted frizzled related protein 1 (SFRP1) functions as an important inhibitor of the Wnt pathway and is a known tumor suppressor gene, which is epigenetically silenced in a variety of tumors e.g. in breast cancer. However, it is still unclear how SFRP1 exactly affects the Wnt pathway. Our aim was to decipher SFRP1 involvement in biochemical signaling in dependency of different breast cancer subtypes and to identify novel SFRP1-regulated genes. We generated SFRP1 over-expressing in vitro breast cancer models, reflecting the two major subtypes by using basal-like BT20 and luminal-like HER2-positive SKBR3 cells. DNA microarray expression profiling of these models revealed that SFRP1 expression potentially modulates Bone morphogenetic protein- and Smoothened signaling (p〈0.01), in addition to the known impact on Wnt signaling. Importantly, further statistical analysis revealed that in dependency of the cancer subtype model SFRP1 may affect the canonical and non-canonical Wnt pathway (p〈0.01), respectively. While SFRP1 re-expression generally mediated distinct patterns of transcriptionally induced or repressed genes in BT20 and SKBR3 cells, brain derived neurotrophic factor ( BDNF ) was identified as a SFRP1 induced gene in both cell lines. Although BDNF has been postulated as a putative oncogene, the co-regulation with SFRP1 indicates a potential suppressive function in breast cancer. Indeed, a positive correlation between SFRP1 and BDNF protein expression could be shown (p〈0.001) in primary breast cancer samples. Moreover, TCGA dataset based analysis clearly underscores that BDNF mRNA is down-regulated in primary breast cancer samples predicting a poor prognosis of these patients. In line, we functionally provide evidence that stable BDNF re-expression in basal-like BT20 breast cancer cells blocks tumor cell proliferation. Hence, our results suggest that BDNF might rather mediate suppressive than promoting function in human breast cancer whose mode of action should be addressed in future studies.
    Keywords: Research Article ; Biology And Life Sciences
    E-ISSN: 1932-6203
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  • 2
    Language: English
    In: PLoS ONE, 01 January 2018, Vol.13(9), p.e0204318
    Description: BACKGROUND AND OBJECTIVES:Microneedling therapy is a widely used technique in dermatology. However, little is known about the underlying molecular effects of this therapy on extracellular matrix remodeling, wound healing, and inflammation. The aim of this study was to examine morphological...
    Keywords: Sciences (General)
    E-ISSN: 1932-6203
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  • 3
    Language: English
    In: PLoS ONE, July 18, 2014, Vol.9(7)
    Description: Secreted frizzled related protein 1 (SFRP1) functions as an important inhibitor of the Wnt pathway and is a known tumor suppressor gene, which is epigenetically silenced in a variety of tumors e.g. in breast cancer. However, it is still unclear how SFRP1 exactly affects the Wnt pathway. Our aim was to decipher SFRP1 involvement in biochemical signaling in dependency of different breast cancer subtypes and to identify novel SFRP1-regulated genes. We generated SFRP1 over-expressing in vitro breast cancer models, reflecting the two major subtypes by using basal-like BT20 and luminal-like HER2-positive SKBR3 cells. DNA microarray expression profiling of these models revealed that SFRP1 expression potentially modulates Bone morphogenetic protein- and Smoothened signaling (p0.01), in addition to the known impact on Wnt signaling. Importantly, further statistical analysis revealed that in dependency of the cancer subtype model SFRP1 may affect the canonical and non-canonical Wnt pathway (p0.01), respectively. While SFRP1 re-expression generally mediated distinct patterns of transcriptionally induced or repressed genes in BT20 and SKBR3 cells, brain derived neurotrophic factor (BDNF) was identified as a SFRP1 induced gene in both cell lines. Although BDNF has been postulated as a putative oncogene, the co-regulation with SFRP1 indicates a potential suppressive function in breast cancer. Indeed, a positive correlation between SFRP1 and BDNF protein expression could be shown (p0.001) in primary breast cancer samples. Moreover, TCGA dataset based analysis clearly underscores that BDNF mRNA is down-regulated in primary breast cancer samples predicting a poor prognosis of these patients. In line, we functionally provide evidence that stable BDNF re-expression in basal-like BT20 breast cancer cells blocks tumor cell proliferation. Hence, our results suggest that BDNF might rather mediate suppressive than promoting function in human breast cancer whose mode of action should be addressed in future studies.
    Keywords: Breast Cancer – Analysis ; DNA Microarrays – Analysis ; Bone Morphogenetic Proteins – Analysis ; RNA – Analysis
    ISSN: 1932-6203
    Source: Cengage Learning, Inc.
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  • 4
    Language: English
    In: Microarrays, 01 June 2014, Vol.3(3), pp.168-179
    Description: Colorectal cancer, a clinically diverse disease, is a leading cause of cancer-related death worldwide. Application of novel molecular diagnostic tests, which are summarized in this article, may lead to an improved survival of colorectal cancer...
    Keywords: Colorectal Cancer ; Microarray ; Molecular Diagnostics ; Anatomy & Physiology
    E-ISSN: 2076-3905
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  • 5
    Language: English
    In: Journal of Surgical Education, November 2015, Vol.72(6), pp.e218-e225
    Description: Controversy exists over the optimal use of the Milestones in the process of resident evaluation and feedback. We sought to evaluate the performance of a Milestones-based feedback system in comparison to a traditional model. The traditional evaluation system (TES) consisted of a generic 16-item survey using a 5-point Likert scale ranging from 1 to 5, and a free-text comments section. The Milestones-based evaluation system (MBES) was launched in July 2014, ranging from 0 to 4. Individual milestones were mapped to rotations based on resident educational goals by postgraduate year (PGY). The MBES consisted of a survey with a maximum of 7 items, followed by a free-text comment section. Within each evaluation system, an overall composite score was calculated for each categorical general surgical resident. To scale the 2 systems for comparison, TES scores were adjusted downward by 1 point. Descriptive statistics were performed. Univariate analysis was performed with the Wilcoxon signed-rank test. A test for trend across PGY was used for the MBES only. In the traditional system, the median score was 3.66 (range: 3.2-4.0). There was no meaningful difference in the median score by PGY. In the new system, the median score was 2.69 (range: 1.5-3.7, p 〈 0.01). The median score differed across PGY and increased by PGY of training (p 〈 0.01). There was an increase in differences between median scores by PGY. On using the milestones to facilitate faculty evaluation of resident knowledge and skill, there was a trend in increasing score by PGY of training. In the MBES, scores could be used to better discriminate resident skill and knowledge levels and resulted in improved differentiation in scoring by PGY. The use of the milestones as a basis for evaluation enabled the program to provide more meaningful feedback to residents and represents an improvement in surgical education.
    Keywords: Milestones ; Resident Evaluation ; Feedback ; Likert ; Competencies ; Next Accreditation System ; Patient Care ; Medical Knowledge ; Professionalism ; Interpersonal and Communication Skills ; Practice-Based Learning and Improvement ; Systems-Based Practice
    ISSN: 1931-7204
    E-ISSN: 1878-7452
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  • 6
    In: Experimental Dermatology, December 2016, Vol.25(12), pp.997-999
    Description: Photodynamic therapy (PDT) with methyl aminolaevulinate (MAL) is a well-established treatment of actinic keratosis (AK) in field-cancerized skin (1). The underlying mechanism is a photoactivation of protoporphyrin IX (PpIX) when in presence of oxygen exposed to light of specific wavelengths (2, 3). This reaction produces reactive oxygen species (ROS), which are extremely aggressive inducing either autophagy or cellular necrosis as well as apoptosis in case of oxidative stress by thus far unknown mechanisms (4). Tumor cells with increased metabolism generate PpIX at an increased rate, hereby selectivity of the photosensitizer enrichment in neoplastic cells is achieved (5). The therapeutic efficacy of topical drugs is related to their ability to penetrate and distribute into skin layers, reaching target cells (6). The outermost layer of the skin, the stratum corneum, is the major rate-limiting step for percutaneous drug absorption (7). Moreover, in the treatment of nonmelanoma skin cancer (NMSC) and AKs, thicker lesions have shown to be more resistent to PDT due to the inadequate depth of penetration by topical photosensitizers (7). It is obvious that there is a clinical need for improving the PDT-response in thick lesions (8). Pretreatments can increase the efficacy of PDT by improving penetration of the photosensitizer (9). In this context, ablative fractional laser resurfacing (AFXL) is an attractive therapeutic concept that creates microscopic vertical holes of ablated tissue, each surrounded by a thin layer of coagulated tissue, constituting microscopic treatment zones (MTZ) (8). As 3D skin equivalents are an useful in vitro model for studying skin biology (S1), our study is to our knowlegde the first that uses this technique to investigate the benefit of AFXL in PDT. This article is protected by copyright. All rights reserved.
    Keywords: 3d Actinic Keratosis Skin Model ; Ablative Fractional Laser Treatment ; Laser‐Assisted Drug Delivery ; Methyl Aminolevulinate ; Photodynamic Therapy
    ISSN: 0906-6705
    E-ISSN: 1600-0625
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  • 7
    Language: English
    In: Skin pharmacology and physiology, 2019, Vol.32(6), pp.337-343
    Description: In addition to its role as a broad-spectrum imidazole antifungal drug, data from animal models as well as human clinical trials also demonstrated an anti-inflammatory efficacy of bifonazole (BFZ). In the histamine wheal test and after UV radiation, BFZ... Performing an in vitro study we used full-thickness three-dimensional (3D) skin models containing macrophages as mediators of inflammation. We conducted two sets of experiments. In a first set we exposed our models to UVB irradiation to provoke an inflammation.... Histological examination showed that the BFZ-containing ointment reconstituted UVB- and histamine-mediated disorders within the skin models. Performing gene expression profiling in models that were treated with the BFZ-containing ointment after UVB irradiation,... We present the first in vitro study showing anti-inflammatory effects of BFZ in human 3D skin models. To our knowledge, this is the first time that these effects could be translated from human clinical trials into an in vitro test system, allowing a more...
    Keywords: Anti-Inflammatory Effects ; Bifonazole ; Skin Model
    ISSN: 16605527
    E-ISSN: 1660-5535
    Source: MEDLINE/PubMed (U.S. National Library of Medicine)
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  • 8
    Language: English
    In: Cutaneous and Ocular Toxicology, 03 July 2019, Vol.38(3), pp.274-278
    Description: Background: Laser therapy with an ablative CO 2 laser is a prominent treatment option for photo-damaged skin. The healing process and therefore the success of a laser can be supported by an appropriate...
    Keywords: Clinical Trial ; Fractional Ablative CO ; Laser Therapy ; Photo-Damaged Skin ; Wound Healing ; Dexpanthenol-Containing Ointment ; Molecular Effects ; Medicine
    ISSN: 1556-9527
    E-ISSN: 1556-9535
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  • 9
    Language: English
    In: American Journal of Psychiatry, Feb, 2016, Vol.173(2), p.138(9)
    Description: Objective: For at-risk (single parent, low income, low support) mothers, healthy adaptation and the ability to manage stress have clear implications for parenting and the social-emotional well-being of their young offspring. The purpose of this longitudinal study was to examine associations between defense mechanisms in pregnant women and their toddlers' attachment security, social-emotional, and behavioral adjustment. Method: Participants were 84 pregnant women during their last trimester of pregnancy, recruited from community agencies primarily serving low-income families. Women were followed prospectively from pregnancy through 2 years after birth and completed several multimethod assessments during that period. Observations of mother-child interactions were also coded after the postnatal visits. Results: Multiple regression analyses revealed that mothers' defense mechanisms were significantly associated with several toddler outcomes. Mature, healthy defenses were significantly associated with greater toddler attachment security and social-emotional competence and fewer behavior problems, and less mature defenses (disavowal in particular) were associated with lower levels of attachment security and social-emotional competence. Associations remained significant, or were only slightly attenuated, after controlling for demographic variables and partner abuse during pregnancy. Conclusions: The study findings suggest that defensive functioning in parents preparing for and parenting toddlers influences the parent-child attachment relationship and social-emotional adjustment in the earliest years of life. Possible mechanisms for these associations may include parental attunement and mentalization, as well as specific caregiving behavior toward the child. Defensive functioning during times of increased stress (such as the prenatal to postnatal period) may be especially important for understanding parental influences on the child. doi: 10.1176/appi.ajp.2015.15020173
    Keywords: Pregnant Women -- Psychological Aspects ; Defense Mechanisms (Psychology) -- Observations ; Attachment (Psychology) -- Social Aspects ; Behavior Problems -- Social Aspects ; Mother-Child Relations -- Psychological Aspects
    ISSN: 0002-953X
    Source: Cengage Learning, Inc.
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  • 10
    Language: English
    In: Journal of the American Chemical Society, 22 November 2017, Vol.139(46), pp.16959-16966
    Description: London dispersion forces are the weakest interactions between molecules. Because of this, their influence on chemical processes is often low, but can definitely not be ignored, and even becomes important in cases of molecules with large contact surfaces. Hierarchically assembled dinuclear titanium(IV) helicates represent a rare example in which the direct observation of London dispersion forces is possible in solution even in the presence of strong cohesive solvent effects. Hereby, the dispersion forces do not unlimitedly support the formation of the dimeric complexes. Although they have some favorable enthalpic contribution to the dimerization of the monomeric complex units, large flexible substituents become conformationally restricted by the interactions leading to an entropic disadvantage. The dimeric helicates are entropically destabilized.
    Keywords: Helicases – Analysis ; Entropy (Thermodynamics) – Analysis ; Dimer Acids – Electric Properties;
    ISSN: 00027863
    E-ISSN: 1520-5126
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