29 research outputs found
A Marine Anthraquinone SZ-685C Overrides Adriamycin-Resistance in Breast Cancer Cells through Suppressing Akt Signaling
Breast cancer remains a major health problem worldwide. While chemotherapy represents an important therapeutic modality against breast cancer, limitations in the clinical use of chemotherapy remain formidable because of chemoresistance. The HER2/PI-3K/Akt pathway has been demonstrated to play a causal role in conferring a broad chemoresistance in breast cancer cells and thus justified to be a target for enhancing the effects of anti-breast cancer chemotherapies, such as adriamycin (ADR). Agents that can either enhance the effects of chemotherapeutics or overcome chemoresistance are urgently needed for the treatment of breast cancer. In this context, SZ-685C, an agent that has been previously shown, as such, to suppress Akt signaling, is expected to increase the efficacy of chemotherapy. Our current study investigated whether SZ-685C can override chemoresistance through inhibiting Akt signaling in human breast cancer cells. ADR-resistant cells derived from human breast cancer cell lines MCF-7, MCF-7/ADR and MCF-7/Akt, were used as models to test the effects of SZ-685C. We found that SZ-685C suppressed the Akt pathway and induced apoptosis in MCF-7/ADR and MCF-7/Akt cells that are resistant to ADR treatment, leading to antitumor effects both in vitro and in vivo. Our data suggest that use of SZ-685C might represent a potentially promising approach to the treatment of ADR-resistant breast cancer
On the Origin of the Supergiant HI Shell and Putative Companion in NGC 6822
We present new Hubble Space Telescope Advanced Camera for Surveys imaging of
six positions spanning 5.8 kpc of the HI major axis of the Local Group dIrr NGC
6822, including both the putative companion galaxy and the large HI hole. The
resulting deep color magnitude diagrams show that NGC 6822 has formed >50% of
its stars in the last ~5 Gyr. The star formation histories of all six positions
are similar over the most recent 500 Myr, including low-level star formation
throughout this interval and a weak increase in star formation rate during the
most recent 50 Myr. Stellar feedback can create the giant HI hole, assuming
that the lifetime of the structure is longer than 500 Myr; such long-lived
structures have now been observed in multiple systems and may be the norm in
galaxies with solid-body rotation. The old stellar populations (red giants and
red clump stars) of the putative companion are consistent with those of the
extended halo of NGC 6822; this argues against the interpretation of this
structure as a bona fide interacting companion galaxy and against its being
linked to the formation of the HI hole via an interaction. Since there is no
evidence in the stellar population of a companion galaxy, the most likely
explanation of the extended HI structure in NGC 6822 is a warped disk inclined
to the line of sight.Comment: The Astrophysical Journal, in press. Full-resolution version
available on request from the first autho
Navigating a river by its bends. A study on transnational social networks as resources for the transformation of Cambodia
This article explores in what ways first generation Cambodian French and Cambodian American returnees create and employ the social capital available in their transnational social networks upon their return to Cambodia. The triangular interdependence between the returnees, their overseas immigrant communities and homeland society is taken as a starting point. The central argument is that Cambodian French and Cambodian American returnees build different relationships to Cambodia due to: (1) the influence of their immigrant communities in the countries of resettlement; and (2) the contexts of their exit from Cambodia. Regarding debates on the contribution of returnees to an emergent nation, findings in this multisited casestudy bring forward that ideas of return held by the three parties involved may force remigrants into transnationalism in both host and home countries. Findings also demonstrate that social capital may be seen as a resource or a restraint in the lives of returnees
Eugenics and Individual Phenotypic Variation: To What Extent Is Biology a Predictive Science?
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White matter hyperintensities and CSF Alzheimer disease biomarkers in preclinical Alzheimer disease.
ObjectiveRecent studies suggest that white matter hyperintensities (WMH) on MRI, which primarily reflect small vessel cerebrovascular disease, may play a role in the evolution of Alzheimer disease (AD). In a longitudinal study, we investigated whether WMH promote the progression of AD pathology, or alter the association between AD pathology and risk of progression from normal cognition to mild cognitive impairment (MCI).MethodsTwo sets of analyses were conducted. The relationship between whole brain WMH load, based on fluid-attenuated inversion recovery MRI, obtained in initially cognitively normal participants (n = 274) and time to onset of symptoms of MCI (n = 60) was examined using Cox regression models. In a subset of the participants with both MRI and CSF data (n = 204), the interaction of WMH load and CSF AD biomarkers was also evaluated.ResultsBaseline WMH load interacted with CSF total tau (t-tau) with respect to symptom onset, but not with CSF β-amyloid 1-42 or phosphorylated tau (p-tau) 181. WMH volume was associated with time to symptom onset of MCI among individuals with low t-tau (hazard ratio [HR] 1.35, confidence interval [CI] 1.06-1.73, p = 0.013), but not those with high t-tau (HR 0.86, CI 0.56-1.32, p = 0.47). The rate of change in the CSF biomarkers over time was not associated with the rate of change in WMH volumes.ConclusionThese results suggest that WMH primarily affect the risk of progression when CSF measures of neurodegeneration or neuronal injury (as reflected by t-tau) are low. However, CSF biomarkers of amyloid and p-tau and WMH appear to have largely independent and nonsynergistic effects on the risk of progression to MCI
Association Between Left Atrial Abnormality on ECG and Vascular Brain Injury on MRI in the Cardiovascular Health Study
A recombinant fungal compound induces anti-proliferative and pro-apoptotic effects on colon cancer cells
Genetic and environmental modulation of neurodevelopmental disorders: translational insights from labs to beds
Neurodevelopmental disorders (NDDs) are a heterogeneous group of prevalent neuropsychiatric illnesses with various degrees of social, cognitive, motor, language and affective deficits. NDDs are caused by aberrant brain development due to genetic and environmental perturbations. Common NDDs include autism spectrum disorder (ASD), intellectual disability, communication/speech disorders, motor/tic disorders and attention deficit hyperactivity disorder. Genetic and epigenetic/environmental factors play a key role in these NDDs with significant societal impact. Given the lack of their efficient therapies, it is important to gain further translational insights into the pathobiology of NDDs. To address these challenges, the International Stress and Behavior Society (ISBS) has established the Strategic Task Force on NDDs. Summarizing the Panel's findings, here we discuss the neurobiological mechanisms of selected common NDDs and a wider NDD+ spectrum of associated neuropsychiatric disorders with developmental trajectories. We also outline the utility of existing preclinical (animal) models for building translational and cross-diagnostic bridges to improve our understanding of various NDDs