Results 1 - 10 of 18443
Results 1 - 10 of 18443. Search took: 0.057 seconds
|Sort by: date | relevance|
[en] Our purpose was to perform an in vivo validation of ultrasound imaging for intrafraction motion estimation using the Elekta Clarity Autoscan system during prostate radiation therapy. The study was conducted as part of the Clarity-Pro trial (NCT02388308).
[en] Highlights: • MiR-139-5p suppresses the migration and invasion of osteosarcoma cell lines. • MiR-139-5p decreases DNMT1 expressions in osteosarcoma lines. • MiR-139-5p reduces the osteosarcoma cell migration and invasion by regulating DNMT1 and suppresses osteosarcoma tumor growth in vivo. Accumulating evidence has suggested the crucial roles of differentially expressed miRNAs in osteosarcoma progression. MiR-139-5p was decreased in various cancers. However, the role of miR-139-5p in the development of osteosarcoma and the underlying mechanism remain to be addressed.
[en] Multiple myeloma (MM) is an incurable B-cell malignancy. Therefore, new targets and drugs are urgently needed to improve patient outcome. Epigenetic aberrations play a crucial role in development and progression in cancer, including MM. To target these aberrations, epigenetic modulating agents, such as DNA methyltransferase inhibitors (DNMTi) and histone deacetylase inhibitors (HDACi), are under intense investigation in solid and hematological cancers. A clinical benefit of the use of these agents as single agents and in combination regimens has been suggested based on numerous studies in pre-clinical tumor models, including MM models. The mechanisms of action are not yet fully understood but appear to involve a combination of true epigenetic changes and cytotoxic actions. In addition, the interactions with the BM niche are also affected by epigenetic modulating agents that will further determine the in vivo efficacy and thus patient outcome. A better understanding of the molecular events underlying the anti-tumor activity of the epigenetic drugs will lead to more rational drug combinations. This review focuses on the involvement of epigenetic changes in MM pathogenesis and how the use of DNMTi and HDACi affect the myeloma tumor itself and its interactions with the microenvironment
[en] The development of Superconducting QUantum Interference Device (SQUID)-based magnetometer for two applications, in vivo prepolarized, ultra-low field MRI of humans and dispersive readout of SQUIDs for micro- and nano-scale magnetometery, are the focus of this thesis.
[en] It has been recently reported that the centrosome of neurons does not have microtubule nucleating activity. Microtubule nucleation requires γ-tubulin as well as its recruiting proteins, GCP-WD/NEDD1 and CDK5RAP2 that anchor γ-tubulin to the centrosome. Change in the localization of these proteins during in vivo development of brain, however, has not been well examined. In this study we investigate the localization of γ-tubulin, GCP-WD and CDK5RAP2 in developing cerebral and cerebellar cortex with immunofluorescence. We found that γ-tubulin and its recruiting proteins were localized at centrosomes of immature neurons, while they were lost at centrosomes in mature neurons. This indicated that the loss of microtubule nucleating activity at the centrosome of neurons is due to the loss of γ-tubulin-recruiting proteins from the centrosome. RT-PCR analysis revealed that these proteins are still expressed after birth, suggesting that they have a role in microtubule generation in cell body and dendrites of mature neurons. Microtubule regrowth experiments on cultured mature neurons showed that microtubules are nucleated not at the centrosome but within dendrites. These data indicated the translocation of microtubule-organizing activity from the centrosome to dendrites during maturation of neurons, which would explain the mixed polarity of microtubules in dendrites
[en] The data published over the past 15 years on the search for newer anticonvulsant drugs are generalized. Pyrrolidinedione, quinazolinone, xanthone, hydrazine and thiadiazole derivatives manifesting anticonvulsant activity in model in vivo tests in rodents are considered.
[en] A P1 (jun/fos) transcription factors (c-jun, jun B, jun D, c-fos, Fos B, Fr a-1, and Fr a-2) are key regulators of epidermal keratinocyte survival and differentiation and important drivers of cancer development. Understanding the role of these factors in epidermis is complicated by the fact that each protein is expressed, at different levels, in multiple cells layers in differentiating epidermis, and because A P1 transcription factors regulate competing processes (i.e., proliferation, apoptosis, and differentiation). Various in vivo genetic approaches have been used to study these proteins including targeted and conditional knockdown, overexpression, and expression of dominant-negative inactivating A P1 transcription factors in epidermis. Taken together, these studies suggest that individual A P1 transcription factors have different functions in the epidermis and in cancer development and that altering A P1 transcription factor function in the basal versus supra basal layers differentially influences the epidermal differentiation response and disease and cancer development.
[en] Our focus in the past several years has been on the identification of novel and effective pan-Bcl-2 antagonists. We have recently reported a series of Apogossypolone (ApoG2) derivatives, resulting in the chiral compound (±) BI97D6. We report here the synthesis and evaluation on its optically pure (−) and (+) atropisomers. Compound (−) BI97D6 potently inhibits the binding of BH3 peptides to Bcl-XL, Bcl-2, Mcl-1, and Bfl-1 with IC50 values of 76 ± 5, 31 ± 2, 25 ± 8, and 122 ± 28 nM, respectively. In a cellular assay, compound (−) BI97D6 effectively inhibits cell growth in the PC-3 human prostate cancer and H23 human lung cancer cell lines with EC50 values of 0.22 ± 0.08 and 0.14 ± 0.02 μM, respectively. Similarly, compound (−) BI97D6 effectively induces apoptosis in the BP3 human lymphoma cell line in a dose-dependent manner. The compound also shows little cytotoxicity against bax−/−/bak−/− cells, suggesting that it kills cancers cells predominantly via a Bcl-2 pathway. Moreover, compound (−) BI97D6 displays in vivo efficacy in both a Bcl-2-transgenic mouse model and in a prostate cancer xenograft model in mice. Therefore, compound (−) BI97D6 represents a promising drug lead for the development of novel apoptosis-based therapies for cancer.
[en] Shear wave elastography (SWE) techniques have received substantial attention in recent years. Strong experimental data in SWE suggest that shear wave speed changes significantly due to the known acoustoelastic effect (AE). This presents both challenges and opportunities toward in vivo characterization of biological soft tissues. In this work, under the framework of continuum mechanics, we model a tissue-mimicking material as a homogeneous, isotropic, incompressible, hyperelastic material. Our primary objective is to quantitatively and qualitatively compare experimentally measured acoustoelastic data with model-predicted outcomes using multiple strain energy functions. Our analysis indicated that the classic Neo-Hookean and Mooney–Rivlin models are inadequate for modeling the AE in tissue-mimicking materials. However, a subclass of strain energy functions containing both high-order/exponential term(s) and second-order invariant dependence showed good agreement with experimental data. Based on data investigated, we also found that discrepancies may exist between parameters inversely estimated from uniaxial compression and SWE data. Overall, our findings may improve our understanding of clinical SWE results. (paper)
[en] Highlights: • miR-199a-5p expression is downregulated in PTC tissues and cells. • miR-199a-5p overexpression suppressed the progression of PTC cells. • SNAI1 is a target of miR-199a-5p and miR-199a-5p suppressed SNAI1 expression in PTC cells. • SNAI1 knockdown inhibited the progression of PTC cells. • miR-199a-5p overexpression hindered tumor growth in PTC in vivo. Increasing evidence has emphasized the important roles of differentially expressed miRNAs in papillary thyroid cancer (PTC) development. miR-199a-5p was previously documented to be downregulated in PTCs compared with normal thyroids. However, the role of miR-199a-5p in the progression of PTC and the underlying mechanism remain to be further addressed.