84 research outputs found

    Inferior Parathyroid Gland Preservation In Situ during Central Neck Dissection for Thyroid Papillary Carcinoma

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    Hypoparathyroidism is the most common and a potentially serious complication of thyroid surgery; therefore, it becomes very important for thyroid surgeons to preserve the parathyroid glands in situ during the thyroid operation. Because of the application of “meticulous capsular dissection,” the problem about how to preserve the parathyroid gland in thyroidectomy has become minor. Because inferior parathyroid glands enjoy a more variable position in the adult neck and they are located in the area of central neck lymph node dissection, how to preserve them in situ during central neck dissection is regarded as a major problem. To solve it, a new operation concept, “a layer of thymus-blood vessel-inferior parathyroid gland,” is mainly introduced in this chapter

    Backward and Forward Compatibility

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    In response to the European Union (EU) Restriction of Hazardous Substances (RoHS) and other countries’ impending lead-free directives, the electronics industry is moving toward lead-free soldering. Total lead-free soldering requires not only lead-free solder paste but also lead-free printed circuit board (PCB) finish and lead-free component/packages. Transitioning tin-lead (SnPb) soldering to totally lead-free soldering is a complex issue and involves movement of the whole electronics industry supply chain. In reality, there is a transition period

    Aberrant nuclear factor-kappa B activity in acute myeloid Leukemia: from molecular pathogenesis to therapeutic target

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    The overall survival of patients with acute myeloid leukemia (AML) has not been improved significantly over the last decade. Molecularly targeted agents hold promise to change the therapeutic landscape in AML. The nuclear factor kappa B (NF-κB) controls a plethora of biological process through switching on and off its long list of target genes. In AML, constitutive NF-κB has been detected in 40% of cases and its aberrant activity enable leukemia cells to evade apoptosis and stimulate proliferation. These facts suggest that NF-κB signaling pathway plays a fundamental role in the development of AML and it represents an attractive target for the intervention of AML. This review summarizes our current knowledge of NF-κB signaling transduction including canonical and non-canonical NF-κB pathways. Then we specifically highlight what factors contribute to the aberrant activation of NF-κB activity in AML, followed by an overview of 8 important clinical trials of the first FDA approved proteasome inhibitor, Bortezomib (Velcade®), which is a NF-κB inhibitor too, in combination with other therapeutic agents in patients with AML. Finally, this review discusses the future directions of NF-κB inhibitor in treatment of AML, especially in targeting leukemia stem cells (LSCs)

    ABT-869, a promising multi-targeted tyrosine kinase inhibitor: from bench to bedside

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    Tyrosine Kinase Inhibitors (TKI) have significantly changed the landscape of current cancer therapy. Understanding of mechanisms of aberrant TK signaling and strategies to inhibit TKs in cancer, further promote the development of novel agents

    Chromospheric Activity of HAT-P-11: an Unusually Active Planet-Hosting K Star

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    Kepler photometry of the hot Neptune host star HAT-P-11 suggests that its spot latitude distribution is comparable to the Sun's near solar maximum. We search for evidence of an activity cycle in the CaII H & K chromospheric emission SS-index with archival Keck/HIRES spectra and observations from the echelle spectrograph on the ARC 3.5 m Telescope at APO. The chromospheric emission of HAT-P-11 is consistent with a 10\gtrsim 10 year activity cycle, which plateaued near maximum during the Kepler mission. In the cycle that we observed, the star seemed to spend more time near active maximum than minimum. We compare the logRHK\log R^\prime_{HK} normalized chromospheric emission index of HAT-P-11 with other stars. HAT-P-11 has unusually strong chromospheric emission compared to planet-hosting stars of similar effective temperature and rotation period, perhaps due to tides raised by its planet.Comment: 16 pages, 8 figures; accepted to the Astrophysical Journa

    Engineering the First Chimeric Antibody in Targeting Intracellular PRL-3 Oncoprotein for Cancer Therapy in Mice

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    Antibodies are considered as ‘magic bullets’ because of their high specificity. It is believed that antibodies are too large to routinely enter the cytosol, thus antibody therapeutic approach has been limited to extracellular or secreted proteins expressed by cancer cells. However, many oncogenic proteins are localized within the cell. To explore the possibility of antibody therapies against intracellular targets, we generated a chimeric antibody targeting the intracellular PRL-3 oncoprotein to assess its antitumor activities in mice. Remarkably, we observed that the PRL-3 chimeric antibody could efficiently and specifically reduce the formation of PRL-3 expressing metastatic tumors. We further found that natural killer (NK) cells were important in mediating the therapeutic effect, which was only observed in a nude mouse model (T-cell deficient), but not in a Severe Combined Immunodeficiency’ (scid) mouse model (B- and T-cell deficient), indicating the anticancer effect also depends on host B-cell activity. Our study involving 377 nude and scid mice suggests that antibodies targeting intracellular proteins can be developed to treat cancer

    PRL-3, a Metastasis Associated Tyrosine Phosphatase, Is Involved in FLT3-ITD Signaling and Implicated in Anti-AML Therapy

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    Combination with other small molecule drugs represents a promising strategy to improve therapeutic efficacy of FLT3 inhibitors in the clinic. We demonstrated that combining ABT-869, a FLT3 inhibitor, with SAHA, a HDAC inhibitor, led to synergistic killing of the AML cells with FLT3 mutations and suppression of colony formation. We identified a core gene signature that is uniquely induced by the combination treatment in 2 different leukemia cell lines. Among these, we showed that downregulation of PTP4A3 (PRL-3) played a role in this synergism. PRL-3 is downstream of FLT3 signaling and ectopic expression of PRL-3 conferred therapeutic resistance through upregulation of STAT (signal transducers and activators of transcription) pathway activity and anti-apoptotic Mcl-1 protein. PRL-3 interacts with HDAC4 and SAHA downregulates PRL-3 via a proteasome dependent pathway. In addition, PRL-3 protein was identified in 47% of AML cases, but was absent in myeloid cells in normal bone marrows. Our results suggest such combination therapies may significantly improve the therapeutic efficacy of FLT3 inhibitors. PRL-3 plays a potential pathological role in AML and it might be a useful therapeutic target in AML, and warrant clinical investigation

    Aberrant non-canonical NF-κB signalling reprograms the epigenome landscape to drive oncogenic transcriptomes in multiple myeloma

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    In multiple myeloma, abnormal plasma cells establish oncogenic niches within the bone marrow by engaging the NF-κB pathway to nurture their survival while they accumulate pro-proliferative mutations. Under these conditions, many cases eventually develop genetic abnormalities endowing them with constitutive NF-κB activation. Here, we find that sustained NF-κB/p52 levels resulting from such mutations favours the recruitment of enhancers beyond the normal B-cell repertoire. Furthermore, through targeted disruption of p52, we characterise how such enhancers are complicit in the formation of super-enhancers and the establishment of cis-regulatory interactions with myeloma dependencies during constitutive activation of p52. Finally, we functionally validate the pathological impact of these cis-regulatory modules on cell and tumour phenotypes using in vitro and in vivo models, confirming RGS1 as a p52-dependent myeloma driver. We conclude that the divergent epigenomic reprogramming enforced by aberrant non-canonical NF-κB signalling potentiates transcriptional programs beneficial for multiple myeloma progression
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