Acute myeloid leukemia (AML) patients with the FMS-related receptor tyrosine kinase 3 internal tandem duplication (FLT3/ITD) mutation have a poorer prognosis, and treatment with FLT3 tyrosine kinase inhibitors (TKIs) has been hindered by resistance mechanisms. One such mechanism is known as adaptive resistance, in which downstream signaling pathways are reactivated after initial inhibition. Past work has shown that FLT3/ITD cells undergo adaptive resistance through the reactivation of extracellular signal-regulated kinase (ERK) signaling within 24 h of sustained FLT3 inhibition.
View Article and Find Full Text PDFInternal tandem duplication mutations of FLT3 (FLT3/ITD) confer poor prognosis in AML. FLT3 tyrosine kinase inhibitors (TKIs) alone have limited and transient clinical efficacy thus calling for new targets for more effective combination therapy. In a loss-of-function RNAi screen, we identified NOTCH4 as one such potential target whose inhibition proved cytotoxic to AML cells, and also sensitized them to FLT3 inhibition.
View Article and Find Full Text PDFRecent studies have reported the impact of previous COVID-19 infection on the early clinical outcome after total knee arthroplasty (TKA). However, the timing of infection before the surgery was not constant and a study on patients with COVID-19 infection within 1 week after TKA is lacking. This study aimed to determine the effect of COVID-19 infection within one week after TKA on the postoperative outcomes and to compare the early clinical outcomes to those who were not infected with COVID-19 before and after surgery.
View Article and Find Full Text PDFH84T-Banana Lectin (BanLec) CAR-NK cells bind high mannose glycosites that decorate the SARS-CoV-2 envelope, thereby decreasing cellular infection in a model of SARS-CoV-2. H84T-BanLec CAR-NK cells are innate effector cells, activated by virus. This novel cellular agent is a promising therapeutic, capable of clearing circulating SARS-CoV-2 virus and infected cells.
View Article and Find Full Text PDFTyrosine kinase inhibitors (TKIs) targeting FLT3 have shown activity but when used alone have achieved limited success in clinical trials, suggesting the need for combination with other drugs. We investigated the combination of FLT3 TKIs (Gilteritinib or Sorafenib), with Venetoclax, a BCL-2 selective inhibitor (BCL-2i), on FLT3/ITD leukemia cells. The combination of a FLT3 TKI and a BCL-2i synergistically reduced cell proliferation and enhanced apoptosis/cell death in FLT3/ITD cell lines and primary AML samples.
View Article and Find Full Text PDFThe FMS-like tyrosine kinase 3 (FLT-3) is the most frequently mutated gene in acute myeloid leukemia (AML), a high-risk feature, and now the target of tyrosine kinase inhibitors (TKIs), which are approved and in development. The most common mutation is the internal tandem duplication (ITD). We present a novel mutation, FLT-3/Q575Δ, identified in a patient with AML through next-generation sequencing (NGS).
View Article and Find Full Text PDFPurpose: To compare outcomes (i.e., clinical and radiological findings, postoperative complication) in the fixation of intertrochanteric fractures with U-blade Gamma3 and Gamma3 nails.
View Article and Find Full Text PDFBreast cancer is one of the leading causes of morbidity and mortality among women. Epidermal growth factor receptor (EGFR) and proto-oncogene tyrosine-protein kinase Src (c-Src) are critical components of the signaling pathways that are associated with breast cancer. However, the regulatory mechanism of histone deacetylase 3 (HDAC3) in these pathways remains unclear.
View Article and Find Full Text PDFPurpose: Because of disease heterogeneity, limited studies on effective chemotherapies and therapeutic agents for advanced gastric cancer are available. Erythrocyte membrane protein band 4.1-like 5 (EPB41L5) has critical roles in renal and breast cancer metastasis.
View Article and Find Full Text PDFBackground: The treatment of modified Mason Type III or IV fractures is controversial. Many authors report open reduction and internal fixation (ORIF) with reconstruction of the radial head, but others advocate radial head arthroplasty (RHA). This study compares the clinical and radiological outcomes of ORIF and RHA in modified Mason Type III or IV radial head fracture and evaluates correlations between prognostic factors and postoperative clinical outcomes.
View Article and Find Full Text PDFThe role of histone deacetylase 3 (HDAC3) is to repress the expression of various genes by eliminating acetyl group from histone. Thus, the regulation of HDAC3 activity is essential to maintain cellular homeostasis. In this study, we found that HDAC3 interacts with c-Src kinase.
View Article and Find Full Text PDFGastric cancer is the fourth most common cancer worldwide. Despite the high incidence of gastric cancer, efficient chemotherapy treatments still need to be developed. In this study, we examined the anticancer effects of endoplasmic reticulum (ER) stress inducer tunicamycin in gastric cancer.
View Article and Find Full Text PDFAlthough programed cell death 5 (PDCD5) is an important protein in p53-mediated proapoptotic signaling, very little is known about PDCD5-related cell death. In this study, we report that serine/threonine kinase 31 (STK31) interacts with PDCD5, which maintains the stability of PDCD5. STK31 overexpression significantly activated PDCD5 stabilization and p53-mediated apoptosis in response to etoposide (ET).
View Article and Find Full Text PDFProc Natl Acad Sci U S A
May 2018
Programmed cell death 5 (PDCD5) has been associated with human cancers as a regulator of cell death; however, the role of PDCD5 in the endothelium has not been revealed. Thus, we investigated whether PDCD5 regulates protein kinase B (PKB/AKT)-endothelial nitric oxide synthase (eNOS)-dependent signal transduction in the endothelium and affects atherosclerosis. Endothelial-specific PDCD5 knockout mice showed significantly reduced vascular remodeling compared with wild-type (WT) mice after partial carotid ligation.
View Article and Find Full Text PDFWntless/GPR177 functions as WNT ligand carrier protein and activator of WNT/β-catenin signaling, however, its molecular role in gastric cancer (GC) has remained elusive. We investigated the role of GPR177 in gastric tumorigenesis and provided the therapeutic potential of a clinical development of anti-GPR177 monoclonal antibodies. GPR177 mRNA expression was assessed in GC transcriptome data sets (GSE15459, n = 184; GSE66229, n = 300); protein expression was assessed in independent patient tumor tissues (Yonsei TMA, n = 909).
View Article and Find Full Text PDFProgrammed cell death 5 (PDCD5) is believed to play a crucial role in p53 activation; however, the underlying mechanism of how PDCD5 function is regulated during apoptosis remains obscure. Here, we report that the serine/threonine phosphatase PPEF-1 interacts with and dephosphorylates PDCD5 at Ser-119, which leads to PDCD5 destabilization. Overexpression of wild-type PPEF-1, but not inactive PPEF-1, efficiently suppressed CK2α-mediated stabilization of PDCD5 and p53-mediated apoptosis in response to etoposide (ET).
View Article and Find Full Text PDFChronic inflammation is strongly associated with prostate cancer pathogenesis. Transducin β-like protein (TBL1) and Transducin β-like 1X-linked receptor 1 (TBLR1) have been identified recently as a coactivator for NF-κB-mediated transcription; however, the underlying mechanism by which TBL1 and TBLR1 activate NF-κB function during inflammation remains unknown. Here, we demonstrate that cytokine production is significantly elevated in androgen-independent PC-3 prostate cancer cells compared with androgen-dependent LNCaP prostate cancer cells.
View Article and Find Full Text PDFHealth Qual Life Outcomes
September 2015
Objectives: This paper aimed to employ subject matter experts (SMEs) to assess the extent to which the Korean version of the short-form of the OHIP (OHIP-14 K) is culturally valid and equivalent in Korean.
Methods: We approached 17 bilingual Korean SMEs from which 10 independently rated the clarity, relevance, and cultural equivalence of the OHIP-14 K. SME's varied between 10 and 41 years of clinical experience and were mostly males (# 7).
The inhibition of p53 activity by histone deacetylase 3 (HDAC3) has been reported, but the precise molecular mechanism is unknown. Here we show that programmed cell death 5 (PDCD5) selectively mediates HDAC3 dissociation from p53, which induces HDAC3 cleavage and ubiquitin-dependent proteasomal degradation. Casein kinase 2 alpha phosphorylates PDCD5 at Ser-119 to enhance its stability and importin 13-mediated nuclear translocation of PDCD5.
View Article and Find Full Text PDFOxidative stress and inflammation are associated with skeletal muscle atrophy. Because the activation of toll-like receptor (TLR) 2 induces oxidative stress and inflammation, TLR2 may be directly linked to skeletal muscle atrophy. This study examined the role of TLR2 in skeletal muscle atrophy in wild-type (WT) and TLR2 knockout (KO) mice.
View Article and Find Full Text PDFProgrammed cell death 5 (PDCD5) plays a crucial role in TP53-mediated apoptosis, but the regulatory mechanism of PDCD5 itself during apoptosis remains obscure. We identified YY1-associated factor 2 (YAF2) as a novel PDCD5-interacting protein in a yeast two-hybrid screen for PDCD5-interacting proteins. We found that YY1-associated factor 2 (YAF2) binds to and increases PDCD5 stability by inhibiting the ubiquitin-dependent proteosomal degradation pathway.
View Article and Find Full Text PDFBackground: We evaluated interobserver and intraobserver reliability of the classification and treatment of acromioclavicular (AC) joint dislocations and assessed the impact of adding 3-dimensional computed tomography (3D CT) on the reliability of classification and treatment choice.
Methods: Ten surgeons independently reviewed plain radiographs and 3D CT in 28 cases with AC joint dislocation. Images from each case were randomly presented to the observers, with plain radiographs alone being presented first, followed by plain radiographs plus 3D CT 2 weeks later.
Aims: The present study examined the effect of the heme oxygenase (HO)-1 inducer hemin on skeletal muscle atrophy induced by single limb immobilization in mice.
Main Methods: Immobilization was conducted in the left hindlimb of C57BL/6 mice for 1 week and the right hindlimb was used as a control. Hemin (30 mg/kg) was administered intraperitoneally once a day during the immobilization period.