Cuspal Shape Alterations by Bmp4 Directing Cell Proliferation and Apoptosis.

The enamel knot (EK), located at the center of cap stage tooth germs, is a transitory cluster of nondividing epithelial cells. The EK acts as a signaling center that provides positional information for tooth morphogenesis and regulates the growth of tooth cusps. To identify species-specific cuspal patterns, this study analyzed the cellular mechanisms in the EK that were related to bone morphogenetic protein (Bmp), which plays a crucial role in cell proliferation and apoptosis. To understand the cellular mechanisms in the EK, the differences between 2 species showing different cuspal patterning, mouse (pointy bunodont cusp) and gerbil (flat lophodont cusp), were analyzed with quantitative reverse transcriptase polymerase chain reaction and immunofluorescent staining. Based on these, we performed protein-soaked bead implantation on tooth germs of the 2 different EK regions and compared the cellular behavior in the EKs of the 2 species. Many genes related with cell cycle, cell apoptosis, and cell proliferation were involved in BMP signaling in the EK during tooth development. A comparison of the cell proliferation and apoptosis associated with Bmp revealed distinctive patterns of the cellular mechanisms. Our findings indicate that the cellular mechanisms, such as cell proliferation and apoptosis, in the EK are related to Bmp4 and play an important role in tooth morphogenesis.

Humeral shaft fracture and radial nerve palsy in Korean soldiers: focus on arm wrestling related injury.

INTRODUCTION: Humeral shaft fractures can lead to radial nerve injury and may require surgery and rehabilitation. We determined the causative events of humeral fracture, including arm wrestling, in young Korean soldiers and examined whether humeral fracture is related to demographic characteristics and the presence of radial nerve palsy. METHODS: We reviewed 7.5 years (July 2012 to June 2019) of medical records covering patients who had experienced a humeral shaft fracture after entering military service and had received surgery for open reduction and internal fixation. Data were obtained on basic demographics, initial event provoking the fracture, presence of radial nerve palsy, initial and follow-up severity of the weakness, and any discharge from military service because of prolonged radial nerve palsy. RESULTS: Of 123 cases, arm wrestling was the leading cause (52.8%). A high energy injury, such as falling from a height (11.4%), and sports related slips (10.6%) were other causes. All humeral shaft fractures caused by forceful contraction were spiral, while 40% of the fractures caused by external force related events were of a transverse type. The percentage of left-sided fractures was significantly higher for fractures arising from an external force than in those caused by forceful contraction related events. Radial nerve palsy was found in 34 patients (27.6%), and 16 were discharged from the military because of prolonged radial nerve palsy 6 months after the fracture. The causative events and other factors did not affect the presence of radial nerve palsy. CONCLUSION: Arm wrestling was the leading cause of humeral fracture in young Korean soldiers but the chance of developing comorbid radial nerve palsy did not differ from that of other causes. These epidemiologic findings in this young active group may help in understanding the causes of humeral shaft fracture in soldiers and in the wider young population.

An Explanation for How FGFs Predict Species-Specific Tooth Cusp Patterns.

Species-specific cusp patterns result from the iterative formation of enamel knots, the epithelial signaling centers, at the future cusp positions. The expressions of fibroblast growth factors (FGFs), especially Fgf4, in the secondary enamel knots in the areas of the future cusp tips are generally used to manifest the appearance of species-specific tooth shapes. However, the mechanism underlying the predictive role of FGFs in species-specific cusp patterns remains obscure. Here, we demonstrated that gerbils, which have a lophodont pattern, exhibit a striped expression pattern of Fgf4, whereas mice, which have a bunodont pattern, have a spotted expression pattern, and these observations verify the predictive role of Fgf4 in species-specific cusp patterns. By manipulating FGFs' signaling in the inner dental epithelium of gerbils, we provide evidence for the intracellular participation of FGF signaling, specifically FGF4 and FGF20, in Rac1- and RhoA-regulated cellular geometry remolding during the determination of different cusp patterns. Our study presents a novel explanation of how different FGF expression patterns produce different cusp patterns and implies that a conserved intracellular FGF-GTPase signaling module might represent an underlying developmental basis for evolutionary changes in cusp patterns.

RaRF confers RA resistance by sequestering RAR to the nucleolus and regulating MCL1 in leukemia cells.

Retinoic acid (RA) has broad clinical applications for the treatment of various cancers, particularly acute promyelocytic leukemia. However, RA-based therapy is limited by relapse in patients associated with RA resistance, the mechanism of which is poorly understood. Here, we suggest a new molecular mechanism of RA resistance by a repressor, named RA resistance factor (RaRF). RaRF suppressed transcriptional activity of the RA receptor (RAR) by directly interacting with and sequestering RAR to the nucleolus in response to RA. RaRF was highly expressed in RA-resistant leukemia cells and its expression was strongly correlated with RA sensitivity. MCL1 was upregulated by RA treatment upon RaRF depletion, accompanying leukemic myeloblast differentiation, which is negatively regulated by ectopic RaRF expression. Collectively, we propose that RaRF may be a factor in the resistance mechanism and thus a potential target for leukemia therapy using RA.

ASXL2 promotes proliferation of breast cancer cells by linking ERα to histone methylation.

Estrogen receptor alpha (ERα) has a pivotal role in breast carcinogenesis by associating with various cellular factors. Selective expression of additional sex comb-like 2 (ASXL2) in ERα-positive breast cancer cells prompted us to investigate its role in chromatin modification required for ERα activation and breast carcinogenesis. Here, we observed that ASXL2 interacts with ligand E2-bound ERα and mediates ERα activation. Chromatin immunoprecipitation-sequencing analysis supports a positive role of ASXL2 at ERα target gene promoters. ASXL2 forms a complex with histone methylation modifiers including LSD1, UTX and MLL2, which all are recruited to the E2-responsive genes via ASXL2 and regulate methylations at histone H3 lysine 4, 9 and 27. The preferential binding of the PHD finger of ASXL2 to the dimethylated H3 lysine 4 may account for its requirement for ERα activation. On ASXL2 depletion, the proliferative potential of MCF7 cells and tumor size of xenograft mice decreased. Together with our finding on the higher ASXL2 expression in ERα-positive patients, we propose that ASXL2 could be a novel prognostic marker in breast cancer.

Incidence and risk factors for backpack palsy in young Korean soldiers.

OBJECTIVES: Backpack palsy (BPP) is a common aetiology of brachial plexopathy in military hospitals. We aimed to determine the incidence and risk factors of BPP in young Korean soldiers. METHODS: We identified enlisted patients who were diagnosed with BPP from a review of the medical records of all the Korean military hospitals in 2011 and 2012 and investigated their clinical findings and medical study results. To identify risk factors of BPP, we also surveyed, by questionnaire, healthy recruits of a company in a training centre who had just finished night marches. We divided them according to whether they had paresthaesia and/or weakness in their arm(s) during marching and compared their characteristics. RESULTS: The incidence of BPP in Korean soldiers was 29.7 per 100,000 person-years (95% CI 17.2 to 24.3). Body mass index (BMI) was significantly lower in patients with BPP than it was in healthy recruits. Among healthy recruits, those who had experienced paresthaesia and/or weakness during marching had a significantly lower BMI than did those who had not. CONCLUSIONS: We report the incidence of BPP in young Korean soldiers. A low BMI was a risk factor for BPP. These results may be helpful in establishing a strategy for the prevention of BPP in the setting of military training.

The brain-derived neurotrophic factor Val66Met polymorphism and degeneration of the corticospinal tract after stroke: a diffusion tensor imaging study.

BACKGROUND AND PURPOSE: A common single nucleotide polymorphism, Val66Met, in the human brain-derived neurotrophic factor (BDNF) gene has a potential role in the pathogenesis and treatment of stroke. The relevance of the BDNF Val66Met polymorphism to long-term stroke outcomes was examined, specifically with respect to changes in corticospinal integrity. METHODS: Thirty-five stroke patients with unilateral motor weakness were genotyped within 2 weeks after onset (T1), and changes in the integrity of the ipsilesional corticospinal tract (CST) as well as alterations in motor function at 1 month (T2) and 3 months after onset (T3) were tracked. RESULTS: On the basis of the Fugl-Meyer assessment upper extremity score, carriers of the Met allele (Val/Met and Met/Met) showed poorer motor outcomes at T2 and T3 compared to carriers of only the Val allele (Val/Val). For both BDNF allele types, patients exhibited characteristic degeneration of the CST compared to healthy controls. There were no differences between the two genotypes with respect to time-dependent changes in diffusion-tensor-imaging-derived parameters of the CST. However, the two groups showed different relationships between motor outcomes and directional diffusivities according to the elapsed time after onset. Poorer motor function was associated with lower axial diffusivity values for the Val/Val genotype group in the sub-acute phase (T1 and T2) but with higher radial diffusivity values for the Val/Met and Met/Met genotype group in the early chronic phase (T3). CONCLUSIONS: Motor recovery in stroke patients may be affected by the BDNF Val66Met polymorphism, possibly through its effects on distinct pathological processes underlying corticospinal degeneration.

Cognitive impairments associated with morphological changes in cortical and subcortical structures in multiple system atrophy of the cerebellar type.

BACKGROUND AND PURPOSE: Patients with the cerebellar variant of multiple system atrophy (MSA-C) often show cognitive deficits in various cognitive domains. The association between morphometric changes in cortical and subcortical structures and cognitive impairments in MSA-C were investigated to explore the neural correlates responsible for cognitive deficits in MSA-C patients. METHODS: Using surface-based morphometry, region-of-interest cortical thickness and the volumes and shapes of subcortical structures were examined in 18 patients who fulfilled the criteria of probable MSA-C and were compared to 50 healthy controls. The association between regional changes and cognitive functions in MSA-C were investigated by applying linear regression analyses after controlling for confounding factors. RESULTS: Compared with controls, the patients with MSA-C showed significant cortical thinning in the fronto-temporo-parietal regions and volume reduction in subcortical structures with shape changes. Cerebellar volume had no significant effect on cortical and subcortical volumes. The severity of atrophic changes in the bilateral thalamus, the left cerebellum and the left pericalcarine gyrus were significantly correlated with attentional, executive and visuospatial dysfunctions. CONCLUSION: Cognitive impairment in MSA-C might result from functional disruption of the corticostriatal and pontocerebellar circuit mediated by primary cortical, cerebellar or thalamic pathology.

The LIM-only transcription factor LMO2 determines tumorigenic and angiogenic traits in glioma stem cells.

Glioblastomas (GBMs) maintain their cellular heterogeneity with glioma stem cells (GSCs) producing a variety of tumor cell types. Here we interrogated the oncogenic roles of Lim domain only 2 (LMO2) in GBM and GSCs in mice and human. High expression of LMO2 was found in human patient-derived GSCs compared with the differentiated progeny cells. LMO2 is required for GSC proliferation both in vitro and in vivo, as shRNA-mediated LMO2 silencing attenuated tumor growth derived from human GSCs. Further, LMO2 is sufficient to induce stem cell characteristics (stemness) in mouse premalignant astrocytes, as forced LMO2 expression facilitated in vitro and in vivo growth of astrocytes derived from Ink4a/Arf null mice and acquisition of GSC phenotypes. A subset of mouse and human GSCs converted into vascular endothelial-like tumor cells both in vitro and in vivo, which phenotype was attenuated by LMO2 silencing and promoted by LMO2 overexpression. Mechanistically, the action of LMO2 for induction of glioma stemness is mediated by transcriptional regulation of Jagged1 resulting in activation of the Notch pathway, whereas LMO2 directly occupies the promoter regions of the VE-cadherin gene for a gain of endothelial cellular phenotype. Subsequently, selective ablation of human GSC-derived VE-cadherin-expressing cells attenuated vascular formation in mouse intracranial tumors, thereby significantly prolonging mouse survival. Clinically, LMO2 expression was elevated in GBM tissues and inversely correlated with prognosis of GBM patients. Taken together, our findings describe novel dual roles of LMO2 to induce tumorigenesis and angiogenesis, and provide potential therapeutic targets in GBMs.

Berberine induces apoptosis via ROS generation in PANC-1 and MIA-PaCa2 pancreatic cell lines

Pancreatic cancer is the fourth leading cause of cancer death. Gemcitabine is widely used as a chemotherapeutic agent for the treatment of pancreatic cancer, but the prognosis is still poor. Berberine, an isoquinoline alkaloid extracted from a variety of natural herbs, possesses a variety of pharmacological properties including anticancer effects. In this study, we investigated the anticancer effects of berberine and compared its use with that of gemcitabine in the pancreatic cancer cell lines PANC-1 and MIA-PaCa2. Berberine inhibited cell growth in a dose-dependent manner by inducing cell cycle arrest and apoptosis. After berberine treatment, the G1 phase of PANC-1 cells increased by 10% compared to control cells, and the G1 phase of MIA-PaCa2 cells was increased by 2%. Whereas gemcitabine exerts antiproliferation effects through S-phase arrest, our results showed that berberine inhibited proliferation by inducing G1-phase arrest. Berberine-induced apoptosis of PANC-1 and MIA-PaCa2 cells increased by 7 and 2% compared to control cells, respectively. Notably, berberine had a greater apoptotic effect in PANC-1 cells than gemcitabine. Upon treatment of PANC-1 and MIA-PaCa2 with berberine at a half-maximal inhibitory concentration (IC50), apoptosis was induced by a mechanism that involved the production of reactive oxygen species (ROS) rather than caspase 3/7 activation. Our findings showed that berberine had anti-cancer effects and may be an effective drug for pancreatic cancer chemotherapy.

Measuring the burden of disease due to climate change and developing a forecast model in South Korea.

OBJECTIVES: Climate change influences human health in various ways, and quantitative assessments of the effect of climate change on health at national level are becoming essential for environmental health management. STUDY DESIGN: This study quantified the burden of disease attributable to climate change in Korea using disability-adjusted life years (DALY), and projected how this would change over time. METHODS: Diseases related to climate change in Korea were selected, and meteorological data for each risk factor of climate change were collected. Mortality was calculated, and a database of incidence and prevalence was established. After measuring the burden of each disease, the total burden of disease related to climate change was assessed by multiplying population-attributable fractions. Finally, an estimation model for the burden of disease was built based on Korean climate data. RESULTS: The total burden of disease related to climate change in Korea was 6.85 DALY/1000 population in 2008. Cerebrovascular diseases induced by heat waves accounted for 72.1% of the total burden of disease (hypertensive disease 1.82 DALY/1000 population, ischaemic heart disease 1.56 DALY/1000 population, cerebrovascular disease 1.56 DALY/1000 population). According to the estimation model, the total burden of disease will be 11.48 DALY/1000 population in 2100, which is twice the total burden of disease in 2008. CONCLUSIONS: This study quantified the burden of disease caused by climate change in Korea, and provides valuable information for determining the priorities of environmental health policy in East Asian countries with similar climates.

Effects of pancreatectomy on nutritional state, pancreatic function and quality of life.

BACKGROUND: There are concerns about the extent of impaired endocrine and exocrine pancreatic function and poor quality of life (QoL) after pancreatectomy, but there is little information from large prospective follow-up studies. METHODS: Consecutive patients undergoing pancreaticoduodenectomy or distal pancreatectomy between 2007 and 2011 were included. Relative bodyweight (RBW), triceps skinfold thickness (TSFT), serum protein, albumin, transferrin, fasting blood glucose, postprandial 2-h glucose (PP2), glycosylated haemoglobin A1c and stool elastase measurements, and European Organization for Research and Treatment of Cancer QLQ-C30 questionnaires were collected serially for 1 year. RESULTS: Some 136 patients undergoing pancreatic resection completed the study. RBW and TSFT recovered to over 90 per cent of the preoperative value by 12 months, whereas transferrin, albumin and protein had returned to preoperative levels by 3 months. Diabetes mellitus, impaired fasting glucose or raised PP2 was present in 42 of 76 patients at 6 months and 36 of 76 at 12 months. Although steatorrhoea and diarrhoea had mainly resolved by 3 months, stool elastase level decreased after operation and showed no recovery. Nutritional status, pancreatic endocrine function and QoL returned to preoperative levels in 63 (46·3 per cent), 72 (52·9 per cent) and 77 (56·6 per cent) of 136 patients within 6 months of pancreatectomy. Multivariable analysis revealed that age 60 years or more, operation type, chronic pancreatitis and malignant disease had a significant impact on nutritional index, pancreatic function and QoL. CONCLUSION: About half of all patients can expect recovery from pancreatectomy after 6 months, but those with risk factors need more careful follow-up and supportive management.

Mutual regulation between DNA-PKcs and Snail1 leads to increased genomic instability and aggressive tumor characteristics.

Although the roles of DNA-dependent protein kinase catalytic subunits (DNA-PKcs) in the non-homologous end joining (NHEJ) of DNA repair are well-recognized, the biological mechanisms and regulators by DNA-PKcs besides DNA repair, have not been clearly described. Here, we show that active DNA-PKcs caused by ionizing radiation, phosphorylated Snail1 at serine (Ser) 100, led to increased Snail1 stability. Furthermore, phosphorylated Snail1 at Ser100 reciprocally inhibited the kinase activity of DNA-PKcs, resulting in an inhibition of DNA repair activity. Moreover, Snail1 phosphorylation by DNA-PKcs was involved in genomic instability and aggressive tumor characteristics. Our results describe novel cellular mechanisms that affect genomic instability, sensitivity to DNA-damaging agents, and the migration of tumor cells by reciprocal regulation between DNA-PKcs and Snail1.

Measuring the burden of chronic diseases in Korea in 2007.

OBJECTIVES: This study was performed to measure the burden of disease from premature death and disability for chronic diseases in Korea in 2007. STUDY DESIGN: Chronic diseases were defined using the WHO definitions. Disability-adjusted life years (DALY) were used to analyse insurance claim data. METHODS: This was a population-based study and included the total population of Korea. DALYs were used to analyse insurance claim data. Years of life lost (YLL) and years lost to disability (YLD) were measured in terms of incidence rate and number of deaths. DALYs were aggregated to YLL and YLD. To ensure code validity, only patients who had visited a tertiary hospital or a clinic three or more times for the same disease were included. RESULTS: Cerebrovascular disease was the leading contributor to the chronic disease burden, with a value of 907.4, followed by diabetes mellitus (899), ischaemic heart disease (710), cirrhosis of the liver (616.5), chronic obstructive pulmonary disease (512.9), asthma (503.1), hypertensive heart disease (407.5), stomach cancer (356) and peptic ulcer disease (292.5). As these results demonstrate, the highest ranked diseases were cardio-cerebrovascular or related diseases, as well as the fact that hypertension, diabetes mellitus and related complications, which are associated diseases, have became increasingly severe problems. And the rural areas have a higher burden of disease than metropolitan cities. According to difference in social status, Medicaid 2 group has more burden of disease than other groups. CONCLUSIONS: It has been possible to present evidence regarding the burden of diseases and the relatively high risk of cardio-cerebrovascular disease. If the various types of cancer were combined and then the calculating tool applied, the burden would likely be greater than that of cardio-cerebrovascular disease. However, based on DALY, ischaemic heart disease demonstrated a remarkable increase compared to the rate in the previous study based on 2002 data. Underprivileged people in particular have been struggling - with chronic diseases.

Lamotrigine increases intracellular Ca(2+) levels and Ca(2+)/calmodulin-dependent kinase II activation in mouse dorsal root ganglion neurones.

AIM: Lamotrigine is a neuroprotective agent that is used clinically for the treatment of seizures and neuropathic pain. A significant volume of literature has reported that lamotrigine exerts analgesic effect by blocking Ca(2+) channels. However, little is known regarding the effect of lamotrigine on the intracellular Ca(2+) concentration ([Ca(2+)](i)). The aim of this study was to determine whether lamotrigine modulates [Ca(2+)](i) in sensory neurones. METHODS: Lamotrigine-induced changes in [Ca(2+)](i) were measured in mouse dorsal root ganglion (DRG) neurones using the Ca(2+)-sensitive fluorescent indicator Fluo 3-AM and a confocal laser scanning microscope. Ca(2+)/calmodulin-dependent kinase II (CaMKII) activation was assessed by the fluorescence intensity using immunocytochemical procedures. RESULTS: Treatment with 1, 10, 30 or 100 µM lamotrigine transiently increased [Ca(2+)](i) in DRG neurones in a dose-dependent manner. Treatment with 100 µM lamotrigine induced a significant (threefold) increase in the Ca(2+) peak in the presence or absence of extracellular Ca(2+). The lamotrigine-induced Ca(2+) increase was abolished or decreased by the treatment with a specific PLC inhibitor (U73122), IP3R antagonist (xestospongin C) or RyR antagonist (dantrolene). In some cells, treatment with 100 µM lamotrigine caused a transient Ca(2+) increase, and the Ca(2+) levels quickly fell to below the basal Ca(2+) level observed prior to lamotrigine application. The decrease in basal Ca(2+) levels was blocked by the treatment with a CaMKII inhibitor (KN93). Immunocytochemical analysis indicated that lamotrigine treatment increased the expression of phosphorylated CaMKII in DRG neurones. CONCLUSION: Treatment with lamotrigine increased [Ca(2+)](i) apparently as a result of Ca(2+) release from intracellular stores and CaMKII activity.

Lactobacillus pentosus var. plantarum C29 protects scopolamine-induced memory deficit in mice.

AIMS: In the preliminary study, kimchi, a traditional food fermented with Chinese cabbage, protected scopolamine-induced mouse memory deficit in passive avoidance test. Therefore, we screened protective ingredients, particularly lactic acid bacteria, from Chinese cabbage kimchi against scopolamine-induced memory deficit in mice. METHODS AND RESULTS: Lactic acid bacteria, isolated from Chinese cabbage kimchi, were identified by 16S rDNA sequence analysis, G+C content and cellular fatty acid composition and sugar fermentation test. Memory deficit was induced in mice by intraperitoneally injecting with scopolamine. Kimchi, particularly its supernatant, protected scopolamine-induced memory deficit in mice in passive avoidance test. Of kimchi ingredients, a lactic acid bacterium, strain C29, potently protected scopolamine-induced memory deficit in mice. C29 was a gram-positive, catalase-negative, anaerobic and non-motile rod. Its pylogenetic property was near to Lactobacillus pentosus (99%) and Lact. plantarum (99%). However, C29 fermented inulin and L-rhamnose and grew in pH 3 and at 45°C in contrast with Lact. pentosus and Lact. plantarum. Therefore, it named to be Lact pentosus var. plantarum C29. The strain C29 protected scopolamine-induced memory deficit in Y-maze and Morris water maze tests. Furthermore, C29 increased hippocampal BDNF and p-CREB expressions, which were reduced by scopolamine. CONCLUSION: Lactobacillus pentosus var. plantarum C29 may protect memory deficit by inducing BDNF and p-CREB expressions. SIGNIFICANCE AND IMPACT OF THE STUDY: Lactic acid bacteria, such as Lact pentosus var. plantarum C29, may prevent memory deficit and its contained fermented foods may be beneficial for dementia.

Poly(ADP-ribosyl)ation of p53 induces gene-specific transcriptional repression of MTA1.

The metastasis-associated protein 1 (MTA1) is overexpressed in various human cancers and is closely connected with aggressive phenotypes; however, little is known about the transcriptional regulation of the MTA1 gene. This study identified the MTA1 gene as a target of p53-mediated transrepression. The MTA1 promoter contains two putative p53 response elements (p53REs), which were repressed by the p53-inducing drug 5-fluorouracil (5-FU). Notably, 5-FU treatment decreased MTA1 expression only in p53 wild-type cells. p53 and histone deacetylases 1/2 were recruited, and acetylation of H3K9 was decreased on the promoter region including the p53REs after 5-FU treatment. Proteomics analysis of the p53 repressor complex, which was pulled down by the MTA1 promoter, revealed that the poly(ADP-ribose) polymerase 1 (PARP-1) was part of the complex. Interestingly, p53 was poly(ADP-ribose)ylated by PARP-1, and the p53-mediated transrepression of the MTA1 gene required poly(ADP-ribose)ylation of p53. In summary, we report a novel function for poly(ADP-ribose)ylation of p53 in the gene-specific regulation of the transcriptional mode of p53 on the promoter of MTA1.

Reduction of breast cancer cell migration via up-regulation of TASK-3 two-pore domain K+ channel.

AIM: Many kinds of K(+) channels are expressed in a variety of cells, including cancer cells. However, only a small amount of research has explored the relationship between voltage-independent K(+) channels and breast cancer. This study was performed to investigate whether changes in two-pore domain K(+) (K(2P) ) channel expression levels are related to the migration of human breast cancer cells. METHODS: K(2P) channel gene/protein expression levels were compared between MCF-7 (a non-invasive cell) and MDA-MB-231 (an invasive cell) using reverse transcriptase (RT)-polymerase chain reaction (PCR), real-time PCR, Western blotting and immunocytochemistry. The relationship between K(2P) channel expression level and cell migration was analysed using gene overexpression and knock-down techniques. Functional expression of TASK-3 in MCF-7 and MDA-MB-231 cells was recorded using patch-clamp technique. RESULTS: Of K(2P) channels, TASK-3 mRNA and protein were highly expressed in MCF-7 cells compared with those in MDA-MB-231 cells. Overexpression of TASK-3 in breast cancer cells reduced migration and invasion, whereas silencing of TASK-3 increased the migration and invasion. The TASK-3 expression level was decreased by phorbol myristate acetate (PMA), a PKC activator. PMA also enhanced the cell migration in MDA-MB-231 cells. CONCLUSION: These results show that an increase in TASK-3 expression levels, which could be modulated by PKC activation, reduces cell migration/invasion in breast cancer cells and suggest that modulation of TASK-3 expression may regulate metastasis of breast cancer cells.

Glucose metabolism in sporadic Creutzfeldt-Jakob disease: a statistical parametric mapping analysis of (18) F-FDG PET.

BACKGROUND AND PURPOSE: Reports describing functional neuroimaging techniques, such as positron emission tomography (PET) and single-photon emission computed tomography (SPECT), in sporadic Creutzfeldt-Jakob disease (sCJD) have consistently suggested that these tools are sensitive for the identification of areas of hypoperfusion or hypometabolism, even in the early stages of sCJD. However, there are few reports on the use of [18F]fluoro-2-deoxy-D-glucose (FDG) PET in sCJD, and most of them are single case reports. Only two small cohort studies based on visual inspection or a region of interest method have been published to date. Using a statistical parametric mapping (SPM) analysis of (18) F-FDG PET, we investigated whether there are brain regions preferentially affected in sCJD. METHODS: After controlling for age and gender, using SPM 2, we compared the glucose metabolism between (i) 11 patients with sCJD and 35 controls and (ii) the subset of five patients with the Heidenhain variant of sCJD and 35 controls. RESULTS: The patients with sCJD showed decreased glucose metabolism in bilateral parietal, frontal and occipital cortices. The Heidenhain variant of sCJD showed glucose hypometabolism mainly in bilateral occipital areas. CONCLUSIONS: Glucose hypometabolism in sCJD was detected in extensive cortical regions; however, it was not found in the basal ganglia or thalamus, which are frequently reported to be affected on diffusion-weighted images. The medial temporal area, which is possibly resistant to the prion deposits, was also less involved in sCJD.