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A sustainable CO2 polymerization using surface activated zinc glutarate catalysts produces industrially useful polymers with good catalytic activity.

Physical activity has been known to improve survival and quality of life of patients with breast cancer. To find factors associated with physical activity, we analyzed the dataset of the multicenter controlled trial of exercise intervention. Three hundred fifty-six participants were assigned to two groups: “Smart After-Care” (smartphone application and pedometer were provided) or exercise education only. Physical activity was measured by International Physical Activity Questionnaire–Short Form (IPAQ-SF) at baseline and after 12 weeks. The association between physical activity and other clinical characteristics was analyzed. At baseline, physical activity amount was 2315.5 ± 3513.2 MET min/week: 33.0% inactive, 49.6% minimally active, and 17.4% health-enhancing physical activity (HEPA) active. Factors associated with HEPA include cancer stage and grip strength. A significantly lower proportion was HEPA active among those with advanced stage than among those with stage 0. After intervention, physical activity was increased to 3466.2 ± 4712.5 MET min/week: 15.3% inactive, 50.4% minimally active, and 34.2% HEPA active. Physical activity was increased in 63.4% of the participants. Factors associated with physical activity increase include cancer stage, diarrhea, and type of exercise intervention. Participants with advanced stage have a 3.3 times higher chance of increasing physical activity. Participants who received “Smart After-Care” have a 64% higher chance of increasing physical activity. Before the intervention, participants with advanced stage are less likely to be HEPA active. Exercise intervention was more beneficial for those with advanced stage or physical symptoms. “Smart After-Care” was more effective than education only in increasing physical activity.

To investigate and compare the effects of mobile health (mHealth) and pedometer with conventional exercise program using a brochure on physical function and quality of life (QOL).The study was a prospective, quasi-randomized multicenter trial where 356 patients whose cancer treatment had been terminated were enrolled. All patients were instructed to perform a 12-week regimen of aerobic and resistance exercise. The mHealth group received a pedometer and a newly developed smartphone application to provide information and monitor the prescribed exercises. Those in the conventional group received an exercise brochure. Physical measurements were conducted at baseline, 6 weeks, and 12 weeks. Self-reported physical activity (international physical activity questionnaire-short form), general QOL (European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30), and breast cancer-specific QOL (Quality of Life Questionnaire Breast Cancer Module 23) were assessed at baseline and 12 weeks. A user satisfaction survey was assessed in the mHealth group.Basic characteristics were not different between the two groups except for age and previous radiotherapy. Physical function, physical activity, and QOL scores were significantly improved regardless of the intervention method, and changes were not significantly different between the two groups. Additionally, the mean Likert scale response for overall satisfaction with the service was 4.27/5 in the mHealth group.Overall, both the mHealth coupled with pedometer and conventional exercise education using a brochure were effective in improving physical function, physical activity, and QOL. This study provides a basis of mHealth research in breast cancer patients for progressing further developing field, although superiority of the mHealth over the conventional program was not definitely evident.

// Hyun Gyu Lee 1 , Hyemi Kim 1, 2 , Taekwon Son 3 , Youngtae Jeong 4 , Seung Up Kim 5 , Seung Myung Dong 6 , Young Nyun Park 2, 7 , Jong Doo Lee 8 , Jae Myun Lee 1, 2 , Jeon Han Park 1 1 Department of Microbiology and Immunology, Institute for Immunology and Immunological Diseases, Yonsei University College of Medicine, Seoul, Republic of Korea 2 Brain Korea 21 PLUS Project for Medical Sciences, Yonsei University College of Medicine, Seoul, Republic of Korea 3 Research Institute of Pharmaceutical Sciences, College of Pharmacy, Seoul National University, Seoul, Republic of Korea 4 Stanford Cancer Institute and Institute for Stem Cell Biology and Regenerative Medicine, Stanford University School of Medicine, Stanford, California, USA 5 Department of Internal Medicine, Institute of Gastroenterology, Yonsei University College of Medicine, Seoul, Republic of Korea 6 Research Institute, National Cancer Center, Goyang, Gyeonggi-do, Republic of Korea 7 Department of Pathology, Yonsei University College of Medicine, Seoul, Republic of Korea 8 Department of Nuclear Medicine, International St. Mary's Hospital, Catholic Kwandong University College of Medicine, Incheon, Republic of Korea Correspondence to: Jeon Han Park, email: jhpark5277@yuhs.ac Keywords: hexokinase 2, HumanMethylation450 BeadChip, HK2-CIMP, hypoxia response element, HIF-1α Received: March 22, 2016 Accepted: May 23, 2016 Published: May 30, 2016 ABSTRACT Hexokinase 2 (HK2) is a rate-determining enzyme in aerobic glycolysis, a process upregulated in tumor cells. HK2 expression is controlled by various transcription factors and epigenetic alterations and is heterogeneous in hepatocellular carcinomas (HCCs), though the cause of this heterogeneity is not known. DNA methylation in the HK2 promoter CpG island ( HK2 -CGI) and its surrounding regions (shore and shelf) has not previously been evaluated, but may provide clues about the regulation of HK2 expression. Here, we compared HK2 promoter methylation in HCCs and adjacent non-cancerous liver tissues using a HumanMethylation450 BeadChip array. We found that, while the HK2 -CGI N-shore was hypomethylated, thereby enhancing HK2 expression, the HK2 -CGI was itself hypermethylated in some HCCs. This hypermethylation suppressed HK2 expression by inhibiting interactions between HIF-1α and a hypoxia response element (HRE) located at –234/–230. HCCs that were HK2 negative and had distinct promoter CGI methylation were denoted as having a HK2 -CGI methylation phenotype ( HK2 -CIMP), which was associated with poor clinical outcome. These findings indicate that HK2 -CGI N-shore hypomethylation and HK2 -CGI hypermethylation affect HK2 expression by influencing the interaction between HIF 1α and HRE. HK2 -CGI hypermethylation induces HK2 -CIMP and could represent a prognostic biomarker for HCC.

Background Long-term cigarette smoking induces sensitization of incentive salience and conditioning of contextual cues which involves brain function alteration across multiple regions. Understanding how nicotine affects hub-based functional connectivities involved in affective and cognitive function can help us determine the treatment strategy for nicotine dependence. Method Functional MRI was conducted on 30 smokers and 30 non-smokers while mentally simulating neutral and smoking hand movements. Smoking cue and mental simulation processing-related changes in functional connectivity strengths of the subcallosal and posterior cingulate cortex (SCC and PCC) with major brain network nodes were examined. Results Compared to non-smokers, smokers showed cue-induced SCC functional connectivities which were enhanced with the intraparietal sulcus and reduced with the medial prefrontal cortex. The PCC activation and functional connectivity enhancements with the anterior insula cortex and rostro-lateral prefrontal cortex was found during smoking mental simulation. The PCC-lateral prefrontal cortex functional connectivity correlated with nicotine dependence severity. Conclusion The present results demonstrate that smokers can be identified by cue-induced SCC functional connectivity strength decline and increment in the default mode and dorsal attention network nodes. However, nicotine dependence was associated with smoking mental simulation-related PCC-lateral prefrontal cortex functional connectivity strength, suggesting that the development of nicotine dependence may depend on the strength of coupling between the default mode network and the central executive network at the cognitive level.

Objectives To evaluate the clinical implications of lymph node (LN) density on 18F-FDG PET/CT for mediastinal LN characterization in non-small cell lung cancer (NSCLC).

509 Objectives Left atrial fibrosis is a prominent feature in patients with atrial fibrillation (AF) and the degree of fibrosis as measured by delayed enhancement magnetic resonance imaging (MRI) has prognostic and therapeutic implications. However, MRI imaging of the thin-walled left atrium can be technically challenging and is prone to artifacts. FDG-PET has the potential to assess left atrial fibrosis as the absence of metabolism. In this study, we evaluated the feasibility of assessing left atrial fibrosis using FDG-PET and compare the degree of fibrosis in clinically-referred patients in sinus rhythm and AF. Methods 28 patients in sinus rhythm and 31 with paroxysmal AF were randomly selected from patients undergoing FDG-PET myocardial viability assessment from 2013 to 2015. Gated rest Rb-82 and F-18 FDG-PET imaging with CT attenuation correction were performed. Images were manually segmented to isolate the left atrium. Volumetric assessment was performed over all vertical long axis, horizontal long axis, and short axis images to visually score extent of FDG uptake on a semi-quantitative basis. The extent of FDG uptake defects was defined as small or normal ( 50%). Results Images for the classification of FDG uptake defects are shown in Figure 1. In patients in sinus rhythm, 8 (28.6%) patients were classified as having small or normal FDG uptake defects, 3 (10.7%) with medium, 6 (21.4%) with large, and 11 (39.4%) with extensive. In patients with paroxysmal AF, 5 (16.1%) had small or normal FDG uptake defects, 6 (19.4%) had medium, 3 (9.7%) had large, and 17 (54.8%) had extensive defects. Overall, patients with paroxysmal AF had more FDG uptake defects than those in sinus rhythm. (P Conclusions FDG-PET appears capable of assessing left atrial myopathy in patients with and without AF. Patients with AF have a higher burden of left atrial fibrosis compared to those in sinus rhythm. Further research is required to determine if FDG-PET can be used to identify those at risk for developing AF or predict therapeutic response to ablation.

Hepatocellular carcinoma (HCC) is one of the most lethal cancers worldwide; however, the genetic mechanisms underlying its pathogenesis are incompletely understood. Genetically engineered mouse (GEM) models of HCC have been developed to elucidate the role of individual cancer-related genes in hepatocarcinogenesis. However, the expensive and time-consuming processes related to generating a GEM model discourage the development of diverse genotype models. Recently, a simple and inexpensive liver-specific transgenic approach was developed, in which a hydrodynamics-based transfection (HT) method was coupled with the Sleeping Beauty transposase system. Various HT models in which different oncogenic pathways are activated and/or tumor-suppressing pathways inactivated have been developed in recent years. The applicability of HT models in liver cancer research is expected to broaden and ultimately elucidate the cooperation between oncogenic signaling pathways and aid in designing molecular therapy to target altered pathways.

Purpose: As Parkinson’s disease (PD) can be considered a network abnormality, the effects of deep brain stimulation (DBS) need to be investigated in the aspect of networks. This study aimed to examine how DBS of the bilateral subthalamic nucleus (STN) affects the motor networks of patients with idiopathic PD during motor performance and to show the feasibility of the network analysis using crosssectional positron emission tomography (PET) images in DBS studies. Materials and Methods: We obtained [ 15 O]H2O PET images from ten patients with PD during a sequential finger-to-thumb opposition task and during the resting state, with DBS-On and DBS-Off at STN. To identify the alteration of motor networks in PD and their changes due to STN-DBS, we applied independent component analysis (ICA) to all the cross-sectional PET images. We analysed the strength of each component according to DBS effects, task effects and interaction effects. Results: ICA blindly decomposed components of functionally associated distributed clusters, which were comparable to the results of univariate statistical parametric mapping. ICA further revealed that STN-DBS modifies usage-strengths of components corresponding to the basal ganglia-thalamo-cortical circuits in PD patients by increasing the hypoactive basal ganglia and by suppressing the hyperactive cortical motor areas, ventrolateral thalamus and cerebellum. Conclusion: Our results suggest that STN-DBS may affect not only the abnormal local activity, but also alter brain networks in patients with PD. This study also demonstrated the usefulness of ICA for cross-sectional PET data to reveal network modifications due to DBS, which was not observable using the subtraction method.

Dysregulation of cellular energy metabolism is closely linked to cancer development and progression. Calorie or glucose restriction (CR or GR) inhibits energy-dependent pathways, including IGF-1/PI3K/Akt/mTOR, in cancer cells. However, alterations in proton dynamics and reversal of the pH gradient across the cell membrane, which results in intracellular alkalinization and extracellular acidification in cancer tissues, have emerged as important etiopathogenic factors. We measured glucose, lactate, and ATP production after GR, plant-derived CR-mimetic curcumin treatment, and curcumin plus GR in human hepatoma cells. Intracellular pH regulatory effects, in particular, protein&ndash, protein interactions within mTOR complex-1 and its structural change, were investigated. Curcumin treatment or GR mildly inhibited Na+/H+ exchanger-1 (NHE1). vATPase, monocarboxylate transporter (MCT)-1, and MCT4 level. Combination treatment with curcumin and GR further enhanced the inhibitory effects on these transporters and proton-extruding enzymes, with intracellular pH reduction. ATP and lactate production decreased according to pH change. Modeling of mTOR protein revealed structural changes upon treatments, and curcumin plus GR decreased binding of Raptor and G&beta, L to mTOR, as well as of Rag A and Rag B to Raptor. Consequently, 4EBP1 phosphorylation was decreased and cell migration and proliferation were inhibited in a pH-dependent manner. Autophagy was increased by curcumin plus GR. In conclusion, curcumin treatment combined with GR may be a useful supportive approach for preventing intracellular alkalinization and cancer progression.

Manifestation of the functionalities from the structural brain network is becoming increasingly important to understand a brain disease. With the aim of investigating the differential structure-function couplings according to network systems, we investigated the structural and functional brain networks of patients with spastic diplegic cerebral palsy with periventricular leukomalacia compared to healthy controls. The structural and functional networks of the whole brain and motor system, constructed using deterministic and probabilistic tractography of diffusion tensor magnetic resonance images and Pearson and partial correlation analyses of resting-state functional magnetic resonance images, showed differential embedding of functional networks in the structural networks in patients. In the whole-brain network of patients, significantly reduced global network efficiency compared to healthy controls were found in the structural networks but not in the functional networks, resulting in reduced structural-functional coupling. On the contrary, the motor network of patients had a significantly lower functional network efficiency over the intact structural network and a lower structure-function coupling than the control group. This reduced coupling but reverse directionality in the whole-brain and motor networks of patients was prominent particularly between the probabilistic structural and partial correlation-based functional networks. Intact (or less deficient) functional network over impaired structural networks of the whole brain and highly impaired functional network topology over the intact structural motor network might subserve relatively preserved cognitions and impaired motor functions in cerebral palsy. This study suggests that the structure-function relationship, evaluated specifically using sparse functional connectivity, may reveal important clues to functional reorganization in cerebral palsy. Hum Brain Mapp 38:5292-5306, 2017. © 2017 Wiley Periodicals, Inc.

Recent developments from science and medical science show a growing interest in the anti-inflammatory activity of natural materials. Inflammation is the body’s physiologic response to injurious stimulation and is known to be mediated by various pro-inflammatory cytokines (e.g. TNF-α, IL-1β, IL-6 etc) and iNOS (inducible nitric oxide synthase). Quantum energy living body (QELBY) powder is a fusion of a special ceramic powder with natural clay mineral classified as quantum energy radiating material (QERM). The powder, composed mostly of silicon dioxide, is known to radiate reductive radiant energy. This study was designed to evaluate the anti-inflammatory activities of QELBY powder on RAW 264.7 mouse macrophage cells. QELBY powder was mixed with DMEM media and was allowed to stand for 48 hours. Afterwards, the supernatant was taken and diluted to various concentrations (0,5,10,20,40 μg/ml) prior to use. CCK-8 assay was done to determine the effects on cell viability. In addition, NO assay performed to elucidate the effect of QELBY on the NO production of LPS-stimulated macrophages. Lastly, RT-PCR and Western blot analysis for the detection of the mRNA and protein expressions, respectively, of proinflammatory cytokines and iNOS was made. Results demonstrated that QELBY powder causes both an increase in cell proliferation and a concentration-dependent decrease in NO production. Moreover, the mRNA and protein expressions of pro-inflammatory cytokines and iNOS were also inhibited. Taken together, these show that QELBY powder has anti-inflammatory activity and could therefore be used further in the development of materials that induce such kinds of benefits.

This study aimed to assess the prognostic value of (18)F-FDG uptake in hepatocellular carcinoma (HCC) patients who had transarterial chemoembolization (TACE) or concurrent intraarterial chemotherapy with external-beam radiotherapy (CCRT) and to compare the prognosis between patients treated with TACE and those with CCRT according to (18)F-FDG uptake.Two hundred fourteen intermediate-to-advanced-stage HCC patients without extrahepatic metastasis who underwent staging (18)F-FDG PET/CT before TACE (153 patients) or CCRT (61 patients) were recruited from 7 hospitals. Progression-free survival (PFS) and overall survival (OS) were compared using an optimal cutoff value for tumor-to-normal liver uptake ratio (TLR). Further, PFS and OS were compared according to treatment modalities (TACE vs. CCRT) using the same TLR cutoff value.On multivariate analysis, age and TLR were independent prognostic factors for PFS (P0.050). For OS, Child-Pugh classification and TLR were independent prognostic factors (P0.050). When the TLR was greater than 2.0, patients treated with CCRT showed significantly better PFS and OS than those treated with TACE after adjusting for tumor size and number (P= 0.014, for all). In contrast, there was no significant difference in PFS and OS between patients treated with TACE or CCRT when the TLR was 2.0 or less.(18)F-FDG uptake was an independent prognostic factor for PFS and OS in HCC patients treated with TACE or CCRT. Especially, in HCCs with high (18)F-FDG uptake, patients treated with CCRT showed better survival than those treated with TACE. (18)F-FDG PET/CT may help determine the treatment modality for intermediate-to-advanced-stage HCCs.

Purpose This study aimed to evaluate the prognostic value of pretreatment 18 F-fluorodeoxyglucose (FDG) positron emission tomography (PET) in pediatric neuroblastoma patients. Methods The study included 50 pediatric neuroblastoma patients who underwent diagnostic work-up FDG PET before any treatment. The maximum standardized uptake value (SUV max ) of the primary tumor lesion ( P max ), the SUV max of all the tumor lesions, including the primary tumor lesion and metastatic lesions ( T max ), and the uptake ratio of T max to mean SUV of normal liver tissue ( T max / L mean ) were calculated and tested as prognostic factors. Results Of the 50 patients, 15 (30.0%) experienced disease progression and 21 (42.0%) died during the follow-up period. On univariate analysis, the histopathology, tumor stage, bone marrow involvement, serum levels of lactate dehydrogenase (LDH), neuron-specific enolase, and ferritin, primary tumor size, P max , T max , and T max / L mean were significant prognostic factors for disease progression-free survival (PFS), whereas the tumor stage, serum level of LDH, T max , and T max / L mean were determined to be significant for predicting overall survival (OS). On multivariate analysis, the histopathology and serum level of LDH were independent prognostic factors for PFS, and only the T max / L mean was an independent prognostic factor for OS. The 2-year PFS and OS rates were over 80.0% in patients with low FDG uptake, meanwhile, patients with high FDG uptake showed the 2-year PFS of less than 30.0% and OS of less than 55.0%. Conclusion FDG PET was an independent prognostic factor for OS in neuroblastoma patients. FDG PET can provide effective information on the prognosis for neuroblastoma patients.

This study evaluated the predictive value of 18F-FDG PET for distant metastasis-free survival and peritoneal recurrence-free survival as well as recurrence-free survival and overall survival after curative surgical resection in patients with advanced gastric cancer (AGC).Two hundred seventy-nine patients with AGC who underwent preoperative 18F-FDG PET and subsequent curative surgical resection were included. The tumor-to-normal liver uptake ratio (TLR) of cancer lesions was measured, and the prognostic significance of TLR and tumor factors for distant metastasis-free survival, peritoneal recurrence-free survival, recurrence-free survival, and overall survival was assessed.The 5-y recurrence-free survival, peritoneal recurrence-free survival, distant metastasis-free survival, and overall survival rates were 46.9%, 68.5%, 76.0%, and 58.1%, respectively. Depth of tumor invasion, lymph node metastasis, lymphovascular invasion, and TLR were independent prognostic factors for both recurrence-free survival and overall survival (P0.05). For distant metastasis-free survival, lymphovascular invasion and TLR were independent risk factors (P0.05). In patients with a TLR of 2.0 or less, the 5-y distant metastasis-free survival rate was 95.5%; in patients with a TLR greater than 2.0, the 5-y distant metastasis-free survival rate was 68.8%. For peritoneal recurrence-free survival, TLR showed no statistical significance (P=0.7) whereas pT stage, lymph node metastasis, Lauren classification, and Bormann type were independent prognostic factors (P0.05).18F-FDG uptake of AGC is an independent prognostic factor for distant metastasis-free survival, recurrence-free survival, and overall survival. The possibility of distant metastasis during follow-up should be considered in patients with high 18F-FDG uptake.

To evaluate the clinical implications of lymph node (LN) density onOne hundred and fifty-two patients with 271 mediastinal LNs who underwent PET/CT and endobronchial ultrasound-guided transbronchial needle aspiration for staging were enrolled. Maximum standardized uptake value (SUVmax), short axis diameter, LN-to-primary cancer ratio of SUVmax, and median Hounsfield unit (HU) based on CT histogram were correlated to histopathology.Of 271 nodes, 162 (59.8 %) were malignant. SUVmax, short axis diameter, and LPR of malignant LNs were higher than those of benign nodes. Among malignant LNs, 71.0 % had median HU between 25 and 45, while 78.9 % of benign LNs had values25 HU or45 HU. Using a cutoff value of 4.0, SUVmax showed the highest diagnostic ability for detecting malignant LNs with a specificity of 94.5 %, but showing a sensitivity of 70.4 %. Using additional density criteria (median HU 25-45) in LNs with 2.0SUVmax ≤4.0, the sensitivity increased to 88.3 % with the specificity of 82.6 %.LN density is useful for the characterization of LNs with mild• SUVmax showed the highest diagnostic ability for detecting malignant LNs. • LN density was useful in characterization of LNs with mild FDG uptake. • SUVmax and LN density together could stratify the risk of LN metastasis.

Hepatocellular carcinoma (HCC) is one of the most lethal cancers worldwide; however, the genetic mechanisms underlying its pathogenesis are incompletely understood. Genetically engineered mouse (GEM) models of HCC have been developed to elucidate the role of individual cancer-related genes in hepatocarcinogenesis. However, the expensive and time-consuming processes related to generating a GEM model discourage the development of diverse genotype models. Recently, a simple and inexpensive liver-specific transgenic approach was developed, in which a hydrodynamics-based transfection (HT) method was coupled with the Sleeping Beauty transposase system. Various HT models in which different oncogenic pathways are activated and/or tumor-suppressing pathways inactivated have been developed in recent years. The applicability of HT models in liver cancer research is expected to broaden and ultimately elucidate the cooperation between oncogenic signaling pathways and aid in designing molecular therapy to target altered pathways.

Calorie restriction or a low-carbohydrate diet (LCD) can increase life span in normal cells while inhibiting carcinogenesis. Various phytochemicals also have calorie restriction-mimetic anticancer properties. We investigated whether an isocaloric carbohydrate-restriction diet and AMP-activated protein kinase (AMPK)-activating phytochemicals induce synergic tumor suppression. We used a mixture of AMPK-activating phytochemical extracts including curcumin, quercetin, catechins, and resveratrol. Survival analysis was carried out in a B16F10 melanoma model fed a control diet (62.14% kcal carbohydrate, 24.65% kcal protein and 13.2% kcal fat), a control diet with multiple phytochemicals (MP), LCD (16.5, 55.2, and 28.3% kcal, respectively), LCD with multiple phytochemicals (LCDmp), a moderate-carbohydrate diet (MCD, 31.9, 62.4, and 5.7% kcal, respectively), or MCD with phytochemicals (MCDmp). Compared with the control group, MP, LCD, or MCD intervention did not produce survival benefit, but LCDmp (22.80±1.58 vs. 28.00±1.64 days, P=0.040) and MCDmp (23.80±1.08 vs. 30.13±2.29 days, P=0.008) increased the median survival time significantly. Suppression of the IGF-1R/PI3K/Akt/mTOR signaling, activation of the AMPK/SIRT1/LKB1pathway, and NF-κB suppression were the critical tumor-suppression mechanisms. In addition, SIRT1 suppressed proliferation of the B16F10 and A375SM cells under a low-glucose condition. Alterations in histone methylation within Pten and FoxO3a were observed after the MCDmp intervention. In the transgenic liver cancer model developed by hydrodynamic transfection of the HrasG12V and shp53, MCDmp and LCDmp interventions induced significant cancer-prevention effects. Microarray analysis showed that PPARα increased with decreased IL-6 and NF-κB within the hepatocytes after an MCDmp intervention. In conclusion, an isocaloric carbohydrate-restriction diet and natural AMPK-activating agents induce synergistic anticancer effects. SIRT1 acts as a tumor suppressor under a low-glucose condition.