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1.
Dalton Trans ; 51(43): 16620-16627, 2022 Nov 08.
Article in English | MEDLINE | ID: mdl-36268818

ABSTRACT

Zinc-glutarate (ZnGA) is a promising catalyst that can form polymers from CO2 and epoxides, thereby contributing to the development of CO2 utilization technologies and future sustainability. One of the obstacles to commercializing ZnGA in polymer industries is its low catalytic activity. In this study, we introduced activated two-dimensional (2D) ZnGA to improve its catalytic activity in polymerization. The morphology-controlled 2D ZnGA was treated with H3Co(CN)6, and a porous granular-type Co-modified ZnGA (Co-ZnGA) was prepared. The morphology of 2D ZnGA is a prerequisite for the activation by H3Co(CN)6. The catalytic properties of Co-ZnGA were evaluated by copolymerization of various epoxides and CO2, and exhibited catalytic activity of 855, 1540, 1190, and 148 g g-cat-1 with propylene oxide, 1,2-epoxyhexane, 1,2-epoxybutane, and styrene oxide, respectively. This study provided a new strategy using 2D ZnGA instead of conventional ZnGA for increasing the catalytic activity in CO2 polymerization.

2.
Article in English | MEDLINE | ID: mdl-31647945

ABSTRACT

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.


Subject(s)
Gyrus Cinguli/physiopathology , Imagination/physiology , Parietal Lobe/physiopathology , Prefrontal Cortex/physiopathology , Smokers/psychology , Smoking/psychology , Adult , Aged , Case-Control Studies , Cues , Humans , Magnetic Resonance Imaging , Male , Middle Aged , Neural Pathways/physiopathology , Tobacco Use Disorder/physiopathology , Young Adult
3.
Int J Mol Sci ; 20(10)2019 May 14.
Article in English | MEDLINE | ID: mdl-31091659

ABSTRACT

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-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 GßL 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.


Subject(s)
Antineoplastic Agents/pharmacology , Carcinoma, Hepatocellular/metabolism , Curcumin/pharmacology , Glucose/deficiency , Liver Neoplasms/metabolism , Alkalies/metabolism , Cell Line , Cell Proliferation/drug effects , Glucose/metabolism , Hep G2 Cells , Humans , Monocarboxylic Acid Transporters/metabolism , Regulatory-Associated Protein of mTOR/metabolism , Vacuolar Proton-Translocating ATPases/metabolism
4.
Support Care Cancer ; 27(5): 1747-1754, 2019 May.
Article in English | MEDLINE | ID: mdl-30145738

ABSTRACT

PURPOSE: 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. METHODS: 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. RESULTS: 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. CONCLUSION: 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.


Subject(s)
Breast Neoplasms, Male/physiopathology , Breast Neoplasms, Male/rehabilitation , Breast Neoplasms/physiopathology , Breast Neoplasms/rehabilitation , Exercise Therapy/methods , Actigraphy , Adult , Breast Neoplasms/pathology , Breast Neoplasms/therapy , Breast Neoplasms, Male/pathology , Breast Neoplasms, Male/therapy , Exercise , Female , Humans , Male , Middle Aged , Neoplasm Staging , Prospective Studies , Quality of Life , Smartphone
5.
Hum Brain Mapp ; 38(10): 5292-5306, 2017 10.
Article in English | MEDLINE | ID: mdl-28731515

ABSTRACT

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.


Subject(s)
Brain/diagnostic imaging , Brain/physiopathology , Cerebral Palsy/diagnostic imaging , Cerebral Palsy/physiopathology , Adolescent , Adult , Brain/pathology , Brain Mapping , Cerebral Palsy/pathology , Child , Diffusion Tensor Imaging , Female , Humans , Magnetic Resonance Imaging , Male , Neural Pathways/diagnostic imaging , Neural Pathways/pathology , Neural Pathways/physiopathology , Rest , Young Adult
6.
Breast Cancer Res Treat ; 161(3): 443-452, 2017 02.
Article in English | MEDLINE | ID: mdl-27933450

ABSTRACT

PURPOSE: 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). METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.


Subject(s)
Breast Neoplasms/therapy , Exercise Therapy , Actigraphy , Adult , Breast Neoplasms/diagnosis , Combined Modality Therapy , Comorbidity , Exercise , Exercise Therapy/instrumentation , Exercise Therapy/methods , Female , Humans , Middle Aged , Neoplasm Staging , Physical Fitness , Quality of Life , Self Report , Telemedicine/instrumentation , Telemedicine/methods , Treatment Outcome
7.
Oncotarget ; 7(27): 41798-41810, 2016 Jul 05.
Article in English | MEDLINE | ID: mdl-27260001

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 HK2negative 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.


Subject(s)
Carcinoma, Hepatocellular/genetics , CpG Islands/genetics , DNA Methylation , Hexokinase/genetics , Liver Neoplasms/genetics , Promoter Regions, Genetic , Biomarkers, Tumor/genetics , Carcinoma, Hepatocellular/metabolism , Carcinoma, Hepatocellular/pathology , Cell Line, Tumor , Disease Progression , Gene Expression Regulation, Neoplastic , Hexokinase/metabolism , Humans , Hypoxia-Inducible Factor 1, alpha Subunit/genetics , Hypoxia-Inducible Factor 1, alpha Subunit/metabolism , Liver/metabolism , Liver Neoplasms/metabolism , Liver Neoplasms/pathology , Prognosis
8.
Eur Radiol ; 26(12): 4515-4523, 2016 Dec.
Article in English | MEDLINE | ID: mdl-26943133

ABSTRACT

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). METHODS: One 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. RESULTS: 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 values <25 HU or >45 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 2.0< SUVmax ≤4.0, the sensitivity increased to 88.3 % with the specificity of 82.6 %. CONCLUSIONS: LN density is useful for the characterization of LNs with mild 18F-FDG uptake. The risk of mediastinal LN metastasis in NSCLC patients could be further stratified using both 18F-FDG uptake and LN density. KEY POINTS: • 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.


Subject(s)
Carcinoma, Non-Small-Cell Lung/diagnostic imaging , Cone-Beam Computed Tomography/methods , Fluorodeoxyglucose F18/metabolism , Lung Neoplasms/diagnostic imaging , Lymph Nodes/diagnostic imaging , Neoplasm Staging/methods , Positron Emission Tomography Computed Tomography/methods , Adult , Aged , Aged, 80 and over , Biopsy, Fine-Needle , Carcinoma, Non-Small-Cell Lung/pathology , Female , Humans , Lung Neoplasms/pathology , Lymph Nodes/pathology , Lymphatic Metastasis/pathology , Male , Mediastinum/pathology , Middle Aged , Multimodal Imaging , Radiopharmaceuticals , Retrospective Studies , Sensitivity and Specificity , Tomography, X-Ray Computed
9.
J Nucl Med ; 57(4): 509-16, 2016 04.
Article in English | MEDLINE | ID: mdl-26742711

ABSTRACT

UNLABELLED: 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. METHODS: 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. RESULTS: On multivariate analysis, age and TLR were independent prognostic factors for PFS (P< 0.050). For OS, Child-Pugh classification and TLR were independent prognostic factors (P< 0.050). 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. CONCLUSION: (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.


Subject(s)
Carcinoma, Hepatocellular/metabolism , Carcinoma, Hepatocellular/therapy , Fluorodeoxyglucose F18/metabolism , Liver Neoplasms/metabolism , Liver Neoplasms/therapy , Radiopharmaceuticals/metabolism , Adult , Aged , Aged, 80 and over , Aging/metabolism , Carcinoma, Hepatocellular/radiotherapy , Chemoradiotherapy , Cohort Studies , Disease-Free Survival , Embolization, Therapeutic , Female , Humans , Image Processing, Computer-Assisted , Liver/metabolism , Liver Neoplasms/radiotherapy , Male , Middle Aged , Neoplasm Metastasis , Predictive Value of Tests , Prognosis , Retrospective Studies , Survival Analysis
10.
Eur J Cancer Prev ; 25(1): 54-64, 2016 Jan.
Article in English | MEDLINE | ID: mdl-25747515

ABSTRACT

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.


Subject(s)
AMP-Activated Protein Kinases/metabolism , Dietary Carbohydrates/administration & dosage , Dietary Supplements , Liver Neoplasms, Experimental/prevention & control , Melanoma, Experimental/prevention & control , Phytochemicals/administration & dosage , Sirtuin 1/metabolism , Animals , Biomarkers, Tumor/genetics , Biomarkers, Tumor/metabolism , Cell Proliferation/drug effects , Chromatin Immunoprecipitation , Dietary Carbohydrates/pharmacology , Drug Synergism , Liver Neoplasms, Experimental/metabolism , Liver Neoplasms, Experimental/mortality , Liver Neoplasms, Experimental/pathology , Male , Melanoma, Experimental/metabolism , Melanoma, Experimental/mortality , Melanoma, Experimental/pathology , Mice , Mice, Inbred C57BL , Mice, Transgenic , Oligonucleotide Array Sequence Analysis , Phosphorylation , Phytochemicals/pharmacokinetics , Signal Transduction , Sirtuin 1/genetics , Survival Rate , Tumor Cells, Cultured
11.
Int J Cancer ; 138(7): 1601-8, 2016 Apr 01.
Article in English | MEDLINE | ID: mdl-26220477

ABSTRACT

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.


Subject(s)
Carcinoma, Hepatocellular/genetics , Liver Neoplasms, Experimental/genetics , Transfection/methods , Animals , Antineoplastic Agents/pharmacology , Carcinoma, Hepatocellular/drug therapy , Hydrodynamics , Liver Neoplasms, Experimental/drug therapy , Mice , Mice, Transgenic , Molecular Targeted Therapy
12.
Eur J Radiol ; 84(12): 2633-9, 2015 Dec.
Article in English | MEDLINE | ID: mdl-26462795

ABSTRACT

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.


Subject(s)
Fluorodeoxyglucose F18 , Neuroblastoma/diagnostic imaging , Positron-Emission Tomography , Radiopharmaceuticals , Child, Preschool , Disease Progression , Disease-Free Survival , Female , Follow-Up Studies , Humans , Male , Prognosis , Retrospective Studies , Survival Rate
13.
J Nucl Med ; 56(10): 1494-500, 2015 Oct.
Article in English | MEDLINE | ID: mdl-26251414

ABSTRACT

UNLABELLED: 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). METHODS: 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. RESULTS: 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 (P<0.05). For distant metastasis-free survival, lymphovascular invasion and TLR were independent risk factors (P<0.05). 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 (P<0.05). CONCLUSION: 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.


Subject(s)
Positron-Emission Tomography/methods , Stomach Neoplasms/diagnostic imaging , Stomach Neoplasms/surgery , Adult , Aged , Aged, 80 and over , Disease-Free Survival , Female , Fluorodeoxyglucose F18 , Gastrectomy , Humans , Lymphatic Metastasis , Male , Middle Aged , Neoadjuvant Therapy , Neoplasm Recurrence, Local , Predictive Value of Tests , Radiopharmaceuticals , Retrospective Studies , Young Adult
14.
Yonsei Med J ; 56(5): 1296-306, 2015 09.
Article in English | MEDLINE | ID: mdl-26256972

ABSTRACT

PURPOSE: Dickkopf-1 (DKK-1) is a Wnt/ß-catenin signaling pathway inhibitor. We investigated whether DKK-1 is related to progression in hepatocellular carcinoma (HCC) cells and HCC patients. MATERIALS AND METHODS: In vitro reverse-transcription polymerase chain reaction (RT-PCR), wound healing assays, invasion assays, and ELISAs of patient serum samples were employed. The diagnostic accuracy of the serum DKK-1 ELISA was assessed using receiver operating characteristic (ROC) curves and area under ROC (AUC) analyses. RESULTS: RT-PCR showed high DKK-1 expression in Hep3B and low in 293 cells. Similarly, the secreted DKK-1 concentration in the culture media was high in Hep3B and low in 293 cells. Wound healing and invasion assays using 293, Huh7, and Hep3B cells showed that DKK-1 overexpression promoted cell migration and invasion, whereas DKK-1 knock-down inhibited them. When serum DKK-1 levels were assessed in 370 participants (217 with HCC and 153 without), it was significantly higher in HCC patients than in control groups (median 1.48 ng/mL vs. 0.90 ng/mL, p<0.001). The optimum DKK-1 cutoff level was 1.01 ng/mL (AUC=0.829; sensitivity 90.7%; specificity 62.0%). Although DKK-1 had a higher AUC than alpha-fetoprotein (AFP) and des-gamma-carboxy prothrombin (DCP) (AUC=0.829 vs. 0.794 and 0.815, respectively), they were statistically similar (all p>0.05). When three biomarkers were combined (DKK-1 plus AFP plus DCP), they showed significantly higher AUC (AUC=0.952) than single marker, DKK-1 plus AFP, or DKK-1 plus DCP (all p<0.001). CONCLUSION: DKK-1 might be a key regulator in HCC progression and a potential therapeutic target in HCC. Serum DKK-1 could complement the diagnostic accuracy of AFP and DCP.


Subject(s)
Carcinoma, Hepatocellular/diagnosis , Intercellular Signaling Peptides and Proteins/blood , Intercellular Signaling Peptides and Proteins/metabolism , Liver Neoplasms/diagnosis , Reverse Transcriptase Polymerase Chain Reaction/methods , Area Under Curve , Biomarkers/blood , Biomarkers/metabolism , Biomarkers, Tumor/blood , Carcinoma, Hepatocellular/blood , Enzyme-Linked Immunosorbent Assay , Female , Humans , Liver Neoplasms/blood , Male , Middle Aged , Protein Precursors/blood , Protein Precursors/metabolism , Prothrombin/metabolism , ROC Curve , Sensitivity and Specificity , alpha-Fetoproteins/analysis , alpha-Fetoproteins/metabolism
15.
Yonsei Med J ; 56(3): 726-36, 2015 May.
Article in English | MEDLINE | ID: mdl-25837179

ABSTRACT

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 cross-sectional positron emission tomography (PET) images in DBS studies. MATERIALS AND METHODS: We obtained [¹5O]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.


Subject(s)
Brain/diagnostic imaging , Deep Brain Stimulation/methods , Functional Laterality/physiology , Parkinson Disease/therapy , Subthalamic Nucleus/physiopathology , Aged , Cross-Sectional Studies , Female , Humans , Male , Middle Aged , Parkinson Disease/diagnostic imaging , Positron-Emission Tomography , Severity of Illness Index
16.
J Comput Assist Tomogr ; 39(3): 349-55, 2015.
Article in English | MEDLINE | ID: mdl-25700225

ABSTRACT

OBJECTIVES: We aimed to assess the usefulness of F-fluorodeoxyglucose (F-FDG) positron emission tomography-computed tomography (PET/CT) in the monitoring of adhesive capsulitis (AC), a joint problem commonly observed in the upper arm after breast cancer treatment. METHODS: This retrospective study included 230 patients who underwent F-FDG PET/CT before and after modified radical mastectomy of whom 22 patients were identified as having AC and categorized into 2 groups: with severely and mildly limited range of motion in the shoulder joint. The F-FDG uptake patterns and mean and maximum standardized uptake values (SUVs) were analyzed. RESULTS: The overall incidence of AC after MRM was 9.57%. The SUVs were significantly higher in patients with severely limited range of motion compared with the other group. There was no association between the SUV and radiotherapy. The F-FDG uptake pattern differed between the groups. CONCLUSIONS: F-fluorodeoxyglucose PET/CT is useful in evaluating AC after breast cancer treatment.


Subject(s)
Breast Neoplasms/surgery , Bursitis/diagnosis , Bursitis/etiology , Fluorodeoxyglucose F18 , Mastectomy, Radical/adverse effects , Positron-Emission Tomography/methods , Tomography, X-Ray Computed/methods , Breast Neoplasms/complications , Breast Neoplasms/diagnosis , Humans , Middle Aged , Multimodal Imaging/methods , Observer Variation , Radiopharmaceuticals , Reproducibility of Results , Sensitivity and Specificity , Treatment Outcome
17.
Ann Nucl Med ; 29(5): 400-8, 2015 Jun.
Article in English | MEDLINE | ID: mdl-25652647

ABSTRACT

OBJECTIVE: The aim of this study was to evaluate the prognostic value of metabolic tumor volume (MTV) on pre-treatment F-18 fluorodeoxyglucose (FDG) PET/CT in patients with hepatocellular carcinoma (HCC). METHODS: A total of 59 HCC patients who underwent FDG PET/CT before transarterial chemoembolization (TACE) or transarterial chemotherapy infusion (TACI) were retrospectively enrolled. The region of interest was drawn in the HCC and normal liver tissue. MTV2SD, defined as the sum of the voxels with higher standardized uptake values (SUV) than the SUV of the 97.5th percentile of voxels of the normal liver for each patient, was calculated using an intensity-volume histogram (IVH). The ratio of the maximum SUV of the tumor to the mean SUV of normal liver (T max/L mean) was also calculated. The prognostic significance of MTV2SD and Tmax/Lmean for progression-free survival (PFS) and overall survival (OS) was evaluated along with other clinical factors. RESULTS: The tumor number, Tmax/Lmean, and MTV2SD were significant prognostic factors affecting PFS (p < 0.05), whereas tumor number, serum alpha-fetoprotein level, tumor stage, portal vein thrombosis, Tmax/Lmean, and MTV2SD were significant prognostic factors for OS (p < 0.05). In multivariate analysis, the tumor number and MTV2SD were independent prognostic factors for PFS (p < 0.05), whereas the independent prognostic factors for OS were tumor number, tumor stage, and MTV2SD (p < 0.05). The mean PFS and OS in patients with low MTV2SD (15.4 and 63.1 months, respectively) were significantly longer than those in patients with high MTV2SD (6.0 and 15.2 months, respectively; p = 0.005 and p < 0.0001, respectively). CONCLUSIONS: Metabolic tumor volume was an independent prognostic factor for PFS and OS in patients with HCC. Therefore, FDG PET/CT can provide valuable prognostic information for HCC patients who undergo TACE or TACI.


Subject(s)
Antineoplastic Agents/therapeutic use , Carcinoma, Hepatocellular/therapy , Liver Neoplasms/therapy , Liver/pathology , Tumor Burden , Adult , Aged , Aged, 80 and over , Carcinoma, Hepatocellular/diagnosis , Carcinoma, Hepatocellular/diagnostic imaging , Carcinoma, Hepatocellular/pathology , Chemoembolization, Therapeutic , Female , Fluorodeoxyglucose F18 , Humans , Liver/diagnostic imaging , Liver Neoplasms/diagnosis , Liver Neoplasms/diagnostic imaging , Liver Neoplasms/pathology , Male , Middle Aged , Multimodal Imaging , Neoplasm Staging , Positron-Emission Tomography/methods , Prognosis , Radiopharmaceuticals , Retrospective Studies , Tomography, X-Ray Computed/methods , Treatment Outcome
18.
Eur J Nucl Med Mol Imaging ; 42(6): 841-7, 2015 May.
Article in English | MEDLINE | ID: mdl-25216749

ABSTRACT

PURPOSE: The purpose of this study was to investigate the prognostic value of (18)F-fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT) in patients with ampullary adenocarcinoma (AAC) after curative surgical resection. METHODS: Fifty-two patients with AAC who had undergone (18)F-FDG PET/CT and subsequent curative resections were retrospectively enrolled. The maximum standardized uptake value (SUVmax) and tumor to background ratio (TBR) were measured on (18)F-FDG PET/CT in all patients. The prognostic significances of PET/CT parameters and clinicopathologic factors for recurrence-free survival (RFS) and overall survival (OS) were evaluated by univariate and multivariate analyses. RESULTS: Of the 52 patients, 19 (36.5%) experienced tumor recurrence during the follow-up period and 18 (35.8%) died. The 3-year RFS and OS were 62.3 and 61.5%, respectively. Preoperative CA19-9 level, tumor differentiation, presence of lymph node metastasis, SUVmax, and TBR were significant prognostic factors for both RFS and OS (p < 0.05) on univariate analyses, and patient age showed significance only for predicting RFS (p < 0.05). On multivariate analyses, SUVmax and TBR were independent prognostic factors for RFS, and tumor differentiation, SUVmax, and TBR were independent prognostic factors for OS. CONCLUSION: SUVmax and TBR on preoperative (18)F-FDG PET/CT are independent prognostic factors for predicting RFS and OS in patients with AAC; patients with high SUVmax (>4.80) or TBR (>1.75) had poor survival outcomes. The role of and indications for adjuvant therapy after curative resection of AAC are still unclear. (18)F-FDG uptake in the primary tumor could provide additive prognostic information for the decision-making process regarding adjuvant therapy.


Subject(s)
Adenocarcinoma/diagnostic imaging , Ear Neoplasms/diagnostic imaging , Fluorodeoxyglucose F18 , Positron-Emission Tomography , Radiopharmaceuticals , Adult , Aged , Aged, 80 and over , Female , Humans , Male , Middle Aged , Multimodal Imaging , Predictive Value of Tests , Preoperative Period , Prognosis , Tomography, X-Ray Computed
20.
Clin Nucl Med ; 40(2): 97-102, 2015 Feb.
Article in English | MEDLINE | ID: mdl-25546187

ABSTRACT

PURPOSE: This study aimed to evaluate the diagnostic accuracy of contrast-enhanced FDG PET/CT for unexpected ovarian lesions in patients with nongynecologic cancers. PATIENTS AND METHODS: The present retrospective study was approved by the hospital institutional review board. We enrolled 72 nongynecologic cancer patients (33 colorectal cancer, 20 breast cancer, and 19 gastric cancer) who showed unexpected ovarian lesions on contrast-enhanced FDG PET/CT and subsequently underwent surgical resection of the ovarian lesions. The SUVmax values of the ovarian lesions were compared according to the histopathological results, and the accuracy of PET/CT was evaluated. RESULTS: A total of 103 ovarian lesions were surgically resected from 72 patients (64 ovarian lesions were metastases, 21 were benign, and 18 were malignant primary ovarian cancer). SUVmax among the 3 groups were different (P < 0.0001). Using a cutoff SUVmax of 2.5, the sensitivity, specificity, and accuracy of PET/CT for detecting malignant ovarian lesions were 80.5%, 81.0%, and 80.6%, respectively. Detection rates of PET/CT for colorectal, breast, and gastric cancer metastases, as well as primary ovarian cancers were 91.4%, 83.3%, 47.8%, and 100.0%, respectively. Using contrast-enhanced CT findings with SUVmax, the sensitivity, specificity, and accuracy of contrast-enhanced FDG PET/CT were improved to 95.1%, 76.2%, and 91.3%, respectively (P = 0.003). CONCLUSIONS: Conventional FDG PET/CT showed moderate diagnostic accuracy for the detection of malignant ovarian lesions mainly due to low detection rate in gastric cancer metastases. The PET/CT detection rate of malignant ovarian lesions can be improved using contrast-enhanced CT findings with FDG uptake measurement.


Subject(s)
Breast Neoplasms/pathology , Colorectal Neoplasms/pathology , Fluorodeoxyglucose F18 , Ovarian Neoplasms/diagnostic imaging , Positron-Emission Tomography , Radiopharmaceuticals , Tomography, X-Ray Computed , Adult , Aged , Aged, 80 and over , Breast Neoplasms/diagnostic imaging , Case-Control Studies , Colorectal Neoplasms/diagnostic imaging , Contrast Media , Diagnosis, Differential , Female , Humans , Middle Aged , Multimodal Imaging , Ovarian Neoplasms/secondary , Retrospective Studies , Sensitivity and Specificity
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