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1.
J Ginseng Res ; 48(3): 245-252, 2024 May.
Article in English | MEDLINE | ID: mdl-38707644

ABSTRACT

Ginseng is a traditional herbal medicine used for prevention and treatment of various diseases as a tonic. Recent scientific cohort studies on life prolongation with ginseng consumption support this record, as those who consumed ginseng for more than 5 years had reduced mortality and cognitive decline compared to those who did not. Clinical studies have also shown that acute or long-term intake of ginseng total extract improves acute working memory performance or cognitive function in healthy individuals and those with subjective memory impairment (SMI), mild cognitive impairment (MCI), or early Alzheimer's disease (AD) dementia who are taking AD medication(s). Ginseng contains various components ranging from classical ginsenosides and polysaccharides to more recently described gintonin. However, it is unclear which ginseng component(s) might be the main candidate that contribute to memory or cognitive improvements or prevent cognitive decline in older individuals. This review describes recent clinical contributors to ginseng components in clinical tests and introduces emerging evidence that ginseng components could be novel candidates for cognitive improvement in older individuals, as ginseng components improve SMI cognition and exhibits add-on effects when co-administered with early AD dementia drugs. The mechanism behind the beneficial effects of ginseng components and how it improves cognition are presented. Additionally, this review shows how ginseng components can contribute to SMI, MCI, or early AD dementia when used as a supplementary food and/or medicine, and proposes a novel combination therapy of current AD medicines with ginseng component(s).

2.
Exp Mol Med ; 56(4): 904-921, 2024 Apr.
Article in English | MEDLINE | ID: mdl-38556548

ABSTRACT

Sarcopenia, the progressive decline in skeletal muscle mass and function, is observed in various conditions, including cancer and aging. The complex molecular biology of sarcopenia has posed challenges for the development of FDA-approved medications, which have mainly focused on dietary supplementation. Targeting a single gene may not be sufficient to address the broad range of processes involved in muscle loss. This study analyzed the gene expression signatures associated with cancer formation and 5-FU chemotherapy-induced muscle wasting. Our findings suggest that dimenhydrinate, a combination of 8-chlorotheophylline and diphenhydramine, is a potential therapeutic for sarcopenia. In vitro experiments demonstrated that dimenhydrinate promotes muscle progenitor cell proliferation through the phosphorylation of Nrf2 by 8-chlorotheophylline and promotes myotube formation through diphenhydramine-induced autophagy. Furthermore, in various in vivo sarcopenia models, dimenhydrinate induced rapid muscle tissue regeneration. It improved muscle regeneration in animals with Duchenne muscular dystrophy (DMD) and facilitated muscle and fat recovery in animals with chemotherapy-induced sarcopenia. As an FDA-approved drug, dimenhydrinate could be applied for sarcopenia treatment after a relatively short development period, providing hope for individuals suffering from this debilitating condition.


Subject(s)
Autophagy , Transcriptome , Animals , Autophagy/drug effects , Mice , Humans , Protein Biosynthesis/drug effects , Disease Models, Animal , Muscle, Skeletal/metabolism , Muscle, Skeletal/drug effects , Muscle, Skeletal/pathology , Gene Expression Profiling , Sarcopenia/drug therapy , Sarcopenia/metabolism , Sarcopenia/pathology , Muscular Dystrophy, Duchenne/drug therapy , Muscular Dystrophy, Duchenne/genetics , Muscular Dystrophy, Duchenne/metabolism , Muscular Dystrophy, Duchenne/pathology
3.
J Ginseng Res ; 47(6): 735-742, 2023 Nov.
Article in English | MEDLINE | ID: mdl-38107399

ABSTRACT

Background: Gintonin is a new material of ginseng that acts through the ginseng-derived lysophosphatidic acid (LPA) receptor ligand. The gintonin-enriched fraction (GEF) inhibits amyloid plaque accumulation in the cortex and hippocampus, improves cognitive dysfunction by increasing acetylcholine levels, and promoted hippocampal neurogenesis in an animal model of Alzheimer's disease. We evaluated the effect of the GEF on the cognitive performance of subjects with subjective memory impairment (SMI). Methods: In this eight-week, randomized, assessor- and participant-blinded, placebo-controlled study, participants with SMI were assigned to three groups receiving placebo, GEF 300 mg/day or GEF 600 mg/day. The Korean versions of the Alzheimer's Disease Assessment Scale (K-ADAS), Mini-Mental State Examination (K-MMSE), and Stroop color-word test (K-SCWT) were also evaluated along with the safety profiles. Results: One hundred thirty-six participants completed the study. After eight weeks, we analyzed intergroup differences in primary or secondary outcome score changes. When we compared the GEF group with the placebo group, we observed significant improvements in the K-ADAS and K-SCWT scores. The GEF group did not show a significant improvement in K-MMSE and BDI scores compared to the placebo group. No adverse events were observed in the gintonin and placebo groups for eight weeks. Conclusion: The GEF is safe and effective in improving subjective cognitive impairment related to both the K-ADAS and K-SCWT in this study. However, further large-scale and randomized controlled studies are warranted to secure other cognitive function tests besides the K-ADAS and K-SCWT, and to confirm the findings of the current study.

4.
Materials (Basel) ; 16(21)2023 Oct 26.
Article in English | MEDLINE | ID: mdl-37959477

ABSTRACT

The development of high-performance concrete using carbon nanotubes (CNTs), which is used in various industries owing to its excellent mechanical properties, has attracted much attention, leading to ongoing research in this area. However, when mixing CNTs into cement paste, there has been limited focus on the dispersibility, and, in most cases, aqueous dispersions of CNTs used in other industrial sectors are used. Because CNTs form the structures of bundles or aggregates owing to their high aspect ratio and van der Waals force between particles, the desired dispersibility cannot be obtained when mixing CNTs in powder form with other materials. Therefore, in this study, we examined the applicability of CNT aqueous dispersions using PC-based plasticizer used in concrete. Aqueous dispersions of CNT using PC-based surfactants are prepared and their properties are compared with those of a PVP-based aqueous dispersion. To analyze the mechanical properties, the compressive strength and flexural strength are measured on the 28th day. Then, the dispersibility and microstructure are analyzed using scanning electron microscopy image analysis, thermogravimetric analysis, and BET (Brunauer-Emmett-Teller) analysis. The analysis results show the enhancement of mechanical properties due to the mixing of the CNT dispersion, and the results confirm the applicability of the proposed CNT aqueous dispersions using PC-based surfactants.

5.
Radiat Res ; 198(2): 190-199, 2022 08 01.
Article in English | MEDLINE | ID: mdl-35930015

ABSTRACT

The effects of mild-temperature hyperthermia (MTH) and metformin, alone or in combination, on the efficacy of high-dose hypofractionated radiation against experimental tumors were investigated. FSaII fibrosarcoma grown subcutaneously in the hind legs of C3H mice was irradiated with a single 15 Gy dose using a 60Co irradiator. The radio frequency capacitive method was used to heat the tumors at 41.0°C for 30 min. Metformin was intraperitoneally (i.p.) administered daily to tumor-bearing mice at a dose of 150 mg/kg. The expression levels of hypoxia-inducible factor-1α (HIF-1α), vascular endothelial growth factor (VEGF), and programmed cell death-ligand 1 (PD-L1) were determined by immunohistochemical staining of the excised tumor tissues. The apoptosis of tumor cells in vivo was quantified by terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) staining and cleaved caspase-3 staining of the excised tumor tissues. Irradiation of tumors markedly increased the expression of HIF-1α, VEGF, and PD-L1, and MTH and metformin used either alone or in combination significantly abrogated the radiation-induced upregulation of these proteins. MTH and metformin alone or combined increased the radiation-induced apoptosis in tumor cells and enhanced the radiation-induced suppression of tumor growth. The findings indicated that the increased tumor response to 15 Gy irradiation by MTH and metformin alone or in combination was due, in part, to the abrogation of the radiation-induced upregulation of HIF-1α and its downstream targets VEGF and PD-L1.


Subject(s)
Fibrosarcoma , Hyperthermia, Induced , Metformin , Animals , B7-H1 Antigen , Fibrosarcoma/metabolism , Fibrosarcoma/therapy , Hypoxia-Inducible Factor 1, alpha Subunit , Metformin/pharmacology , Mice , Mice, Inbred C3H , Vascular Endothelial Growth Factor A
6.
Anticancer Res ; 42(2): 867-876, 2022 Feb.
Article in English | MEDLINE | ID: mdl-35093884

ABSTRACT

BACKGROUND/AIM: This study examined whether metformin can enhance the radiation response in a hepatocellular carcinoma (HCC) xenograft mice model and patient population. MATERIALS AND METHODS: Huh-7 human HCC-bearing xenograft mice were treated with gamma-ray, metformin, neutron therapy, and their combinations. Tumour growth and lung colonies were assessed. Overall, 145 patients who underwent radiotherapy for HCC were retrospectively analysed. RESULTS: The combinations of gamma-ray and metformin and neutron radiation and metformin inhibited tumour growth and metastatic lung nodule formation when compared to the monotherapy and gamma-ray groups, respectively. In patients who received radiotherapy for HCC, the overall survival rate was higher in the metformin-treated group than in the non-metformin group. CONCLUSION: Metformin inhibited tumour growth and metastasis in HCC by enhancing the radiation response in animal experiments. Additionally, metformin was also found to be associated with a higher survival outcome in patients with HCC.


Subject(s)
Carcinoma, Hepatocellular/drug therapy , Liver Neoplasms/drug therapy , Metformin/therapeutic use , Animals , Carcinoma, Hepatocellular/mortality , Carcinoma, Hepatocellular/pathology , Carcinoma, Hepatocellular/radiotherapy , Cell Line, Tumor , Chemotherapy, Adjuvant , Gamma Rays/therapeutic use , Humans , Liver Neoplasms/mortality , Liver Neoplasms/pathology , Liver Neoplasms/radiotherapy , Mice , Neutrons/therapeutic use , Retrospective Studies , Survival Rate , Treatment Outcome , Xenograft Model Antitumor Assays
7.
Integr Med Res ; 11(1): 100773, 2022 Mar.
Article in English | MEDLINE | ID: mdl-34504764

ABSTRACT

BACKGROUND: Gintonin inhibits ß-amyloid production, increases acetylcholine level in the brain, and promotes neurogenesis. We evaluated the efficacy of gintonin-enriched fraction (GEF) in improving the cognitive performance in subjective memory impairment. METHODS: In this 8-week, randomized, assessor and participant blinded, placebo-controlled study, participants with subjective memory impairment but preserved cognitive function (Korean Mini-Mental State Examination [K-MMSE] score ≥23) were assigned to GEF 300mg/day or placebo. K-MMSE, Korean versions of the Alzheimer's disease assessment scale, color-word stroop test (K-CWST), clinical dementia rating, and Beck depression inventory-II were evaluated along with the safety profiles. The primary outcome was set as the change in the K-MMSE. RESULTS: Seventy-six participants complete the study protocol. After 8 weeks, there was no inter-group difference in the primary or secondary outcome score changes. However, GEF group showed an improvement in the K-MMSE scores (P= 0.026), and in the number of correct answers in both word reading (P= 0.008) and color reading (P= 0.005) of K-CWST, although only the improvement in the K-CWST scores were higher than the minimum clinically important difference. The frequency of adverse events was comparable between the groups and all were of mild severity. CONCLUSION: GEF is safe but might not be effective in treating subjective memory impairment within the current study setting. However, GEF showed a trend of improving the global cognition and the frontal executive function. Further large-sized studies with longer follow-up period are warranted. CLINICAL TRIAL REGISTRATION: This clinical trial was registered at Clinical Research Information Service of Korea Centers for Disease Control and Prevention: KCT0004636.

8.
Materials (Basel) ; 14(24)2021 Dec 15.
Article in English | MEDLINE | ID: mdl-34947358

ABSTRACT

In this study, we experimentally analyzed the deformation shape of stacked layers developed using three-dimensional (3D) printing technology. The nozzle traveling speed was changed to 80, 90, 100, and 110 mm/s when printing the layers to analyze its effect on layer deformation. Furthermore, the cross-sectional area and the number of layers were analyzed by printing five layers with overall dimensions of 1000 (w) × 2200 (l) × 50 (h) mm (each layer was 10 mm high) using Vernier calipers. Moreover, we analyzed the interface and cross-sectional area of layers that are difficult to confirm visually using X-ray computed tomography (X-ray CT) analysis. As a result of measuring the deformation at the center of the layer, it was confirmed that the deformation was greater for lower nozzle traveling speeds. Consequently, the X-ray CT analysis verified that the layer had the same cross-sectional area irrespective of the layer printing order at the same nozzle travel speed, even if the layer was deformed.

9.
Materials (Basel) ; 14(21)2021 Oct 21.
Article in English | MEDLINE | ID: mdl-34771801

ABSTRACT

Three-dimensional concrete printing (3DCP) materials require a relatively low water-to-binder ratio (W/B) of 0.3 or less to ensure their buildability and flow properties are sufficiently maintained after mixing. In this study, the rheological properties of 3DCP materials with W/B 0.28 were evaluated up to 60 min after mixing, and the yield stress and plastic viscosity were analyzed over time. A gradual decrease in flow rate with time was observed during the transport of 200 kg of material per batch through a 20 m hose. To examine the time-dependent changes in flow rate and layer volume, a 2200 mm × 1000 mm test specimen was printed. The dependence of the layer width over time during the printing process was measured and analyzed. The experimental analyses showed that the flow rate and layer volume of the 3DCP material gradually decreased with time after mixing, which was correlated with the rheological properties.

10.
Transl Clin Pharmacol ; 29(1): 21-32, 2021 Mar.
Article in English | MEDLINE | ID: mdl-33854998

ABSTRACT

Along with the multiple neuroprotective effect, recent studies suggest that gintonin might increase the blood brain barrier permeability. We evaluated the effect of gintonin on the vascular permeability changes in different brain segments, using dynamic contrast-enhanced (DCE) magnetic resonance imaging (MRI). In this 8-week, randomized, open label pilot study, ten participants with subjective memory impairment but preserved cognitive function assigned to gintonin-enriched fraction (GEF) 300 mg/day or placebo groups. Korean versions of the Alzheimer's disease assessment scale (ADAS-K) and DCE-MRI parameters including Ktrans and Vp in different brain segments were evaluated at baseline and at 8 weeks after treatment. Nine participants completed the study protocol. No adverse events occurred during the observation period for 8 weeks in both groups. Following gintonin administration, increment trends of the brain permeability that did not reach a statistical significance were observed in the left hippocampus (Ktrans and Vp, both, p = 0.062), left thalamus and in left putamen (Ktrans, p = 0.062), and left insula and right amygdala (Vp, p = 0.062), but not in the control placebo group. The increment of the Ktrans value in the left thalamus from the baseline was highly correlated with the change of the ADAS scores (r = -0.900, p = 0.037). Gintonin might enhance the blood-brain barrier (BBB) permeability in the brain structures involved in cognitive functions. Further efficacy exploration for the synergistic effect of gintonin's BBB permeability enhancement to its other cognitive enhancing mechanisms are warranted. TRIAL REGISTRATION: Clinical Research Information Service Identifier: KCT0003418.

11.
Materials (Basel) ; 12(24)2019 Dec 08.
Article in English | MEDLINE | ID: mdl-31817981

ABSTRACT

The mechanical properties of 3D-printed mortars are determined in terms of their compressive and direct tensile bond strengths. To determine such properties using existing methods, a preliminary experiment was conducted. The compressive strength of the printed mortar was compared to mold-casted specimens and it was found that the compressive strength decreased by ~30%. Among the fabrication variables, an increase in nozzle height negatively influenced the direct tensile bond strength. For the same conditions and age, the direct tensile strength decreased by as much as 16-29% when the number of layers increased from 2 to 6. When the specimens were fabricated using a specially designed stainless steel frame and core drill, followed by extraction and the application of physical impact, the 28 days compressive strength of the specimen decreased by ~50%.

12.
Int J Oncol ; 53(2): 703-712, 2018 Aug.
Article in English | MEDLINE | ID: mdl-29901072

ABSTRACT

Cyclin-dependent kinases (CDK) are considered to be potential targets of anticancer drugs that can interrupt the uncontrolled division of cancer cells. In this study, we selected two selective CDK inhibitors, AT7519 and SNS­032, from current clinical trials and examined their anticancer and radiosensitizing effects in a cervical cancer model. SNS­032 was found to be more potent than AT7519, with a lower half maximal inhibitory concentration (IC50) value. Both AT7519 and SNS­032 induced the apoptosis, premature senescence and cytostasis of cervical cancer cells, which led to the attenuation of tumor growth in vivo. Moreover, using these CDK inhibitors together with radiation synergistically inhibited tumor growth in a human xenograft tumor model. The concomitant activation of the p53 tumor suppressor and the suppression of cell cycle checkpoint responses mediated by Chk1 led to the cytostasis of cervical cancer cells. Finally, AT7519 and SNS­032 inhibited cancer cell migration, invasion and angiogenesis in vitro, and suppressed lung metastases in a spontaneous metastasis model. On the whole, the findings of this study indicate that the utilization of AT7519 and SNS­032 as part of an adjuvant treatment may help control cervical cancer progression.


Subject(s)
Antineoplastic Agents/pharmacology , Cyclin-Dependent Kinases/antagonists & inhibitors , Lung Neoplasms/therapy , Oxazoles/pharmacology , Piperidines/pharmacology , Pyrazoles/pharmacology , Radiation-Sensitizing Agents/pharmacology , Thiazoles/pharmacology , Uterine Cervical Neoplasms/therapy , Animals , Cell Line, Tumor , Cell Proliferation/drug effects , Cell Survival/drug effects , Drug Synergism , Female , Gene Expression Regulation, Neoplastic , HeLa Cells , Humans , Lung Neoplasms/enzymology , Lung Neoplasms/secondary , Mice , Uterine Cervical Neoplasms/enzymology , Xenograft Model Antitumor Assays
13.
Int J Hyperthermia ; 34(3): 276-283, 2018 05.
Article in English | MEDLINE | ID: mdl-28659004

ABSTRACT

PURPOSE: Mild temperature hyperthermia (MTH) increases blood flow and oxygenation in tumours. On the other hand, high-dose-per-fraction irradiation damages blood vessels, decreases blood flow and increases hypoxia in tumours. The radiation-induced hypoxia in tumours activates hypoxia-inducible factor-1α (HIF-1α) and its target genes, such as vascular endothelial growth factor (VEGF), promoting revascularization and recurrence. In the present study, we examined the hypothesis that MTH inhibits radiation-induced upregulation of HIF-1α and its target genes by increasing tumour oxygenation. MATERIALS AND METHODS: FSaII fibrosarcoma tumours grown subcutaneously in the legs of C3H mice were used. Tumours were irradiated with 15 Gy using a 60Co irradiator or heated at 41 °C for 30 min using an Oncothermia heating unit. Blood perfusion and hypoxia in tumours were assessed with Hoechst 33342 and pimonidazole staining, respectively. Expression levels of HIF-1α and VEGF were determined using immunohistochemical techniques. Apoptosis of tumour cells was quantitated via TUNEL staining and the effects of treatments on tumour growth rate were assessed by measuring tumour diameters. RESULTS: Irradiation of FSaII tumours with a single dose of 15 Gy led to significantly decreased blood perfusion, increased hypoxia and upregulation of HIF-1α and VEGF. On the other hand, MTH at 41 °C for 30 min increased blood perfusion and tumour oxygenation, thereby suppressing radiation-induced HIF-1α and VEGF in tumours, leading to enhanced apoptosis of tumour cells and tumour growth delay. CONCLUSION: MTH enhances the anti-tumour effect of high-dose irradiation, at least partly by inhibiting radiation-induced upregulation of HIF-1α.


Subject(s)
Hyperthermia, Induced/methods , Hypoxia-Inducible Factor 1, alpha Subunit/therapeutic use , Neoplasms/radiotherapy , Animals , Humans , Hypoxia-Inducible Factor 1, alpha Subunit/pharmacology , Mice
14.
Arch Plast Surg ; 44(1): 5-11, 2017 Jan.
Article in English | MEDLINE | ID: mdl-28194341

ABSTRACT

BACKGROUND: Conscious sedation has been widely utilized in plastic surgery. However, inadequate research has been published evaluating adequate drug dosage and depth of sedation. In clinical practice, sedation is often inadequate or accompanied by complications when sedatives are administered according to body weight alone. The purpose of this study was to identify variables influencing the depth of sedation during conscious sedation for plastic surgery. METHODS: This prospective study evaluated 97 patients who underwent plastic surgical procedures under conscious sedation. Serum aspartate aminotransferase (AST), alanine aminotransferase (ALT), creatinine, and glucose levels were measured. Midazolam and ketamine were administered intravenously according to a preset protocol. Bispectral index (BIS) recordings were obtained to evaluate the depth of sedation 4, 10, 15, and 20 minutes after midazolam administration. Associations between variables and the BIS were assessed using multiple regression analysis. RESULTS: Alcohol intake and female sex were positively associated with the mean BIS (P<0.01). Age was negatively associated with the mean BIS (P<0.01). Body mass index (P=0.263), creatinine clearance (P=0.832), smoking history (P=0.398), glucose (P=0.718), AST (P=0.729), and ALT (P=0.423) were not associated with the BIS. CONCLUSIONS: Older patients tended to have a greater depth of sedation, whereas females and patients with greater alcohol intake had a shallower depth of sedation. Thus, precise dose adjustments of sedatives, accounting for not only weight but also age, sex, and alcohol consumption, are required to achieve safe, effective, and predictable conscious sedation.

15.
Oncotarget ; 7(5): 6074-87, 2016 Feb 02.
Article in English | MEDLINE | ID: mdl-26756216

ABSTRACT

Cardiac glycosides are clinically used for cardiac arrhythmias. In this study, we investigated the mechanism responsible for anti-cancer and radiosensitizing effects of lanatoside C in colorectal cancer cells. Lanatoside C-treated cells showed classic patterns of autophagy, which may have been caused by lanatoside C-induced mitochondrial aggregation or degeneration. This mitochondrial dysfunction was due to disruption of K+ homeostasis, possibly through inhibition of Na+/K+-ATPase activity. In addition, lanatoside C sensitized HCT116 cells (but not HT-29 cells) to radiation in vitro. γ-H2AX, a representative marker of DNA damage, were sustained longer after combination of irradiation with lanatoside C, suggesting lanatoside C impaired DNA damage repair processes. Recruitment of 53BP1 to damaged DNA, a critical initiation step for DNA damage repair signaling, was significantly suppressed in lanatoside C-treated HCT116 cells. This may have been due to defects in the RNF8- and RNF168-dependent degradation of KDM4A/JMJD2A that increases 53BP1 recruitment to DNA damage sites. Although lanatoside C alone reduced tumor growth in the mouse xenograft tumor model, combination of lanatoside C and radiation inhibited tumor growth more than single treatments. Thus, lanatoside C could be a potential molecule for anti-cancer drugs and radiosensitizing agents.


Subject(s)
Colorectal Neoplasms/drug therapy , DNA Repair/drug effects , Lanatosides/pharmacology , Mitochondria/drug effects , Animals , Autophagy/drug effects , Cell Growth Processes/drug effects , Colorectal Neoplasms/genetics , Colorectal Neoplasms/pathology , DNA Damage , HCT116 Cells , HT29 Cells , Humans , Mice , Mitochondria/genetics , Radiation Tolerance/drug effects , Radiation-Sensitizing Agents/pharmacology , Random Allocation , Signal Transduction
16.
Oncotarget ; 7(5): 5118-30, 2016 Feb 02.
Article in English | MEDLINE | ID: mdl-26802028

ABSTRACT

X-linked inhibitor of apoptosis (XIAP)-associated factor 1 (XAF1) is well known as an antagonist of XIAP-mediated caspase inhibition. Although XAF1 serves as a tumor-suppressor gene, the role of XAF1 in cellular senescence remains unclear. We found that XAF1 expression was increased by genotoxic agents, such as doxorubicin and ionizing radiation in pulmonary microvascular endothelial cells, consequently leading to premature senescence. Conversely, downregulation of XAF1 in premature senescent cells partially overcame endothelial cell senescence. p53 knockdown, but not p16 knockdown, abolished senescence phenotypes caused by XAF1 induction. XAF1 expression was transcriptionally regulated by Bromodomain 7 (BRD7). XAF1 induction with interferon-gamma (IFN-γ) treatment was abrogated by BRD7 knockdown, which resulted in blocking interferon-induced senescence. In lung cancer cells, XAF1 tumor suppressor activity was decreased by BRD7 knockdown, and inhibition of tumor growth by IFN-γ did not appear in BRD7-depleted xenograft tumors. These data suggest that XAF1 is involved in BRD7-associated senescence and plays an important role in the regulation of endothelial senescence through a p53-dependent pathway. Furthermore, regulation of the BRD7/XAF1 system might contribute to tissue or organismal aging and protection against cellular transformation.


Subject(s)
Cellular Senescence/genetics , Chromosomal Proteins, Non-Histone/genetics , Chromosomal Proteins, Non-Histone/metabolism , Endothelial Cells/metabolism , Neoplasm Proteins/genetics , X-Linked Inhibitor of Apoptosis Protein/genetics , X-Linked Inhibitor of Apoptosis Protein/metabolism , Cell Line, Tumor , Humans , Transfection
17.
Cancer Res Treat ; 48(2): 727-37, 2016 Apr.
Article in English | MEDLINE | ID: mdl-26323643

ABSTRACT

PURPOSE: This study was conducted to evaluate the biological features of murine hepatocarcinoma according to different tumor microenvironmental models and to determine the change in molecular and immunologic responses after radiation. MATERIALS AND METHODS: Tumor models were established in the liver (orthotopic) and thigh (heterotopic) of male C3H/HeN mice. Tumor growth and lung metastasis were assessed in these models. To evaluate the radiation effect, the tumors were irradiated with 10 Gy. Factors associated with tumor microenvironment including vascular endothelial growth factor (VEGF), cyclooxygenase-2 (COX-2), transforming growth factor beta1 (TGF-ß1), CD31, and serum interleukin-6 (IL-6) were evaluated. Tumor-infiltrating regulatory immune cells, regulatory T cells (Tregs), and myeloid-derived suppressor cells (MDSCs) were also analyzed. RESULTS: A higher number of lung metastases were observed in the orthotopic tumor model than in the heterotopic tumor model. VEGF, CD31, COX-2, and TGF-ß1 expression was more prominent in the orthotopic tumor model than in the heterotopic tumor model. Expression of the angiogenic factor VEGF and key regulatory molecules (TGF-ß1 and COX-2) decreased following radiation in the orthotopic tumor model, while the serum IL-6 level increased after radiation. In the orthotopic tumor model, the number of both Tregs and MDSCs in the tumor burden decreased after radiation. CONCLUSION: The orthotopic tumor model showed higher metastatic potential and more aggressive molecular features than the heterotopic tumor model. These findings suggest that the orthotopic tumor mouse model may be more reflective of the tumor microenvironment and suitable for use in the translational research of radiation treatment.


Subject(s)
Liver Neoplasms/pathology , Liver Neoplasms/radiotherapy , Tumor Microenvironment , Animals , Cell Line, Tumor , Cyclooxygenase 2/metabolism , Interleukin-6/blood , Liver Neoplasms/immunology , Lymphocytes, Tumor-Infiltrating/immunology , Lymphocytes, Tumor-Infiltrating/radiation effects , Male , Mice , Mice, Inbred C3H , Myeloid-Derived Suppressor Cells/immunology , Myeloid-Derived Suppressor Cells/radiation effects , Neoplasm Transplantation , Platelet Endothelial Cell Adhesion Molecule-1/metabolism , T-Lymphocytes, Regulatory/immunology , T-Lymphocytes, Regulatory/radiation effects , Transforming Growth Factor beta1/metabolism , Tumor Microenvironment/radiation effects , Vascular Endothelial Growth Factor A/metabolism
18.
Arch Craniofac Surg ; 17(1): 25-27, 2016 Mar.
Article in English | MEDLINE | ID: mdl-28913248

ABSTRACT

Cutaneous horns are conical, circumscribed protuberances formed by densely layered keratin. These lesions originate from basal keratinocytes and may manifest as benign, premalignant, or malignant cutaneous pathology in chronically sun-damaged areas. Complete surgical excision with histologic examination is needed for potential malignancy. In this report, we describe two elderly women presenting with solitary facial cutaneous horns, which were respectively diagnosed as actinic keratosis and squamous cell carcinoma.

19.
PLoS One ; 10(4): e0123133, 2015.
Article in English | MEDLINE | ID: mdl-25849377

ABSTRACT

Suppressor of cytokine signaling (SOCS) family is an important negative regulator of cytokine signaling and deregulation of SOCS has been involved in many types of cancer. All cervical cancer cell lines tested showed lower expression of SOCS1, SOCS3, and SOCS5 than normal tissue or cell lines. The immunohistochemistry result for SOCS proteins in human cervical tissue also confirmed that normal tissue expressed higher level of SOCS proteins than neighboring tumor. Similar to the regulation of SOCS in other types of cancer, DNA methylation contributed to SOCS1 downregulation in CaSki, ME-180, and HeLa cells. However, the expression of SOCS3 or SOCS5 was not recovered by the inhibition of DNA methylation. Histone deacetylation may be another regulatory mechanism involved in SOCS1 and SOCS3 expression, however, SOCS5 expression was neither affected by DNA methylation nor histone deacetylation. Ectopic expression of SOCS1 or SOCS3 conferred radioresistance to HeLa cells, which implied SOCS signaling regulates the response to radiation in cervical cancer. In this study, we have shown that SOCS expression repressed by, in part, epigenetically and altered SOCS1 and SOCS3 expression could contribute to the radiosensitive phenotype in cervical cancer.


Subject(s)
DNA Methylation , Gene Expression Regulation, Neoplastic , Histones/metabolism , RNA Interference , Radiation Tolerance/genetics , Suppressor of Cytokine Signaling Proteins/antagonists & inhibitors , Uterine Cervical Neoplasms/genetics , Acetylation , Blotting, Western , Cells, Cultured , Cervix Uteri/metabolism , Cytokines/metabolism , Down-Regulation , Female , Humans , Immunoenzyme Techniques , Promoter Regions, Genetic/genetics , RNA, Messenger/genetics , RNA, Small Interfering/genetics , Radiotherapy , Real-Time Polymerase Chain Reaction , Reverse Transcriptase Polymerase Chain Reaction , Signal Transduction/genetics , Suppressor of Cytokine Signaling Proteins/genetics , Suppressor of Cytokine Signaling Proteins/metabolism , Transcription Factors/metabolism , Uterine Cervical Neoplasms/metabolism , Uterine Cervical Neoplasms/pathology , Uterine Cervical Neoplasms/radiotherapy
20.
Obes Surg ; 25(5): 824-9, 2015 May.
Article in English | MEDLINE | ID: mdl-25381478

ABSTRACT

BACKGROUND: In Asia, laparoscopic sleeve gastrectomy (LSG) is the leading weight loss procedure for treating morbid obesity. However, long-term results of isolated LSG performed in patients with lower body mass index (BMI) (30-35 kg/m(2)) are scarce. METHODS: We retrospectively reviewed 75 patients with BMI of 30-35 kg/m(2) who underwent LSG from January 2003 to January 2013. Seventy-one of these patients who had more than 6 months of follow-up were included in this report. LSG was performed laparoscopically using a linear stapler over a 48-French bougie from 2003 to 2006. Since 2007, 36-French bougie was used for resection, and a continuous seromuscular suture at the resection margin was added. RESULTS: Mean age at the time of surgery was 33.7 ± 10.3 years in our patients. Mean weight was 85.7 ± 9.0 kg and mean BMI was 32.4 ± 1.6 kg/m(2) preoperatively. The percentage of excess BMI loss (%EBL) in the postoperative first, third, and fifth year was 84.1 ± 25.5, 79.8 ± 31.0, and 78.5 ± 28.5%, respectively. Follow-up rate at the first, third, and fifth year was 90.0, 71.9, and 42.9%. There were no 30-day perioperative mortality and major complications including bleeding and leakage. CONCLUSIONS: These findings show that LSG is a safe and effective weight loss option for Korean patients with lower BMI. Randomized prospective control studies between gastric banding, or Roux-en-Y gastric bypass, and LSG are needed to confirm long-term weight loss effect and safety of LSG in this group of patients.


Subject(s)
Gastrectomy/methods , Laparoscopy/methods , Adult , Body Mass Index , Comorbidity , Female , Humans , Male , Middle Aged , Obesity/epidemiology , Obesity/surgery , Republic of Korea , Retrospective Studies , Surgical Stapling , Treatment Outcome , Weight Loss , Young Adult
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