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1.
Int J Stem Cells ; 17(2): 158-181, 2024 May 30.
Article in English | MEDLINE | ID: mdl-38777830

ABSTRACT

This study offers a comprehensive overview of brain organoids for researchers. It combines expert opinions with technical summaries on organoid definitions, characteristics, culture methods, and quality control. This approach aims to enhance the utilization of brain organoids in research. Brain organoids, as three-dimensional human cell models mimicking the nervous system, hold immense promise for studying the human brain. They offer advantages over traditional methods, replicating anatomical structures, physiological features, and complex neuronal networks. Additionally, brain organoids can model nervous system development and interactions between cell types and the microenvironment. By providing a foundation for utilizing the most human-relevant tissue models, this work empowers researchers to overcome limitations of two-dimensional cultures and conduct advanced disease modeling research.

2.
Int J Mol Sci ; 23(4)2022 Feb 12.
Article in English | MEDLINE | ID: mdl-35216164

ABSTRACT

Tim-3/Gal-9 and the NLRC4 inflammasome contribute to glioma progression. However, the underlying mechanisms involved are unclear. Here, we observed that Tim-3/Gal-9 expression increased with glioma malignancy and found that Tim-3/Gal-9 regulate NLRC4 inflammasome formation and activation. Tim-3/Gal-9 and NLRC4 inflammasome-related molecule expression levels increased with WHO glioma grade, and this association was correlated with low survival. We investigated NLRC4 inflammasome formation by genetically regulating Tim-3 and its ligand Gal-9. Tim-3/Gal-9 regulation was positively correlated with the NLRC4 inflammasome, NLRC4, and caspase-1 expression. Tim-3/Gal-9 did not trigger IL-1ß secretion but were strongly positively correlated with caspase-1 activity as they induced programmed cell death in glioma cells. A protein-protein interaction analysis revealed that the FYN-JAK1-ZNF384 pathways are bridges in NLRC4 inflammasome regulation by Tim-3/Gal-9. The present study showed that Tim-3/Gal-9 are associated with poor prognosis in glioma patients and induce NLRC4 inflammasome formation and activation. We proposed that a Tim-3/Gal-9 blockade could be beneficial in glioma therapy as it would reduce the inflammatory microenvironment by downregulating the NLRC4 inflammasome.


Subject(s)
Brain Neoplasms/metabolism , CARD Signaling Adaptor Proteins/metabolism , Calcium-Binding Proteins/metabolism , Galectins/metabolism , Glioma/metabolism , Hepatitis A Virus Cellular Receptor 2/metabolism , Brain Neoplasms/pathology , Caspase 1/metabolism , Cell Line, Tumor , Glioma/pathology , Humans , Inflammasomes/metabolism , Janus Kinase 1/metabolism , Protein Binding , Trans-Activators/metabolism
3.
Accid Anal Prev ; 144: 105589, 2020 Sep.
Article in English | MEDLINE | ID: mdl-32593780

ABSTRACT

Numerous studies have developed intersection crash prediction models to identify crash hotspots and evaluate safety countermeasures. These studies largely considered only micro-level crash contributing factors such as traffic volume, traffic signals, etc. Some recent studies, however, have attempted to include macro-level crash contributing factors, such as population per zone, to predict the number of crashes at intersections. As many intersections are located between multiple zones and thus affected by factors from the multiple zones, the inclusion of macro-level factors requires boundary problems to be resolved. In this study, we introduce an advanced multilevel model, the multiple membership multilevel model (MMMM), for intersection crash analysis. Our objective was to reduce heterogeneity issues between zones in crash prediction model while avoiding misspecification of the model structure. We used five years of intersection crash data (2009-2013) for the City of Regina, Saskatchewan, Canada and identified micro- and macro-level factors that most affected intersection crashes. We compared the fitting performance of the MMMM with that of two existing models, a traditional single model (SM) and a conventional multilevel model (CMM). The MMMM outperformed the SM and CMM in terms of fitting capability. We found that the MMMM avoided both the underestimation of macro-level variance and the type I statistical error that tend to occur when the crash data are analyzed using a SM or CMM. Statistically significant micro-level and macro-level crash contributing factors in Regina included major roadway AADT, four legs, traffic signals, speed, young drivers, and different types of land use.


Subject(s)
Accidents, Traffic/prevention & control , Accidents, Traffic/statistics & numerical data , Built Environment/statistics & numerical data , Humans , Models, Statistical , Multilevel Analysis , Saskatchewan
4.
J Nanosci Nanotechnol ; 19(3): 1533-1537, 2019 Mar 01.
Article in English | MEDLINE | ID: mdl-30469218

ABSTRACT

Owing to the energy and environmental issues, energy recovery technologies attract an increasing interest. Thermoelectric power generation is a recycling technology, which directly converts heat energy into electric energy by reusing waste heat. In this study, n-type Bi2Te2.7Se0.3 thermoelectric materials doped with Cu were fabricated by hot pressing. The Bi-Te system has excellent thermoelectric properties in the middle- and low-temperature ranges; when a certain amount of Cu dopant is added, the thermoelectric properties are improved. The thermoelectric properties of the samples doped with Cu were compared with those of the intrinsic Bi-Te-based sample without Cu doping. In addition, the effects of the Cu concentration on the thermoelectric-material structures were investigated.

5.
J Nanosci Nanotechnol ; 19(3): 1645-1648, 2019 Mar 01.
Article in English | MEDLINE | ID: mdl-30469238

ABSTRACT

Intrinsic Cu- and Ni-added Cu electrodes were prepared to study Sn-3Ag-0.5Cu lead-free solder joints. Our work focused on three categories: (1) formation and role of intermetallic compounds, (2) structural and compositional change of intermetallic compounds due to thermal aging effects, and (3) mechanical bonding strength of solder joints. A series of SEM, EDX, and bonding test analyses were performed on two electrode types to study joint morphologies, the types of intermetallic compounds formed, and bonding strengths, respectively. As a result, after heat treatments at 150 °C for 10 h, 100 h, and 300 h, Cu6Sn5 and (Ni, Cu)3Sn4 were obtained at the interfaces of the intrinsic Cu electrode and the Ni-added Cu electrode, respectively. In the Ni-added Cu electrode samples, the growth rate of the intermetallic compounds was reduced, but the mechanical bonding strength had a higher value compared to that of the intrinsic Cu electrode. The bonding characteristics under different heat treatment conditions are also discussed.

6.
J Nanosci Nanotechnol ; 19(3): 1699-1703, 2019 Mar 01.
Article in English | MEDLINE | ID: mdl-30469249

ABSTRACT

Higher manganese silicide is generally used in thermoelectric devices between 700 K and 900 K. MnSi1.73Al0.005 samples were fabricated by two continuous solid-state reactions followed by hot pressing because the electrical conductivity of all the samples is strongly dependent on Al doping, showing superior thermoelectric performance to the as-synthesized higher manganese silicide. The solid-state-reaction was performed at 1173 K for 6 hours. The effects of the sintering temperature were examined by sintering at three different temperatures: 1273 K, 1323 K and 1373 K. For the surface, microstructural, and electrical properties, scanning electron microscopy, X-ray diffraction, and a series of electric conductivity, Seebeck coefficient, and thermal conductivity analyses were conducted, respectively. As a result, the optimal process temperature for Al-doped higher manganese silicide using a hot-press technique was determined.

7.
PLoS One ; 13(9): e0203379, 2018.
Article in English | MEDLINE | ID: mdl-30192797

ABSTRACT

PURPOSE: To perform in vitro high-resolution 900 MHz magnetic resonance spectroscopy (NMR) analysis of human brain tumor tissue extracts and analyze for the oncometabolite 2-hydroxyglutarate (2HG) and other brain metabolites, not only for 1H but also for 13C with indirect detection by heteronuclear single quantum correlation (HSQC). MATERIAL AND METHODS: Four surgically removed human brain tumor tissue samples were used for extraction and preparation of NMR samples. These tissue samples were extracted with 4% perchloric acid and chloroform, freeze-dried, then dissolved into 0.28 mL of deuterium oxide (D2O, 99.9 atom % deuterium) containing 0.025 wt % sodium 3-(trimethylsilyl)propionate-2,2,3,3-d4 (TSP). All samples were adjusted to pH range of 6.9-7.1 before finally transferred to 5 mm Shigemi™ NMR microtube. NMR experiments were performed on Bruker DRX 900 MHz spectrometer with 1H/13C/15N Cryo-probe™ with Z-gradient, without further temperature control for the samples. All chemical shift values were presented relative to TSP at 0.00 ppm for both 1H and 13C. 1H 1D, 1H-13C HSQC, 1H-1H correlation spectroscopy (COSY) and 1H-13C heteronuclear multiple bond correlation (HMBC) spectra were acquired and analyzed. RESULTS: 2-hydroxyglutarate, an oncometabolite associated with gliomas with IDH mutations, was successfully detected and assigned by both 1H-13C HSQC and 1H-1H COSY experiments as well as 1H 1D experiments in two of the tissue samples. In particular, to our knowledge this work shows the first example of detecting 900 MHz 13C-NMR spectral lines of 2-hydroxyglutarate in human brain tumor tissue samples. In addition to the oncometabolite 2-hydroxyglutarate, at least 42 more metabolites were identified from our series of NMR experiment. CONCLUSION: The detection of 2-hydroxyglutarate and other metabolites can be facilitated by homonuclear and heteronuclear two-dimensional 900 MHz NMR spectroscopy even in case of real tumor tissue sample extracts without physical separation of metabolites.


Subject(s)
Brain Neoplasms/metabolism , Carbon-13 Magnetic Resonance Spectroscopy/methods , Glioma/metabolism , Glutarates/analysis , Proton Magnetic Resonance Spectroscopy/methods , Tissue Extracts/analysis , Brain/metabolism , Brain/pathology , Carbon-13 Magnetic Resonance Spectroscopy/instrumentation , Chloroform/chemistry , Deuterium Oxide/chemistry , Humans , Hydrogen-Ion Concentration , Perchlorates/chemistry , Propionates/chemistry , Proton Magnetic Resonance Spectroscopy/instrumentation , Reproducibility of Results , Trimethylsilyl Compounds/chemistry
8.
Sci Total Environ ; 633: 1148-1155, 2018 Aug 15.
Article in English | MEDLINE | ID: mdl-29758866

ABSTRACT

Estrogens originated from humans can reach ambient water and possibly cause significant ecological risks. In this study, the quantities of human-origin estrone (E1) and 17ß-estradiol (E2) in the influent and effluent of four sewer treatment plants (STPs) in Seoul, South Korea were estimated using a demographic model. A Monte Carlo simulation was used to assess the quantitative uncertainty of estimated E1 and E2 concentrations. Mean concentrations of E1 and E2 estimated for STP influents ranged from 29.5 to 38.4 and 7.5 to 9.7ng/L, respectively. Meanwhile, mean concentrations of E1 and E2 estimated for STP effluents were 4.9 to 6.6 and 0.28 to 0.36ng/L, respectively. These estimated values are similar to measured data as reported in the literatures within the range of uncertainty based on the Monte Carlo simulation. The hazard quotient (HQ) value in the main stem of the Han River was calculated to be far less than 1 because of the dilution effect of the Han River's abundant flow, indicating that most of the Han River ecosystem will not be influenced by these endogenous estrogens. With a 95% cumulative probability, HQ values in the main stem of the Han River for the Jungrang, Nanji, Tanchun, and Seonam STPs were less than 0.18, 0.07, 0.08, and 0.15, respectively. Nevertheless, HQ values >1 were observed in the vicinity of the STP outlets when using the numerical modeling. Our results show that the endocrine disruption potential of E1 and E2 around STP outlets in the main stem of the Han River must be monitored carefully.


Subject(s)
Environmental Monitoring , Estradiol/analysis , Estrone/analysis , Water Pollutants, Chemical/analysis , Endocrine Disruptors/analysis , Estrogens , Humans , Rivers , Sewage , Waste Disposal, Fluid , Water Pollution, Chemical/statistics & numerical data
9.
J Nanosci Nanotechnol ; 18(3): 1847-1850, 2018 Mar 01.
Article in English | MEDLINE | ID: mdl-29448670

ABSTRACT

The surface activated bonding (SAB) method generally has the advantage of high bonding strength, low contact resistance, and high microstructural stability at room temperature. In this study, Ti-Al laminates were produced by surface activated bonding with aluminum and titanium foils. Heat treatment was conducted at the temperature range from 200 to 550 °C in vacuum. The bonding strength Ti-Al laminates was measured by a peel test, and the interfacial characteristics were investigated microstructural observation. The results showed that the bonding strength was the highest with heat treatment at 400 °C, microstructure observation revealed that the bonding strength of the Ti-Al laminate was influenced by the interfacial characteristics.

10.
Oncol Rep ; 34(4): 2047-53, 2015 Oct.
Article in English | MEDLINE | ID: mdl-26260219

ABSTRACT

Gastric cancer is the second most common cause of cancer-related death worldwide. Although brain metastasis is a rare complication of gastric cancer, no standard therapy for gastric cancer brain metastasis has been established. We attempted to identify biological markers that predict brain metastasis, and investigated how to modulate such markers. A case-control study of patients newly diagnosed with gastric cancer who had developed brain metastasis during follow-up, was conducted. These patients were compared with patients who had advanced gastric cancer but no evidence of brain metastasis. Immunohistochemistry was used to analyze the expression of E-cadherin, N-cadherin, MSS1, claudin-3, claudin-4, Glut1, clusterin, ITGB4, vascular endothelial growth factor (VEGF), epidermal growth factor receptor (EGFR) and p53. The expression of VEGF tended to be higher in the case group (33.3 vs. 0%, p=0.055). Median survival was significantly correlated with vascular invasion (12 vs. 33 months, p=0.008) and N-cadherin expression (36 vs. 12 months, p=0.027). We also investigated the effects of metformin in tumor-bearing mouse models. VEGF expression was decreased and E-cadherin increased in the metformin­treated group when compared with the control group. The expression of the mesenchymal marker MMP9 was decreased in the metformin-treated group. Brain metastasis of advanced gastric cancer was associated with the expression of VEGF. Metformin treatment may be useful for modulating the metastatic capacity by reducing VEGF expression and blocking epithelial-to-mesenchymal transition.


Subject(s)
Antigens, CD/metabolism , Brain Neoplasms/metabolism , Brain Neoplasms/secondary , Cadherins/metabolism , Metformin/administration & dosage , Stomach Neoplasms/metabolism , Vascular Endothelial Growth Factor A/metabolism , Adult , Aged , Aged, 80 and over , Animals , Brain Neoplasms/drug therapy , Brain Neoplasms/pathology , Case-Control Studies , Cell Line, Tumor , Epithelial-Mesenchymal Transition/drug effects , Female , Gene Expression Regulation, Neoplastic/drug effects , Humans , Male , Metformin/pharmacology , Mice , Middle Aged , Stomach Neoplasms/drug therapy , Stomach Neoplasms/pathology , Xenograft Model Antitumor Assays
11.
Int J Oncol ; 45(6): 2403-10, 2014 Dec.
Article in English | MEDLINE | ID: mdl-25270520

ABSTRACT

Although the incidence of brain metastasis in gastric cancer is relatively low, its prevalence may increase with improved therapy and longer survival tumors. The molecular mechanisms underlying brain metastases are not well understood. To gain insight into the mechanism of brain metastasis, we studied differences in microRNA (miRNA) expression levels in 8 cases of matched primary gastric adenocarcinoma and brain metastatic adenocarcinoma using the Illumina microRNA microarray chip. We identified 6 upregulated and 2 downregulated miRNAs in all 8 cases simultaneously. Interestingly, 2 out of 8 miRNAs (hsa-miR­141-3p and hsa-miR-200b-3p) belonged to the miR-200 family. Online microRNA database searching revealed that ZEB2 is the top-ranked target gene for hsa-miR141-3p and hsa-miR-200b-3p, prompting us to focus ZEB2 expression in brain metastatic adenocarcinoma. We confirmed that ZEB2 expression was markedly downregulated in some brain metastatic samples. In addition, decreased ZEB2 expression was noted by western blot analysis of 2 metastatic gastric adenocarcinoma cell types that were derived by in vivo selection following intracardiac injection of gastric cancer cell lines. In conclusion, we demonstrate that expression of miRNA-200 family members and ZEB2 are associated with brain metastases of gastric adenocarcinoma, not only in matched patient samples, but also in metastatic cell lines that were derived by in vivo selection.


Subject(s)
Adenocarcinoma/genetics , Brain Neoplasms/genetics , Homeodomain Proteins/biosynthesis , MicroRNAs/biosynthesis , Repressor Proteins/biosynthesis , Stomach Neoplasms/genetics , Adenocarcinoma/pathology , Animals , Brain Neoplasms/pathology , Brain Neoplasms/secondary , Cell Proliferation/genetics , Female , Gene Expression Regulation, Neoplastic , Homeodomain Proteins/genetics , Humans , Lymphatic Metastasis , Male , Mice , MicroRNAs/genetics , Middle Aged , Oligonucleotide Array Sequence Analysis , Repressor Proteins/genetics , Stomach Neoplasms/pathology , Zinc Finger E-box Binding Homeobox 2
12.
Oncol Rep ; 32(4): 1537-42, 2014 Oct.
Article in English | MEDLINE | ID: mdl-25109698

ABSTRACT

The purpose of the present study was to identify a predictive marker associated with tumor progression or recurrence. We investigated the expression of p53, Ki-67, Bax, Bcl-2, vascular endothelial growth factor (VEGF)-A, VEGFR-1, VEGFR-2 and neuropilin-1 (NRP-1) in pituitary adenomas (PAs) with/without tumor progression during follow-up periods. We compared the expression of these molecules in primary and recurrent specimens to identify a predictive marker associated with tumor progression. Nineteen patients had no progression for more than 5-years of follow-up. Nine patients had tumor progression within 5 years of their first transsphenoidal surgery (TSS) surgery and underwent re-TSS for treating progression of adenoma. Tumor size was larger and involvement of the cavernous sinus was more frequent in the progression group than these variables in the no progression group. A strong association was observed between NRP-1 expression and tumor progression. No significant risk for developing tumor progression was associated with Ki-67, p53, Bax, Bcl-2, VEGFR-1, VEGFR-2, or VEGF-A expression. Four of nine patients showed strong NRP-1 immunoreactivity in progression specimens. Negative NRP-1 immunoreactivity in the initial specimens was converted into strong positivity in the progression specimens of five patients. NRP-1 could be a relevant PA marker of progression and could be a potential target for medical therapy.


Subject(s)
Adenoma/metabolism , Neoplasm Recurrence, Local/metabolism , Neuropilin-1/metabolism , Pituitary Neoplasms/metabolism , Adenoma/pathology , Adenoma/surgery , Adult , Aged , Cell Line, Tumor , Disease Progression , Female , Gene Knockdown Techniques , Humans , Immunohistochemistry , Ki-67 Antigen/genetics , Ki-67 Antigen/metabolism , Male , Middle Aged , Neuropilin-1/genetics , Pituitary Neoplasms/pathology , Pituitary Neoplasms/surgery , Prognosis , Proto-Oncogene Proteins c-bcl-2/genetics , Proto-Oncogene Proteins c-bcl-2/metabolism , Tumor Burden , Tumor Suppressor Protein p53/genetics , Tumor Suppressor Protein p53/metabolism , Vascular Endothelial Growth Factor Receptor-1/genetics , Vascular Endothelial Growth Factor Receptor-1/metabolism , Vascular Endothelial Growth Factor Receptor-2/genetics , Vascular Endothelial Growth Factor Receptor-2/metabolism , Young Adult , bcl-2-Associated X Protein/genetics , bcl-2-Associated X Protein/metabolism
13.
J Korean Neurosurg Soc ; 55(1): 26-31, 2014 Jan.
Article in English | MEDLINE | ID: mdl-24570814

ABSTRACT

OBJECTIVE: Early decompressive craniectomy (DC) has been used as the first stage treatment to prevent secondary injuries in cases of severe traumatic brain injury (TBI). Postoperative management is the major factor that influences outcome. The aim of this study is to investigate the effect of postoperative management, using intracranial pressure (ICP) monitoring and including consecutive DC on the other side, on the two-week mortality in severe TBI patients treated with early DC. METHODS: Seventy-eight patients with severe TBI [Glasgow Coma Scale (GCS) score <9] underwent early DC were retrospectively investigated. Among 78 patients with early DC, 53 patients were managed by conventional medical treatments and the other, 25 patients were treated under the guidance of ICP monitoring, placed during early DC. In the ICP monitoring group, consecutive DC on the other side were performed on 11 patients due to a high ICP of greater than 30 mm Hg and failure to respond to any other medical treatments. RESULTS: The two-week mortality rate was significantly different between two groups [50.9% (27 patients) and 24% (6 patients), respectively, p=0.025]. After adjusting for confounding factors, including sex, low GCS score, and pupillary abnormalities, ICP monitoring was associated with a 78% lower likelihood of 2-week mortality (p=0.021). CONCLUSION: ICP monitoring in conjunction with postoperative treatment, after early DC, is associated with a significantly reduced risk of death.

14.
Korean J Neurotrauma ; 10(1): 31-4, 2014 Apr.
Article in English | MEDLINE | ID: mdl-27169030

ABSTRACT

Central pontine myelinolysis occurs inconsistently as a complication of severe and prolonged hyponatremia, particularly when corrected too rapidly. This condition is a concentrated, frequently symmetric, noninflammatory demyelination within the central basis pontis. We describe a head injury patient who developed central pontine and extrapontine myelinolysis following a gradual correction of hyponatremia. More attention should be paid to correcting hyponatremia combined with hypokalemia in patients who have a history of alcoholism.

15.
Oncol Lett ; 5(3): 953-958, 2013 Mar.
Article in English | MEDLINE | ID: mdl-23426399

ABSTRACT

The association between rapamycin and astrocytes in a tumor-bearing mouse model with brain metastases of non-small cell lung cancer (NSCLC) was investigated. For in vitro experiments, NCI-H358, a human lung adenocarcinoma cell line, was co-cultured with immortalized astrocytes, and treated with rapamycin, an mTOR inhibitor. We evaluated the expression of interleukin-1 (IL-1), interleukin-3 (IL-3), interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), transforming growth factor-ß (TGF-ß), insulin-like growth factor-1 (IGF-1), platelet-derived growth factor (PDGF), chemoattractant protein-1 (MCP-1) and macrophage inflammatory protein-1 (MIP-1) in tumor cells in vivo. Rapamycin is cytotoxic in vitro; however, co-culturing tumor cells and astrocytes induced tumor cell survival. IL-1, IL-3, IL-6, TNF-α, TGF-ß, PDGF, MCP-1 and MIP-1 expression were higher in rapamycin-treated mice compared to the control group, however, IGF-1 expression was lower. Notably, treatment with rapamycin before inoculating tumor cells affected cytokine expression in the tumor microenvironment. We suggest that growth factors and cytokines in the tumor microenvironment play a role in the survival of cancer cells in brain metastases.

16.
Brain Tumor Res Treat ; 1(1): 24-7, 2013 Apr.
Article in English | MEDLINE | ID: mdl-24904885

ABSTRACT

OBJECTIVE: This study was performed to assess the postoperative pain of brain tumor patients who underwent elective craniotomy and to evaluate the factors associated with pain intensity. METHODS: From January 2010 to December 2011, 47 patients with newly diagnosed brain tumors who underwent craniotomy were enrolled. The postoperative pain status was assessed daily until discharge using the visual analogue scale (VAS). RESULTS: The study participants comprised of 22 males and 25 females with ages ranging from 18-76 years (median age, 50 years). Patients were divided into two groups: the painful group included patients who had a VAS score of more than 3 during their hospital stay after the craniotomy, and the tolerable group included patients who had a VAS score of 1 to 3 during their hospital stay. There were no differences between the two groups in terms of age, sex, location of surgery, history of diabetes, hypertension and smoking, body mass index, and hospital stay. Univariate analysis revealed that operating time, length of wound, head fixation, and perioperative administration of opioid were not associated with the intensity of postoperative pain. Daily assessment of VAS revealed the two peaks of pain on the operation day and the 4th postoperative day. The intensity of pain during the ambulation period was higher than that during intensive care unit (ICU) stay. CONCLUSION: Pain following elective craniotomy for brain tumor removal is insufficiently managed, especially after discharge from the ICU. More attention needs to be paid to patients' pain throughout the hospital stay.

17.
J Neurooncol ; 109(2): 219-27, 2012 Sep.
Article in English | MEDLINE | ID: mdl-22576972

ABSTRACT

It remains unclear whether patients with non-small-cell lung cancer (NSCLC) develop brain metastasis during or after standard therapy. We attempted to identify biological markers that predict brain metastasis, and investigated how to modulate expression of such markers. A case-control study of patients who were newly diagnosed with NSCLC and who had developed brain metastasis during follow-up was conducted between 2004 and 2009. These patients were compared with a control group of patients who had NSCLC but no evidence of brain metastasis. Immunohistochemical analysis of expression of Ki-67, p53, Bcl-2, Bax, vascular endothelial growth factor, epidermal growth factor receptor, caspase-3, and E-cadherin was conducted. The methylation status of the genes for O(6)-methylguanine-DNA-methyltransferase, tissue inhibitor of matrix metalloproteinase (TIMP)-2, TIMP-3, and death-associated protein-kinase was also determined, by use of a methylation-specific polymerase chain reaction. A significantly increased risk of developing brain metastasis was associated with the presence of primary tumors with low E-cadherin expression in patients with NSCLC. We also investigated the effects of pioglitazone, a peroxisome proliferator-activated receptor γ-activating drug, in tumor-bearing mouse models. We found that E-cadherin expression was proportional to pioglitazone exposure time. Interestingly, pioglitazone pretreatment before cancer cell inoculation prevented loss of E-cadherin expression and reduced expression of MMP9 and fibronectin, compared with the control group. E-cadherin expression could be a predictor of brain metastasis in patients with NSCLC. Preventive treatment with pioglitazone may be useful for modulating E-cadherin expression.


Subject(s)
Brain Neoplasms/pathology , Brain Neoplasms/secondary , Brain/metabolism , Cadherins/metabolism , Carcinoma, Non-Small-Cell Lung/pathology , Gene Expression Regulation, Neoplastic/drug effects , Hypoglycemic Agents/pharmacology , Lung Neoplasms/pathology , Thiazolidinediones/pharmacology , Aged , Animals , Caspase 3/metabolism , Cell Line, Tumor , DNA Modification Methylases/metabolism , DNA Repair Enzymes/metabolism , Disease Models, Animal , ErbB Receptors/metabolism , Female , Follow-Up Studies , Humans , Hypoglycemic Agents/therapeutic use , Magnetic Resonance Imaging , Male , Matrix Metalloproteinase 2 , Matrix Metalloproteinase 9/metabolism , Mice , Mice, Nude , Middle Aged , Oncogene Proteins/metabolism , Pioglitazone , Retrospective Studies , Statistics, Nonparametric , Thiazolidinediones/therapeutic use , Tumor Suppressor Proteins/metabolism , Vascular Endothelial Growth Factor A/metabolism
18.
Cancer Res Treat ; 44(1): 57-62, 2012 Mar.
Article in English | MEDLINE | ID: mdl-22500162

ABSTRACT

PURPOSE: Non-small cell lung carcinoma (NSCLC) comprises 75-85% of all lung cancers, and approximately 25% of all NSCLC patients develop brain metastasis. There are no reliable markers for predicting in which patients this metastasis will occur. DCUN1D1, also known as squamous cell carcinoma-related oncogene, is associated with tumor progression and poor outcomes in NSCLC. The objective of this study was to investigate the role of DCUN1D1 expression in cases of brain metastasis due to NSCLC. MATERIALS AND METHODS: Primary tumor samples from a total of 71 cases of NSCLC, either with (n=40) or without (n=31) brain metastasis, were evaluated for DCUN1D1 expression by immunohistochemistry analysis. RESULTS: DCUN1D1 expression was detected in 16 patients (23%) and tended to correlate with T classification (15% of T1-2 tumors vs. 30% of T3-4 tumors, p=0.083). DCUN1D1 expression was significantly associated with tumor stage. It was observed in none of the patients with stage I disease, 10% of those with stage II disease, and 29% with stage III disease (p=0.009). In addition, 14 of 16 DCUN1D1-positive patients resulted in brain metastasis (p=0.01). The odds ratio of brain metastasis for patients with DCUN1D1 expression was 3.112 (p=0.009). CONCLUSION: DCUN1D1 expression may play a role in tumor progression and development of brain metastasis in patients with NSCLC. Evaluation of DCUN1D1 expression may provide assistance in identifying those patients who are at higher risk for brain metastasis.

19.
Neuromodulation ; 15(4): 381-6, 2012 Jul.
Article in English | MEDLINE | ID: mdl-22376140

ABSTRACT

OBJECTIVE: Hypnic headache is a rare, primary headache disorder that exclusively occurs regularly during sleep. We present a case of hypnic headache successfully managed with occipital nerve stimulation. MATERIALS AND METHODS: A 64-year-old female presented with a four-year history of a right occipital headache that regularly awakened her from sleep. The headache, which was dull and throbbing, would awaken her regularly at 4:00 am, five hours after bedtime at 11:00 pm. No photophobia, nausea or vomiting, lacrimation, or other autonomic symptoms were present. The headache was refractory to various medical treatments, including indomethacin, flunarizine, propranolol. She underwent a trial of occipital nerve stimulation with a lead electrode using a medial approach. RESULTS: During the ten-day trial stimulation, she reported almost complete relief from hypnic headache. Chronic occipital nerve stimulation replicated the trial results. The attacks of hypnic headache recurred in one year with loss of stimulation-induced paresthesia; a subsequent x-ray showed electrode migration. After revision of the electrode to the original location, the effectiveness of the occipital nerve stimulation against hypnic headache was achieved again, and this effect has been consistent through 36 months of follow-up. CONCLUSION: Occipital nerve stimulation was effective in a patient with chronic, refractory hypnic headache.


Subject(s)
Electric Stimulation Therapy/methods , Headache Disorders, Primary/therapy , Spinal Nerves/physiology , Chronic Disease , Drug Resistance , Electrodes, Implanted , Female , Headache Disorders, Primary/diagnostic imaging , Humans , Middle Aged , Paresthesia/etiology , Prosthesis Implantation , Radiography
20.
Neuromodulation ; 15(3): 260-6; discussion 266, 2012.
Article in English | MEDLINE | ID: mdl-22300254

ABSTRACT

OBJECTIVES: Deep brain stimulation (DBS) is an effective modality of treating cardinal motor symptoms of several movement disorders such as Parkinson's disease, essential tremor, and dystonia. Although hardware-related complications of DBS have been reported, the cosmetic satisfaction and discomfort associated with infraclavicular subcutaneous implantation of the pulse generator has not been described. The authors adopted a technique of transaxillary subpectoral implantable pulse generator (IPG) placement and investigated the difference in the discomfort, cosmetic satisfaction, mean operation time for IPG implantation, and severity of postoperative pain between infraclavicular subcutaneous placement and transaxillary subpectoral implantation of IPG. MATERIALS AND METHODS: 25 patients who underwent bilateral, infraclavicular subcutaneous IPG placement for DBS and 15 patients who had bilateral, transaxillary subpectoral IPG placement were investigated. RESULTS: The differences in cosmetic satisfaction and discomfort between the two groups were significant. The cosmetic satisfaction was higher and discomfort was less in the subpectoral IPG implantation group (p = 0.002 and p = 0.000). However, more time was needed for IPG implantation, and the postoperative pain was more severe after subpectoral IPG implantation (p = 0.002 and p = 0.000). There was no difference in cosmetic satisfaction according to sex (p = 0.907). There was one transient intercostobrachial nerve injury in the subpectoral IPG implantation group and two infections which needed removal of one side of the DBS hardware in the infraclavicular IPG implantation group. CONCLUSIONS: These results demonstrated that subpectoral transaxillary IPG implantation can provide better cosmetic satisfaction in patients undergoing DBS, with less discomfort and morbidity related to erosion and infection.


Subject(s)
Axilla/surgery , Deep Brain Stimulation/methods , Patient Satisfaction/statistics & numerical data , Pectoralis Muscles/surgery , Aged , Electrodes, Implanted , Female , Humans , Male , Movement Disorders/therapy , Retrospective Studies , Subcutaneous Tissue/surgery
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