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ABSTRACT: Esophageal squamous cell carcinoma (ESCC) is a common subtype of esophageal cancer that is particularly prevalent in East Asian countries. Our previous expression profile analysis showed that the gene encoding PTK7 is upregulated in ESCC tissues. Here, we aimed to validate PTK7 as a prognostic factor and a candidate target for molecular treatment of ESCC. RT-PCR and western blot analysis of tissues from ESCC patients revealed that PTK7 was significantly upregulated in tumor tissue samples of ESCC. Immunohistochemical staining of PTK7 showed that increased expression of PTK7 was inversely correlated with overall survival (p=0.021). In vitro knockdown of PTK7 inhibited proliferation, survival, wound healing, and invasion of ESCC cells. In addition, PTK7 knockdown decreased phosphorylation of Akt, Erk, and FAK, important determinants of cell proliferation, survival, and migration. Therefore, our findings suggest that PTK7 has potential as a prognostic marker for ESCC and might also be a candidate for targeted therapy in the treatment of ESCC. This article is protected by copyright. All rights reserved.
Cancer Science 05/2013; · 3.33 Impact Factor
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ABSTRACT: The recent DNA methylation studies on cancers have revealed the necessity of profiling an entire human genome and not to restrict the profiling to specific regions of the human genome. It has been suggested that genome-wide DNA methylation analysis enables us to identify the genes that are regulated by DNA methylation in carcinogenesis.
So, we performed whole-genome DNA methylation analysis for human lung squamous cell carcinoma (SCC), which is strongly related with smoking. We also performed microarrays using 21 pairs of normal lung tissues and tumors from patients with SCC. By combining these data, 30 hypermethylated and down-regulated genes, and 22 hypomethylated and up-regulated genes were selected. The gene expression level and DNA methylation pattern were confirmed by semiquantitative reverse-transcriptase polymerase chain reaction and pyrosequencing, respectively.
By these validations, we selected five hypermethylated and down-regulated genes and one hypomethylated and up-regulated gene. Moreover, these six genes were proven to be actually regulated by DNA methylation by confirming the recovery of their DNA methylation pattern and gene expression level using a demethylating agent. The DNA methylation pattern of the CYTL1 promoter region was significantly different between early and advanced stages of SCC.
In conclusion, by combining the whole-genome DNA methylation pattern and the gene expression profile, we identified the six genes (CCDC37, CYTL1, CDO1, SLIT2, LMO3, and SERPINB5) that are regulated by DNA methylation, and we suggest their value as target molecules for further study of SCC.
Journal of thoracic oncology: official publication of the International Association for the Study of Lung Cancer 01/2012; 7(1):20-33. · 4.55 Impact Factor
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ABSTRACT: Remnant lipoproteins (RLPs) are products of partially catabolized chylomicrons and very-low-density lipoprotein, from which some triglycerides have been removed. These particles are smaller and denser than the parent particles and are believed to be strongly atherogenic. We explored the association between RLP cholesterol (RLP-C) and ischemic stroke, including stroke subtypes.
A cohort of 142 ischemic stroke patients (90 men and 52 women; age, 65.2±12.8 years, mean±SD) was enrolled; all had acute infarcts confirmed by diffusion-weighted MRI, and had fasting lipograms. A full stroke-related evaluation was conducted on each patient. An outpatient population of 88 subjects without a history of cerebrovascular or cardiovascular disease served as a control group. Serum RLP fractions were isolated using an immunoaffinity gel containing specific antiapolipoprotein (anti-apo)B-100 and anti-apoA-I antibodies. RLP-C values were considered to be high when they were in the highest quartile of all values in the study.
High RLP-C values were more common in stroke patients than in control patients (31.0% vs. 14.8%, p=0.01), when 5.6 mg/dL (>75th percentile) was used as the cutoff value. Multivariable analyses indicated that RLP-C was a risk factor for stroke, with an odds ratio of 2.54 (p=0.045). The RLP-C level was higher in the large artery atherosclerosis subgroup (5.7±3.9 mg/dL) than in any other stroke subgroup (small vessel occlusion, 4.9±5.9 mg/dL; cardioembolism, 1.8±2.3 mg/dL; stroke of undetermined etiology, 3.1±2.9 mg/dL).
We have found an association between high RLP-C levels and ischemic stroke, and in particular large artery atherosclerotic stroke.
Journal of Clinical Neurology 12/2011; 7(4):203-9. · 1.69 Impact Factor
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ABSTRACT: We report on a 66-year-old woman with a posterior circulation stroke that occurred after bronchial artery embolization (BAE) due to post-tuberculous bronchiectasis. Stroke is a rare complication of BAE and is usually thought to be caused by inadvertent embolization via a bronchial artery-pulmonary vein shunt. However, the possibility of thromboembolic stroke should be considered, because of the patient's possible underlying anatomical variations or atherothrombosis.
Neurological Sciences 11/2011; 33(4):923-6. · 1.32 Impact Factor
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The Canadian journal of neurological sciences. Le journal canadien des sciences neurologiques 11/2011; 38(6):921-4. · 0.97 Impact Factor
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ABSTRACT: The apolipoprotein B (apoB)/apoAI ratio is recognized as a better indicator of cardiovascular disease than other cholesterol measures. Whether intracranial or extracranial atherosclerosis is more closely associated with an increased apoB/apoAI ratio has not been investigated.
A total of 464 statin or fibrate naïve Korean patients with acute ischemic stroke was categorized into 3 groups: intracranial (ICAS, n=236), extracranial (n=44), and no cerebral atherosclerotic stenosis (n=184). The apoB/apoAI ratio and demographics, including the presence of metabolic syndrome, were compared among the groups.
The ICAS group showed a higher apoB/apoAI ratio (0.81±0.02) than both the extracranial atherosclerotic stenosis (0.74±0.03) and no cerebral atherosclerotic stenosis (0.72±0.02) groups (P=0.002). The ratio was substantially increased (0.93±0.03) in patients with advanced ICAS (≥3 intracranial stenoses). With a multivariable analysis, the highest apoB/apoAI ratio quartile was an independent predictor of ICAS (OR, 2.13; 95% CI, 1.05 to 4.33). A dose-response relationship was observed between the presence of advanced ICAS and the apoB/apoAI ratio quartiles (OR, 4.03; 95% CI, 1.26 to 12.88 for the second quartile; OR, 4.88; 95% CI, 1.54 to 15.49 for the third quartile; and OR, 7.79; 95% CI, 2.41 to 25.16 for the fourth quartile when referenced to the first quartile). Patients having more metabolic syndrome components were more likely to have ICAS, advanced ICAS, and a higher apoB/apoAI ratio (P<0.001 for all).
A higher apoB/apoAI ratio is a predictor of ICAS rather than of extracranial atherosclerotic stenosis or no cerebral atherosclerotic stenosis. The apoB/apoAI ratio might be a biomarker for ICAS in Asian patients with stroke.
Stroke 08/2011; 42(11):3040-6. · 5.73 Impact Factor
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ABSTRACT: Central nervous system (CNS) involvement is extremely rare in patients with rheumatoid arthritis (RA). Additionally, most patients with CNS involvement have chronic and severe RA. We present a report of a 66-year-old man who was diagnosed with rheumatoid meningitis and CNS vasculitis without a history of RA. His initial symptom was seizure. Brain magnetic resonance imaging showed leptomeningeal enhancement.CSF analysis revealed slight increase in the number of white blood cells. An examination of viral markers and culture studies for infectious etiology were unremarkable. However, the rheumatoid factor was positive and the levels of anti-cyclic citrullinated peptide antibody were very high. The patient was diagnosed with rheumatoid meningitis and received steroid therapy. However, he developed CNS vasculitis. We suggested that the possibility of rheumatoid meningitis should be considered during the differential diagnosis stage in patients with uncontrolled meningitis, even though RA does not typically show CNS involvement.
Neurological Sciences 08/2011; 32(6):1191-4. · 1.32 Impact Factor
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Soo-Min Shon, Jong-Ho Park,
Matthias Nahrendorf,
Dawid Schellingerhout,
Jeong-Yeon Kim,
Byeong-Teck Kang,
Sang-Wuk Jeong,
Eo-Jin Kim,
Ju Hee Ryu,
Kwangmeyung Kim,
Ick Chan Kwon,
Dong Kun Lee,
Myoung Mook Lee,
Dong-Eog Kim
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ABSTRACT: Few studies have investigated if exercise by itself has anti-atherosclerotic effects, without combining interventions with a low-fat diet. We studied the effects of exercise as a stand-alone intervention on preexisting atheromata by measuring not only plaque size but also the levels of plaque-destabilizing matrix-metalloproteinase (MMP) activity in vivo.
We used near-infrared fluorescent (NIRF) molecular imaging with an MMP-2/9 activatable NIRF probe to visualize the inflammatory protease activity within preexisting atheromata of 17-week-old ApoE(-/-) mice on: (a) normal chow diet (NCD), (b) Western diet (WD), and (c) WD with treadmill exercise for 10 weeks. We also measured tissue levels of aortic lipid peroxidation (LPO) and plasma levels of glucose/lipid/cytokine profiles. Exercise did not attenuate growth of preexisting atheromatous plaques. However, exercise strongly decreased proteolytic activity in plaques for animals on WD, with levels decreasing almost to NCD levels. Exercise was associated with decreased aortic LPO levels and increased blood adiponectin/leptin levels; however, exercise did not affect WD-consumption/weight-gain or improve blood glucose/lipid profiles.
Exercise training reduced aortic MMP activity in mice with preexisting atheromata, even though they remained on a high fat diet and plaque-growth was not attenuated.
Atherosclerosis 02/2011; 216(1):67-73. · 3.79 Impact Factor
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ABSTRACT: The clinical and pathological heterogeneity of progressive supranuclear palsy (PSP) is well established. Even with a well-defined clinical phenotype and a thorough laboratory workup, PSP can be misdiagnosed, especially in its early stages.
A 52-year-old woman, who we initially diagnosed with a behavioral variant of frontotemporal dementia developed parkinsonian features, which then progressed to gait instability and gaze abnormality.
We report herein a pathologically confirmed case of PSP presenting with behavioral changes including agitation and irritability, which eventually led to the cardinal symptoms of progressive supranuclear palsy.
Journal of Clinical Neurology 09/2010; 6(3):148-51. · 1.69 Impact Factor
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ABSTRACT: Vogt-Koyanagi-Harada (VKH) disease is a systemic disease consisting of bilateral granulomatous panuveitis combined with cutaneous and neurologic manifestations. However, there have been few reports of brain magnetic resonance imaging (MRI) in VKH disease. A 54-year-old Korean woman presented with severe periorbital pain, blurred vision and meningismus. Ophthalmologic examination disclosed bilateral optic disc edema with peripapillary nerve fiber hemorrhages. Lumbar puncture revealed monocytic pleocytosis. After a diagnosis of VKH disease was made, the patient was treated with high-dose corticosteroid. Brain MRI showed diffusely thickened posterior ocular walls with retinal detachment and perineural infiltrative changes along the optic nerves and adjacent pachymeningeal enhancement of the anterior temporal lobes bilaterally. We report a case of VKH disease with panuveitis and meningeal involvement of the anterior temporal lobe detected by brain MRI.
Neurological Sciences 03/2010; 31(6):785-8. · 1.32 Impact Factor
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ABSTRACT: We report on a 42-year-old female patient who presented with high arterial blood pressure of 245/150 mmHg and hypertensive brainstem encephalopathy that involved the brainstem and extensive supratentorial deep gray and white matter. The lesions were nearly completely resolved several days after stabilization of the arterial blood pressure. Normal diffusion-weighted imaging findings and high apparent diffusion coefficient values suggested that the main pathomechanism was vasogenic edema owing to severe hypertension. On the basis of a literature review, the absolute value of blood pressure or whether the patient can control his/her blood pressure seems not to be associated with the degree of the lesions evident on magnetic resonance imaging. It remains to be determined if the acceleration rate and the duration of elevated arterial blood pressure might play a key role in the development of the hypertensive encephalopathy pattern.
Neurology International 01/2010; 2(1):e9.
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ABSTRACT: To determine the role of small vertebrobasilar artery (SVBA) in patients with posterior circulation stroke (PCS), we evaluated the ischemic patterns, collateral features, and stroke mechanisms in PCS patients with SVBA.
Ischemic findings on magnetic resonance (MR) imaging were correlated with 3D time-of-flight/contrast-enhanced MR angiography and/or catheter angiography in 18 patients (mean age, 68.0+/-11.8 years; 9 males). SVBA (lumen diameter of <3 mm) was compared with stenotic normal-sized VBA (NVBA) in 14 PCS patients.
Ischemic lesions were predominantly observed in the cerebellum and/or medulla (vertebral artery (VA) territory). All subjects had fetal posterior circulation (FPC) from the internal carotid artery to the posterior cerebral artery. Sixteen patients (88.9%) had distal or diffuse VA stenosis/occlusion. In 14 patients (77.8%), long circumferential artery (LCA) was prominently observed. In atherothrombotic patients, infratentorial PCS might occur following artery-to-artery embolism from the low-flowed or stenotic VA to LCA. Ischemic patterns between subjects with and without VA disease were almost similar. As the degree of VA disease increased, the frequency of LCA prominence showed an increased tendency (P=0.003). Relatively small, scattered infarcts were observed in patients with SVBA than in those with stenotic NVBA.
FPC does not protect against infratentorial PCS. Regardless of extensive arterial lesions, relatively small infarcts may be due to previously established collaterals from the LCA, which could compensate for the defects in the infratentorial area.
Journal of the neurological sciences 09/2009; 287(1-2):227-35. · 2.32 Impact Factor
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ABSTRACT: To elucidate the proteins related to the development and progress of esophageal squamous cell carcinoma (ESCC), we performed gene expression profile analysis of 14 ESCC tissues. We identified 182 genes that were commonly upregulated (p < 10(-5)) and 54 genes that were downregulated in ESCC tissues (p < 10(-6)). In order to validate the gene expression profiles, we did semiquantitative RT-PCR analysis and found 11 genes upregulated in greater than 70% of 19 tissue samples. We further examined the protein expression level and the distribution patterns of four genes: aurora kinase B (AURKB), periostin (POSTN), heat shock protein 47 (HSP47), and matrix metalloprotease 1 (MMP1). Ultimately, three genes (AURKB, HSP47, POSTN) were verified to be increased at both the mRNA and protein levels. Among them, AURKB and HSP47 were found to increase in the early development stage of ESCC and POSTN might be considered to function in the cell-cell interactions between cancer cell and adjacent stromal cells. Accordingly, these studies may provide valuable information for the identification of the genes that are necessary to study further their functions. Moreover, these genes might be used as potential diagnostic or therapeutic target molecules for ESCC patients.
Oncology Research Featuring Preclinical and Clinical Cancer Therapeutics 01/2009; 18(4):141-51. · 1.30 Impact Factor
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ABSTRACT: Basilar artery (BA) dolichoectasia (dilatative arteriopathy) (BAD) causes arterial elongation and enlargement with subsequent hemodynamic changes leading to thrombosis, microembolization and brainstem compression. Little is known about the association between BAD and the pattern of pontine infarct in patients without BA stenosis.
We studied patients with isolated pontine infarcts recruited from a stroke registry. The patients with pontine infarction were divided into 2 groups based on the location of the lesion on magnetic resonance imaging as follows: paramedian pontine infarct (PPI) and lacunar pontine infarct (LPI). We compared the vascular findings and risk factors in the patients with the 2 types of infarcts. Using modified imaging criteria, we compared the following dolichoectatic components of the BA: (1) ectasia, (2) lateral displacement and (3) height.
There were 96 patients (45 women, 51 men). Thirty-five patients had PPI and 61 had LPI. Ectasia of the BA was more frequent in the PPI group than in the LPI group (31.4 vs. 11.5%; p = 0.016). Ectasia of the BA was associated with an elevated odds ratio in the patients with PPI (odds ratio 5.80, 95% CI 1.66-20.21) by multivariate analysis.
Ectasia of the BA other than elongation or angulation appears to contribute to the occurrence of PPI. These findings may be helpful in predicting certain types of stroke.
Cerebrovascular Diseases 12/2008; 27(2):114-8. · 2.72 Impact Factor
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ABSTRACT: An anterior inferior cerebellar artery (AICA) stroke is characterized by vertigo, tinnitus, and deafness in addition to facial weakness, hemiataxia, and hypalgesia. Sometimes, it can present as sudden deafness with vertigo, without brainstem or cerebellar signs. We report a 55-year-old woman with hypertension and diabetes, showing recurrent audiovestibular disturbance before a typical pattern of AICA infarction, which was initially diagnosed as Ménière's disease. In elderly patients with recurrent hearing loss and vertigo lasting several minutes, lack classic brainstem or cerebellar signs, if they have vascular risk factors, physicians may also consider the potential symptom of AICA infarction.
Neurological Sciences 11/2008; 29(5):359-62. · 1.32 Impact Factor
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ABSTRACT: The corticobulbar tract fibers descend near the corticospinal tract, mostly to the upper medulla, where they decussate and ascend in the dorsolateral medulla to connect with the contralateral facial nucleus. Therefore, central type facial palsy can be present in patients with ipsilateral dorsolateral upper medullar lesion. We describe a 71-year-old man with lateral medullary infarction who showed ipsilateral peripheral type facial palsy. Brain diffusion-weighted image showed hyperintensities on the left dorsolateral portion of upper medulla and adjacent inferomedial tegmentum of the lower pons. Transfemoral cerebral angiography depicted prominence of ipsilateral posterior inferior cerebellar artery with focal stenosis. Left posterior inferior cerebellar artery might supply the inferolateral tegmentum of the lower pons, which is usually supplied from anterior inferior cerebellar artery. The peripheral type facial palsy in our patient may have resulted from facial infranuclear involvement of the caudal pons extended from dorsolateral upper medullary lesion in ascending pathway of corticobulbar tract fibers.
Journal of stroke and cerebrovascular diseases: the official journal of National Stroke Association 10/2008; 17(5):263-5.
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Im Il Na,
Gi Jeong Cheon,
Du Hwan Choe,
Byung Hyun Byun,
Hye Jin Kang,
Jae Soo Koh, Jong Ho Park,
Heejong Baek,
Baek-Yeol Ryoo,
Jae Cheol Lee,
Sung Hyun Yang
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ABSTRACT: This study evaluated the potential role of (18)F-fluoro-2-deoxy-glucose (FDG) uptake by primary tumors and N2 nodes on positron emission tomography (PET) in patients with stage IIIA N2 non-small-cell lung cancer (NSCLC). We retrospectively analyzed PET scans of 57 NSCLC patients who received surgical resection and proved pathologically to have stage IIIA N2 disease between January 2000 and April 2005. On each patient's PET scan, FDG uptake by the primary tumor and N2 nodes was evaluated using the maximum standardized uptake value (SUV). The SUV of the primary tumor (SUVt) and the highest value of the N2 nodes (SUVn) in each patient were treated as continuous variables for initial analysis. The SUVn and T stage (T1-2 vs. T3) were significant prognostic factors in univariate analysis (P=0.004 and 0.017, respectively), but the SUVt was not. Adjusted for the size of the N2 node (<or=1cm vs.>1cm), SUVt, and T stage (T1-2 vs. T3), the SUVn was associated with survival (P=0.019). Patients were divided into those with a low and high SUVn using a cutoff value. Controlling for the size of N2 nodes and T stages, patients with a low SUVn showed a tendency for prolonged survival (P=0.053). These results suggest that FDG uptake by the N2 node may predict survival of patients with stage IIIA N2 NSCLC.
Lung Cancer 04/2008; 60(1):69-74. · 3.43 Impact Factor
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ABSTRACT: To elucidate the relationship between MetS and ischemic stroke, we evaluated the association of MetS and individual components with frequency of ischemic stroke lesions and investigated the independent associations between them in acute ischemic stroke patients.
We evaluated 370 acute ischemic stroke patients who underwent brain magnetic resonance (MR) imaging and MR angiography. The stroke subgroups were categorized as intracranial large artery atherosclerosis (IC-LAA, n=151), extracranial large artery atherosclerosis (EC-LAA, n=35), and nonatherosclerosis (NA, n=184). MetS was defined using the criteria of the International Diabetes Federation.
Patients with IC-LAA group showed a higher rate of MetS and previous ischemic lesions (predominantly deep gray/white matter) than those with EC-LAA and NA (all P<0.001). The number of previous ischemic lesions showed a tendency to increase as the number of MetS components increased in the IC-LAA group (P=0.004). In the IC-LAA group, age (OR, 1.04) and MetS (OR, 3.28) were independently associated with previous ischemic lesions (all P<0.001), which was prominent with more severe MetS components after adjustment for risk factors (P<0.001). Among the component conditions, high blood pressure, impaired fasting glucose, and abdominal obesity were more associated with previous ischemic lesions (all P<0.001) than low high-density lipoprotein and high triglyceride levels (P=0.010 and 0.028, respectively).
Our study showed a strong association between MetS and previous ischemic lesions, more in patients with IC-LAA.
Clinical Neurology and Neurosurgery 03/2008; 110(3):215-21. · 1.58 Impact Factor
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ABSTRACT: We studied four patients with diabetes mellitus and chronic renal failure who developed sudden choreic movement disorders. The clinical manifestations, laboratory findings, MR imaging findings, and clinical outcome in each patient were evaluated.
All four patients had long-term diabetes mellitus and severe azotaemia. Brain MR findings consisted of bilateral symmetric basal ganglia lesions, with decreased signal intensity on T1-weighted images and increased signal intensity on T2-weighted images. All three patients who underwent diffusion-weighted MR imaging (DWI) showed signal intensities similar to those of the surroundings in regions corresponding to increased signal intensity on T2-weighted images, with slightly increased apparent diffusion coefficient (ADC) values. Two of the patients showed small focal areas of restricted diffusion within the basal ganglia lesions. After haemodialysis, follow-up MR imaging in all patients demonstrated that the basal ganglia lesions had regressed markedly, with some residual changes. The movement disorders also improved in all patients.
A syndrome associated with acute bilateral basal ganglia lesions in diabetic uraemic patients is rare, with reversible changes demonstrated by clinical and imaging findings. DWI showed that the bilateral basal ganglia lesions in this syndrome were primarily vasogenic in origin, although there were small foci of cytotoxic oedema within the lesions.
Neuroradiology 01/2008; 49(12):1009-13. · 2.82 Impact Factor
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ABSTRACT: In patients with posterior inferior cerebellar artery infarction (PICAI) or lateral medullary infarction (LMI), the ipsilateral vertebral artery is often hypoplastic and therefore at an increased risk of ischaemic stroke.
To investigate the frequency and clinical relevance of hypoplastic vertebral artery (HVA) in patients with ischaemic stroke with or without vertebral artery territory and in normal healthy people.
529 patients with ischaemic stroke, including vertebral artery territory infarction (LMI or PICAI), were classified according to their stroke location (303 anterior circulation strokes (ACS) and 226 posterior circulation strokes (PCS)) by MRI. The frequency of HVA, defined as a diameter of < or = 2 mm by magnetic resonance angiography, was measured in comparison with 306 normal healthy people.
185 patients (35.2%) from the cohort had HVA (3.4%, bilaterally). Patients with PCS showed a higher rate of HVA than those with ACS (45.6% vs 27.1%, p<0.001). The HVA frequency of those with ACS was similar to that of the normal group (26.5%). Of the 112 patients with vertebral artery territory stroke, 58 (51.8%) had HVA (bilateral HVA in 10), and all of 48 showed ipsilateral HVA territory stroke. In 102 patients with vertebral artery territory stroke, classification of the ipsilateral vertebral artery as hypoplastic (vs dominant or symmetric) tended to predict the involvement of multiple and extensive lesions, and a higher incidence of steno-occlusion (p<0.001).
HVA is not rare in the normal population, and is frequent in patients with PCS. People with HVA may have a high probability of PCS, with atherosclerotic susceptibility and ipsilateral lesions in the vertebral artery territory.
Journal of neurology, neurosurgery, and psychiatry 10/2007; 78(9):954-8. · 4.87 Impact Factor
