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1.
Br J Cancer ; 112(2): 357-64, 2015 Jan 20.
Article in English | MEDLINE | ID: mdl-25321194

ABSTRACT

BACKGROUND: SET and MYND domain-containing protein 2 (SMYD2) is a lysine methyltransferase for histone H3, p53 and Rb and inhibits their transactivation activities. In this study, we tested whether SMYD2 (1q42) acts as a cancer-promoting factor by being overexpressed in gastric cancer. METHODS: We analysed 7 gastric cancer cell lines and 147 primary tumor samples of gastric cancer, which were curatively resected in our hospital. RESULTS: SET and MYND domain-containing protein 2 was detected in these cell lines (five out of seven cell lines; 71.4%) and primary tumor samples (fifty-six out of one hundred and forty-seven cases; 38.1%). Knockdown of SMYD2 using specific small interfering RNA inhibited proliferation, migration and invasion of SMYD2-overexpressing cells in a TP53 mutation-independent manner. Overexpression of SMYD2 protein correlated with larger tumor size, more aggressive lymphatic invasion, deeper tumor invasion and higher rates of lymph node metastasis and recurrence. Patients with SMYD2-overexpressing tumours had a worse overall rate of survival than those with non-expressing tumours (P=0.0073, log-rank test) in an intensity and proportion score-dependent manner. Moreover, multivariate analysis demonstrated that SMYD2 was independently associated with worse outcome (P=0.0021, hazard ratio 4.25 (1.69-10.7)). CONCLUSIONS: These findings suggest that SMYD2 has a crucial role in tumor cell proliferation by its overexpression and highlight its usefulness as a prognostic factor and potential therapeutic target in gastric cancer.


Subject(s)
Gene Expression , Histone-Lysine N-Methyltransferase/metabolism , Stomach Neoplasms/enzymology , Adult , Aged , Aged, 80 and over , Cell Line, Tumor , Cell Proliferation , Female , Gene Knockdown Techniques , Histone-Lysine N-Methyltransferase/genetics , Humans , Kaplan-Meier Estimate , Male , Middle Aged , Multivariate Analysis , Proportional Hazards Models , Stomach Neoplasms/mortality , Stomach Neoplasms/surgery , Treatment Outcome , Tumor Suppressor Protein p53/genetics
2.
Br J Cancer ; 109(2): 401-7, 2013 Jul 23.
Article in English | MEDLINE | ID: mdl-23820256

ABSTRACT

BACKGROUND: This study investigated the usefulness of a novel inflammation-based prognostic system, named the COP-NLR (COmbination of Platelet count and Neutrophil to Lymphocyte Ratio), for predicting the postoperative survival of patients with colorectal cancer (CRC). METHODS: The COP-NLR was calculated on the basis of data obtained on the day of admission: patients with both an elevated platelet count (>30 Ɨ 10(4) mm(-3)) and an elevated NLR (>3) were allocated a score of 2, and patients showing one or neither were allocated a score of 1 or 0, respectively. RESULTS: Four-hundred and eighty patients were enrolled. Multivariate analysis of clinical characteristics selected by univariate analysis showed that the COP-NLR (1, 2/0) (odds ratio, 0.464; 95% confidence interval, 0.267-0.807; P=0.007) had an association with cancer-specific survival, along with pathology, lymph node metastasis, the serum levels of carcinoembryonic antigen, C-reactive protein and albumin, and the Glasgow Prognostic Score. Kaplan-Meier analysis and log-rank test revealed that the COP-NLR was able to divide such patients into three independent groups (P<0.001). CONCLUSION: The COP-NLR is considered to be a useful predictor of postoperative survival in patients with CRC.


Subject(s)
Blood Platelets/pathology , Colorectal Neoplasms/mortality , Colorectal Neoplasms/surgery , Lymphocytes/pathology , Neutrophils/pathology , Aged , Aged, 80 and over , Blood Cell Count , Colorectal Neoplasms/blood , Female , Humans , Male , Middle Aged , Postoperative Period , Prognosis , Retrospective Studies , Survival Analysis , Treatment Outcome
3.
Br J Cancer ; 108(10): 2123-9, 2013 May 28.
Article in English | MEDLINE | ID: mdl-23591203

ABSTRACT

BACKGROUND: We recently isolated vasohibin-1 (VASH1), a novel angiogenic molecule that is specifically expressed in activated vascular endothelial cells (ECs), and the status of VASH1 expression has been documented in various cancer angiogenesis. The aim of this study was to assess the prognostic value of VASH1 expression in prostate cancer (PCa). METHODS: In this study, we retrospectively analysed the clinical records and evaluated the VASH1 expression of tumour microvessels in 167 patients with PCa who underwent radical prostatectomy. We immunohistochemically examined the microvessels positive for anti-CD34 as microvessel density (MVD) and the microvessels with activated ECs positive for VASH1 density. RESULTS: We found that the VASH1 expression was restricted to ECs in the tumour stroma. VASH1 density was significantly associated with pathological T stage, Gleason score and MVD. The 5-year PSA recurrence-free survival rate was 58.8% in patients with higher VASH1 density (Ć¢Ā‰Ā§12 per mm(2)) and 89.1% in patients with lower VASH1 density (<12 per mm(2)), respectively (P<0.001). Microvessel density was not an independent predictor of PSA recurrence. Multivariate analysis revealed that high VASH1 density was an independent prognostic indicator of PSA recurrence (P=0.007, HR=2.950). CONCLUSION: VASH1 density represents a clinically relevant predictor of patient prognosis and can be a new biomarker that would provide additional prognostic information in PCa.


Subject(s)
Carcinoma/diagnosis , Cell Cycle Proteins/metabolism , Prostatic Neoplasms/diagnosis , Aged , Biomarkers, Tumor/metabolism , Carcinoma/blood supply , Carcinoma/metabolism , Carcinoma/mortality , Cell Count , Humans , Male , Microvessels/metabolism , Microvessels/pathology , Middle Aged , Neovascularization, Pathologic/diagnosis , Neovascularization, Pathologic/metabolism , Prognosis , Prostate-Specific Antigen/metabolism , Prostatic Neoplasms/blood supply , Prostatic Neoplasms/metabolism , Prostatic Neoplasms/mortality , Retrospective Studies , Survival Analysis
4.
Br J Cancer ; 108(6): 1324-31, 2013 Apr 02.
Article in English | MEDLINE | ID: mdl-23422756

ABSTRACT

BACKGROUND: Several studies have demonstrated that YWHAZ (14-3-3ƎĀ¶), included in the 14-3-3 family of proteins, has been implicated in the initiation and progression of cancers. We tested whether YWHAZ acted as a cancer-promoting gene through its activation/overexpression in gastric cancer (GC). METHODS: We analysed 7 GC cell lines and 141 primary tumours, which were curatively resected in our hospital between 2001 and 2003. RESULTS: Overexpression of the YWHAZ protein was frequently detected in GC cell lines (six out of seven lines, 85.7%) and primary tumour samples of GC (72 out of 141 cases, 51%), and significantly correlated with larger tumour size, venous and lymphatic invasion, deeper tumour depth, and higher pathological stage and recurrence rate. Patients with YWHAZ-overexpressing tumours had worse overall survival rates than those with non-expressing tumours in both intensity and proportion expression-dependent manner. YWHAZ positivity was independently associated with a worse outcome in multivariate analysis (P=0.0491, hazard ratio 2.3 (1.003-5.304)). Knockdown of YWHAZ expression using several specific siRNAs inhibited the proliferation, migration, and invasion of YWHAZ-overexpressing GC cells. Higher expression of the YWHAZ protein was significantly associated with the lower expression of miR-375 in primary GC tissues (P=0.0047). CONCLUSION: These findings suggest that YWHAZ has a pivotal role in tumour cell proliferation through its overexpression, and highlight its usefulness as a prognostic factor and potential therapeutic target in GC.


Subject(s)
14-3-3 Proteins/metabolism , Biomarkers, Tumor/metabolism , Cell Proliferation , Neoplasm Recurrence, Local/pathology , Stomach Neoplasms/pathology , 14-3-3 Proteins/antagonists & inhibitors , 14-3-3 Proteins/genetics , Adult , Aged , Aged, 80 and over , Apoptosis , Biomarkers, Tumor/genetics , Blotting, Western , Cell Adhesion , Cell Movement , Female , Follow-Up Studies , Gene Expression Profiling , Humans , Immunoenzyme Techniques , Lymphatic Metastasis , Male , MicroRNAs/genetics , Middle Aged , Neoplasm Recurrence, Local/genetics , Neoplasm Recurrence, Local/metabolism , Neoplasm Staging , Oligonucleotide Array Sequence Analysis , Prognosis , RNA, Messenger/genetics , RNA, Small Interfering/genetics , Real-Time Polymerase Chain Reaction , Reverse Transcriptase Polymerase Chain Reaction , Stomach Neoplasms/genetics , Stomach Neoplasms/metabolism , Survival Rate , Tumor Cells, Cultured
5.
Br J Cancer ; 108(9): 1822-9, 2013 May 14.
Article in English | MEDLINE | ID: mdl-23579215

ABSTRACT

BACKGROUND: Several recent studies demonstrated that microRNAs are stably detectable in plasma/serum. We tested whether miR-18a, which is located in the miR-17-92 cluster and reported to be highly expressed in tissues of oesophageal squamous cell carcinoma (ESCC), served as a plasma biomarker in patients with ESCC. METHODS: This study was divided into three steps: (1) confirmation of higher miR-18a levels in primary ESCC tissues and cell lines than normal ESCC tissues and a human fibroblast cell line. (2) Evaluation of the plasma miR-18a assay using quantitative RT-PCR by comparing results from 106 consecutive patients with ESCC and 54 healthy volunteers. (3) Evaluation of the assay for monitoring tumour dynamics in patients with ESCC. RESULTS: (1) Expression of miR-18a was significantly higher in ESCC tissues (P=0.0020) and ESCC cell lines (P=0.0121) than normal tissues and fibroblasts. (2) Plasma concentrations of miR-18a were significantly higher in ESCC patients than healthy volunteers (P<0.0001; ESCC patients vs healthy volunteers (meanĀ±s.d.): 11.77Ā±13.45 vs 0.73Ā±0.54 amol Āµl(-1)). The value of the area under the receiver-operating characteristic (ROC) curve (AUC) was 0.9449. Furthermore, the ROC curves to detect early ESCC such as pTis-1 and pStage0-I showed AUCs of 0.9479 and 0.9642, respectively. (3) Plasma levels of miR-18a were significantly lower in postoperative samples than preoperative samples (P=0.0076). CONCLUSION: Plasma miR-18a may be a very useful biomarker for cancer detection and the monitoring of tumour dynamics in patients with ESCC.


Subject(s)
Biomarkers, Tumor/blood , Carcinoma, Squamous Cell/blood , Esophageal Neoplasms/blood , MicroRNAs/blood , Aged , Biomarkers, Tumor/genetics , Carcinoma, Squamous Cell/diagnosis , Carcinoma, Squamous Cell/genetics , Cell Line, Tumor , Esophageal Neoplasms/diagnosis , Esophageal Neoplasms/genetics , Humans , MicroRNAs/biosynthesis , MicroRNAs/genetics , Prognosis , ROC Curve
6.
Br J Cancer ; 108(2): 361-9, 2013 Feb 05.
Article in English | MEDLINE | ID: mdl-23329235

ABSTRACT

BACKGROUND: Several recent studies have demonstrated that microRNAs (miRNAs) are stably detectable in plasma/serum. We tested miR-221 and miR-375, which are frequently reported to be highly and poorly expressed in pancreatic cancer (PCa), as candidates for plasma biomarkers in PCa. METHODS: This study was divided into three parts: (1) Confirmation of higher miR-221 levels in primary PCa tissue and cell lines than normal pancreatic tissues. (2) Evaluation of plasma miR-221 and miR-375 concentrations by comparing results from 47 consecutive PCa patients and 30 healthy volunteers. (3) Evaluation of the assay for monitoring tumour dynamics in PCa patients. RESULTS: (1) Expression of miR-221 was significantly higher in PCa tissues and cell lines than normal pancreatic tissues. (2) Plasma miR-221 concentrations were significantly higher in PCa patients than that in benign pancreatic tumours (P=0.016) and controls (P<0.0005), while plasma miR-375 concentrations tended to be lower in PCa patients (P=0.064), and the miR-221/miR-375 ratio was significantly higher (P<0.0001) in PCa patients than in controls. (3) Plasma miR-221 concentrations were significantly reduced in postoperative samples (P=0.018). Furthermore, PCa patients with high plasma miR-221 concentrations had significant correlation with distant metastasis (P=0.041), and non-resectable status (P=0.021). CONCLUSION: Plasma miR-221 could be a useful biomarker for cancer detection, monitoring tumour dynamics and predicting malignant outcomes in PCa patients, and may contribute to clinical decision making in PCa treatments.


Subject(s)
MicroRNAs/blood , Pancreatic Neoplasms/blood , Pancreatic Neoplasms/genetics , Aged , Biomarkers, Tumor/blood , Biomarkers, Tumor/genetics , Cell Line, Tumor , Female , Humans , Male
7.
Br J Cancer ; 106(4): 740-7, 2012 Feb 14.
Article in English | MEDLINE | ID: mdl-22262318

ABSTRACT

BACKGROUND: Recently, it was reported that plasma microRNAs (miRNAs) are low-invasive useful biomarkers for cancer. We attempted to isolate gastric cancer (GC)-associated miRNAs comparing pre- and post-operative paired plasma, thereby excluding the possible effects of individual variability. METHODS: This study was divided into four steps: (1) microarray analysis comparing pre- and post-operative plasma; (2) validation of candidate miRNAs by quantitative RT-PCR; (3) validation study of selected miRNAs using paired plasma; and (4) comparison of the levels of selected miRNAs in plasma between healthy controls and patients. RESULTS: From the results of microarray analysis, nine candidate miRNAs the levels of which were markedly decreased in post-operative plasma were selected for further studies. After confirmation of their post-operative marked reduction, two candidate miRNAs, miR-451 and miR-486, were selected as plasma biomarkers, considering the abundance in plasma, and marked decrease in post-operative samples. In validation, the two miRNAs were found to decrease in post-operative plasma in 90 and 93% of patients (both P<0.01). In comparison with healthy controls, the levels of both miRNAs were found to be significantly higher in patients, and the area under the curve values were high at 0.96 and 0.92. CONCLUSION: Plasma miR-451 and miR-486 could be useful blood-based biomarkers for screening GC.


Subject(s)
MicroRNAs/blood , Stomach Neoplasms/genetics , Biomarkers, Tumor/blood , Early Detection of Cancer , Female , Humans , Male , Microarray Analysis , Postoperative Period , Preoperative Period , Stomach Neoplasms/blood , Stomach Neoplasms/surgery , Validation Studies as Topic
8.
Br J Anaesth ; 108(6): 936-42, 2012 Jun.
Article in English | MEDLINE | ID: mdl-22474310

ABSTRACT

BACKGROUND: The purpose of this observational study was to investigate the relationship between splanchnic and renal blood flow during infrarenal aortic cross-clamp (XC) and postoperative gastrointestinal perfusion and function. METHODS: Descending aortic blood flow (DABF) was continuously monitored with an oesophageal Doppler monitor (Cardio-Q, Deltex Ltd, Chichester, UK) in 31 patients undergoing elective abdominal aortic aneurysm repair. Cardiac output (CO) was determined by indocyanine green dilution before, during, and after XC. Perioperative gastrointestinal perfusion was assessed by gastric intramucosal pH (pHi, Tonocap, GE Healthcare, Helsinki, Finland). Postoperative gastrointestinal recovery was assessed by the number of postoperative days until the patient successfully resumed solid food intake. The relationship between the mean DABF during XC and gastric pHi after XC release and postoperative gastrointestinal recovery was analysed with Spearman's correlation coefficient. RESULTS: accounted for Ć¢ĀˆĀ¼ 55% of CO during XC and significantly decreased during XC, despite arterial pressure remaining within an optimal range. There were two distinct relationships between DABF during XC and gastric pHi after XC release. Gastric pHi steeply and linearly declined when indexed DABF was below 0.82 litre min(-1) m(-2). Above this critical value, there was no linear relationship between them. The duration of postoperative gastrointestinal dysfunction was inversely correlated with the mean DABF during XC. The best cut-off value of the mean indexed DABF during XC to prevent prolonged gastrointestinal dysfunction was 1.2 litre min(-1) m(-2). CONCLUSIONS: Decreased DABF during XC associates splanchnic hypoperfusion after XC release and delayed recovery of gastrointestinal function.


Subject(s)
Aorta, Thoracic/physiopathology , Aortic Aneurysm, Abdominal/surgery , Gastrointestinal Tract/physiopathology , Splanchnic Circulation , Adult , Aged , Aged, 80 and over , Aortic Aneurysm, Abdominal/physiopathology , Cardiac Output , Female , Gastric Acidity Determination , Humans , Male , Middle Aged , Postoperative Period , Regional Blood Flow
9.
Int J Immunogenet ; 39(2): 119-25, 2012 Apr.
Article in English | MEDLINE | ID: mdl-22117627

ABSTRACT

Abnormal immunological responses to certain microbial agents may play a crucial role in the pathogenesis of Kawasaki disease (KD). The association studies between histo-blood group genes (Lewis and ABO blood types) and various types of infectious diseases or vasculopathy have been carried out based on the fact that glycosylated antigens could directly mediate microbial infections. We attempted to clarify the role of blood type antigens in the development of KD and coronary artery lesions in KD patients. The subjects included 164 KD patients enrolled from 1998 to 2003 (1st group), 232 patients from 2004 to 2009 (2nd group), and 223 healthy children and 118 patients with growth hormone deficiency as controls. The genotyping of the FUT2 and FUT3 genes, and ABO genotypes, was determined with the TaqMan SNP assay and allele-specific polymerase chain reaction. No significant differences were observed in the genotypes and allele frequencies of the FUT2 and FUT3 genes between the groups. The frequency of the BB blood genotype was significantly higher in KD patients with coronary artery lesions in the 1st and 2nd groups than in the controls (17% and 14% vs. 5%, P = 0.0020). This is the first report to investigate the roles of ABO and Lewis blood types in the development of KD, and in the formation of coronary artery lesions in KD patients. These data suggest that the ABO blood type may play a role in the development of coronary artery lesions in KD patients.


Subject(s)
ABO Blood-Group System/genetics , Coronary Artery Disease/genetics , Coronary Vessels/pathology , Genetic Predisposition to Disease , Mucocutaneous Lymph Node Syndrome/blood , Polymorphism, Genetic , Alleles , Case-Control Studies , Child, Preschool , Coronary Artery Disease/blood , Coronary Artery Disease/pathology , Female , Fucosyltransferases/genetics , Gene Frequency , Genotyping Techniques , Humans , Infant , Lewis Blood Group Antigens/genetics , Male , Mucocutaneous Lymph Node Syndrome/genetics , Mucocutaneous Lymph Node Syndrome/pathology , Seasons , Galactoside 2-alpha-L-fucosyltransferase
10.
Br J Cancer ; 105(1): 104-11, 2011 Jun 28.
Article in English | MEDLINE | ID: mdl-21673684

ABSTRACT

BACKGROUND: Several recent studies demonstrated that microRNAs (miRNAs) are stably detectable in plasma/serum. We hypothesised that plasma miRNAs concentrations contributed to potential biomarkers in patients with oesophageal squamous cell carcinoma (ESCC). METHODS: We selected three oncogenic miRNAs (miR-21, miR-184, miR-221) and one tumour suppressive miRNA (miR-375), which are frequently reported in squamous cell carcinoma, as candidate targets for this plasma miRNA assay. This study was divided into three steps: (1) Determination of appropriate plasma miRNAs in preliminary tests. (2) Evaluation of whether the plasma miRNA assays could monitor tumour dynamics. (3) Validation study on the clinical application of plasma miRNA assays in 50 ESCC patients and 20 healthy volunteers. RESULTS: (1) In preliminary tests, the plasma level of miR-21 was significantly higher (P=0.0218) and that of miR-375 (P=0.0052) was significantly lower in ESCC patients than controls. (2) The high plasma miR-21 levels reflected tumour levels in all cases (100%). The plasma level of miR-21 was significantly reduced in postoperative samples (P=0.0058). (3) On validation analysis, the plasma level of miR-21 tended to be higher in ESCC patients (P=0.0649), while that of miR-375 was significantly lower (P<0.0001) and the miR-21/miR-375 ratio was significantly higher (P<0.0001) in ESCC patients than in controls. The value of the area under the receiver-operating characteristic curve (AUC) was 0.816 for the miR-21/miR-375 ratio assay. Patients with a high plasma level of miR-21 tended to have greater vascular invasion (P=0.1554) and to show a high correlation with recurrence (P=0.0164). CONCLUSION: Detection of circulating miRNAs might provide new complementary tumour markers for ESCC.


Subject(s)
Biomarkers, Tumor/blood , Carcinoma, Squamous Cell/blood , Esophageal Neoplasms/blood , MicroRNAs/blood , Aged , Carcinoma, Squamous Cell/diagnosis , Carcinoma, Squamous Cell/genetics , Case-Control Studies , Esophageal Neoplasms/diagnosis , Esophageal Neoplasms/genetics , Female , Humans , Lymphatic Metastasis , Male , Neoplasm Recurrence, Local/blood , Neoplasm Recurrence, Local/diagnosis , Neoplasm Recurrence, Local/genetics , Prognosis , Survival Rate
11.
Br J Cancer ; 105(11): 1733-40, 2011 Nov 22.
Article in English | MEDLINE | ID: mdl-22045190

ABSTRACT

BACKGROUND: Several recent studies have demonstrated that microRNAs (miRNAs) are stably detectable in the plasma/serum. We hypothesised that miR-18a in the plasma is a potential biomarker in patients with pancreatic cancer. METHODS: miR-18a is located in the miR-17-92 cluster and reported to be highly expressed in pancreatic cancer tissues. This study was divided into three parts: (1) Confirmation of higher miR-18a levels in primary pancreatic cancer tissues and cell lines than in normal pancreatic tissues and a human fibroblast cell line. (2) Evaluation of the plasma miR-18a assay using quantitative RT-PCR by comparing plasma results obtained from 36 patients with pancreatic cancer and from 30 healthy volunteers. (3) Evaluation of the assay for monitoring tumour dynamics in patients with pancreatic cancer. RESULTS: (1) The expression of miR-18a was significantly higher in pancreatic cancer tissues (P=0.012) and pancreatic cancer cell lines (P=0.015) than in normal tissues and fibroblasts. (2) Plasma concentrations of miR-18a were significantly higher in pancreatic cancer patients than in controls (P<0.0001). The value of the area under the receiver-operating characteristic curve (AUC) was 0.9369. (3) Plasma levels of miR-18a were significantly lower in postoperative samples than in preoperative samples (P=0.0077). CONCLUSION: Circulating miR-18a might provide new complementary tumour markers for pancreatic cancer.


Subject(s)
Biomarkers, Tumor/blood , MicroRNAs/blood , Pancreatic Neoplasms/genetics , Adolescent , Adult , Aged , Aged, 80 and over , Biomarkers, Tumor/genetics , Cell Line, Tumor , Child , Child, Preschool , Female , Fibroblasts/metabolism , Genetic Testing/methods , Humans , Infant , Infant, Newborn , Male , MicroRNAs/genetics , Middle Aged , Pancreatic Neoplasms/blood , Pancreatic Neoplasms/pathology , Real-Time Polymerase Chain Reaction/methods , Reverse Transcriptase Polymerase Chain Reaction/methods , Young Adult
12.
Eur Surg Res ; 46(2): 57-64, 2011.
Article in English | MEDLINE | ID: mdl-21135561

ABSTRACT

BACKGROUND: Surgical resection is the most effective treatment for patients with stage II colorectal cancer (CRC). However, a few patients with early-phase CRC suffer postoperative cancer death. AIMS: To investigate the risk factors for postoperative cancer death in patients who undergo surgery for stage II CRC. METHODS: Prognostic significance was analyzed by χ(2) test, univariate analyses, Kaplan-Meier analysis and log-rank test using clinicopathological factors from the database. RESULTS: A total of 205 patients with stage II CRC were evaluated. Age (≤ 65/>65 years), venous invasion (negative/positive), number of dissected lymph nodes (≤ 9/≥ 10), grade of lymph node dissection (sufficient/insufficient) and albumin level (< 3.5/≥ 3.5 g/dl) were associated with shorter overall survival. Univariate analysis of the clinicopathological factors revealed that only the grade of lymph node dissection (sufficient/insufficient) was associated with postoperative cancer death (odds ratio 2.993, 95% confidence interval 1.216-7.368, p = 0.017).Kaplan-Meier analysis and log-rank test revealed that the group with insufficient lymph node dissection had a higher incidence of postoperative cancer death than the group with sufficient dissection (p < 0.001). CONCLUSIONS: Insufficient lymph node dissection is an independent risk factor for postoperative cancer death in patients who undergo surgery for stage II CRC.


Subject(s)
Colorectal Neoplasms/mortality , Colorectal Neoplasms/surgery , Lymph Node Excision , Aged , Colorectal Neoplasms/blood , Colorectal Neoplasms/pathology , Female , Humans , Hypoalbuminemia/complications , Japan/epidemiology , Kaplan-Meier Estimate , Lymph Node Excision/adverse effects , Lymph Node Excision/methods , Male , Middle Aged , Neoplasm Invasiveness , Neoplasm Staging , Postoperative Period , Prognosis , Retrospective Studies , Risk Factors , Serum Albumin/metabolism
13.
AJNR Am J Neuroradiol ; 41(2): 219-223, 2020 02.
Article in English | MEDLINE | ID: mdl-31857330

ABSTRACT

BACKGROUND AND PURPOSE: The newly developed ultra-high-resolution CT is equipped with a 0.25-mm detector, which has one-half the conventional section thickness, one-half the in-plane detector element width, and one-half the reconstructed pixel width compared with conventional-detector CT. Thus, the ultra-high-resolution CT scanner should provide better image quality for microvasculature than the conventional-detector CT scanners. This study aimed to determine whether ultra-high-resolution CT produces superior-quality images of the lenticulostriate arteries compared with conventional-detector CT. MATERIALS AND METHODS: From February 2017 to June 2017, thirteen patients with aneurysms (4 men, 9 women; mean age, 61.2 years) who underwent head CTA with both ultra-high-resolution CT and conventional-detector CT were enrolled. Two board-certified radiologists determined the number of all lenticulostriate arteries on the CTA coronal images of the MCA M1 segment reconstructed from 512 matrixes on conventional-detector CT and 1024 matrixes on ultra-high-resolution CT. RESULTS: There were statistically more lenticulostriate arteries identified on ultra-high-resolution CT (average, 2.85 Ā± 0.83; 95% CI, 2.509-3.183) than on conventional-detector CT (average, 2.17 Ā± 0.76; 95% CI, 1.866-2.480) (P = .009) in 16 of the total 26 MCA M1 segments. CONCLUSIONS: Improvements in lenticulostriate artery visualization were the result of the combined package of the ultra-high-resolution CT scanner plus the ultra-high-resolution scanning protocol, which includes higher radiation doses with lower than the national diagnostic reference levels and stronger adaptive iterative dose-reduction processing. This package for ultra-high-resolution CT is a simple, noninvasive, and easily accessible method to evaluate microvasculature such as the lenticulostriate arteries.


Subject(s)
Arteries/diagnostic imaging , Brain/blood supply , Brain/diagnostic imaging , Computed Tomography Angiography/methods , Neuroimaging/methods , Adult , Aged , Female , Humans , Male , Middle Aged , Radionuclide Imaging/methods , Retrospective Studies
14.
J Cell Biol ; 126(6): 1341-51, 1994 Sep.
Article in English | MEDLINE | ID: mdl-8089169

ABSTRACT

ICRF-193, a novel noncleavable, complex-stabilizing type topoisomerase (topo) II inhibitor, has been shown to target topo II in mammalian cells (Ishida, R., T. Miki, T. Narita, R. Yui, S. Sato, K. R. Utsumi, K. Tanabe, and T. Andoh. 1991. Cancer Res. 51:4909-4916). With the aim of elucidating the roles of topo II in mammalian cells, we examined the effects of ICRF-193 on the transition through the S phase, when the genome is replicated, and through the M phase, when the replicated genome is condensed and segregated. Replication of the genome did not appear to be affected by the drug because the scheduled synthesis of DNA and activation of cdc2 kinase followed by increase in mitotic index occurred normally, while VP-16, a cleavable, complex-stabilizing type topo II inhibitor, inhibited all these processes. In the M phase, however, late stages of chromosome condensation and segregation were clearly blocked by ICRF-193. Inhibition at the stage of compaction of 300-nm diameter chromatin fibers to 600-nm diameter chromatids was demonstrated using the drug during premature chromosome condensation (PCC) induced in tsBN2 baby hamster kidney cells in early S and G2 phases. In spite of interference with M phase chromosome dynamics, other mitotic events such as activation of cdc2 kinase, spindle apparatus reorganization and disassembly and reassembly of nuclear envelopes occurred, and the cells traversed an unusual M phase termed "absence of chromosome segregation" (ACS)-M phase. Cells then continued through further cell cycle rounds, becoming polyploid and losing viability. This effect of ICRF-193 on the cell cycle was shown to parallel that of inactivation of topo II on the cell cycle of the ts top2 mutant yeast. The results strongly suggest that the essential roles of topo II are confined to the M phase, when the enzyme decatenates intertwined replicated chromosomes. In other phases of the cycle, including the S phase, topo II may thus play a complementary role with topo I in controlling the torsional strain accumulated in various genetic processes.


Subject(s)
Cell Cycle/drug effects , Cell Cycle/genetics , Chromosomes/physiology , DNA Topoisomerases, Type II/physiology , Piperazines/pharmacology , Polyploidy , Animals , CHO Cells , Cell Line , Cell Survival/drug effects , Chromosomes/drug effects , Cricetinae , Diketopiperazines , HeLa Cells , Humans , Nuclear Envelope/drug effects , Topoisomerase II Inhibitors
15.
Transplant Proc ; 41(1): 422-4, 2009.
Article in English | MEDLINE | ID: mdl-19249570

ABSTRACT

The shortage of organ donors has impeded the development of human hepatocyte transplantation. Immortalized hepatocytes, however, could provide an unlimited supply of transplantable cells. To determine whether immortalized hepatocytes could provide global metabolic support in end-stage liver disease, rat hepatocyte clones were developed by transduction with the gene encoding the simian virus 40 T antigen (SVLT) using the new technique of human artificial mini chromosome (HAC). Immortalized rat hepatocyte clones were developed by transduction with the gene encoding the SV40 using HAC. Many clones were obtained using this technique. From comparison of the properties of all these clones using the normal hepatocytes and reverse transcription-polymerase chain reaction (RT-PCR), the characteristics of the cell clones (at least partially characterized, and assayed for albumin, glucose-6-phosphate and dipeptidyl peptidase-4, gamma-glutamyltranspeptidase, SVLT and beta-actin expression by RT-PCR) showed no differences other than the immortalization. We compared the albumin bands of the first-day (0-day) and 30-day cells by RT-PCR, showing conditions to be stable for at least 1 month. Three experimental animal model groups were used for albumin analysis: nonalbumin rats with 2/3 hepatectomy only (R-NARs; n = 4); R-NARs with intrasplenic transplantation of 3 x 10(7) primary hepatocytes (pHTx; n = 4); and R-NARs with intrasplenic transplantation of 3 x 10(7) immortalized hepatocytes (iHTx; n = 4). All HTx groups produced albumin, but the immortalized hepatocyte group did not generate significantly elevated albumin levels compared with primary hepatocytes. The results presented herein have demonstrated an initial step toward the development of immortalized hepatocytes for transplantable cells or artificial organs using HAC technology.


Subject(s)
Chromosomes, Artificial, Human/genetics , Hepatocytes/transplantation , Serum Albumin/genetics , Animals , CHO Cells , Chromosomes, Artificial, Human/physiology , Cricetinae , Cricetulus , Female , Hepatocytes/physiology , Humans , Male , Rats , Rats, Inbred Lew , Reverse Transcriptase Polymerase Chain Reaction
16.
Eur Surg Res ; 43(3): 286-90, 2009.
Article in English | MEDLINE | ID: mdl-19648751

ABSTRACT

BACKGROUND: The Centers for Disease Control and Prevention guideline recommended the use of 2% chlorhexidine as a percutaneous disinfectant for central venous catheter (CVC) insertion. However, in Japan, 0.05% chlorhexidine is commonly used as well as 10% povidone-iodine, instead of 2% chlorhexidine. PURPOSE: It was the aim of this study to examine whether the use of 0.05% chlorhexidine is inferior to conventional 10% povidone-iodine as a percutaneous disinfectant for preventing CVC-related bloodstream infection (CVC-RBSI). METHODS: Between September 2006 and July 2008, the time interval from insertion to development of CVC-RBSI was compared prospectively between patients prepared with 0.05% chlorhexidine (group 1, n = 286 CVCs) and those prepared with conventional 10% povidone-iodine (group 2, n = 298 CVCs). RESULTS: Two hundred and thirty-nine patients received 584 CVCs for a total of 6,205 catheter-days. CVC-RBSI (3.22 per 1,000 catheter-days) was diagnosed in 20 cases. There were no significant differences in patient background factors between group 1 and 2, except for blood culture positivity (p = 0.0450). However, Kaplan-Meier analysis and the log rank test revealed no significant difference between group 1 and 2 in the time interval from insertion until development of CVC-RBSI. CONCLUSIONS: Use of 0.05% chlorhexidine is not inferior to conventional 10% povidone-iodine as a cutaneous disinfectant for the prevention of CVC-RBSI.


Subject(s)
Anti-Infective Agents, Local/therapeutic use , Catheter-Related Infections/prevention & control , Catheterization, Central Venous/adverse effects , Chlorhexidine/therapeutic use , Povidone-Iodine/therapeutic use , Aged , Colorectal Neoplasms/therapy , Female , Humans , Male , Middle Aged , Prospective Studies
17.
Environ Technol ; 30(1): 111-7, 2009 Jan.
Article in English | MEDLINE | ID: mdl-19213473

ABSTRACT

In this paper, a submerged membrane bioreactor was used to treat 'higher-load' grey water: (a) kitchen-sink wastewater only, and (b) a mixture of kitchen-sink wastewater and washing-machine wastewater. For each type of wastewater, three systems operated at different hydraulic retention times (HRTs) were investigated. In the mixture of kitchen-sink wastewater and washing-machine wastewater, the reactor with a short HRT of four hours was stopped due to foaming. It has been observed that for both types of wastewater, an HRT of eight hours or longer can be used for the treatment. However, it has been observed that a higher COD in the permeate of the mixture can be obtained compared with that of the kitchen-sink wastewater only. This indicated that washing-machine wastewater has some component that is not easily biodegradable. The total linear akylbenzene sulfonate (LAS) removal was > 99% even at a concentration of 10-23 mg 1(-1).


Subject(s)
Bioreactors , Membranes, Artificial , Waste Disposal, Fluid/methods , Conservation of Natural Resources
18.
J Nutr Health Aging ; 23(6): 532-537, 2019.
Article in English | MEDLINE | ID: mdl-31233074

ABSTRACT

OBJECTIVES: To determine the association between sarcopenia and overactive bladder (OAB) in elderly diabetic patients using the Japanese version of SARC-F called SARC-F-J. DESIGN: Cross-sectional study. SETTINGS AND PARTICIPANTS: The study included 329 elderly diabetic patients (aged ≥65 years) who regularly visited the outpatient clinic at Community hospital in Japan. MEASUREMENTS: The condition of OAB was evaluated using the OAM symptom score, which involves a self-administered questionnaire, and sarcopenia was evaluated using the self-administered SARC-F-J questionnaire comprising five items. The odds ratio for OAB due to sarcopenia was calculated using multiple logistic regression analysis, with OAB as the dependent variable and sarcopenia as the explanatory variable. RESULTS: A total of 329 patients (186 males, 143 females) were included for analysis in the present study. Of these patients, 22.9% had sarcopenia and 18.7% had OAB. After adjusting the variables, the odds ratio for OAB due to sarcopenia was 4.46 (95% confidence interval [CI], 1.14-17.36, P = 0.031) and 2.09 (95% CI, 0.52-8.26, P = 0.293) for males and females, respectively. CONCLUSION: This study found that sarcopenia was significantly associated with OAB in elderly diabetic male patients based on SARC-F-J. Moreover, the possibility of the development of OAB should be considered during the medical examinations of elderly diabetic male patients with sarcopenia.


Subject(s)
Diabetes Complications/complications , Sarcopenia/complications , Urinary Bladder, Overactive/etiology , Aged , Aged, 80 and over , Cross-Sectional Studies , Female , Humans , Male , Surveys and Questionnaires
19.
Transplant Proc ; 40(2): 379-81, 2008 Mar.
Article in English | MEDLINE | ID: mdl-18374074

ABSTRACT

Although islet transplantation has been remarkably improved by the Edmonton protocol, the insulin independence rate after islet transplantation from one donor pancreas has remained low. The c-Jun NH2-terminal kinases (JNKs) are classic stress-activated protein kinases; many cellular stresses have been shown to stimulate JNK activation. JNK in the pancreas is activated during brain death, pancreas procurement, and organ preservation, and its activity is progressively increased during the isolation procedure. Moreover, JNK activity in the transplanted liver after islet transplantation increases markedly within 24 hours. In this study, we show the effect of a JNK inhibitor during islet isolation and transplantation. Use of the JNK inhibitor in pancreas preservation, islet culture, and/or islet transplantation prevents islet cell apoptosis and improves islet graft function. These findings suggest that inhibition of JNK could prevent the impairment of islet cells and improve outcomes after pancreatic islet transplantation.


Subject(s)
Enzyme Inhibitors/therapeutic use , Islets of Langerhans Transplantation/physiology , Islets of Langerhans/cytology , MAP Kinase Kinase 4/antagonists & inhibitors , Animals , Blood Glucose/metabolism , Cell Separation , Diabetes Mellitus, Experimental/surgery , Islets of Langerhans/drug effects , Mice , Treatment Outcome
20.
Transplant Proc ; 40(2): 441-3, 2008 Mar.
Article in English | MEDLINE | ID: mdl-18374095

ABSTRACT

BACKGROUND: Islet transplantation is gradually gaining acceptance for the treatment of type 1 diabetes mellitus. One of the unknown questions is alcohol intake; we have prohibited alcohol intake after islet transplantation although there is no solid evidence to support this. MATERIALS AND METHODS: In this study, we employed a mouse model to determine the effect of oral ethanol intake on transplanted islets. Either 500 or 150 islets were infused selectively into the right liver lobe of chemically induced diabetic mice. After transplantation, mice were orally administered either water (as a control) or various concentrations of ethanol for 14 consecutive days occasionally (once per day) or continuously (all intake was alcohol). Blood glucose levels were monitored and oral glucose tolerance tests (OGTT) performed. RESULTS: After 500 islets had been transplanted, all mice were cured from diabetes, but the continuous alcohol intake group showed significantly prolonged time to diabetes reversal and significantly lower glucose clearance rates by OGTT compared with the control group. After 150 islet transplantations, the diabetes cure rate in the continuous alcohol intake group was significantly lower than the control group (continuous alcohol vs control: 3/8 vs 11/12, P < .05). However, the occasional alcohol intake group showed no difference from the control group, even with as few as 150 islets transplanted per mouse. CONCLUSION: The present results demonstrated that continuous but not occasional alcohol intake reduced the success of intraportal islet transplantation.


Subject(s)
Alcohol Drinking/adverse effects , Diabetes Mellitus, Experimental/surgery , Islets of Langerhans Transplantation/physiology , Animals , Blood Glucose/metabolism , Diabetes Mellitus, Experimental/complications , Disease Models, Animal , Male , Mice , Mice, Inbred BALB C , Portal Vein , Transplantation, Isogeneic
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