Publications by authors named "Takuya Nagata"

91 Publications

N-Terminal Pro-B-Type Natriuretic Peptide and Incident CKD.

Kidney Int Rep 2021 Apr 16;6(4):976-985. Epub 2021 Jan 16.

Department of Epidemiology and Public Health, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.

Introduction: Serum N-terminal pro-B-type natriuretic peptide (NT-proBNP) levels have been associated with the progression of kidney impairment among patients with chronic kidney disease (CKD), but only a few studies have investigated the association between serum NT-proBNP levels and incident CKD in general populations.

Methods: A total of 2486 Japanese community-dwelling residents ≥40 years of age without CKD at baseline were followed up by repeated annual health examinations for 10 years. Participants were divided into 4 groups according to serum NT-proBNP levels. CKD was defined as an estimated glomerular filtration rate (eGFR) <60 ml/min/1.73m or the presence of proteinuria. Cox proportional hazards models were used to estimate hazard ratios (HRs) for risk of CKD. Linear mixed models were used to compare changes in eGFR.

Results: During the follow-up period, 800 participants developed CKD. The multivariable-adjusted HRs (95% confidence intervals [CIs]) for developing CKD were 1.00 (reference), 1.32 (1.11-1.57), 1.40 (1.10-1.78), and 1.94 (1.38-2.73) for serum NT-proBNP levels of <55, 55-124, 125-299, and ≥300 pg/ml, respectively ( for trend <0.001). The decline of eGFR during the follow-up was significantly more rapid among participants with higher serum NT-proBNP levels ( for trend <0.001). Adding serum NT-proBNP to the model composed of known risk factors for CKD improved the predictive ability for developing CKD.

Conclusions: Higher serum NT-proBNP levels were associated with greater risks of developing CKD and greater decline in eGFR. Serum NT-proBNP could be a useful biomarker for assessing the future risk of CKD in a general Japanese population.
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http://dx.doi.org/10.1016/j.ekir.2021.01.006DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8071624PMC
April 2021

Serum NT-proBNP levels and histopathological myocardial fibrosis in autopsied cases from a Japanese community: The Hisayama Study.

J Cardiol 2021 Apr 13. Epub 2021 Apr 13.

Department of Epidemiology and Public Health, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan; Center for Cohort Studies, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan. Electronic address:

Background: natriuretic peptide is associated with myocardial fibrosis in animal models and among patients with heart disease. However, it remains unclear whether serum N-terminal pro-B-type peptide (NT-proBNP) levels are associated with histopathologically proven myocardial fibrosis among individuals without apparent heart disease. This study aimed to evaluate the association between serum NT-proBNP levels and the histopathologically estimated myocardial fibrotic area in autopsied samples from a community.

Methods: we selected 63 cases without apparent heart disease with available data of serum NT-proBNP concentrations within six years before death (average age: 82 years; male: 52%) from autopsied cases in a community, and evaluated the percentage areas of myocardial fibrosis in four cardiac segments from each case (i.e. 252 cardiac segments in total). The association between serum NT-proBNP levels and the percentage area of myocardial fibrosis was estimated using a linear mixed model for repeated measures.

Results: serum NT-proBNP levels were positively correlated with myocardial fibrotic area [Pearson's correlation coefficient: r = 0.49 (95% confidence interval: 0.28-0.66), p <0.001]. Serum NT-proBNP levels were significantly associated with the percentage areas of myocardial fibrosis after adjusting for potential confounding factors. There was no evidence of heterogeneity in the association between the subgroups with and without reduced estimated glomerular filtration rate (<60 mL/min/1.73 m).

Conclusions: the present study demonstrated that elevated serum NT-proBNP levels were associated with the histopathologically measured myocardial fibrotic area in autopsied cases from a community. These findings may help clarify the association between elevated serum NT-proBNP levels and myocardial fibrosis and their influence on prognosis.
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http://dx.doi.org/10.1016/j.jjcc.2021.03.014DOI Listing
April 2021

Urinary N-terminal pro-B-type natriuretic peptide as a biomarker for cardiovascular events in a general Japanese population: the Hisayama Study.

Environ Health Prev Med 2021 Apr 12;26(1):47. Epub 2021 Apr 12.

Department of Epidemiology and Public Health, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.

Background: Epidemiological evidence has shown that serum N-terminal pro-brain natriuretic peptide (NT-proBNP) concentrations, a diagnostic biomarker for heart failure, are positively associated with cardiovascular risk. Since NT-proBNP in serum is excreted in urine, it is hypothesized that urinary NT-proBNP concentrations are correlated with serum concentrations and linked with cardiovascular risk in the general population.

Methods: A total of 3060 community-dwelling residents aged ≥ 40 years without history of cardiovascular disease (CVD) were followed up for a median of 8.3 years (2007-2015). Serum and urinary concentrations of NT-proBNP at baseline were compared. The hazard ratios (HRs) and their 95% confidence intervals (CIs) for the association between NT-proBNP concentrations and the risk of developing CVD were computed using the Cox proportional hazards model.

Results: The median values (interquartile ranges) of serum and urinary NT-proBNP concentrations at baseline were 56 (32-104) pg/mL and 20 (18-25) pg/mL, respectively. There was a strong quadratic correlation between the serum and urinary concentrations of NT-proBNP (coefficient of determination [R] = 0.72): urinary concentrations of 20, 27, and 43 pg/mL were equivalent to serum concentrations of 55, 125, and 300 pg/mL, respectively. During the follow-up period, 170 subjects developed CVD. The age- and sex-adjusted risk of CVD increased significantly with higher urinary NT-proBNP levels (P for trend < 0.001). This association remained significant after adjustment for traditional cardiovascular risk factors (P for trend = 0.009). The multivariable-adjusted risk of developing CVD almost doubled in subjects with urinary NT-proBNP of ≥ 43 pg/mL as compared to those with urinary NT-proBNP of ≤ 19 pg/mL (HR 2.07, 95% CI 1.20-3.56).

Conclusions: The present study demonstrated that urinary NT-proBNP concentrations were well-correlated with serum concentrations and were positively associated with cardiovascular risk. Given that urine sampling is noninvasive and does not require specially trained personnel, urinary NT-proBNP concentrations have the potential to be an easy and useful biomarker for detecting people at higher cardiovascular risk.
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http://dx.doi.org/10.1186/s12199-021-00970-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8042718PMC
April 2021

Clinical study of modulated electro-hyperthermia for advanced metastatic breast cancer.

Mol Clin Oncol 2021 May 17;14(5):103. Epub 2021 Mar 17.

Department of Science and Surgery, University of Toyama, Toyama 930-0194, Japan.

Modulated electro-hyperthermia (mEHT) is a new treatment modality developed to overcome the problems associated with traditional hyperthermia; mEHT uses a precise impedance-matched system and modulated radiofrequency current flow to malignant tumors. It selects the malignant cells based on their biophysical differences, due to their high metabolic rate, individual (autonomic) behavior and membrane status. The aim of the present study was to report the outcomes of mEHT in the treatment of advanced breast cancer. mEHT was examined in 10 patients with advanced metastatic breast cancer and recurrent disease, who were considered incurable by standard therapy protocols. Of the 10 patients, partial response was achieved in 3, disease stability in 3, and progressive disease in 4; however, their quality of life was improved based on their subjective reports. No adverse effects were observed in any of the 10 patients. The present study demonstrated the feasibility of mEHT as a possible therapy for advanced breast cancer cases when standard therapies fail. Moreover, mEHT had no side effects and may be combined with various treatments for long-term therapy.
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http://dx.doi.org/10.3892/mco.2021.2265DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8010507PMC
May 2021

Risk Prediction Model for Incident Atrial Fibrillation in a General Japanese Population - The Hisayama Study.

Circ J 2021 Feb 23. Epub 2021 Feb 23.

Department of Epidemiology and Public Health, Graduate School of Medical Sciences, Kyushu University.

Background: The risk prediction of incident atrial fibrillation (AF) is useful to prevent AF and its complications. The aim of this study is to develop a new risk prediction model for incident AF using the prospective longitudinal data from a general Japanese population.Methods and Results:A total of 2,442 community-dwelling AF-free residents aged ≥40 years were followed up from 1988 to 2012 (46,422 person-years). The development of AF was confirmed by a standard 12-lead electrocardiogram at repeated health examinations and by medical records at clinics or hospitals. The risk prediction model for incident AF was developed using a Cox proportional hazards model. During the follow up, 230 AF events were confirmed. Age, sex, systolic blood pressure, waist circumference, estimated glomerular filtration rate, abnormal cardiac murmur, high R-wave amplitude, and arrhythmia other than AF were selected for inclusion in the model. This model showed good discrimination (Harrell's c statistics: 0.785) and calibration (Greenwood-Nam-D'Agostino test: P=0.87) for AF risk at 10 years.

Conclusions: The new risk prediction model showed good performance on the individual risk assessment of the future onset of AF in a general Japanese population. As this model included commonly used clinical parameters, it may be useful for determining the requirements for the careful evaluation of AF, such as frequent electrocardiogram examinations in clinical settings, and subsequent reductions in the risk of AF-related complications.
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http://dx.doi.org/10.1253/circj.CJ-20-0794DOI Listing
February 2021

Serum High-Sensitivity C-Reactive Protein Levels and the Development of Atrial Fibrillation in a General Japanese Population - The Hisayama Study.

Circ J 2021 Feb 18. Epub 2021 Feb 18.

Department of Epidemiology and Public Health, Graduate School of Medical Sciences, Kyushu University.

Background: Atrial fibrillation (AF) is a common arrhythmia in the elderly, and causes complications such as cardioembolic stroke. Serum high-sensitivity C-reactive protein (hs-CRP), a marker of systemic inflammation, has been reported to be a risk factor for developing AF in Western countries. However, few community-based studies have examined this issue in general Asian populations.Methods and Results:A total of 2,510 community-dwelling Japanese participants aged ≥40 years without a history of AF were divided into 4 groups according to the sex-specific quartiles of serum hs-CRP concentrations (Q1, lowest and Q4, highest) and followed up for 24 years. The hazard ratios and their 95% confidence intervals for the development of AF were estimated using a Cox proportional hazards model. During the follow up, 234 subjects developed AF. The risk of AF increased significantly with elevating serum hs-CRP levels after adjustment for potential confounding factors (hazard ratio [95% confidence interval], Q1, 1.00 [reference]; Q2, 1.26 [0.83-1.92]; Q3, 1.77 [1.18-2.66]; and Q4, 1.89 [1.24-2.86]; P for trend <0.001).

Conclusions: The study findings suggest that elevated serum hs-CRP levels are an independent risk factor for the development of AF in a general Japanese population.
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http://dx.doi.org/10.1253/circj.CJ-20-0751DOI Listing
February 2021

Multi-functionality of a tryptophan residue conserved in substrate-binding groove of GH19 chitinases.

Sci Rep 2021 Jan 28;11(1):2494. Epub 2021 Jan 28.

Department of Advanced Bioscience, Kindai University, 3327-204 Nakamachi, Nara, 631-8505, Japan.

GH19 and GH22 glycoside hydrolases belonging to the lysozyme superfamily have a related structure/function. A highly conserved tryptophan residue, Trp103, located in the binding groove of a GH19 chitinase from moss Bryum coronatum (BcChi-A) appears to have a function similar to that of well-known Trp62 in GH22 lysozymes. Here, we found that mutation of Trp103 to phenylalanine (W103F) or alanine (W103A) strongly reduced the enzymatic activity of BcChi-A. NMR experiments and the X-ray crystal structure suggested a hydrogen bond between the Trp103 side chain and the -2 sugar. Chitooligosaccharide binding experiments using NMR indicated that the W103F mutation reduced the sugar-binding abilities of nearby amino acid residues (Tyr105/Asn106) in addition to Trp103. This appeared to be derived from enhanced aromatic stacking of Phe103 with Tyr105 induced by disruption of the Trp103 hydrogen bond with the -2 sugar. Since the stacking with Tyr105 was unlikely in W103A, Tyr105/Asn106 of W103A was not so affected as in W103F. However, the W103A mutation appeared to reduce the catalytic potency, resulting in the lowest enzymatic activity in W103A. We concluded that Trp103 does not only interact with the sugar, but also controls other amino acids responsible for substrate binding and catalysis. Trp103 (GH19) and Trp62 (GH22) with such a multi-functionality may be advantageous for enzyme action and conserved in the divergent evolution in the lysozyme superfamily.
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http://dx.doi.org/10.1038/s41598-021-81903-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7844276PMC
January 2021

Emotional loneliness is associated with a risk of dementia in a general Japanese older population: the Hisayama Study.

J Gerontol B Psychol Sci Soc Sci 2020 Nov 10. Epub 2020 Nov 10.

Center for Cohort Studies, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.

Objectives: To investigate the association of loneliness and its component subscales with the risk of dementia in a general Japanese older population.

Method: A total of 1,141 community-dwelling Japanese residents aged ≥65 years without dementia were prospectively followed up for a median 5.0 years. We evaluated any loneliness and its component subscales-namely, social and emotional loneliness-by using the 6-Item de Jong Gierveld Loneliness Scale. Cox proportional hazards models were used to estimate hazard ratios (HRs) of each loneliness type on the risk of dementia controlling for demographic factors, lifestyle factors, physical factors, social isolation factors, and depression.

Results: During the follow-up, 114 participants developed dementia. The age- and sex-adjusted incidence rate of dementia was significantly greater in participants with any loneliness and emotional loneliness than those without. The multivariable-adjusted HRs (95% confidence intervals) of participants with any loneliness and emotional loneliness on incident dementia were 1.61 (1.08-2.40) and 1.65 (1.07-2.54), respectively, as compared to those without. However, there was no significant association between social loneliness and dementia risk. In subgroup analyses of social isolation factors, excess risks of dementia associated with emotional loneliness were observed in participants who had a partner, lived with someone, or rarely communicated with relatives or friends, but such association was not significant in participants who had no partner, lived alone, or frequently communicated with friends or relatives.

Discussion: The present study suggested that loneliness, especially emotional loneliness, was a significant risk factor for the development of dementia in the general older population in Japan.
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http://dx.doi.org/10.1093/geronb/gbaa196DOI Listing
November 2020

Expression of laminin-5 gamma 2 chain predicts invasion of extramammary Paget's disease cell.

APMIS 2021 Jan 21;129(1):3-8. Epub 2020 Oct 21.

Departments of Surgery and Science, Faculty of Medicine, Academic Assembly, University of Toyama, Toyama City, Japan.

Extramammary Paget's disease (EMPD) is a rare malignant skin neoplasm characterized by intraepidermal proliferation of tumor cells. The tumor cells of EMPD may sometimes invade into the dermis or metastasize into the regional lymph nodes. Several studies have proposed mechanisms underlying the increased invasiveness of EMPD; however, molecular markers indicating invasiveness have yet to be well characterized. Laminin-5 (Lam-5), a heterotrimer composed of three chains (α3, β3, and γ2), is a major component of the basement membrane in many tissues. One of the chains, Lam-5 γ2, is a marker of invasion, because it often develops as a monomer in malignant neoplasms. We investigated the expression of Lam-5 γ2 and its role for the invasiveness in EMPD. Paraffin-embedded specimens of EMPD obtained from 36 patients were examined immunohistochemically for Lam-5 γ2. The cases adopted into this study comprised 16 cases of intraepidermal lesions and 20 cases with dermal invasion. The basement membrane seen in normal skin disappeared in one-third of non-invasive cases and in most invasive cases. The disappearance of Lam-5 γ2 in the basement membrane and its cytoplasmic expression was more observed in the invasive cases than non-invasive cases. Expression of Lam-5 γ2 may be a biological marker to predict invasiveness of EMPD.
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http://dx.doi.org/10.1111/apm.13086DOI Listing
January 2021

Severe Drowsiness with Fever Induced by Transdermal Fentanyl Administration.

J Palliat Med 2020 08;23(8):1006-1008

Department of Hospital Pharmaceutics, School of Pharmacy, Showa University, Shinagawa-ku, Japan.

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http://dx.doi.org/10.1089/jpm.2020.0113DOI Listing
August 2020

Serum N-terminal pro-B-type natriuretic peptide as a predictor for future development of atrial fibrillation in a general population: the Hisayama Study.

Int J Cardiol 2020 Dec 24;320:90-96. Epub 2020 Jun 24.

Department of Epidemiology and Public Health, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582, Japan; Center for Cohort Studies, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582, Japan.

Background: Biomarkers for predicting future development of atrial fibrillation (AF) have not been fully established in general populations. The aim of this study was to assess the predictive ability of serum N-terminal pro-B-type natriuretic peptide (NT-proBNP) for the development of AF.

Methods And Results: A total of 3126 community-dwelling Japanese subjects aged ≥ 40 years without a history of AF in 2002 were followed up for a median of 10.2 years. Serum NT-proBNP levels at baseline were divided into four categories (≤ 54, 55-124, 125-299, and ≥ 300 pg/mL) according to the current guidelines and prior reports. The hazard ratios for the development of AF were estimated using a Cox proportional hazards model. During the follow-up period, 153 subjects developed new-onset AF. The age- and sex-adjusted cumulative incidence of AF increased significantly with higher serum NT-proBNP levels (p < 0.001 for trend). The association remained significant after adjustment for known risk factors for AF and cardiovascular disease (hazard ratio [95% confidence interval]: ≤ 54 pg/mL: 1.00 [reference]; 55-124 pg/mL: 1.72 [1.00-2.97]; 125-299 pg/mL: 3.95 [2.23-6.98]; ≥ 300 pg/mL: 8.51 [4.48-16.17]; p < 0.001 for trend). Furthermore, incorporation of serum NT-proBNP levels into the model consisting of known risk factors for AF and cardiovascular disease significantly improved the predictive ability for developing AF (Harrell's c-statistics: 0.828 to 0.844, p = 0.01; continuous net reclassification improvement: 0.41, p < 0.001; integrated discrimination improvement: 0.031, p < 0.001).

Conclusions: Serum NT-proBNP levels can be a risk biomarker for predicting future development of AF in a general Japanese population.
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http://dx.doi.org/10.1016/j.ijcard.2020.06.018DOI Listing
December 2020

Relationship between T cell receptor clonotype and PD-1 expression of tumor-infiltrating lymphocytes in colorectal cancer.

Eur J Immunol 2020 10 3;50(10):1580-1590. Epub 2020 Jun 3.

Department of Immunology, Faculty of Medicine, Academic Assembly, University of Toyama, Toyama, Japan.

Adoptive T cell therapy using tumor-specific T cells or TCR-modified T cells is a promising next-generation immunotherapy. The major source of tumor-reactive T cells is PD-1 tumor-infiltrating lymphocytes (TILs). In contrast, PD-1 TILs have received little attention. Here, we analyzed the TCR-β repertoires of PD-1 and PD-1 CD8 TILs derived from colorectal cancer and breast cancer. Approximately 40-60% of the PD-1 population consisted of oligoclonal populations in both colorectal cancer and breast cancer. In contrast, approximately 37% of the PD-1 population consisted of an oligoclonal population in colorectal cancer, whereas 14% of them were oligoclonal in breast cancer. In colorectal cancer, the TCR repertoires of PD-1 CD8 TILs and PD-1 CD8 TILs hardly overlapped. Interestingly, clonally expanded CD8 TILs in primary tumors and the metastases expressing the same clonotypic TCR showed the same phenotype regarding the PD-1-expression. These results suggest that the intrinsic properties of TCRs determine the fate of TILs in terms of whether they become PD-1 or PD-1 in the tumor microenvironment. Further functional analysis of TCRs in TILs will allow us to better understand the regulatory mechanisms for PD-1 expression on TILs and may contribute to tumor immunotherapy.
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http://dx.doi.org/10.1002/eji.201948399DOI Listing
October 2020

Pulmonary lymphangitic carcinomatosis from gallbladder cancer mimicking diffuse alveolar haemorrhage.

Respirol Case Rep 2020 Apr 17;8(3):e00540. Epub 2020 Feb 17.

Department of Internal Medicine Kagawa Rosai Hospital Marugame Japan.

Diagnosis in cases with pulmonary lymphangitic carcinomatosis as a primary manifestation is difficult due to unawareness of the cancer. An 81-year-old man was admitted due to a one-week history of dyspnoea and haemoptysis. Chest computed tomography showed diffuse bilateral ground-grass opacity and partial consolidation. We suspected diffuse alveolar haemorrhage. High-dose methylprednisolone and cyclophosphamide did not improve his condition and he died from respiratory failure. Autopsy revealed pulmonary lymphangitic carcinomatosis of whole lungs and primary gallbladder cancer. We should consider pulmonary lymphangitic carcinomatosis in the differential diagnosis of patients with haemoptysis and diffuse lung opacity of unknown origin.
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http://dx.doi.org/10.1002/rcr2.540DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7026625PMC
April 2020

Pathophysiological properties of CLIC3 chloride channel in human gastric cancer cells.

J Physiol Sci 2020 Feb 17;70(1):15. Epub 2020 Feb 17.

Department of Surgery and Sciences, Graduate School of Medicine and Pharmaceutical Sciences, University of Toyama, Toyama, 930-0194, Japan.

Pathophysiological functions of chloride intracellular channel protein 3 (CLIC3) in human gastric cancer have been unclear. In the tissue microarray analysis using 107 gastric cancer specimens, CLIC3 expression was negatively correlated with pathological tumor depth, and the patients with lower expression of CLIC3 exhibited poorer prognosis. CLIC3 was expressed in the plasma membrane of cancer cells in the tissue. CLIC3 expression was also found in a human gastric cancer cell line (MKN7). In whole-cell patch-clamp recordings of the cells expressing CLIC3, NPPB-sensitive outwardly rectifying Cl currents were observed. Cell proliferation was significantly accelerated by knockdown of CLIC3 in MKN7 cells. On the other hand, the proliferation was attenuated by exogenous CLIC3 expression in human gastric cancer cells (KATOIII and NUGC-4) in which endogenous CLIC3 expression is negligible. Our results suggest that CLIC3 functions as a Cl channel in the plasma membrane of gastric cancer cells and that decreased expression of CLIC3 results in unfavorable prognosis of gastric cancer patients.
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http://dx.doi.org/10.1186/s12576-020-00740-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7026216PMC
February 2020

Metachronous rupture of a residual pancreaticoduodenal aneurysm after release of the median arcuate ligament: a case report.

Surg Case Rep 2020 Feb 3;6(1):34. Epub 2020 Feb 3.

Department of Surgery and Science, Graduate School of Medicine and Pharmaceutical Sciences, University of Toyama, 2630, Sugitani, Toyama, 930-0194, Japan.

Background: Multiple pancreaticoduodenal artery aneurysms in association with median arcuate ligament syndrome (MALS) are relatively rare. A treatment option, such as a median arcuate ligament (MAL) release or embolization of the aneurysms, should be considered in such cases, but the treatment criteria remain unclear.

Case Report: A 75-year-old man was transferred to our hospital because of a ruptured pancreaticoduodenal aneurysm. Emergency angiography showed stenosis of the root of the celiac axis (CA), a ruptured aneurysm of the posterior inferior pancreaticoduodenal artery (PIPDA), and an unruptured aneurysm of the anterior inferior pancreaticoduodenal artery (AIPDA). Coil embolization of the PIPDA was performed. Five days after embolization, the gallbladder became necrotic due to decreased blood flow in the CA region, and an emergency operation was performed. We performed a cholecystectomy and released the MAL to normalize the blood flow of the CA region. However, the patient died on postoperative day 8 because of rupture of the untreated aneurysm of the AIPDA.

Conclusions: This is the first report of metachronous ruptures of multiple pancreaticoduodenal aneurysms due to MALS, even after a MAL release. Although rare, a residual aneurysm in the pancreatic head region may need to be embolized quickly.
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http://dx.doi.org/10.1186/s40792-020-0784-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6997311PMC
February 2020

Risk factors for postoperative pneumonia after general and digestive surgery: a retrospective single-center study.

Surg Today 2020 May 11;50(5):460-468. Epub 2019 Nov 11.

Department of Surgery and Science, Graduate School of Medicine and Pharmaceutical Sciences, University of Toyama, 2630 Sugitani, Toyama, 930-0194, Japan.

Purpose: Pneumonia is the second-most common complication in postoperative patients and is associated with significant morbidity and high costs of care. We aimed to determine the risk factors for pneumonia after general and digestive surgery.

Methods: The medical records of 1,016 patients who underwent general and digestive surgery between January 2016 and March 2019 in our hospital were reviewed.

Results: Of the 1,016 patients, 67 (6.6%) developed postoperative pneumonia. The multivariate analysis showed that significant predictors of postoperative pneumonia were a poor Eastern Cooperative Oncology Group performance status (ECOG-PS), low forced vital capacity and low forced expiratory volume in one second in the spirometry test, malnutrition (low serum albumin levels and low controlling nutritional status scores and prognostic nutritional index [PNI] values), esophagectomy, upper gastrointestinal surgery, and nonlaparoscopic surgery. Of these factors, the combination of PNI and ECOG-PS clearly stratified patients into low-, intermediate-, and high-risk groups with respect to developing postoperative pneumonia (area under the curve: 0.709).

Conclusions: Although postoperative pneumonia is associated with many clinical variables, active medical intervention for the prevention of pneumonia in patients with multiple risk factors can improve the postoperative course. In particular, perioperative nutritional care may prevent postoperative pneumonia in patients with malnutrition and a poor PS.
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http://dx.doi.org/10.1007/s00595-019-01911-9DOI Listing
May 2020

NT-proBNP and Risk of Dementia in a General Japanese Elderly Population: The Hisayama Study.

J Am Heart Assoc 2019 09 24;8(17):e011652. Epub 2019 Aug 24.

Department of Epidemiology and Public Health Graduate School of Medical Sciences Kyushu University Fukuoka Japan.

Background Epidemiological evidence implies a link between heart disease and dementia. However, few prospective studies have assessed the association between serum NT-proBNP (N-terminal pro-B-type natriuretic peptide) levels and dementia. Methods and Results A total of 1635 community-dwelling Japanese elderly aged ≥60 years without dementia (57% women, mean age±SD 70.8±7.7 years) were followed up for 10 years. Serum NT-proBNP levels were divided into 4 categories (≤54, 55-124, 125-299, and ≥300 pg/mL). The hazard ratios were estimated using a Cox proportional hazards model. During the follow-up period, 377 subjects developed all-cause dementia, 247 Alzheimer disease, and 102 vascular dementia. The age- and sex-adjusted incidence of all-cause dementia was 31.5 per 1000 person-years and increased significantly with higher serum NT-proBNP levels, being 16.4, 32.0, 35.7, and 45.5, respectively (P for trend <0.01). Subjects with serum NT-proBNP levels of ≥300 pg/mL had a significantly higher risk of all-cause dementia (hazard ratio=2.46, 95% CI 1.63-3.71) than those with serum NT-proBNP levels of ≤54 pg/mL after adjusting for confounders. Similar risks were observed for Alzheimer disease and vascular dementia. Incorporation of the serum NT-proBNP level into a model with known risk factors for dementia significantly improved the predictive ability for incident dementia (c-statistics 0.780-0.787, P=0.02; net reclassification improvement 0.189, P=0.001; integrated discrimination improvement 0.011, P=0.003). Conclusions Higher serum NT-proBNP levels were significantly associated with an increased risk of dementia. Serum NT-proBNP could be a novel biomarker for predicting future risk of dementia in the general elderly population.
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http://dx.doi.org/10.1161/JAHA.118.011652DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6755853PMC
September 2019

Mediastinoscopic salvage esophagectomy for recurrent esophageal squamous cell carcinoma after definitive chemoradiotherapy in a previously pneumonectomized patient.

Asian J Endosc Surg 2019 Oct 8;12(4):452-456. Epub 2018 Nov 8.

Department of Surgery and Science, Graduate School of Medicine and Pharmaceutical Sciences, University of Toyama, Toyama, Japan.

We herein report a case of mediastinoscopic salvage esophagectomy for recurrent esophageal squamous cell carcinoma after definitive chemoradiotherapy in a previously pneumonectomized patient. A 66-year-old man with a medical history of left-sided pneumonectomy for lung cancer was diagnosed with local recurrence of lower esophageal squamous cell carcinoma (cT3N0M0 cStage II) 9 years after definitive chemoradiotherapy. The mediastinoscopic cervical approach and laparoscopic transhiatal approach were combined, and the thoracic esophagus was safely mobilized to separate the esophagus from the stump of the left bronchus and to divide dense adhesions between the esophagus and fibrotic tissue at the site of the previous left mediastinal pleural resection. The esophagectomy was uneventful and followed by reconstruction with a gastric conduit via the retrosternal route. The pathological diagnosis was esophageal squamous cell carcinoma (pT3-AD, pN1, M0, pStage III), indicating R0 resection. Even as salvage surgery, mediastinoscopic esophagectomy is a safe and curative treatment strategy for esophageal cancer patients who have previously undergone pneumonectomy.
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http://dx.doi.org/10.1111/ases.12658DOI Listing
October 2019

Highly efficient capture of cancer cells expressing EGFR by microfluidic methods based on antigen-antibody association.

Sci Rep 2018 08 13;8(1):12005. Epub 2018 Aug 13.

Department of Nanobio Drug Discovery, Graduate School of Pharmaceutical Sciences, Kyoto University, 46-29 Yoshida Shimoadachi-cho, Sakyo-ku, Kyoto, 606-8501, Japan.

Epidermal growth factor receptor (EGFR) was evaluated as a target antigen for cancer cell capture by microfluidic methods based on antigen-antibody association. A polymer CTC-chip microfluidic device was surface-functionalized with three different anti-EGFR antibodies and used to capture EGFR-expressing cancer cells. Capture efficacy depended on the type of antibody used, and cetuximab efficiently captured cancer cell lines that had a wide range of EGFR expression. Capture efficiency was analyzed from the viewpoint of antigen-antibody association in a kinetic process, i.e., cell rolling well-known in leukocyte adhesion, and antibodies with a smaller dissociation constant were shown to result in more efficient capture. Moreover, a lower limit of cellular EGFR expression level for the capture was estimated and methods to decrease the limit were discussed based on densities of anti-EGFR antibody on the device surface.
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http://dx.doi.org/10.1038/s41598-018-30511-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6089922PMC
August 2018

Identification of Tumoricidal TCRs from Tumor-Infiltrating Lymphocytes by Single-Cell Analysis.

Cancer Immunol Res 2018 04 23;6(4):378-388. Epub 2018 Feb 23.

Department of Immunology, Graduate School of Medicine and Pharmaceutical Sciences (Medicine), Toyama, Japan.

T-cell receptor (TCR) gene therapy is a promising next-generation antitumor treatment. We previously developed a single-T-cell analysis protocol that allows the rapid capture of paired TCRα and β cDNAs. Here, we applied the protocol to analyze the TCR repertoire of tumor-infiltrating lymphocytes (TIL) of various cancer patients. We found clonally expanded populations of T cells that expressed the same clonotypic TCR in 50% to 70% of CD137CD8 TILs, indicating that they responded to certain antigens in the tumor environment. To assess the tumor reactivity of the TCRs derived from those clonally expanded TILs in detail, we then analyzed the CD137CD8 TILs from the tumor of B16F10 melanoma cells in six C57BL/6 mice and analyzed their TCR repertoire. We also found clonally expanded T cells in 60% to 90% of CD137CD8 TILs. When the tumor reactivity of dominant clonotypic TCRs in each mouse was analyzed, 9 of 13 TCRs induced the secretion of IFNγ in response to, and showed killing of, B16F10 cells , and 2 of them showed strong antitumor activity Concerning their antigen specificity, 7 of them reacted to p15E peptide of endogenous murine leukemia virus-derived envelope glycoprotein 70, and the rest reacted to tumor-associated antigens expressed on EL4 lymphoma as well as B16 melanoma cells. These results show that our strategy enables us to simply and rapidly obtain the tumor-specific TCR repertoire with high fidelity in an antigen- and MHC haplotype-independent manner from primary TILs. .
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http://dx.doi.org/10.1158/2326-6066.CIR-17-0489DOI Listing
April 2018

The Clinical Features and Outcomes of Patients with Takotsubo Syndrome: The Experience at an Emergency General Hospital.

Intern Med 2018 Mar 20;57(5):641-645. Epub 2017 Nov 20.

Department of Cardiology, Japan Community Healthcare Organization Kyushu Hospital, Japan.

Objective We aimed to elucidate clinical characteristics, contemporary practice and outcomes of patients with takotsubo syndrome who were hospitalized in an emergency general hospital with angiography capabilities. Methods This retrospective study included a total of 42 consecutive patients who were admitted between January 2010 and August 2014. Results The study population included 11 men (26%) and 31 women (74%) [median age 76 years (interquartile range, 66-83)]. Physical stress and emotional stress were identified as triggers in 28 (67%) patients and 5 (12%) patients, respectively. Electrocardiographic changes were observed in 41 (98%) patients, with ST-segment elevation being the most common (71%) finding. In-hospital complications occurred in 24 (57%) patients, and acute pulmonary congestion or cardiogenic shock was seen in 21 (50%) patients. Five patients died during hospitalization (in-hospital mortality: 12%). Conclusion Takotsubo syndrome was associated with significant morbidity and mortality among elderly patients who were treated at an emergency general hospital. Physicians and surgeons in all departments should be aware of the condition, especially in acutely ill subjects.
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http://dx.doi.org/10.2169/internalmedicine.9249-17DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5874333PMC
March 2018

Peptide Drug Release Behavior from Biodegradable Temperature-Responsive Injectable Hydrogels Exhibiting Irreversible Gelation.

Gels 2017 Oct 15;3(4). Epub 2017 Oct 15.

Department of Chemistry and Materials Engineering, Faculty of Chemistry, Materials and Bioengineering, 3-3-35 Yamate, Suita, Osaka 564-8680, Japan.

We investigated the release behavior of glucagon-like peptide-1 (GLP-1) from a biodegradable injectable polymer (IP) hydrogel. This hydrogel shows temperature-responsive irreversible gelation due to the covalent bond formation through a thiol-ene reaction. In vitro sustained release of GLP-1 from an irreversible IP formulation () was observed compared with a reversible (physical gelation) IP formulation (). Moreover, pharmaceutically active levels of GLP-1 were maintained in blood after subcutaneous injection of the irreversible IP formulation into rats. This system should be useful for the minimally invasive sustained drug release of peptide drugs and other water-soluble bioactive reagents.
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http://dx.doi.org/10.3390/gels3040038DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6318690PMC
October 2017

Flow Cytometric Detection of Circulating Tumor Cells Using a Candidate Stem Cell Marker, p75 Neurotrophin Receptor (p75NTR).

Methods Mol Biol 2017 ;1634:211-217

Department of Nanobio Drug Discovery, Graduate School of Pharmaceutical Sciences, Kyoto University, 46-29 Yoshida-Shimo-Adachi-cho, Sakyo-ku, Kyoto, 606-8501, Japan.

The most widely studied detection for circulating tumor cells (CTCs) in peripheral blood of cancer patients has been based on immunomagnetic enrichment using antibodies against epithelial cell adhesion molecule (EpCAM), which is overexpressed in epithelial cells. A neurotrophin receptor p75 (p75NTR) is expressed in a candidate stem cell fraction in esophageal squamous cell carcinoma (ESCC), which shows significantly higher colony formation, enhanced tumor formation in mice, along with strong expression of epithelial mesenchymal transition-related genes. Here, we describe a method to detect CTCs in ESCC based on the combined expression of EpCAM and p75NTR using flow cytometry, demonstrating the feasibility of expression analysis of multiple cell surface markers in viable cells.
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http://dx.doi.org/10.1007/978-1-4939-7144-2_18DOI Listing
April 2018

Isoform switch of CD44 induces different chemotactic and tumorigenic ability in gallbladder cancer.

Int J Oncol 2017 Sep 3;51(3):771-780. Epub 2017 Jul 3.

Department of Surgery and Science, Graduate School of Medicine and Pharmaceutical Sciences, University of Toyama, Toyama City, Toyama 930-0194, Japan.

Gallbladder cancer (GBC) is one of the most unfavorable prognostic tumor, and immediate growth and distant metastasis are important factors associated with the poor prognosis of patients with this disease. Standard and variant isoforms of CD44 are associated with tumor growth, metastasis, and epithelial-mesenchymal transition (EMT), although their roles in GBC are unclear. We investigated the relationship between the CD44 isoforms with EMT, chemotaxis, and tumorigenicity. We analyzed CD44 expression in the GBC cell line NOZ and found that it comprises a major population that expressed CD44std+/CD44v9- (CD44s) and the minor population that expressed CD44std-/CD44v9+ (CD44v). CD44s cells exhibited increased chemotaxis and invasiveness compared with CD44v cells in in vitro cell migration and invasion assays. CD44s cells expressed higher and lower levels of mRNAs that encode vimentin and E-cadherin, respectively, compared with those of CD44v cells. CD44s cells expressed high levels of the transcription factors ZEB1 and ZEB2 that mediate EMT, and low levels of a splicing factor ESRP1 that controls the CD44 isoform switch. We performed in vivo mouse xenotransplantation analyses of CD44s and CD44v cells and found that CD44v cells exhibited relatively increased tumorigenicity. Immunohistochemical analysis of tissue microarrays revealed that high levels of CD44v9 and CD44std were associated with poorer prognosis. The expression of CD44std was also associated with poorly differentiated tumors and distant metastasis. In conclusion, CD44s was associated with a mesenchymal phenotype, increased chemotaxis and invasiveness, and decreased tumorigenicity. In contrast, CD44v cells exhibited an epithelial phenotype, decreased chemotaxis, decreased invasiveness, and increased tumorigenicity. These findings suggest that CD44v and CD44s cells play differently important roles in the progression and metastasis of GBC and the isoform switch triggers EMT.
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http://dx.doi.org/10.3892/ijo.2017.4063DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5564409PMC
September 2017

Clinical Relevance of a Candidate Stem Cell Marker, p75 Neurotrophin Receptor (p75NTR) Expression in Circulating Tumor Cells.

Adv Exp Med Biol 2017 ;994:247-254

Department of Nanobio Drug Discovery, Graduate School of Pharmaceutical Sciences, Kyoto University, 46-29 Yoshida-Shimo-Adachi-cho, Sakyo-ku, Kyoto, 606-8501, Japan.

Despite advances in its diagnosis and multimodal therapies, the prognosis of esophageal squamous cell carcinoma (ESCC) patients remains poor, because of high incidences of metastasis . Recent reports suggested that circulating tumor stem cells (CTSCs), rather than circulating tumor cells (CTCs), were more accurate diagnostic marker for metastasis, because tumor stem cells or cancer stem cells (CSCs) are more responsible for metastasis through processes such as epithelial mesenchymal transition (EMT) and tumor initiation. A neurotrophin receptor p75 (p75NTR) is expressed in a candidate CSC s in ESCC, which possess enhanced tumorigenicity along with strong expression of EMT-related genes. Our recent report using two-color flow cytometry demonstrated that CTC counts based on a combined expression of epithelial cell adhesion molecule (EpCAM) and p75NTR was significantly higher in peripheral blood samples of ESCC patients than healthy controls. In addition, EpCAM + p75NTR+, but not EpCAM + p75NTR- CTC counts, correlated with clinically diagnosed distant metastasis and pathological venous invasion in surgically resected primary ESCC tumors. Malignant cytology of the isolated EpCAM + p75NTR+ cells was microscopically confirmed as well. These results demonstrated that EpCAM + p75NTR+ CTC count was a more accurate diagnostic marker than EpCAM+ CTC count, suggesting the highly metastatic potential of CTCs with p75NTR expression.Investigation using the isolated EpCAM + p75NTR+ CTCs to assess their stem cell properties may shed light on their roles in tumor metastasis in ESCC.Further investigations based on large-scale prospective studies with long term follow up may provide us with evidences for its clinical use.
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http://dx.doi.org/10.1007/978-3-319-55947-6_13DOI Listing
October 2017

Enhanced cancer stem cell properties of a mitotically quiescent subpopulation of p75NTR-positive cells in esophageal squamous cell carcinoma.

Int J Oncol 2017 Jul 16;51(1):49-62. Epub 2017 May 16.

Department of Surgery and Science, Graduate School of Medicine and Pharmaceutical Sciences, University of Toyama, Toyama city, Toyama 930-0194, Japan.

Mitotically quiescent cancer stem cells (CSCs) possess higher malignant potential than other CSCs, indicating their higher contribution to therapeutic resistance than that of other CSCs. In esophageal squamous cell carcinoma (ESCC), p75 neurotrophin receptor (p75NTR) is expressed in a candidate CSC population showing high tumorigenicity and chemoresistance. In the present study, we isolated and characterized quiescent CSCs population in ESCC based on p75NTR expression and cell cycle status. Expression of p75NTR and Ki-67 in ESCC cell lines (KYSE cells) and surgically resected ESCC specimens was detected by performing immunocytochemical analysis. p75NTR-positive KYSE cells were fractionated into quiescent and proliferating cells by performing flow cytometry with a fluorescent DNA-staining dye to determine their CSC phenotype. Immunocytochemical analysis showed that 21.8 and 36.5% of the p75NTR-positive cells were Ki-67-negative (G0), which accounted for 11.4 and 15.7% of cells in KYSE-30 and KYSE-140 cell lines, respectively. Flow cytometric cell sorting showed that p75NTR-positive cells in the G0-G1 phase (p75NTR-positive/G0-1 cells) but not in the S-G2-M phase (p75NTR-positive/S-G2-M cells) showed strong expression of stem cell-related genes Nanog, BMI-1, and p63; high colony formation ability; high tumorigenicity in a mouse xenograft model; and strong chemoresistance against cisplatin because of the expression of drug resistance genes ABCG2 and ERCC1. Label-retention assay showed that 3.4% p75NTR-positive cells retained fluorescent cell-tracing dye, but p75NTR-negative cells did not. Immunohistochemical analysis of ESCC specimens showed p75NTR expression in 39 of 95 (41.1%) patients, with a median of 13.2% (range, 3.0-80.1%) p75NTR-positive/Ki-67-negative cells, which were found to be associated with poorly differentiated histology. Our results suggest that p75NTR-positive/G0-1 cells represent quiescent CSCs in ESCC and indicate that these cells can be used as targets to investigate molecular processes regulating CSC phenotype and to develop novel therapeutic strategies.
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http://dx.doi.org/10.3892/ijo.2017.4001DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5467780PMC
July 2017

The efficacy of steroids for postoperative persistent inflammatory reaction in a patient with barium peritonitis: A case report.

Int J Surg Case Rep 2017 15;36:38-41. Epub 2017 May 15.

Department of Surgery and Science, Graduate School of Medicine and Pharmaceutical, Sciences for Research, University of Toyama, 2630 Sugitani, Toyama City, Toyama 930-0194, Japan, Japan. Electronic address:

Introduction: Barium peritonitis is a serious and life-threatening disease requiring intensive care. Residual barium in the intraperitoneal cavity can cause persistent inflammation, postoperatively.

Presentation Of Case: An 80-year-old woman was admitted to our hospital because of abdominal pain and vomiting after barium meal examination. Physical and radiographic examination showed sigmoid colon perforation. Barium sulfate extravasation was noted in the intraperitoneal cavity. We diagnosed the patient with barium peritonitis, and performed Hartmann's procedure and thorough lavage of the intraperitoneal cavity with 20-L saline. Postoperative blood examination results were not readily improved because of the residual barium in the intraperitoneal and retroperitoneal cavities. We excluded the presence of any other inflammation origin, except that from residual barium. Methylprednisolone 500mg/body/day was administered for 3days and the dose was gradually decreased thereafter. The white blood cell count and serum C-reactive protein levels immediately improved to normal levels.

Discussion: Barium peritonitis is associated with high mortality. Residual barium in the intraperitoneal cavity can cause chemical peritonitis, leading to granuloma formation and ileus, postoperatively. Therefore, complete removal of barium in the abdominal cavity with aggressive drainage and large quantity of saline is necessary to prevent postoperative inflammatory reaction. The use of steroids improves the persistent inflammation caused by residual barium, unless any infectious origins are present, which can worsen with steroid-use.

Conclusion: Residual barium in the intraperitoneal cavity causes persistent inflammatory reaction in patients with barium peritonitis. The use of steroids is effective for postoperative persistent inflammation due to the residual barium.
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http://dx.doi.org/10.1016/j.ijscr.2017.05.012DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5440279PMC
May 2017

Erratum to: Carbon ion radiotherapy for desmoid tumor of the abdominal wall: a case report.

World J Surg Oncol 2017 05 3;15(1):95. Epub 2017 May 3.

Department of Nanobio Drug Discovery, Graduate School of Pharmaceutical Sciences, Kyoto University, Yoshida-honmachi, Sakyo-ku, Kyoto 606-8501, Japan.

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http://dx.doi.org/10.1186/s12957-017-1154-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5414378PMC
May 2017

Contemporary practice and outcomes of an elderly cohort of Japanese patients with non-ST-elevation acute coronary syndrome in the era of routine early invasive strategy.

Int J Cardiol 2017 Aug 30;240:49-54. Epub 2017 Mar 30.

Department of Cardiology, Japan Community Healthcare Organization Kyushu Hospital, Kitakyushu, Japan. Electronic address:

Background: An early invasive strategy for patients with non-ST-segment elevation acute coronary syndrome (NSTE-ACS) has been recommended. However, patients at greater risk including the elderly are more often managed conservatively. We aimed to elucidate contemporary practice and outcomes of patients with NSTE-ACS who were referred to our hospital located in Kitakyushu City, one of the most aging metropolises in Japan.

Methods: A total of 270 consecutive NSTE-ACS patients hospitalized between January 2012 and December 2014 were retrospectively studied.

Results: Median [interquartile range] age was 73 [64, 80]years. Coronary angiography was performed in 264 (98%) patients. Importantly, 75% and 89% underwent angiography within 24h and 72h after admission, respectively. Revascularization was done in 124 (79%). The all-cause, in-hospital mortality was 3.7% and was higher in patients aged ≥80years (8.5% vs. 2.0% in those aged <80years, p<0.0001). No patient developed major bleeding or stroke during hospitalization. Killip class IV at presentation (odds ratio [OR] 8.77, 95% confidence intervals [CI] 1.64-47.6) and left main trunk disease (OR 7.58, 95% CI 1.28-45.5) were independently associated with in-hospital death. These two variables and a high (≥140) GRACE score were associated with a higher 1-year mortality by Kaplan-Meier survival analysis (p<0.0001).

Conclusions: An early invasive strategy was safely done in an elderly cohort of Japanese patients with NSTE-ACS. In addition to early invasive approach, a further therapeutic strategy, most probably targeting a shock status, is needed to improve both short- and long-term survival.
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http://dx.doi.org/10.1016/j.ijcard.2017.03.118DOI Listing
August 2017

Prognostic significance of KLF4 expression in gastric cancer.

Oncol Lett 2017 Feb 14;13(2):819-826. Epub 2016 Dec 14.

Department of Surgery and Science, Graduate School of Medicine and Pharmaceutical Sciences for Research, University of Toyama, Toyama 930-0194, Japan.

To understand the roles of pluripotent stem cell-inducing genes in gastric cancer, the expression of Krüppel-like factor 4 (KLF4), Nanog, octamer-binding transcription factor 4 (Oct4), avian myelocytomatosis viral oncogene homolog (c-Myc) and sex-determining region Y-box 2 (SOX2) was examined using the newly developed gastric carcinoma tissue microarray. The associations between the immunohistochemical expression levels of the pluripotency-inducing factors and the clinicopathological data of 108 patients with gastric cancer were analyzed. No associations were identified between the expression levels of the five pluripotency-inducing factors and the tumor-node-metastasis (TNM) classification or clinicopathological characteristics of the patients. In addition, multivariate analysis revealed no association of Nanog, Oct4, SOX2 or c-Myc with the prognosis of the gastric cancer patients; however, low expression of KLF4 was determined to be an independent negative prognostic factor (P=0.0331), particularly in patients who underwent R0 resection (TNM stages 2 and 3; P=0.0048). In summary, low KLF4 expression was found to be negatively associated with overall survival, and may therefore be a useful prognostic marker in gastric cancer patients.
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http://dx.doi.org/10.3892/ol.2016.5499DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5351303PMC
February 2017