The neuromodulatory role of dopamine in improved reaction time by acute cardiovascular exercise.

Acute cardiovascular physical exercise improves cognitive performance, as evidenced by a reduction in reaction time (RT). However, the mechanistic understanding of how this occurs is elusive and has not been rigorously investigated in humans. Here, using positron emission tomography (PET) with [11 C]raclopride, in a multi-experiment study we investigated whether acute exercise releases endogenous dopamine (DA) in the brain. We hypothesized that acute exercise augments the brain DA system, and that RT improvement is correlated with this endogenous DA release. The PET study (Experiment 1: n = 16) demonstrated that acute physical exercise released endogenous DA, and that endogenous DA release was correlated with improvements in RT of the Go/No-Go task. Thereafter, using two electrical muscle stimulation (EMS) studies (Experiments 2 and 3: n = 18 and 22 respectively), we investigated what triggers RT improvement. The EMS studies indicated that EMS with moderate arm cranking improved RT, but RT was not improved following EMS alone or EMS combined with no load arm cranking. The novel mechanistic findings from these experiments are: (1) endogenous DA appears to be an important neuromodulator for RT improvement and (2) RT is only altered when exercise is associated with central signals from higher brain centres. Our findings explain how humans rapidly alter their behaviour using neuromodulatory systems and have significant implications for promotion of cognitive health. KEY POINTS: Acute cardiovascular exercise improves cognitive performance, as evidenced by a reduction in reaction time (RT). However, the mechanistic understanding of how this occurs is elusive and has not been rigorously investigated in humans. Using the neurochemical specificity of [11 C]raclopride positron emission tomography, we demonstrated that acute supine cycling released endogenous dopamine (DA), and that this release was correlated with improved RT. Additional electrical muscle stimulation studies demonstrated that peripherally driven muscle contractions (i.e. exercise) were insufficient to improve RT. The current study suggests that endogenous DA is an important neuromodulator for RT improvement, and that RT is only altered when exercise is associated with central signals from higher brain centres.

Systemic Lupus Erythematosus Presenting With Thrombotic Thrombocytopenic Purpura at Onset: A Case Report.

Background: Thrombotic microangiopathy (TMA) is a syndrome associated with hemolytic anemia, thrombocytopenia, and various organ disorders. Thrombotic thrombocytopenic purpura (TTP) is a disease that develops when a disintegrin-like and metalloproteinase with thrombospondin type l motif 13 (ADAMTS13) activity decreases to < 10% of that in normal plasma, causing platelet thrombosis in microvessels throughout the body. Currently, ADAMTS13-deficient TMA is diagnosed as TTP. Systemic lupus erythematosus (SLE)-related TMA includes both acquired TTP, in which ADAMTS13 activity is significantly reduced, and secondary TMA, in which ADAMTS13 activity is not reduced. Both diseases have different prognoses. Case Presentation: An 11-year-old girl was admitted to our hospital on suspicion of TMA with thrombocytopenia and hemolytic anemia. Because the patient had hypocomplementemia, SLE-related TMA or complement-related TMA was considered. Therefore, we initiated plasma exchange (PE) for the patient. Subsequently, she fulfilled the pediatric SLE diagnostic criteria, and ADAMTS13 activity was shown to be decreased and the anti-ADAMTS13 antibody titer increased. She was thus diagnosed with acquired TTP caused by SLE. Treatment response was good as a platelet count and ADAMTS13 activity improved with three times of PE, followed by methylprednisolone pulse therapy and administration of mycophenolate mofetil. Renal pathology showed thrombus formation in glomerular arterioles and lupus nephritis categorized as Class III (A) of the International Society of Nephrology and the Renal Pathology Society classification. Because the patient was thought to be in the high-risk group of SLE, three courses of intravenous cyclophosphamide pulse therapy were administered as an additional induction therapy. No recurrence of TTP was observed. Conclusion: In SLE-related TMA, measurement of ADAMTS13 activity and the anti-ADAMTS13 antibody titer are necessary for diagnosis, and for predicting prognosis and recurrence of the disease; however, in the acute phase of immune-mediated TMA, it is important to initiate proper treatments even before knowing the results to improve prognosis.

[Usefulness of Mohs Paste Against Breast Cancer with Skin Invasion].

We report with the addition of literature because we have experienced 3 cases of locally advanced breast cancer with skin invasion that have alleviated symptoms and improved quality of life by using Mohs paste. In Case 1, Mohs paste reduced exposed tumors, exudation, and bleeding. In Case 2, bleeding, which had been the cause of the marked anemia, was controlled, and tumor shrinkage and epithelialization were observed. Case 3 had a poor prognosis due to systemic metastasis, but the QOL improved for a certain period of time as exudation, bleeding, and foul odor were controlled. From the viewpoint of palliative care, Mohs paste is a safe and effective treatment method against various symptoms such as large amounts of exudation, bleeding, and foul odor caused by breast cancer skin invasion, and depending on the case, prognosis can be expected to be extended by shrinking the tumor. The cooperation of not only doctors but also palliative care teams including pharmacists and nurses is essential for use.

Effects of electrical muscle stimulation on cerebral blood flow.

BACKGROUND: Electrical muscle stimulation (EMS) induces involuntary muscle contraction. Several studies have suggested that EMS has the potential to be an alternative method of voluntary exercise; however, its effects on cerebral blood flow (CBF) when applied to large lower limb muscles are poorly understood. Thus, the purpose of this study was to examine the effects of EMS on CBF, focusing on whether the effects differ between the internal carotid (ICA) and vertebral (VA) arteries. METHODS: The participants performed the experiments under EMS and control (rest) conditions in a randomized crossover design. The ICA and VA blood flow were measured before and during EMS or control. Heart rate, blood pressure, minute ventilation, oxygen uptake, and end-tidal partial pressure of carbon dioxide (PETCO2) were monitored and measured as well. RESULTS: The ICA blood flow increased during EMS [Pre: 330 ± 69 mL min-1; EMS: 371 ± 81 mL min-1, P = 0.001, effect size (Cohen's d) = 0.55]. In contrast, the VA blood flow did not change during EMS (Pre: 125 ± 47 mL min-1; EMS: 130 ± 45 mL min-1, P = 0.26, effect size = 0.12). In the EMS condition, there was a significant positive linear correlation between ΔPETCO2 and ΔICA blood flow (R = 0.74, P = 0.02). No relationships were observed between ΔPETCO2 and ΔVA blood flow (linear: R = - 0.17, P = 0.66; quadratic: R = 0.43, P = 0.55). CONCLUSIONS: The present results indicate that EMS increased ICA blood flow but not VA blood flow, suggesting that the effects of EMS on cerebral perfusion differ between anterior and posterior cerebral circulation, primarily due to the differences in cerebrovascular response to CO2.

Any modality of renal replacement therapy can be a treatment option for Joubert syndrome.

Joubert syndrome (JS) is an inherited ciliopathy characterized by a distinctive cerebellar and brain stem malformation which is known as the "molar tooth sign" on axial brain images, hypotonia, and developmental delay. Approximately 25-30% of patients with JS have kidney disease and many of them progress to end-stage kidney disease (ESKD). However, there are few reports on the outcomes of renal replacement therapy (RRT) in patients with JS and ESKD. In this study, we clarified the clinical features, treatment, and outcomes of patients with JS who underwent RRT. We retrospectively analyzed the medical records and clinical characteristics of 11 patients with JS who underwent RRT between June 1994 and July 2019. Data are shown as the median (range). Gene analysis was performed in 8 of the 11 cases, and CEP290 mutations were found in four patients, two had TMEM67 mutations, one had a RPGRIP1L mutation, and one patient showed no mutation with the panel exome analysis. Complications in other organs included hydrocephalus in two cases, retinal degeneration in eight cases, coloboma in one case, liver diseases in four cases, and polydactyly in one case. Peritoneal dialysis (PD) was introduced in seven cases, with a median treatment duration of 5.4 (3.4-10.7) years. Hemodialysis was performed using arteriovenous fistula in two cases, and kidney transplantation was performed 9 times in eight cases. Only one of the grafts failed during the observation period of 25.6 (8.2-134.2) months. The glomerular filtration rate at the final observation was 78.1 (41.4-107.7) mL/min/1.73 m2. The median age at the final observation was 13.4 (5.6-25.1) years, and all patients were alive except one who died of hepatic failure while on PD. Any type of RRT modality can be a treatment option for patients with JS and ESKD.

IGFBP1 Is a Predictive Factor for Haematogenous Metastasis in Patients With Gastric Cancer.

BACKGROUND/AIM: The clinicopathological significance and prognostic value of insulin-like growth factor binding protein 1 (IGFBP1) in gastric cancer have not been investigated to date. This study aimed to investigate the relationship of IGFBP1 expression with clinicopathological variables and prognosis. MATERIALS AND METHODS: The correlation of IGFBP1 expression with the clinicopathological factors and the correlation of clinicopathogical factors with haematogenous metastasis in 219 gastric cancer patients who underwent surgery was examined. RESULTS: High IGFBP1 expression was significantly associated with a poorer disease-specific survival (p<0.001) and relapse-free survival (p<0.001) in univariable analysis although IGFBP1 was not an independent prognostic factor. High IGFBP1 expression was the only independent risk factor of haematogenous metastasis. CONCLUSION: High IGFBP1 expression was associated with haematogenous metastasis and poor survival. IGFBP1 might become a new prognostic factor and a target of molecular targeted therapy of gastric cancer.

Clinical characteristics of Campylobacter enteritis after pediatric renal transplantation: A retrospective analysis from single center.

BACKGROUND: There are few reports of patients with Campylobacter enteritis after renal transplantation, and only a few case reports of bacteremia have been published. Although antibiotic therapy for 3-5 days has been recommended for immunocompromised patients, the optimal treatment for Campylobacter enteritis after renal transplantation has not been established. This study aimed to clarify the clinical characteristics and treatment outcomes of Campylobacter enteritis after pediatric renal transplantation. METHODS: This retrospective study included patients who underwent pediatric renal transplantation and were found to have Campylobacter species in stool cultures between January 2014 and May 2017. RESULTS: This study included eight patients who underwent pediatric renal transplantation. The median age at the time of renal transplantation was 14 years, and the median period between transplantation and disease occurrence was 4.6 years. Clinical symptoms were abdominal pain for eight patients, diarrhea for eight patients, fever for seven patients, vomiting for three patients, and headache for three patients. Campylobacter jejuni was isolated from the stool cultures of all patients. The median administration period of antibiotics as initial therapy was 7 days (range, 4-11 days). However, clinical relapse was observed in four patients after completing antibiotic therapy. Patients who experienced clinical relapse required a second course of antibiotic therapy for a median duration of 7 days (range, 5-10 days). CONCLUSIONS: Patients with Campylobacter enteritis after pediatric renal transplantation are at high risk for clinical relapse and may require a longer duration of antibiotic therapy than that generally described.

Prognostic Significance of High EphA1-4 Expression Levels in Locally Advanced Gastric Cancer.

BACKGROUND/AIM: Erythropoietin-producing hepatocellular carcinoma receptor A (EphA) is associated with angiogenesis and invasive tumor progression. In this study, we evaluated the EphA1-4 expression levels in advanced gastric cancer. PATIENTS AND METHODS: Tumor tissues obtained from 114 patients with advanced gastric adenocarcinoma who underwent gastrectomy were analyzed. In addition, the impact of EPHA 1-4 mRNA expression on survival was analyzed using the Kaplan-Meier plotter database on the website. RESULTS: High EphA 1, 2, and 4 expression levels were significantly related to recurrence (p<0.01, p=0.04, and p<0.01). Both high EphA 1 and 4 expression levels were independent predictors of relapse-free interval (hazard ratio [HR]=2.0, p=0.03; HR=2.4, p=0.03) and disease-specific survival (HR=2.0, 95% p=0.03; HR=2.5, p=0.02) on multivariate analysis. In the Kaplan-Meier plotter database, high EPHA2 mRNA expression was significantly associated with poor survival in patients with gastric cancer (p=0.0098), and high expression levels of EPHA1 and 4 tended to be associated with poor survival (p=0.050, p=0.052). CONCLUSION: EphA 1, 2, and 4 may play key roles in recurrence and survival in patients with advanced gastric cancer.

Cadherin 5 Is a Significant Risk Factor for Hematogenous Recurrence and a Prognostic Factor in Locally Advanced Gastric Cancer.

BACKGROUND/AIM: Cadherin 5 (CDH5) is important for adhesion in epithelial cells, and expressed in tumor cells in several malignancies. In the present study, we evaluated the clinical significance of CDH5 protein expression in locally advanced gastric cancer. MATERIALS AND METHODS: Tumor tissues obtained from 113 patients with advanced gastric adenocarcinoma who underwent gastrectomy were analyzed. RESULTS: High CDH5 expression was significantly associated with recurrence (p=0.017), especially hematological recurrence (p=0.022). High CDH5 expression was a significant risk factor for hematogenous recurrence on multivariate analysis (odds ratio[OR]=3.9, confidential interval [CI] 1.0-15, p=0.043). Patients with high CDH5 expression had a significantly shorter progression-free interval (RFI, p=0.010) than patients with low CDH5 expression. High CDH5 expression was an independent prognostic factor on multivariate analysis of RFI (hazard ratio[HR]=2.2, 95% CI 1.1-4.3, p=0.021). CONCLUSION: CDH5 may play a key role in hematogenous recurrence of advanced gastric cancer and may be a viable treatment target.

High expression of P21-activated kinase 5 protein is associated with poor survival in gastric cancer.

P21-activated kinase 5 (PAK5), also termed PAK7, is one of the six members of the PAK family of serine/threonine kinases, which are downstream effectors in several cancer signaling pathways. PAK5 promotes neural outgrowth, contributes to microtubule stability and induces resistance to apoptosis. However, the clinical importance of PAK5 in gastric cancer has not been comprehensively investigated. In the present study, PAK5 expression was evaluated in gastric cancer tissue samples. Furthermore, the associations between high expression of PAK5, and clinicopathological features and prognosis were examined. PAK5 expression in primary gastric cancer specimens resected from 279 patients who underwent gastrectomy at the Tokyo Medical and Dental University Hospital was evaluated using immunohistochemistry. Of the 279 patients, 44 (15.8%) exhibited high PAK5 expression, which was significantly associated with the differentiated pathological type (differentiated vs. undifferentiated; P<0.001), depth of tumor invasion (T1 vs. T2-T4; P<0.001), lymph node metastasis (N0 vs. N1-N3; P<0.001), presence of distant metastasis or recurrence (present vs. absent; P=0.038), advanced tumor stage (I vs. II-IV; P=0.001) and worse disease-specific survival (P=0.013). In stage I-III disease, 38/254 (15.0%) patients exhibited high PAK5 expression, and high expression of PAK5 was significantly associated with relapse-free interval (P=0.044). PAK5 may serve an important role in tumor progression and influence the outcome of patients with gastric cancer.

High expression of EphA3 (erythropoietin-producing hepatocellular A3) in gastric cancer is associated with metastasis and poor survival.

BACKGROUND: As the major subfamily of receptor tyrosine, erythropoietin-producing hepatocellular (Eph) receptor has been related to progression and prognosis in different types of tumors. However, the role and mechanism of EPHA3 in gastric cancer is still not well understood. METHODS: Specimen were collected from 202 patients who underwent gastric resection for gastric adenocarcinoma. The expression of EphA3 was studied using immunohistochemistry. We analyzed the clinicopathological factors and prognostic relevance of EphA3 expression in gastric cancer. RESULTS: High expression of EphA3 was associated with male predominance (p = 0.031), differentiated histology (p < 0.001), depth of tumor (p = 0.002), lymph node metastasis (p = 0.001), distant metastasis (p = 0.021), liver metastasis (p = 0.024), advanced stage (p < 0.001), and high HER2 expression (p = 0.017). Relapse-free survival (RFS) was significantly worse in patients with high expression of EphA3 than in those with low expression of EphA3 (p = 0.014). Multivariate analysis for RFS showed that depth of tumor [hazard ratio (HR) 9.333, 95% confidence interval (CI) 2.183-39.911, p = 0.003] and lymph node metastasis [hazard ratio (HR) 5.734, 95% confidence interval (CI) 2.349-13.997, p < 0.001] were independent prognostic factors. CONCLUSIONS: These findings suggest that high expression EphA3 may participate in metastasis and worse survival.

TPX2 expression is associated with poor survival in gastric cancer.

BACKGROUND: Targeting protein for Xenopus kinesin-like protein 2 (TPX2) is a microtubule-associated protein required for microtubule formation in human cells. Several studies have demonstrated that TPX2 is overexpressed in multiple tumor types and promotes tumor growth and metastasis. However, there have been few reports regarding its role in gastric cancer. In this study, we evaluated TPX2 expression and investigated its correlations with gastric cancer clinicopathological features and prognosis. METHODS: Tumor samples were obtained from 290 patients with gastric adenocarcinoma who had undergone gastrectomy. The expression of TPX2 protein was examined using immunohistochemical staining. TPX2 messenger RNA (mRNA) levels were evaluated using real-time quantitative reverse transcription PCR in 19 of the gastric cancer tumors and adjacent normal tissues. RESULTS: The mRNA levels of TPX2 were significantly higher in gastric cancer tissues than in matched adjacent normal tissues (p = 0.004). In the immunohistochemical analysis, TPX2 overexpression was found in 123 (42.4%) of 290 patients. High TPX2 expression was positively associated with age, type of histology, depth of tumor, lymph node metastasis, stage, and remote metastasis or recurrence. High TPX2 expression was significantly associated with poorer disease-specific survival (p = 0.004) and relapse-free interval (p = 0.013). CONCLUSIONS: Our results indicated that high TPX2 expression was associated with tumor progression and poor survival in gastric cancer.

Cadherin 5 expression correlates with poor survival in human gastric cancer.

AIMS: Although expressed in tumour cells of various malignancies, cadherin 5 (CDH5), also known as vascular endothelial cadherin, plays an important role in homotypic cell-cell adhesion among epithelial cells. However, the clinical significance of CDH5 expression in gastric cancer has not been sufficiently demonstrated. In this study, CDH5 expression in gastric cancer was evaluated and the correlations between CDH5 expression and the clinicopathological features and outcomes of the disease were examined. METHODS: Differentiated-type gastric adenocarcinomas obtained from 102 patients who underwent gastrectomy were analysed. CDH5 expression was assessed by immunohistochemical staining of the membranes of the cancer cells. RESULTS: High CDH5 expression was significantly associated with the following clinicopathological variables related to tumour progression: depth of invasion (p=0.012), venous invasion (p=0.013), lymphatic invasion (p=0.001), metastatic lymph nodes (p=0.009), pathological stage (p=0.008) and distant metastasis or recurrent disease (p=0.009). Patients with high CDH5 expression had significantly poorer disease-specific survival (p=0.021), although CDH5 was not determined to be an independent prognostic factor by multivariate analysis. CONCLUSIONS: CDH5 may play a key role in the progression or metastasis of differentiated-type gastric cancer and serve as a target for its treatment.

Prognostic significance of PAK4 expression in gastric cancer.

AIMS: p-21 activated kinase (PAK) 4, part of the six PAK families, plays an important role in growth factor signalling, cytoskeletal remodelling, gene transcription, cell proliferation and oncogenic transformation. However, the clinical significance of PAK4 in gastric cancer has yet to be fully elucidated. PAK4 expression was evaluated, and the correlations of PAK4 expression with clinicopathological features and outcomes in gastric cancer were examined. METHODS: Gastric adenocarcinomas obtained from 217 patients who underwent gastrectomy were analysed. PAK4 expression was evaluated using immunohistochemical staining. RESULTS: PAK4 overexpression was found in 95 (43.8%) of 217 tumours . High PAK4 expression was significantly correlated with clinicopathological variables related to tumour progression, including depth of invasion, metastatic lymph nodes, pathological stage, distant metastasis or recurrent disease. High PAK4 expression was significantly associated with poorer disease-specific survival (DSS) (p<0.001) and relapse-free survival (RFS) (p<0.001). On multivariable analysis, PAK4 was an independent prognostic factor for DSS (HR 2.5 (95% CI 1.4 to 4.7), p=0.003) and RFS (HR 2.8 (95% CI 1.4 to 5.6), p=0.004). Even in stage II and III disease, PAK4 was an independent prognostic factor for RFS (HR 2.2 (95% CI 1.1 to 4.5), p=0.029). CONCLUSIONS: PAK4 may become a new prognostic factor in patients with gastric cancer.

Relationship between expression of IGFBP7 and clinicopathological variables in gastric cancer.

AIMS: Insulin-like growth factor binding protein 7 (IGFBP7) is reported to have tumour suppressor function through an IGF-dependent pathway in various malignant tumours. However, the expression of IGFBP7 in adenocarcinoma and its relationship with tumour progression and survival differs among studies. Our aims were to investigate the relationship between the expression of IGFBP7 and clinicopathological variables and outcomes of patients with gastric cancer. METHODS: Tumour samples were obtained from 219 patients with gastric cancer who underwent gastrectomy. The expression of IGFBP7 protein was examined by immunohistochemical staining. IGFBP7 mRNA levels were analysed using real-time quantitative reverse-transcriptase PCR in 24 of the gastric cancer tumours and in adjacent non-tumour tissues. Correlation of IGFBP7 expression with clinicopathological features was analysed. RESULTS: The protein expression of IGFBP7 was positively correlated with depth of invasion, lymph node metastasis, distant metastasis or recurrence and pathological stage. High expression of IGFBP7 protein was associated with a significantly worse disease-specific survival (p<0.001) and was an independent prognostic factor in multivariable analysis (HR, 4.8; 95% CI 2.1 to 10.6; p<0.001). The IGFBP7 mRNA level was significantly higher in advanced gastric cancer than in early gastric cancer, in tumours with lymph node metastasis than in tumours without lymph node metastasis, and in tumours with distant metastasis or recurrence than in tumours without distant metastasis or recurrence. CONCLUSIONS: Overexpression of IGFBP7 was associated with tumour progression and poor survival in gastric cancer. IGFBP7 may play a role in tumour progression in gastric cancer.

Erythropoietin-Producing Hepatocellular A1 is an Independent Prognostic Factor for Gastric Cancer.

BACKGROUND: Erythropoietin-producing hepatocellular (Eph) receptors are the largest subfamily of receptor tyrosine kinases that have been investigated as a possible target for molecular targeted therapy of various cancers. METHODS: Patients (n = 222) who underwent gastrectomy for primary gastric cancer were enrolled in this study. Tumor protein expression of EphA1 and EphB6 in surgically resected specimen was investigated using immunohistochemistry. The associations between expression of EphA1 and EphB6 and clinicopathological factors and prognosis were analyzed. RESULTS: High expression of EphA1 was associated with undifferentiated histology (P = 0.002), depth of tumor (P < 0.001), lymph node metastasis (P = 0.001), venous invasion (P = 0.015), stage (P = 0.001), and remote metastasis or recurrence (P < 0.001). In univariate analysis, patients with high expression of EphA1 had significantly poorer overall survival and relapse-free survival compared with patients with low EphA1 expression. The expression level of EphB6 was not associated with any clinicopathological factors and patient survival. Multivariate analysis indicated that depth of tumor [hazard ratio (HR) 9.26, 95 % confidence interval (CI) 0.03-0.46, P = 0.003], lymph node metastasis (HR 9.26, 95 % CI 0.07-0.39, P < 0.001), and high expression of EphA1 (HR 1.86, 95 % CI 0.29-0.99, P = 0.048) are independent prognostic factors for relapse-free survival. CONCLUSIONS: EphA1 is a possible target of molecular targeted therapy of gastric cancer.

Clinical significance of platelet derived growth factor-C and -D in gastric cancer.

Platelet-derived growth factor (PDGF)-C and PDGF-D are frequently upregulated in human cancers and play important roles in tumor progression, angiogenesis and metastasis. However, the distribution, frequency and prognostic value of PDGF-C and PDGF-D expression in gastric cancer have not been clarified. The present study evaluated the association between expression of PDGF-C and PDGF-D, clinicopathological factors and outcomes, in patients with gastric cancer. Gastric adenocarcinoma tumor samples were obtained from 204 patients who underwent curative gastrectomy between 2003 and 2007. The expression of PDGF-C and PDGF-D was analyzed by immunohistochemical staining. High expression of PDGF-C and PDGF-D was detected in 114 (56%) and 151 (74%) tumors, respectively. PDGF-D expression was significantly associated with tumor depth (P=0.039), histopathology (P<0.01), tumor stage (P=0.01) and recurrence (P<0.01), whereas PDGF-C expression correlated only with histopathology (P=0.05). High PDGF-D expression was also associated with significantly shorter relapse-free survival (RFS) time (P<0.01), whilst high PDGF-C expression was associated with marginally, but not significantly, shorter RFS (P=0.10). On multivariate analysis, high PDGF-D expression was determined to be an independent prognostic factor (hazard ratio, 3.3; 95% confidence interval, 1.20-9.4; P=0.02). These findings indicate that high PDGF-D expression is strongly associated with tumor progression, recurrence, distant metastasis and poor outcomes in patients with gastric cancer. PDGF-D may therefore be an independent prognostic factor and a novel therapeutic target.

Prognostic significance of the co-overexpression of fibroblast growth factor receptors 1, 2 and 4 in gastric cancer.

The overexpression of fibroblast growth factor receptor (FGFR) 2 is an established prognostic factor and treatment target in gastric cancer. However, the roles of other FGFRs have not been fully elucidated. In this study, we investigated the correlations of the expression of FGFR1-4 with clinicopathological characteristics and outcomes in gastric cancer. Tumor samples were obtained from 222 patients with gastric adenocarcinoma who underwent gastrectomy between 2003 and 2007. The expression of each FGFR was measured in the tumors by immunohistochemical analysis. The overexpression of FGFR1, FGFR2 or FGFR4 was found to be significantly associated with tumor progression, including depth of invasion, lymph node metastasis, pathological stage and distant metastasis or recurrent disease. Patients exhibiting overexpression of FGFR1, FGFR2 or FGFR4 had a significantly poorer disease-specific survival (DSS; P<0.001, P=0.008 and P<0.001, respectively). Moreover, the co-overexpression of all three FGFRs was significantly associated with a poorer DSS compared to the expression of none or only one of the FGFRs (P<0.001 and P=0.001, respectively) and it was found to be an independent prognostic factor (HR=1.71, 95% CI: 1.02-2.85, P=0.041). In conclusion, high expression of FGFR1, FGFR2 or FGFR4 was associated with tumor progression and poor survival in patients with gastric cancer. Similar to FGFR2, FGFR1 and FGFR4 may be considered as prognostic factors and treatment targets in gastric cancer.

Simple and rapid determination of PCDD/Fs in flue gases from various waste incinerators in China using DR-EcoScreen cells.

In developing countries such as China, there is a strong need for simple and rapid bioassays for the determination of polychlorinated dibenzo-p-dioxins and dibenzofurans (PCDD/Fs) in environmental samples; i.e., flue gas and fly ash from waste incinerators. In this study, we applied the DR-EcoScreen cell (DR-cell) assay to determination of PCDD/Fs in 78 flue gas samples obtained from various waste incinerators in China between 2009 and 2011. The flue gas samples were obtained from four kinds of incinerators, classified into hazardous, medical and municipal-solid waste, and iron ore sintering, and the flue gas extracts were cleaned up using an SPD-600 automated-sample preparation device for DR-cell assay. The PCDD/Fs values obtained from the DR-cell assay were compared with those obtained from conventional high resolution gas chromatography-high resolution mass spectrometry (HRGC-HRMS) analysis. The bioanalytical equivalent (BEQ) values obtained from the DR-cell assay were very closely correlated with the international toxicity equivalent (I-TEQ) values from HRGC-HRMS analysis (r2=0.98, n=78), while the BEQ values were 5.52-fold higher than the I-TEQ values, as the PCDFs, which account for 80% of the total I-TEQ value, were overestimated by DR cell-assay. Therefore, we multiplied the BEQ values from the DR-cell assay by a conversion coefficient (0.181, the reciprocal of 5.52), and could approximate the TEQ values from the HRGC-HRMS analysis. These results suggest that the DR-cell assay combined with SPD-600 cleanup provides a promising method for the simple and rapid screening of PCDD/Fs levels in flue gas samples, such as those from various waste incinerators in China.

[Scientific statement] Report of the Salt Reduction Committee of the Japanese Society of Hypertension (3) Assessment and application of salt intake in the management of hypertension.

Salt-reduction guidance to hypertensive patients should be performed by evaluating salt intake of the individuals. However, each method to assess salt intake has both merits and limitations. Therefore, evaluation methods must be selected in accordance with the subject and facility's environment. In special facilities for hypertension treatment, measurement of sodium (Na) excretion with 24-h pooled urine or a survey on dietary contents by dietitians is recommended. In medical facilities in general, measurement of the levels of Na and creatinine (Cr) using second urine samples after waking-up or spot urine samples is recommended. The reliability of this method improves by using formulae including a formula to estimate 24-h Cr excretion. A method to estimate salt intake based on the Na excretion per gram Cr using the Na/Cr ratio in spot urine is simple, but not reliable. The method to estimate the daily excretion of salt from nighttime urine using an electronic salt sensor installed with a formula is recommended to hypertensive patients. Although its reliability is not high, patients themselves can measure this parameter simply at home and thus useful for monitoring salt intake and may intensify consciousness regarding salt reduction. Using these methods, salt intake (excretion) should be evaluated, and salt-reduction guidance targeting <6 g (Na: 100 mmol) per day should be conducted in the management of hypertension.