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Background/Aim: Osteopontin (OPN) is a secretory glycoprotein, which is expressed not only in osteoblasts, but immune cells including macrophages and activated T cells. Its pleiotropic immune functions, such as bone remodeling, cancer progression, immune response, and inflammation have been reported previously. However, the association between OPN and postoperative complications (POC) after colorectal cancer (CRC) surgery has not been studied, so far. Methods: Peripheral blood samples were collected before (pre) and immediately after surgery (post), and on postoperative days (POD) 1, 3, 5, and 7. Serum OPN levels were measured by ELISA. In total, 78 patients who underwent elective CRC surgery were divided into the No-POC (n = 54) and POC (n = 24) groups. Results: The POC group had significantly higher OPN levels than the No-POC group throughout the postoperative observation period. The maximum OPN levels from pre- to postsurgical samples showed the best predictive potential for POCs (cut off: 20.75 ng/mL, area under the curve: 0.724) and were correlated with length of postoperative stays. OPN values were significantly correlated with C-reactive protein on POD3 and were identified as an independent predictive marker for POCs (odds ratio: 3.88, 95% CI: 1.175–12.798, P = 0.026). The severity of POCs was reflected in increased OPN levels. Conclusion: Increased postoperative OPN was associated with increased postoperative inflammatory host responses and POC after CRC surgery. Serum OPN level may be a useful biomarker for early prediction of POC and it may provide additional information for treatment decisions to prevent POC. [ABSTRACT FROM AUTHOR]

Lysophosphatidic acid (LPA) signaling via LPA receptors (LPA1 to LPA6) exhibits a variety of malignant properties in cancer cells. Intracellular ATP depletion leads to the development of necrosis and apoptosis. The present study aimed to evaluate the effects of LPA receptor-mediated signaling on the regulation of cancer cell functions associated with ATP reduction. Long-term ethidium bromide (EtBr) treated (MG63-EtBr) cells were established from osteosarcoma MG-63 cells. The intracellular ATP levels of MG63-EtBr cells were significantly lower than that of MG-63 cells. LPAR2, LPAR3, LPAR4 and LPAR6 gene expressions were elevated in MG63-EtBr cells. The cell motile and invasive activities of MG63-EtBr cells were markedly higher than those of MG-63 cells. The cell motile activity of MG-63 cells was increased by LPA4 and LPA6 knockdowns. In cell survival assay, cells were treated with cisplatin (CDDP) every 24 h for 3 days. The cell survival to CDDP of MG63-EtBr cells was lower than that of MG-63 cells. LPA2 knockdown decreased the cell survival to CDDP of MG-63 cells. The cell survival to CDDP of MG-63 cells was inhibited by (2 S)-OMPT (LPA3 agonist). Moreover, the cell survival to CDDP of MG-63 cells was enhanced by LPA4 and LPA6 knockdowns. These results indicate that LPA signaling via LPA receptors is involved in the regulation of cellular functions associated with ATP reduction in MG-63 cells treated with EtBr. [ABSTRACT FROM AUTHOR]

Safe and noninvasive methods for breast cancer screening with improved accuracy are urgently needed. Volatile organic compounds (VOCs) in biological samples such as breath and blood have been investigated as noninvasive novel markers of cancer. We investigated volatile organic compounds in urine to assess their potential for the detection of breast cancer. One hundred and ten women with biopsy-proven breast cancer and 177 healthy volunteers were enrolled. The subjects were divided into two groups: a training set and an external validation set. Urine samples were collected and analyzed by gas chromatography and mass spectrometry. A predictive model was constructed by multivariate analysis, and the sensitivity and specificity of the model were confirmed using both a training set and an external set with reproducibility tests. The training set included 60 breast cancer patients (age 34–88 years, mean 60.3) and 60 healthy controls (age 34–81 years, mean 58.7). The external validation set included 50 breast cancer patients (age 35–85 years, mean 58.8) and 117 healthy controls (age 18–84 years, mean 51.2). One hundred and ninety-one compounds detected in at least 80% of the samples from the training set were used for further analysis. The predictive model that best-detected breast cancer at various clinical stages was constructed using a combination of two of the compounds, 2-propanol and 2-butanone. The sensitivity and specificity in the training set were 93.3% and 83.3%, respectively. Triplicated reproducibility tests were performed by randomly choosing ten samples from each group, and the results showed a matching rate of 100% for the breast cancer patient group and 90% for the healthy control group. Our prediction model using two VOCs is a useful complement to the current diagnostic tools. Further studies inclusive of benign tumors and non-breast malignancies are warranted. [ABSTRACT FROM AUTHOR]

Background: The short-term safety and efficacy of insertion of a self-expandable metallic colonic stent (SEMS) followed by elective surgery, "bridge to surgery (BTS)", for malignant large bowel obstruction (MLBO) have been well described; however, the influence on long-term oncological outcomes is unclear. The aim of this study was to evaluate changes in oncological characteristics in colorectal cancer (CRC) tissues after SEMS insertion, focusing on growth factors, cell cycle and apoptosis.Methods: From January 2013 to September 2014, a total of 25 patients with MLBO who underwent BTS at our single institution were retrospectively included. Paired CRC tissue samples before (endoscopic biopsy) and after SEMS insertion (surgically resected) were collected from each patient. EGFR, VEGF, Ki-67, p27kip1 and TUNEL expression were determined by immunohistochemistry.Results: No clinical or subclinical perforations evaluated by mechanical ulceration pathologically were observed. Epithelial exfoliation, tumour necrosis, infiltration of inflammatory cells and fibrosis were observed in SEMS-inserted surgically-resected specimens. Overall, 84% (21/25) and 60% (15/25) of patients exhibited no change or a decrease in staining category, respectively, for EGFR and VEGF expression after SEMS insertion. A significant decrease in Ki-67 expression was observed in surgically-resected specimens compared with endoscopic biopsy specimens (P < 0.01). The upstream cell cycle inhibitor, p27kip1, was significantly increased after SEMS insertion (P = 0.049).Conclusions: Although the long-term safety of BTS should be determined in a future clinical trial, mechanical compression by SEMS may suppress cancer cell proliferation and this result could provide some insights into the issue. [ABSTRACT FROM AUTHOR]

Purpose: Lysophosphatidylcholine (LPC), which is generated from phosphatidylcholine (PC) and metabolized by autotaxin (ATX), modulates immune responses via its anti-inflammatory property. We investigated the association between LPC and postoperative complications (POCs) after colorectal cancer surgery (CRC).Methods: The subjects of this study were 43 patients who underwent surgery for CRC. Peripheral blood samples were collected preoperatively and immediately after surgery, and on postoperative days (PODs) 1, 3, 5, and 7. Patients were divided into a No-POC group (n = 33) and a POC group (n = 10). Blood LPC, IL-6, PC, and ATX levels were measured by specific enzymatic assays or ELISA.Results: The postoperative to preoperative LPC ratios were lowest on POD 1 in both groups. The POC group had significantly lower LPC ratios throughout the perioperative period than the No-POC group. The LPC ratios were inversely correlated with IL-6. The predictive impact of LPC ratios on POCs was demonstrated by ROC analysis (cut-off 51.2%, AUC 0.798) and multivariate analysis (OR 15.1, P = 0.01). The postoperative PC ratios decreased more after surgery in the POC group. ATX levels did not change significantly in either group.Conclusions: Decreased postoperative LPC is associated with increased postoperative inflammatory response and POCs. The decreased PC supply to the circulation is a mechanism of the postoperative LPC decrease. [ABSTRACT FROM AUTHOR]

Background: Neoadjuvant chemoradiation (NCRT) has emerged as a component of the standard treatment for esophageal squamous cell carcinoma (SCC). The primary benefit of NCRT is an improvement in long-term survival; however, the impact of NCRT on short-term outcomes is unclear. Methods: A comprehensive electronic literature search was performed via the MEDLINE (PubMed), Cochrane Library, and Google Scholar databases through November 2015 for the inclusion of randomized controlled trials (RCTs) that evaluated short-term outcomes of patients administered NCRT followed by surgery compared with surgery alone for resectable esophageal SCC. The main outcome measures were postoperative mortality and morbidity. A meta-analysis was performed using random-effects models to calculate odds ratios (ORs) with 95 % confidence intervals (CIs). Results: Eight RCTs were included, for a total of 1058 patients. Meta-analysis of the overall postoperative mortality and cardiopulmonary complication rates showed that there was a significant increase for patients administered NCRT followed by surgery compared with surgery alone (OR 1.87, 95 % CI 1.07-3.28, p = 0.03, number of patients needed to harm = 33.3; and OR 2.12, 95 % CI 1.03-4.35, p = 0.04, respectively). Dropout before surgery was higher for patients in the NCRT followed by surgery group compared with patients in the surgery-alone group. NCRT has no statistically impact on anastomosis and other complications compared with surgery alone. Conclusions: NCRT for esophageal SCC significantly increases postoperative mortality and cardiopulmonary complications. [ABSTRACT FROM AUTHOR]

Background: Neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) have been reported to predict oncologic outcomes in patients with various types of cancer. However, their prognostic value in patients with esophageal cancer is unclear. In this meta-analysis, we evaluated the prognostic significance of NLR and PLR in esophageal cancer patients. Methods: We performed comprehensive searches of electronic databases to identify studies that evaluated the prognostic impact of pretreatment NLR and PLR in esophageal cancer patients. The end points were overall survival (OS), disease-free survival, and clinicopathologic parameters. A meta-analysis using random-effects models was performed to calculate hazard ratios (HRs) or odds ratios with 95 % confidence intervals (CIs). Results: Seven retrospective, observational, cohort studies involving 1540 patients were included. All seven studies evaluated NLR, and four evaluated PLR. Both high NLR (HR 1.40, 95 % CI 1.08-1.81, P = 0.01) and high PLR (HR 1.59, 95 % CI 1.14-2.21, P = 0.006) were significantly predictive of poorer OS. NLR was not a significant predictor of disease-free survival. High PLR (HR 1.85, 95 % CI 1.50-2.28, P < 0.00001) but not NLR was significantly predictive of poorer OS in a subgroup of patients who underwent curative surgery without neoadjuvant chemoradiation. Both high NLR and high PLR were significantly associated with deeper tumor invasion and lymph node metastasis. Conclusions: NLR and PLR are associated with tumor progression and are predictive of poorer survival in patients with esophageal cancer. These ratios may thus help to inform treatment decisions and predict treatment outcomes. [ABSTRACT FROM AUTHOR]

Humanin (HN) and its derivatives, such as Colivelin (CLN), suppress neuronal death induced by insults related to Alzheimer's disease (AD) by activating STAT3 in vitro. They also ameliorate functional memory impairment of mice induced by anticholinergic drugs or soluble toxic amyloid-β (Aβ) in vivo when either is directly administered into the cerebral ventricle or intraperitoneally injected. However, the mechanism underlying the in vivo effect remains uncharacterized. In addition, from the standpoint of clinical application, drug delivery methods that are less invasive and specific to the central nervous system (CNS) should be developed. In this study, we show that intranasally (i.n.) administered CLN can be successfully transferred to CNS via the olfactory bulb. Using several behavioral tests, we have demonstrated that i.n. administered CLN ameliorates memory impairment of AD models in a dose-responsive manner. Attenuation of AD-related memory impairment by HN derivatives such as CLN appears to be correlated with an increase in STAT3 phosphorylation levels in the septohippocampal region, suggesting that anti-AD activities of HN derivatives may be mediated by activation of STAT3 in vivo as they are in vitro. We further demonstrate that CLN treatment inhibits an Aβ induced decrease in the number of choline acetyltransferase (ChAT)-positive neurons in the medial septum. Combined with the finding that HN derivatives upregulate mRNA expression of neuronal ChAT and vesicular acetylcholine transporter (VAChT) in vitro, it is assumed that CLN may ameliorate memory impairment of AD models by supporting cholinergic neurotransmission, which is at least partly mediated by STAT3-mediated transcriptional upregulation of ChAT and VAChT.Neuropsychopharmacology (2008) 33, 2020–2032; doi:10.1038/sj.npp.1301591; published online 10 October 2007 [ABSTRACT FROM AUTHOR]

Chiral separation has revealed enantio-specific changes in blood and urinary levels of amino acids in kidney diseases. Blood d-/l-serine ratio has been identified to have a correlation with creatinine-based kidney function. However, the mechanism of distinctive behavior in serine enantiomers is not well understood. This study was performed to investigate the role of renal tubules in derangement of serine enantiomers using a mouse model of cisplatin-induced tubular injury. Cisplatin treatment resulted in tubular damage histologically restricted to the proximal tubules and showed a significant increase of serum d-/l-serine ratio with positive correlations to serum creatinine and blood urine nitrogen (BUN). The increased d-/l-serine ratio did not associate with activity of a d-serine degrading enzyme, d-amino acid oxidase, in the kidney. Screening transcriptions of neutral amino acid transporters revealed that Asc-1, found in renal tubules and collecting ducts, was significantly increased after cisplatin-treatment, which correlates with serum d-serine increase. In vitro study using a kidney cell line showed that Asc-1 is induced by cisplatin and mediated influx of d-serine preferably to l-serine. Collectively, these results suggest that cisplatin-induced damage of proximal tubules accompanies Asc-1 induction in tubules and collecting ducts and leads to serum d-serine accumulation. [ABSTRACT FROM AUTHOR]