Search

Introduction/Background* TCGA molecular classification for endometrial cancer is expected to propose the most appropriate treatment strategy for each patient. Most of the patients in previous studies on this issue from western countries were treated with adjuvant radiation therapy. Thus, the prognostic stratifications by TCGA molecular classification remain unclear when adjuvant chemotherapy is applied. In this study, we aimed to validate a modified TCGA classification. Methodology From 2003 to 2015, the patients with endometrial cancer treated in our hospital were enrolled in this retrospective study. The patients who were surgically staged by hysterectomy, bilateral salpingo-oophorectomy, and systematic lymphadenectomy were included, and postoperative adjuvant chemotherapy was applied for the patients at intermediate or high-risk of recurrence. The patients with follow-up period of less than 3 years were excluded. The patients were molecularly classified in combination with conventional recurrent low-risk, and immunohistochemistry (IHC) for PMS2, MSH6 and p53, resulting in four subgroups: low-risk for recurrence by risk classification (Stage IA, Endometrioid carcinoma, Grade 1or2, negative lymph-vascular space invasion), MMRd (PMS2 and/or MSH6 negative), p53abn (p53 positive), and NSMP (none of the above). The 5-year disease-specific survival rates (5y-DSS) were compared among each group. Result(s)* Total of 175 patients were analyzed. Of 175 patients, 41 patients were classified as low risk for recurrence, 45 patients as MMRd, 19 patients as p53abn, and the remaining 45 patients as NSMP. The median age (58 years old) and follow-up period (104 months) were not significantly different among 4 groups. The distribution of FIGO stage or histological types were also not significantly different except for low-risk group. The 5y-DSS was 100%, 93%, 74%, and 91%, respectively, and the prognosis was stratified into 3 groups: favorable, low-risk for recurrence; intermediate, MMRd and NSMP; unfavorable, p53abn. Conclusion* We conclude that the prognosis can be stratified by a modified TCGA classification in combination with conventional recurrent risk and IHC for PMS2, MSH6 and p53 in surgically-staged endometrial cancer receiving adjuvant chemotherapy.

Purpose: To evaluate the effects of topical hyaluronan (HA) on corneal epithelial wound healing when administered with or without benzalkonium chloride (BAC).Methods: A cultured human corneal epith...

Abdominal fat accumulation causes metabolic syndrome, which is a cluster of metabolic abnormalities such as dyslipidemia, glucose intolerance, insulin resistance or hyperinsulinemia, and hypertension, leading to the development of diabetes and cardiovascular disease. Diets are known to contribute to the development or prevention of metabolic syndrome. Several studies have reported that the quality of dietary proteins may be an important modulator of the risk of this syndrome. We investigated the effects of consuming egg white protein (EWP) or lactic-fermented egg white (LE), an easy-to-consume form of egg white, on the development of metabolic syndrome in animal models and humans. In comparison with casein, dietary EWP decreased lymphatic lipid transport in thoracic lymph duct-cannulated rats. In an in vitro experiment, EWP pepsin hydrolysate decreased the cholesterol micellar solubility and cholesterol transfer rate from micelles to oil phase, and increased water-holding capacity, settling volume in water, and relative viscosity compared with casein pepsin hydrolysate. The daily consumption of LE for 8 weeks reduced serum total cholesterol and LDL cholesterol levels in men with mild hypercholesterolemia. Furthermore, dietary EWP reduced the body fat mass of rats by increasing the body protein mass and accelerating hepatic β-oxidation. The daily consumption of LE for 12 weeks reduced the visceral fat area and improved the ratio of the visceral to subcutaneous fat area. Taken together, these results indicated that dietary EWP and LE would be useful for preventing or alleviating metabolic syndrome.

Background We previously reported that the consumption of 8 g of protein per day in the form of lactic-fermented egg white (LAFEW) improves visceral fat obesity. In this study, we investigated the minimum effective intake of LAFEW for visceral fat reduction in the Japanese males with mild obesity. Methods Twenty-two Japanese adult males with a Body mass index (BMI) ≥24 and a waist circumference ≥ 85 cm were included in this study. The subjects were divided into three groups, that is, control group, LAFEW 6 g group, and LAFEW 8 g group. The LAFEW 6 and 8 g groups consumed 6 and 8 g, respectively, of egg white protein (EWP) in a drink at breakfast for 8 weeks, whereas the control group consumed a drink containing 8 g of milk whey protein. Body weight, body fat percentage, abdominal circumference, and visceral fat (VF) area around the navel were measured at 0 and 8 weeks after initiating the consumption. Results No changes in body weight or body fat percentage were observed in any of the groups. No significant differences between the pre- and posttreatment measurements were found in the VF area around the navel in the control group and the LAFEW 6 g group. In the LAFEW 8 g group, the VF area had decreased significantly after 8 weeks of consumption, when compared to that before consumption, and the average observed decrease (Δcm2) was 13.2 ± 4.7 cm2. Among the subjects with an initial BMI > 25, the VF area was significantly smaller in the LAFEW 8 group, when compared to the week 0 values and those in the control group. Visceral fat/subcutaneous fat values in the LAFEW 8 group were also significantly smaller than those in the control group or at week 0. Conclusion The results suggested that the minimum effective intake of EWP in the LAFEW to reduce the VF area in the Japanese men is 8 g. Trial registration This clinical trial was retrospectively registered with the University hospital Medical Information Network (UMIN) Center, (UMIN000031681; registered on 12/03/2018).

We present the case of a 4-year-old girl in whom a vitelline vessel remnant (VVR) was incidentally detected and then resected during laparoscopic inguinal hernia repair. VVR can cause intestinal obstruction, which is sometimes fatal. There are few reports of asymptomatic VVR that are discovered incidentally during surgery. Inguinal hernia repairs account for a large percentage of the operations performed by pediatric surgeons. Currently, the laparoscopic approach is most often used because of its minimal invasiveness and cosmetic results. The laparoscopic approach can also incidentally detect unknown abnormalities, such as non-symptomatic VVR, in the abdominal cavity, thereby facilitating its treatment in a minimally invasive manner. VVR may have abundant blood flow. Therefore, during laparoscopic resection, attention to bleeding is important.

Hyaluronan (HA) is present in all connective tissues and organs, including the skin and joint fluid. However, few clinical trials have comprehensively evaluated the impacts of oral HA on skin conditions, including wrinkles and moisturization. In this study, we conducted a placebo-controlled, randomized, double-blind trial of daily HA (120 mg) intake for 12 weeks in 40 healthy Asian men and women (aged 35–64 years). Skin condition was determined by the evaluation of wrinkles, stratum corneum water content, the amount of transepidermal water loss, elasticity, and through image analysis. After 12 weeks, skin condition was significantly improved in terms of wrinkle assessment, stratum corneum water content, transepidermal water loss, and elasticity in the HA group compared to the placebo group. Regarding the percentage change from baseline, wrinkle assessment, stratum corneum water content, and skin elasticity were significantly improved in the HA group versus the placebo group after 8 and 12 weeks of ingestion. The present findings indicate that oral ingestion of HA may suppress wrinkles and improve skin condition.

Although most current epidemiologic studies indicate no significant association between consuming one egg daily and blood cholesterol levels and cardiovascular risk, arguments still persist with a positive association. Since the diet is one of the most influential factors for this association, we illustrate characteristic features in Japanese people whose dietary pattern is distinct from that, for example, the US (United States) population. Available epidemiologic studies in healthy Japanese people show no association between consumption of one egg daily and blood cholesterol level, consistent with those observed in the US population. However, when consumption of major nutrients and food sources of cholesterol are compared to the US population, Japanese people may have an extra-reserve against the influence of eggs on cardiovascular risk markers, despite consuming relatively more eggs. Further discussion on the influence of nutrients contained in the egg and dietary pattern, including interaction with gut microbes, is necessary. In addition, special consideration at the personalized level is needed for judgment regarding dietary cholesterol not only for hypercholesterolemic patients but for hyper-responsive healthy persons. Although randomized controlled trials with long-term follow-up are required to evaluate the association between consumption of eggs and human health, available information, at least from the nutritional viewpoint, suggests that egg is a healthy and cost-efficient food worldwide.

Objectives Uterine leiomyosarcoma (uLMS) is one of rare and aggressive gynecologic malignancies. In this study, we aimed to correlate immune cell profiling with clinical outcomes in uLMS. Methods Total of 6 pathologically diagnosed uLMS patients were enrolled in this study. RNAs were extracted from FFPEs of normal and tumor lesions, and Cell Type Profiling analysis was conducted using nCounter, PanCancer Immune Profiling Panel (NanoString). For evaluating the related pathways, the RNAs were used to conduct microarray analysis using SurePrint G3 Human GE microarray 8 × 60K ver.2.0 (Agilent). Results FIGO stage were IB in 4 patients, IIA in one patient, and IVB in one. We divided these patients into three groups by prognosis; good, no recurrence more than 2 years; intermediate, recurrent within 2 years; poor, recurrent immediately after surgery. In good prognostic group, CD8/regulatory T (Treg) ratio and Mast cell score in tumor lesions were elevated, and TP53 network, and DNA damage response signals were upregulated. In intermediate group, total TIL score in normal uterine were elevated, but CD8/Treg ratio was decreased in tumor lesion. And PI3K/AKT/mTOR signal and STAT3, IL8 signaling were upregulated. Finally, in poor prognostic group, total TIL score were decreased in normal and tumor lesions, and Neutrophil score was elevated in tumor lesions. Upregulation of DNA damage response but downregulated TP53 network. Conclusions Immune cell profiling may predict clinical outcomes in uLMS. Further analyses, such as, correlation with signaling pathways affected to immune cell profiling in larger sample size are needed.

Precision medicine is a promising strategy for cancer treatment. In this study, we developed an in‐house clinical sequencing system to perform a comprehensive cancer genomic profiling test as a clinical examination and analyzed the utility of this system. Genomic DNA was extracted from tumor tissues and peripheral blood cells collected from 161 patients with different stages and types of cancer. A comprehensive targeted amplicon exome sequencing for 160 cancer‐related genes was performed using next‐generation sequencing (NGS). The sequencing data were analyzed using an original bioinformatics pipeline, and multiple cancer‐specific gene alterations were identified. The success rate of our test was 99% (160/161), while re‐biopsy was required for 24% (39/161) of the cases. Potentially actionable and actionable gene alterations were detected in 91% (145/160) and 46% (73/160) of the patients, respectively. The actionable gene alterations were frequently detected in PIK3CA (9%), ERBB2 (8%), and EGFR (4%). High tumor mutation burden (TMB) (≥10 mut/Mb) was observed in 12% (19/160) of the patients. The secondary findings in germline variants considered to be associated with hereditary tumors were detected in 9% (15/160) of the patients. Seventeen patients (11%, 17/160) were treated with genotype‐matched therapeutic agents, and the response rate was 47% (8/17). The median turnaround time for physicians was 20 days, and the median survival time after the initial visit was 8.7 months. The results of the present study prove the feasibility of implementing in‐house clinical sequencing as a promising laboratory examination technique for precision cancer medicine., In‐house clinical sequencing system is a promising laboratory examination for precision cancer medicine.

A 47-year-old male patient without a documented past medical history was referred to Sanno Hospital because of constipation and abdominal pain, which he had had for more than 5 years. Abdominal X-ray and CT scan showed an enlarged ascending colon from the cecum to the transverse colon, without apparent mechanical obstruction. The patient was diagnosed with chronic idiopathic colonic pseudo-obstruction, and because his symptoms were resistant to medication, surgical treatment was required. Laparoscopic subtotal colectomy was performed without any complications. Constipation was relieved, and the patient began defecating 2-3 times a day without medication. Pathological specimens showed that Meissner's plexus and Auerbach's plexus had decreased and that there were fewer ganglion cells-findings consistent with chronic idiopathic intestinal pseudo-obstruction.

Glomangiopericytoma (GPC) is a rare mesenchymal tumor arising from the nasal cavity or paranasal sinuses. GPC was categorized as a borderline and low-malignant-potential tumor by the World Health Organization in 2005 and accounts for less than 0.5% of all sinonasal tumors. We report a case of GPC in a 74-year-old woman with a history of recurrent epistaxis and nasal obstruction. A reddish tumor was seen in the right nasal cavity. Enhanced computed tomography showed a mass lesion occupying the right nasal cavity. The tumor, which originated from the nasal septum in the olfactory fissure area, was resected with 5-mm mucosal margins by endoscopic sinus surgery. Histologic examination revealed a uniform proliferation of oval-to-short spindle-shaped cells beneath the epithelium. Immunohistologic analysis demonstrated the tumor cells were positive for α-smooth muscle actin, β-catenin and Vimentin, and negative for AE1/AE3, Bcl-2, CD34, CD117, Factor VIIIR Ag, S-100 protein, or STAT6. The percentage of Ki-67-positive cells was approximately 5%. Genetic analysis using next-generation sequencing revealed a missense mutation in the CTNNB1 gene (c.110C > G, p.S37C). While other CTNNB1 mutations have been described in GPC; this is the first report of this specific mutation. The mutation was confirmed using Sanger sequencing. Electronic supplementary material The online version of this article (10.1007/s12105-018-0961-z) contains supplementary material, which is available to authorized users.

Egg-white protein (EWP) is known to reduce lymphatic TAG transport in rats. In this study, we investigated the effects of dietary EWP on body fat mass. Male rats, 4 weeks old, were fed diets containing either 20 % EWP or casein for 28 d. Carcass protein levels and gastrocnemius leg muscle weights in the EWP group were significantly higher than those in the casein group. In addition, carcass TAG levels and abdominal fat weights in the EWP group were significantly lower than those in the casein group; adipocyte size in abdominal fat in the EWP group was smaller than that in the casein group. To identify the involvement of dietary fat levels in the rats, one of two fat levels (5 or 10 %) was added to their diet along with the different protein sources (EWP and casein). Abdominal fat weight and serum and hepatic TAG levels were significantly lower in the EWP group than in the casein group. Moreover, significantly higher values of enzymatic activity related toβ-oxidation in the liver were observed in the EWP group compared with the casein group. Finally, abdominal fat weight reduction in the EWP group with the 10 % fat diet was lower than that in the EWP group with the 5 % fat diet. In conclusion, our results indicate that, in addition to the inhibition of dietary TAG absorption reported previously, dietary EWP reduces body fat mass in rats through an increase of body protein mass and the acceleration ofβ-oxidation in the liver.

Introduction/Background L1 cell adhesion molecule (L1CAM), a transmembrane protein of the immunoglobulin family that has been implicated in promoting cancer cell proliferation, invasion, migration, and metastasis, has been established as an important predictor of poor survival of early-stage endometrial cancer patients. We aimed to investigate whether L1CAM remains significant predictor of poor survival of the patients with endometrial cancer undergoing extensive surgical staging and adjuvant chemotherapy in this retrospective analysis. Methodology We prepared tissue microarray (TMA) from surgical tissue specimens of 185 endometrial cancer patients who underwent full lymphadenectomy combined with adjuvant chemotherapy for patients at risk for recurrence, and evaluated expression of L1CAM by immunohistochemistry (IHC). L1CAM positivity was correlated with clinicopathological factors and its prognostic significance was investigated by multivariate analysis using Cox regression model. Results Among 169 cases with over three years of follow-up period (median 95 months, 5–186 months), 53 cases (31.4%) showed positivity of L1CAM. L1CAM positivity was significantly correlated with non-endometrioid histology (p Conclusion L1CAM is an independent predictor of poor survival of Japanese patients with advanced-stage endometrial cancer undergoing full lymphadenectomy and adjuvant chemotherapy. New treatment strategy should be developed for L1CAM positive patients with endometrial cancer. Disclosure Nothing to disclose.

L1 cell adhesion molecule (L1CAM) has been established as an important predictor of poor survival of early-stage endometrial cancer patients. We investigated whether L1CAM remains a significant predictor of poor survival of patients with advanced-stage endometrial cancer undergoing extensive surgical staging and adjuvant chemotherapy. We prepared tissue microarray (TMA) from surgical tissue specimens of 161 endometrial cancer patients who underwent full lymphadenectomy combined with adjuvant chemotherapy for patients at risk for recurrence, and evaluated expression of L1CAM using immunohistochemistry. The correlation between L1CAM positivity and clinicopathological factors and the prognostic significance of L1CAM expression was investigated. Among 161 cases who had a follow-up duration of over 3 years, 48 cases (29.8%) showed positive staining for L1CAM. L1CAM positivity was significantly correlated with non-endometrioid histology (p

Aim A new classification of combined hepatocellular cholangiocarcinoma (CHC) was recently reported. Cancer stem cells have been associated with CHC carcinogenesis. This study examined the association of cancer stem cell marker expression and prognosis in CHC classified using the new classification. Methods We enrolled 26 CHC patients and classified them according to the new classification. We evaluated the expression of cancer stem cell markers (CD56, CD133, and epithelial cell adhesion molecule [EpCAM]) by immunohistochemical staining in each component. We analyzed the association between expressions and prognosis. Results Seven cases were hepatocellular carcinoma (HCC) and cholangiocarcinoma (CCA) (cHCC-CCA), 12 were HCC and intermediate cell carcinoma (HCC-INT), and seven were intermediate cell carcinoma (INT). The CD133-positive rate tended to be higher in the CCA (42.9%) and INT component (50.0%) than the HCC component (14.3%) in cHCC-CCA. In HCC-INT, the CD133-positive rate in the INT component (83.3%) was significantly higher than the HCC component (8.3%; P = 0.001). For EpCAM, the positive rate in the CCA component (71.4%) and INT component (50.0%) tended to be higher than the HCC component (14.3%) in cHCC-CCA. Overall survival and disease-free survival were significantly worse in cases with CD133-positive (P = 0.048 and P = 0.048, respectively) or EpCAM-positive (P = 0.041 and P = 0.041, respectively) CCA component in cHCC-CCA. Conclusions INT and CCA components showed higher expression rates of cancer stem cell markers than the HCC component. CD133 or EpCAM expression in the CCA component was associated with poor prognosis in cHCC-CCA.

Epicardial adipose tissue (EAT), a source of adipokines, is metabolically active, but the role of EAT mitochondria in coronary artery disease (CAD) has not been established. We investigated the association between EAT mitochondrial respiratory capacity, adiponectin concentration in the EAT, and coronary atherosclerosis. EAT samples were obtained from 25 patients who underwent elective cardiac surgery. Based on the coronary angiographycal findings, the patients were divided into two groups; coronary artery disease (CAD; n = 14) and non-CAD (n = 11) groups. The mitochondrial respiratory capacities including oxidative phosphorylation (OXPHOS) capacity with non-fatty acid (complex I and complex I + II-linked) substrates and fatty acids in the EAT were significantly lowered in CAD patients. The EAT mitochondrial OXPHOS capacities had a close and inverse correlation with the severity of coronary artery stenosis evaluated by the Gensini score. Intriguingly, the protein level of adiponectin, an anti-atherogenic adipokine, in the EAT was significantly reduced in CAD patients, and it was positively correlated with the mitochondrial OXPHOS capacities in the EAT and inversely correlated with the Gensini score. Our study showed that impaired mitochondrial OXPHOS capacity in the EAT was closely linked to decreased concentration of adiponectin in the EAT and severity of coronary atherosclerosis.

Perturbed lipid metabolism leads to ectopic lipid accumulation in tissues, such as the liver, thereby causing nonalcoholic fatty liver disease (NAFLD) and negatively influencing circulating lipid profile-inducing dyslipidemia. Phospholipids (PLs) with special biological activity are used to treat chronic diseases such as cardiovascular and cerebrovascular disease. PLs derived from egg yolk and soya bean have significant antioxidant and lipid-lowering abilities. This study examined the therapeutic effects of them on hyperlipidemia using a high-fructose-fed rat model, lipid metabolism and anti-inflammatory effects were also analyzed. The results showed that both egg yolk and soya bean phospholipids (EPLs and SPLs) reduced liver weight, hepatic TG, and MDA content as well as serum ALT, AST, TBA, and CRP levels (p &lt, 0.05). The PLs also showed hypolipidemic and anti-inflammatory effects. EPLs and SPLs could inhibit the accumulation of hepatic fatty acids C18:1N9C, C18:0, and C22:6NS of rats fed a high-fat-and-sucrose diet. The intake of EPLs could significantly increase acetylcholine content in the blood and brain tissue. Histological examination showed that PLs intake could ameliorate the damage to liver tissue. This study suggested that EPLs and SPLs had a certain capacity of hypolipidemic and liver protection, and the therapeutic benefits of EPLs tended to be more effective than that of soybean phospholipids.

Neurolymphomatosis is a rare entity defined as nerve infiltration by neurotropic abnormal lymphocytes which can lead to the development of neuropathy, with typical presentations including pain, hypoesthesia, paresthesis and palsy. We herein report two cases where critical bilateral vocal cord paralysis due to neurolymphomatosis in recurrent nerves occurred in refractory Burkitt lymphoma and adult T-cell lymphoma patients. High-dose methotrexate and intrathecal chemotherapy injection for the nervous lesions were ineffective, and the patients died. Neurolymphomatosis of the recurrent nerve is an emergent and difficult complication and should be suspected when sudden onset of aphasia, hoarseness or shortness of breath is found in refractory lymphoma patients.

6042 Background: Ovarian clear cell carcinoma (OCCC) is a distinct entity from other epithelial ovarian cancers such as the most prevalent high-grade serous cancer (HGSC), and often exhibit less sensitivity to platinum-based chemotherapy. Several studies using cell lines have reported that glutathione (GSH) metabolism plays an important role in chemo-resistance of OCCC. Here, we aimed to correlate the prognosis of OCCC and the expression of gamma-glutamyltransferase 1 (GGT1), one of the key enzymes in GSH metabolism. Methods: We prepared a FFPE-tissue microarray, and analyzed 56 OCCC patients with the follow-up periods over 3 years. Expression level of GGT1 was evaluated by immunohistochemistry (IHC) using H-score (0-300), and was correlated with clinical outcomes. The prognostic significance was assessed by multivariate analysis using Cox regression model. To investigate the possible related pathways, we performed transcriptome analysis using Ion AmpliSeq Transcriptome Human Gene Expression Kit (Thermo Fisher Scientific) from the frozen tissue specimens collected from 33 ovarian cancer patients including 15 OCCC patients and 18 HGSC patients. Results: The OCCC patients were divided into two populations in the histogram of H-score in IHC staining, and the cut-off value was 90; 44 cases showed GGT1-high, and remaining 12 cases were GGT1-low. Follow-up periods, FIGO stage, and optimal surgery rate were not significantly different between two groups. However, platinum-resistant recurrent rate was significantly higher (42% vs. 14%, p=0.027), and overall survival (OS) was significantly shorter (5-year OS; 42% vs. 72%, p=0.0226) in GGT1-low OCCC. Multivariate analysis revealed that low expression of GGT1 was one of the independent poor prognostic factors as well as platinum-drug resistance. In enrichment analysis, the genes related to GSH metabolism, such as SLC3A1, GGT1, CSE, and GPX3 were up-regulated and positively correlated with HNF1B expression in OCCC. The expression level of GGT1 was inversely correlated with that of immune suppressive genes (TGF-b, IFNG, IL10, FOXP3, PD-L1, CTLA4) and epithelial-mesenchymal transition (EMT)-related genes (CDH2, VIM, TWIST1, ZEB1, ZEB2) in OCCC samples. Conclusions: Low expression of GGT1 is an independent poor prognostic factor probably in part due to suppression of tumor immunity and induction of EMT in OCCC.

Background Precision medicine guided by comprehensive genome sequencing represents a potential treatment strategy for pancreatic cancer. However, clinical sequencing for pancreatic cancer entails several practical difficulties. We have launched an in-house clinical sequencing system and started genomic testing for patients with cancer in clinical practice. We have analyzed the clinical utility of this system in pancreatic cancer. Methods We retrospectively reviewed 20 patients with pancreatic cancer who visited our division. Genomic DNA was extracted from both tumor tissue and peripheral blood mononuclear cells obtained from the patients. We performed a comprehensive genomic testing using targeted amplicon sequencing for 160 cancer-related genes. The primary endpoints were the detection rates of potential actionable and druggable gene alterations. The secondary endpoints were the detection rate of secondary germline findings, the rate of re-biopsy required for genome sequencing, survival time after the initial visit (post-sequencing survival time), and turnaround time. Results Although re-biopsy was required for 25% (5/20) of all patients, genomic testing was performed in all patients. Actionable and druggable gene alterations were detected in 100% (20/20) and 35% (7/20) of patients, respectively, whereas secondary germline findings were detected in 5% (1/20) of patients. The median turnaround times for physicians and patients were 20 and 26 days, respectively. The median post-sequencing survival time was 10.3 months. Only 10% (2/20) of all patients were treated with therapeutic agents based on the outcomes of genomic testing. Conclusions The clinical application of comprehensive genomic testing for pancreatic cancer was feasible and promising in clinical practice.

It was reported that egg white protein (EWP) reduced body fat in rats. We developed a lactic-fermented egg white (LE) that facilitates the consumption of egg whites by fermenting them with lactobacillus, and were able to study their intake in humans. In this double-blind, placebo-controlled design, we evaluated the effect of LE on visceral fat area (VFA). Participants included 37 adult males and females aged ≥40 years (VFA at navel ≥100 cm2). They were divided into two groups: the control group and the LE group. The control and LE groups consumed drinks containing whey and LE, respectively, for 12 weeks (providing 8 g protein/day). VFA was measured at baseline and at week 12 of intake. Abdominal girth was measured at baseline and at weeks 6 and 12. LE intake decreased VFA significantly compared with baseline (−8.89 cm2, p

Background Lactic-fermented egg white (LE), produced by lactic acid fermentation of egg white, is an easy-to-consume form of egg white. Here we assessed the effect of daily consumption of LE for 8 weeks on serum total cholesterol (TC) levels. Methods The study followed a double-blind, parallel-arm design and included 88 adult men with mild hypercholesterolemia (mean ± standard error) serum TC levels, 229 ± 1.6 mg/dL; range, 204–259 mg/dL). The subjects were randomly divided into three groups, which consumed LE containing 4, 6, or 8 g of protein daily for 8 weeks. Blood samples were collected before starting LE consumption (baseline) and at 4 and 8 weeks to measure serum TC and low-density lipoprotein cholesterol (LDL-C) levels. Results After 8 weeks of consumption, serum TC levels in the 8 g group decreased by 11.0 ± 3.7 mg/dL, a significant decrease compared to baseline (p

Dietary egg white protein (EWP) decreases serum cholesterol levels. We previously showed that EWP decreased cholesterol absorption in the intestine. Rats subjected to permanent lymph duct cannulation were used to investigate the effects of dietary EWP on lipid transport. They were fed diets with 20% EWP and casein, and their lymph was collected to quantify lymphatic lipid levels. Dietary EWP decreased lymphatic cholesterol transport compared with casein. It was previously shown that EWP excluded cholesterol from bile acid micelles. Therefore, pepsin-hydrolyzed EWP and casein were prepared. EWP was not completely digested. Ovalbumin, which is the most abundant protein in EWP, showed resistance to digestion by pepsin. This study investigated the effects of EWP pepsin hydrolysate (EWP-ph) on cholesterol micellar solubility, cholesterol transfer from the micellar to the oil phase, water-holding capacity (WHC), settling volume in water (SV), and relative viscosity and compared them with the effects of casein pepsin hydrolysate (C-ph). EWP-ph significantly decreased the micellar solubility and transfer rate and increased the WHC, SV, and relative viscosity compared with C-ph. Moreover, the pepsin hydrolysate of ovalbumin, a major protein in EWP, played a role in decreasing cholesterol micellar solubility, leading to the inhibition of cholesterol absorption. In conclusion, dietary EWP decreased cholesterol intestinal absorption by exerting combined effects of these physicochemical properties in the gut.

Background: Ovarian clear cell carcinoma (OCCC) is more prevalent in Japan than western countries, exhibits chemoresistant phenotype and poor survival. Although the expression of the genes related to glutathione (GSH) metabolism had been reported as one of the possible chemoresistant mechanisms, correlation between the expressions of these genes and prognosis in OCCC patients remains unclear. In this study, we aim to investigate 1) enrichment pathway analysis in OCCC in comparison with high-grade serous carcinoma (HGSC), and 2) correlation between the expression of gamma-glutamyl transpeptidase 1 (GGT1), one of the enzymes in GSH metabolism and prognosis. Methods: We consecutively collected surgically resected tissue specimens from 33 ovarian cancer patients; 15 patients with OCCC and 18 patients with HGSC. The tissue specimens were collected in the vials containing RNA later® within 10 min. after resection of tumors. Total RNAs were extracted from the tumor tissues, and comprehensive gene expression analysis was performed using Ion AmpliSeq™ Transcriptome Human Gene Expression Kit (Thermo Fisher Scientific). For prognostic analysis, we used a tissue microarray (TMA) from 56 consecutive patients pathologically diagnosed with OCCC in our hospital, and assessed by immunohistochemistry (IHC) using H-score ranging from 0 to 300. Overall survival (OS) was estimated by Kaplan-Meier method, and analyzed by Cox-regression hazard model in multivariate analysis. Results: Gene expression profiles revealed that TCF1/2 target genes were up-regulated in OCCC samples in comparison with HGSC. In addition, genes related with amino-acid transporters, such as SLC3A1, a cystine transporter, and genes related to GSH metabolism, including GGT1, CSE, and GPX3 were also up-regulated. In the OCCC patients with high expression level of GSH-related genes, FOXP3 was down-regulated but the T-cell inflamed genes were not varied compared to the OCCC patients with low expression level. The expression level of GGT1 in gene expression analysis was strongly correlated with H-score of GGT1 in IHC (r = 0.7850, p = 0.0023). In prognostic analysis, there were no significant differences during follow up period (57.5 months vs. 53 months), FIGO stage (I: 50% vs 64%), optimal surgery (92% vs. 98%), or recurrent rate (42% vs. 30%) between GGT1 positive (n = 44) and negative (n = 12) OCCC in IHC. However, platinum-drug resistant recurrent rate was significantly higher in GGT1 negative OCCC than GGT1 positive OCCC (42% vs 14%, p = 0.027). OS in GGT1 negative OCCC was significantly worse than that of GGT1 positive OCCC (5-year OS was 42% vs 72%, p = 0.0226), and negative expression of GGT1 was one of the independent poor prognostic factors in OCCC. Conclusion: Negative expression of GGT1 in OCCC might be a poor prognostic maker via recruitment of regulatory T cells in tumor microenvironments. Citation Format: Hiroshi Asano, Ryosuke Matsuoka, Kanako C. Hatanaka, Yutaka Hatanaka, Tatsuya Kato, Yosuke Konno, Takashi Mitamura, Hirotoshi Akita, Yoshihiro Matsuno, Hidemichi Watari. Correlation between the expression of glutathione metabolism-related genes and prognosis in ovarian clear cell carcinoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 4020.

[Purpose]: Basic fibroblast growth factor is a candidate causative factor of detrusor overactivity in bladder outlet obstruction cases through up-regulation of the gap junction protein connexin 43. We addressed the transcriptional and behavioral implications of this axis. [Materials and Methods]: Cx43 and Cx45 mRNA expression was assessed by real-time reverse transcriptase-polymerase chain reaction in the bladder of a rat bladder outlet obstruction model and in cultured rat bladder smooth muscle cells with and without basic fibroblast growth factor treatment. Involvement of the extracellular signal regulated kinase 1/2-activator protein-1 pathway was evaluated by immunofluorescence study and a promoter-reporter assay in bladder smooth muscle cells. The effect of basic fibroblast growth factor on micturition behavior was measured in unrestrained rats under a 12-hour light/dark cycle using a controlled release system from gelatin hydrogels fixed on the bladder. The expression of extracellular signal regulated kinase 1/2 and connexin 43 protein was assessed by Western blotting of rat bladder protein. [Results]: Cx43 but not Cx45 mRNA expression was increased in the bladder of the obstruction model and in bladder smooth muscle cells treated with basic fibroblast growth factor. The mitogen-activated and extracellular signal-regulated kinase kinase inhibitor PD98059 blocked the stimulatory effect of basic fibroblast growth factor on connexin 43 protein expression and promoter activity, which was also decreased by mutation or deletion of an activator protein-1 cis-element of the connexin 43 promoter. In vivo application of basic fibroblast growth factor on the bladder increased urinary frequency during the latter half of the dark phase, ie the late active phase of rats (F=5.1, 2-way ANOVA p

Free plant sterol-supplemented mayonnaise was examined for its capacity to lower serum cholesterol and evaluation was made of its mayonnaise. This evaluation was done via a double-blind, placebo-controlled study using forty-six normocholesterolemic and mildly hypercholesterolemic Japanese persons (total cholesterol ≥ 200 mg/dL) randomly divided into two groups. The plant sterol (PS) (+) group was given 15 g mayonnaise containing 800 mg free PS daily, while the PS (-) group did 15 g mayonnaise daily for 12 weeks. Serum total cholesterol (TC) and low-density lipoprotein (LDL)-C were reduced by 4.3% and 9.2% in the PS (+) group, on completion of the 12-week period. At that time, serum apolipoprotein (Apo) B had been reduced by 3.6% in the PS (+) group, this being significantly more compared to the PS (-) group. Serum remnant-like particle (RLP)-C and Apo E did not change significantly in either groups. Decrease in TC and LDL-C with PS (+) group was greater for the serum TC ≥ 220 mg/dL subjects compared to the TC

For examination of the title parameters, study was made in which forty healthy male subjects (serum cholesterol concentration 170-309 mg/dL) were fed 0, 200, 400, 600, or 800 mg/day of free plant sterol supplemented in mayonnaise for 4 consecutive weeks. Only the 800 mg/day group significantly reduced serum cholesterol by the paired t-test (Exp.1). Thirty-two healthy males (serum cholesterol, 184-285 mg/dL) were made to consume plant sterol as ester at 0, 800, 1600, or 2400 mg/day. In all cases at more than 800 mg/day reduction in serum cholesterol was noted though without significant difference with paired t-test results (Exp.2). Subsequent to the mayonnaise consumption, normal diets were resumed for a period of 4 weeks. Total cholesterol showed original values at the end of this period. Plant sterol is thus shown to be a dietary component capable of reducing cholesterol by these results. Fifteen healthy subjects (males 10, females 5) were made to consume free plant sterol supplemented in mayonnaise at 2400 mg/day for 4 consecutive weeks. No change in serum vitamin A or vitamin E levels was observed at 2400 mg consumption. At 2400 mg, a significant increase in serum β-sitosterol was noted though it was markedly less than β-sitosterolemia. Clinical trial results, in all cases, were normal (Exp.3). The minimal effective dose of plant sterol on serum cholesterol concentration would thus appear to be 800 mg/day. At 2400 mg/day in mayonnaise, physiological and biochemical safety markers in serum would not undergo abnormal change.

329 Background: Clinical implementation of genome sequencing is recently prevailing in the treatment for cancer. We have launched an in-house clinical sequencing system to perform exhaustive targeted exome sequencing for patients with all types of cancer, as an outpatient service. We have analyzed the clinical utility of this system for patients with gastrointestinal cancer to elucidate real world evidence. Methods: Genomic DNA was extracted from tumor tissues and peripheral blood sera of 86 patients with different types of gastrointestinal cancer, from April 2016 to April 2017. The top five types of primary cancer were colorectal (34%), pancreas (28%), stomach (13%), biliary tract (12%), and esophagus (8%). We performed a targeted amplicon exome sequencing for 160 cancer-related genes. The sequencing data was analyzed using an original bioinformatics pipeline within three days, and we identified cancer-specific somatic gene alterations such as SNV (Single Nucleotide Variation), Ins (Insertion)/Del (Deletion), and CNV (Copy Number Variation). The primary endpoints were the detection rates of potential actionable and druggable genes. The secondary endpoints were the detection rates of incidental germline variants and the period from initial visit to elucidation of the results to the patients. Results: Actionable and druggable gene alterations were detected in 97% (83/86) and 65% (56/86) of the subjects, respectively. Actionable gene alterations were frequently detected in TP53 (64/86), KRAS (38/86), APC (25/86), ARID1A (11/86), and FBXW7 (10/86). Druggable gene alterations were detected in ARID1A (11/86), and FBXW7 (10/86), BRAF (7/86), BRCA1/2 (6/86), and EGFR (4/86). Incidental germline variants were detected only in 6% (5/86) of all the patients. The median period of examination was 30 days (10-78 days). Seven out of the 86 patients (8%) were treated with therapeutic agents, based on the results of our clinical sequencing. Conclusions: Our clinical sequencing system provided a large number of cancer patients with clinically valuable genomic information available in selecting anticancer drugs within about a month.

Hyaluronan (HA) is present in many tissues of the body and is essential to maintain moistness in the skin tissues, which contain approximately half the body's HA mass. Due to its viscosity and moisturizing effect, HA is widely distributed as a medicine, cosmetic, food, and, recently marketed in Japan as a popular dietary supplement to promote skin moisture. In a randomized, double-blind, placebo-controlled clinical study it was found that ingested HA increased skin moisture and improved treatment outcomes for patients with dry skin. HA is also reported to be absorbed by the body distributed, in part, to the skin. Ingested HA contributes to the increased synthesis of HA and promotes cell proliferation in fibroblasts. These effects show that ingestion of HA moisturizes the skin and is expected to improve the quality of life for people who suffer from dry skin. This review examines the moisturizing effects of dry skin by ingested HA and summarizes the series of mechanisms from absorption to pharmacological action.

This study was conducted to investigate the efficacy of oral hyaluronic acid (HA) administration for osteoarthritis (OA) in knee joints. Sixty osteoarthritic subjects (Kellgren-Lawrence grade 2 or 3) were randomly assigned to the HA or placebo group. The subjects in the HA group were given 200 mg of HA once a day everyday for 12 months, while the subjects in the placebo group were given placebo. The subjects in both groups were requested to conduct quadriceps strengthening exercise everyday as part of the treatment. The subjects’ symptoms were evaluated by the Japanese Knee Osteoarthritis Measure (JKOM) score. The symptoms of the subjects as determined by the JKOM score improved with time in both the HA and placebo groups. This improvement tended to be more obvious with the HA group, and this trend was more obvious with the subjects aged 70 years or less. For these relatively younger subjects, the JKOM score was significantly better than the one for the placebo group at the 2nd and 4th months after the initiation of administration. Oral administration of HA may improve the symptoms of knee OA in patients aged 70 years or younger when combined with the quadriceps strengthening exercise.

Eggs are a popular source of dietary cholesterol, but their consumption does not necessarily result in an increased serum cholesterol concentration. We investigated the cholesterol-lowering activity of egg white protein (EWP) and its potential mechanism in rats. The consumption of EWP resulted in a decreased concentration of cholesterol in the serum, liver and intestinal mucosa. The excretion of fecal neutral sterols and bile acids was greater by rats fed with EWP than by those fed with casein. The ratio of cholesterol and bile acids in the micellar phase to those in the solid phase was lower in the intestinal contents from rats fed with EWP than from those fed with casein. These results suggest that the cholesterol-lowering activity of EWP can be attributed to lowering the cholesterol absorption by intervening in the micellar formation in the intestines.

Mechanical strength of a polymer insulator decreases gradually with age due to creep of FRP core rod, but such reduction in mechanical strength can be taken into design to guarantee the strength required for 30 or 50 years. It is reported, however, that some serious mechanical failures of polymer insulators have occurred under very low load conditions in shorter periods in field. The cause of such failures is considered as a kind of stress corrosion (called "brittle fracture") due to exposure of FRP core rod to acid. We tried to reproduce such a failure in laboratory in order to investigate the detailed mechanism and the effect of both acid and mechanical load on brittle fracture. We made special test equipments which can apply mechanical load and acid safely and economically. We succeeded in reproducing such brittle fractures in laboratory and investigated the effect of acid and mechanical load on brittle fracture.