Indirect CRISPR screening with photoconversion revealed key factors of drug resistance with cell-cell interactions.

Comprehensive screenings to clarify indirect cell-cell interactions, such as those in the tumor microenvironment, especially comprehensive assessments of supporting cells' effects, are challenging. Therefore, in this study, indirect CRISPR screening for drug resistance with cell-cell interactions was invented. The photoconvertible fluorescent protein Dendra2 was inducted to supporting cells and explored the drug resistance responsible factors of supporting cells with CRISPR screenings. Random mutated supporting cells co-cultured with leukemic cells induced drug resistance with cell-cell interactions. Supporting cells responsible for drug resistance were isolated with green-to-red photoconversion, and 39 candidate genes were identified. Knocking out C9orf89, MAGI2, MLPH, or RHBDD2 in supporting cells reduced the ratio of apoptosis of cancer cells. In addition, the low expression of RHBDD2 in supporting cells, specifically fibroblasts, of clinical pancreatic cancer showed a shortened prognosis, and a negative correlation with CXCL12 was observed. Indirect CRISPR screening was established to isolate the responsible elements of cell-cell interactions. This screening method could reveal unknown mechanisms in all kinds of cell-cell interactions by revealing live phenotype-inducible cells, and it could be a platform for discovering new targets of drugs for conventional chemotherapies.

Acute Dose-Response Effectiveness of Combined Catechins and Chlorogenic Acids on Postprandial Glycemic Responses in Healthy Men: Results from Two Randomized Studies.

Epidemiologic studies show that the risk of diabetes can be reduced by ingesting green tea or coffee. Previous studies have shown that simultaneously taking green tea catechins (GTC) and coffee chlorogenic acid (CCA) alters postprandial gastrointestinal hormones secretion and improves insulin sensitivity. However, there is no evidence on the acute effects of GTC and CCA on incretin and blood glucose, and on the respective dose of polyphenols. In this randomized, double-blind, placebo-controlled crossover study, we examined the effective dose of GTC and CCA on postprandial glucose, insulin, and incretin responses to a high-fat and high-carbohydrate cookie meal containing 75 g of glucose in healthy men. Study 1 (n = 18) evaluated two doses of GTC (270 or 540 mg) containing a fixed dose of CCA (270 mg) with 113 mg of caffeine and a placebo (0 mg GTC and 0 mg CCA) with 112 mg of caffeine. Study 2 (n = 18) evaluated two doses of CCA (150 or 300 mg) containing a fixed dose of GTC (540 mg) and a placebo with 99 mg of caffeine. The single combined ingestion of GTC and CCA significantly altered the incretin response and suppressed glucose and insulin levels. These findings suggest that the effective minimum dose is 540 mg of GTC and 150 mg of CCA.

Risk factors for febrile neutropenia in neoadjuvant docetaxel, cisplatin, and 5-fluorouracil chemotherapy for esophageal cancer.

PURPOSE: The aim of the present study was to evaluate the incidence and explore the risk factors of febrile neutropenia (FN) in patients with esophageal cancer receiving neoadjuvant docetaxel, cisplatin, and 5-fluorouracil (DCF) chemotherapy in real-world settings. METHODS: We retrospectively reviewed clinical data of 128 consecutive patients with esophageal cancer. Specifically, these patients underwent neoadjuvant DCF chemotherapy with prophylactic antibiotic administration at our institution between July 2009 and January 2015. Two FN-related endpoints were set as follows: definite FN (dFN) defined as grade 4 neutropenia at the onset of fever and clinically suspected FN (csFN), which included both patients with dFN and patients without grade 4 neutropenia but with deteriorating grade 3 neutropenia at the onset of fever who were clinically diagnosed with FN for which they underwent treatment. The risk factors for dFN and csFN were evaluated based on patients' characteristics. RESULTS: A total of 72 (56.3%) patients developed grade 3 or grade 4 neutropenia and 26 (20.3%) developed csFN including 14 (10.9%) with dFN. Multivariate analysis revealed that older age (OR 3.57, CI 1.27-10.1, P = 0.016) and living alone (OR 5.17, 95% CI 1.26-21.3, P = 0.023) were statistically significant risk factors for csFN development. As to dFN, no statistically significant risk factors were identified. CONCLUSIONS: Older age and living alone are significant risk factors for developing FN, and thus, particularly for patients with risk factors for FN, G-CSF should be considered instead of prophylactic antibiotics with careful observation.

Association between breath methane concentration and visceral fat area: a population-based cross-sectional study.

High visceral fat area (VFA) is a stronger predictor of cardiovascular disease and overall mortality, compared with body mass index (BMI) and waist circumference (WC). Recent reports demonstrate that obesity is related to breath gas, which is produced by the intestinal microflora. However, these studies define obesity using BMI, not VFA. In this population-based cross-sectional study, we investigated the relationship between breath gases (methane and hydrogen) and both VFA and BMI. A total of 1033 participants (62% women; age [mean ± standard deviation] 54.4 ± 14.9 years) in the 2015 Iwaki Health Promotion Project in Japan were enrolled in the study. Breath samples were collected using a breath bag and analyzed by gas chromatography. VFA was measured using a visceral fat meter. The proportion of methanogenic bacteria to total intestinal microbiota was measured by polymerase chain reaction and 16S rRNA gene sequencing analysis. Our analysis revealed a significant association between high VFA and low breath methane, even after adjusting for confounding factors (B = -0.024 and P = 0.004). To identify the association between breath methane and VFA in participants with methane-producing bacteria in their intestinal microflora, participants were divided into two groups based on the presence or absence of methanogenic bacteria in their stool. The Methanogen + group was further divided into two subgroups with breath methane higher (Methane-UP) or lower (Methane-LO) than the median breath methane concentration. VFA was significantly lower in the Methane-UP group than in the Methane-LO group. In participants with methanogenic bacteria, breath methane concentration might be an independent biomarker of visceral fat accumulation.

Association between Nutrients and Visceral Fat in Healthy Japanese Adults: A 2-Year Longitudinal Study Brief Title: Micronutrients Associated with Visceral Fat Accumulation.

: High visceral fat area (VFA) is a stronger predictor of cardiovascular disease and overall mortality than body mass index or waist circumference. VFA may be decreased by proper dietary habits. Although previous epidemiologic studies demonstrated an association between nutritional components or foodstuffs and VFA, only the associations of a few nutrients, such as dietary fiber and calcium, are reported. We performed a comprehensive 2-year longitudinal study in more than 624 healthy people and analyzed 33 micronutrients to investigate nutrients that contribute to changes in visceral fat. Our analyses revealed that "macronutrients" and "micronutrients" were "mutual confounders". Therefore, when evaluating the association between VFA and micronutrients, associations were adjusted by macronutrients. The ingestion of 7 nutrients: soluble dietary fiber, manganese, potassium, magnesium, vitamin K, folic acid, and pantothenic acid, which are abundant components in vegetable diets, was significantly inversely correlated with a change in VFA. Additionally, a change in the ingestion of one nutrient, monounsaturated fat, was significantly positively correlated with a change in VFA. These associations were independent of body mass index and waist circumference. Thus, a predominantly vegetable diet may decrease VFA. In addition, adjusting the intake of macronutrients might help to clarify the association of micronutrients with VFA.

Blautia genus associated with visceral fat accumulation in adults 20-76 years of age.

The gut microbiota is reported to be related to obesity, and visceral fat is reported to be strongly associated with cardiovascular disease and overall mortality. However, the association between the gut microbiota and obesity has mainly been studied using body mass index (BMI) as a proxy for obesity. We investigated the relationship of both visceral fat and BMI with the gut microbiota stratified by sex in a population-based cross-sectional study of Japanese men and women 20-76 years of age (n = 1001). Women with a higher visceral fat area (VFA) harboured a higher relative abundance of the Firmicutes phylum (P for trend <0.001) and a lower relative abundance of the Bacteroidetes phylum (P for trend 0.030), whereas men with higher VFA harboured a lower relative abundance of the Firmicutes phylum (P for trend 0.076) and a higher relative abundance of the Bacteroidetes phylum (P for trend 0.013). Similar results were obtained using BMI as an index, but the differences were not significant in men. At the genus level, Blautia was the only gut microbe significantly and inversely associated with VFA regardless of sex. In conclusion, at the genus level we found that Blautia was the only gut microbe significantly and inversely associated with VFA, regardless of sex.

Glucose Response during the Night Is Suppressed by Wheat Albumin in Healthy Participants: A Randomized Controlled Trial.

Postprandial blood glucose excursions are important for achieving optimal glycemic control. In normal-weight individuals, glucose tolerance is diminished in the evening compared to glucose tolerance in the morning. Wheat albumin (WA) has the potential to suppress the postprandial glucose response with a relatively small dose, compared to the dose required when using dietary fiber. In the present study, the effect of WA on glycemic control during the night was investigated after a late evening meal. A randomly assigned crossover trial involving a single oral ingestion in healthy male participants was performed in a double-blind placebo-controlled manner. The participants ingested the placebo (PL) tablets or the WA (1.5 g)-containing tablets 3 min before an evening meal at 22:00 hour, and blood samples were drawn during the night until 07:00 hour using an intravenous cannula. The participants slept from 00:30 hour to 06:30 hour. Glucose response, as a primary outcome during the night, was suppressed significantly by the WA treatment compared to the PL treatment, but the insulin response was not. Plasma glucose-dependent insulinotropic polypeptide concentration during the night was lowered significantly by the WA treatment compared to the PL treatment. In conclusion, WA may be a useful food constituent for glycemic control during the night.

Wheat Albumin Increases the Ratio of Fat to Carbohydrate Oxidation during the Night in Healthy Participants: A Randomized Controlled Trial.

Not only are energy expenditure (EE) and the respiratory quotient (RQ) parameters of the energy nutrient utilization and energy balance, they are also related to the development of obesity. In this study, post-meal night-time energy metabolism was investigated following the oral ingestion of wheat albumin (WA) with a late evening meal. A randomly assigned, double-blind, placebo-controlled crossover trial for a single oral ingestion in healthy participants was completed. The participants ingested the placebo (PL) or WA (1.5 g) containing tablets 3 minutes before the late evening meal at 22:00 hour, and energy metabolism was measured using a whole-room indirect calorie meter until wake-up. The participants were in bed from 00:00 hour until 06:30 hour. Twenty healthy participants completed the trial and were included in the analyses. Night-time RQ and carbohydrate oxidation were significantly lower following the WA treatment as compared with the PL treatment. Although the total EE was not significantly different between treatments, postprandial fat oxidation was significantly higher following the WA treatment as compared with the PL treatment. In conclusion, WA has the potential to shift the energy balance to a higher ratio of fat to carbohydrate oxidation during the night.

Consumption of alpha-linolenic acid-enriched diacylglycerol induces increase in dietary fat oxidation compared with alpha-linolenic acid-enriched triacylglycerol: A randomized, double-blind trial.

Fat metabolism is an important consideration in obesity. Alpha-linolenic acid-enriched diacylglycerol (ALA-DAG), which mainly occurs as ALA esterifies to 1,3-diacyl-sn-glycerol (1,3-DAG), has beneficial effects on fat metabolism and body weight compared with triacylglycerol (TAG). Moreover, compared with ALA-TAG, ALA-DAG enhances ß-oxidation activity in the small intestine and liver in rodents. We hypothesized that ALA-DAG consumption may increase dietary fat oxidation compared with ALA-TAG in humans. To examine this hypothesis, we conducted a randomized double-blind cross-over trial in 17 normal and moderately obese men and women (BMI: 25.7±2.0 kg/m2, mean±SD). Each participant was assigned to a 4-week intervention period with 2.5 g/day of ALA-DAG or ALA-TAG consumption, followed by a 4-week washout period between consumption of each diet. Dietary fat oxidation, assessed based on the 13CO2 recovery rate in the breath, was significantly increased by ALA-DAG consumption compared with ALA-TAG consumption (17.0±4.5% and 14.1±5.9%, respectively, P<.05). In addition, ALA-DAG consumption significantly decreased the visceral fat area compared with ALA-TAG (102.9±51.9 cm2 and 110.9±51.7 cm2, respectively; P<.05). These results indicate that ALA-DAG consumption may be useful for preventing obesity.

Diacylglycerol Enhances the Effects of Alpha-Linolenic Acid Against Visceral Fat: A Double-Blind Randomized Controlled Trial.

OBJECTIVE: To investigate the effect of alpha-linolenic acid-rich diacylglycerol (ALA-DAG) compared with alpha-linolenic acid-rich triacylglycerol (ALA-TAG) on visceral fat area (VFA) in people with overweight. METHODS: Subjects with overweight were recruited to a randomized, double-blind, controlled, parallel-group designed trial and randomly allocated to two groups that consumed either 2.5 g/d ALA-TAG or ALA-DAG for 12 weeks. Two 4-week nontreatment periods were placed before and after the treatment period. One hundred fourteen subjects (n = 57 in the ALA-TAG group, n = 57 in the ALA-DAG group) were enrolled into the analysis set for efficacy evaluation. RESULTS: The VFA and BMI were significantly decreased by the ALA-DAG treatment with a treatment-by-time interaction compared with the ALA-TAG treatment (P < 0.05). Additionally, the change from baseline of the fasting serum TAG concentration at week 12 was significantly decreased by ALA-DAG treatment compared with ALA-TAG treatment (P < 0.05). Safety parameters such as urinary measurements, hematologic parameters and blood biochemistry, and the incidence of adverse events did not differ significantly between groups, and no ALA-DAG-associated adverse effects were detected. CONCLUSIONS: Incorporation of ALA-DAG in a regular diet for 12 weeks may lead to a reduction in VFA, BMI, and serum TAG in men and women with overweight.

Retrospective analysis of premedication, glucocorticosteroids, and H1-antihistamines for preventing infusion reactions associated with cetuximab treatment of patients with head and neck cancer.

Objectives We evaluated infusion-related reactions associated with cetuximab combination chemotherapy comprising an H1-receptor antagonist plus dexamethasone as anti-allergy premedications for patients with head and neck cancer. Methods We retrospectively evaluated 248 patients who received a cetuximab combination regimen between December 2012 and August 2015. All patients received 5 mg intravenous dichlorpheniramine (H1-receptor antagonist), and dexamethasone (DEX) was adjusted from 6.6 mg to 13.2 mg according to the emetogenic risk. Results We identified 248 subjects, including 13 (5.2%) with infusion-related reactions (grade 1 in five [2.0%], grade 2 in seven [2.8%], and grade 4 in one [0.4%]). The incidence of these reactions in cetuximab combination regimens, each employing an H1-receptor antagonist, using a higher dose of dexamethasone (13.2 mg) was not significantly lower compared with those using 6.6 mg DEX (2.4% vs 8.3%, respectively; p = 0.43). Twelve patients experienced infusion-related reactions associated with the first cetuximab administration, and one reaction occurred after the third administration. Conclusions The incidence of infusion-related reactions was lower compared with those of previous studies. Dexamethasone combined with an H1-receptor antagonist was useful for preventing allergic responses. The incidence of infusion-related reactions was not lower with 13.2 mg dexamethasone, and 6.6 mg DEX prevented infusion-related reactions.

Alpha Linolenic Acid-enriched Diacylglycerol Consumption Enhances Dietary Fat Oxidation in Healthy Subjects: A Randomized Double-blind Controlled Trial.

Consumption of alpha linolenic acid-enriched diacylglycerol (ALA-DAG) reduces visceral fat area. In this study, we performed a randomized, placebo-controlled, double-blind, crossover intervention trial to investigate the effect of ALA-DAG on dietary fat oxidation in comparison with control triacylglycerol (TAG). Each subject (n=16) consumed either 2.5 g/d of ALA-DAG or TAG for 14-d, separated by a 21-d washout period. At the end of each consumption period, we assessed dietary fat oxidation. ALA-DAG consumption significantly enhanced dietary fat utilization as energy compared to TAG consumption.

Evaluation of community pharmacist ability to ensure the safe use of oral anticancer agents: a nationwide survey in Japan.

OBJECTIVES: A recent study of community pharmacists in Canada reported that they required additional education. We conducted a survey of community pharmacists to evaluate the adequacy of education and training in oral anticancer agents in Japan. METHODS: Between May and June 2014, community pharmacists were asked to complete a questionnaire by using two different survey strategies, one online and one via postal mail. RESULTS: Three hundred community pharmacists responded to an online survey and 283 community pharmacists responded to a mailed survey. Only 6-10% of respondents felt that they had received adequate education in oncology or oral chemotherapy. Although 81% of Japanese pharmacists had attended at least one continuing education event related to oncology in the past 2 years, only 54% felt comfortable dispensing oral anticancer agents and only 40% felt comfortable educating patients about oral chemotherapy. In a multivariate analysis, confidence in educating patients about oral chemotherapy was associated with an understanding of chemotherapy cycles and doses (odds ratio = 4.89, 95% confidence interval [2.53-9.45]) and the number of continuing education events they had attended (odds ratio = 1.67, 95% confidence interval [1.35-2.08]). CONCLUSIONS: This is the first report to evaluate whether community pharmacists are equipped to ensure the safe use of oral anticancer agents in Japan. The results are similar to those previously reported for Canadian pharmacists, namely a low rate of positive responses for education in oncology and oral chemotherapy, demonstrating a similar need for additional education and training in oral chemotherapy.

Chemotherapy regimen checks performed by pharmacists contribute to safe administration of chemotherapy.

Background Computerized provider order entry (CPOE) has been developed and implemented within cancer center hospitals nationwide in Japan. To ensure that high-quality services are routinely provided by oncology pharmacists, this study was designed to evaluate the interventions through reviewing the orders that are generated by CPOE. Methods The objective of this retrospective chart review was to evaluate how pharmacists contributed to safe cancer treatment using paper-based pharmacy records. Data were collected from a total of 35,062 chemotherapy regimens for 18,515 outpatients between January and December 2013. Results Of these 35,062 chemotherapy regimens, the rate of pharmacists' interventions was 1.1% ( n = 408). Among them, 53.1% (217/408) of the chemotherapy prescriptions were modified due to pharmacist interventions. The reasons for interventions included "changes in the chemotherapy regimen were unclear" in 49.5%, "physicians' prescription errors" (22.0%), "pharmacist suggestions to improve chemotherapy" (15.1%), and "finding differences between physicians' chemotherapy records and their chemotherapy prescriptions" (13.2%). The top three reasons for the 217 prescription modifications due to pharmacist interventions were "finding prescription errors" (34.5%), "reasons for change in the chemotherapy regimen were unclear" (32.7%), and "finding differences between physicians' chemotherapy records and their chemotherapy prescriptions" (28.5%). Conclusion The computer could not evaluate chemotherapy protocols or adjust doses of anticancer medicines according to patients' conditions. Therefore, oncology pharmacists should continue to ensure safe and appropriate administration of cancer chemotherapy.

Development of a double-stranded siRNA labelling method by using 99mTc and single photon emission computed tomography imaging.

In vivo biodistribution of small interfering RNAs (siRNAs) is important to develop them for medical use. Therefore, novel single photon emitter-labelled siRNA was prepared by using diethylenetriamine-N,N,N',N″,N″-pentaacetic acid (DTPA) and poly(A) polymerase, and subsequently, real-time analysis of siRNA trafficking was performed by using single photon emission computed tomography (SPECT). This study aimed at assessing the use of 99mTc-radiolabelled siRNA targeting lacZ to detect lacZ expression in vivo. siRNA targeting lacZ was radiolabelled with 99mTc by using the bifunctional chelator DTPA, and the labelling efficiency and specific activity were determined. The probe stability in RNaseA was assessed. SPECT imaging was performed in mice overexpressing the lacZ gene in the liver. Radiolabelled siRNA remained highly stable in RNaseA solution at 37 °C. In SPECT imaging, significant 99mTc accumulation in the liver was observed in mice overexpressing the lacZ gene. 99mTc-labelled lacZ siRNA shows ß-galactosidase-specific accumulation and appears promising for the visualisation of lacZ expression in vivo. Our labelled siRNA should be deliverable to specific regions overexpressing the target gene.

Clinical significance of NOTCH1 intracellular cytoplasmic domain translocation into the nucleus in gastric cancer.

Recent studies have shown constitutive activation of the Notch signaling pathway in various types of malignancies. However, it remains unclear whether this signaling pathway is activated in gastric cancer. In the present study, the aim was to investigate the role of Notch signaling in gastric cancer by investigating the subcellular localization of Notch-associated proteins in tissue samples from gastric cancer patients. Samples were obtained from 115 gastric cancer patients who had undergone surgery at the Department of Gastroenterological Surgery, Nagoya City University Graduate School of Medical Science without pre-operative chemotherapy or radiation. Subsequently the correlation between translocation of NOTCH1 intracellular cytoplasmic domain (NICD) into the nucleus (as measured by immunostaining) and survival in gastric cancer patients after surgery was investigated. The results were analyzed in reference to the patients' clinicopathological characteristics and the effects of these results on patient prognosis were determined. Significant correlations were observed between NICD nuclear localization and clinicopathological characteristics, such as tumor status (T factor), lymph node status (N factor), pathological stage and differentiation status. No significant correlations were observed between NICD nuclear localization and age, gender, tumor location, vein invasion or lymphatic invasion. Patients with >30% of cancer cell nuclei positively stained for NICD (as revealed by immunostaining) were associated with a significantly shorter survival following surgery than patients with <30% NICD-positive cancer cell nuclei (log-rank test, P=0.0194). Univariate analysis revealed that among the clinicopathological factors examined, T factor [risk rate (RR)=10.870; P=0.0016], N factor (RR=41.667; P=0.0003), lymphatic invasion (RR=13.158; P=0.0125), vein invasion (RR=25.000; P= 0.0019) and translocation of NICD to the nucleus (RR=3.937; P=0.0312) were all identified to be statistically significant prognostic factors. However, multivariate analysis revealed that translocation of NICD to the nucleus was not independently associated with an unfavourable prognosis in patients with gastric cancer. The present results suggest that NOTCH1 acts as an oncogene in gastric cancer. It is hypothesized that translocation of NICD into the nucleus may be used as a therapeutic target in gastric cancer.

[The Usefulness of Outpatient Pharmacy Services in Adjuvant Chemotherapy for Gastric Cancer].

Outpatient pharmacy services were established since June 2009 for educating about the signs and symptoms that required treatment, explaining how to receive an emergency service, improving a patient's adherence, and managing side effects. In this study, we evaluated the usefulness of one of our outpatient pharmacy services, which aims to help patients receiving adjuvant chemotherapy including S-1 monotherapy for gastric cancer. In total, 34 and 80 patients received S-1 monotherapy without or with the intervention of outpatient pharmacy services, respectively; additionally, the median ages of the former and latter were 68 and 65 years, respectively. The treatment completion rates(82.4% versus 67.5%)were similar between the 2 groups(odds ratio[OR]: 0.45, 95% confidence interval[CI]: 0.16-1.21, p=0.106). Their emergency visit rates were 23.5% and 8.8%(OR: 0.31, 95% Cl: 0.10-0.94, p<0.05). Emergency hospitalization was required for 8.8% and 0% of the population from each group(OR: 0.00, 95% CI: not significant, p<0.05). We suggest that outpatient pharmacy services are useful because they are likely to improve a patient's safety.

The impact of pharmacist certification on the quality of chemotherapy in Japan.

Background In the Japanese healthcare system, board certification not only maintains the quality of daily practice but is also required for hospitals to receive healthcare reimbursement. To date, no data on the effects of the board certification system in Japanese hospitals have been reported. Objective We performed a survey to clarify the impact of pharmacist certification on the quality of chemotherapy. Setting A nationwide mailing survey was conducted in Japan. Method We surveyed oncology pharmacists from 388 cancer designated hospitals (DHs) and 984 randomly selected general hospitals (GHs). Main outcome measure Multivariate analysis of factors for compliance with standard cancer chemotherapy to clarify the impact of pharmacist certification on the quality of chemotherapy. Results The response rate was 70.6 % (274/388) at the DHs and 43.4 % (428/984) at the GHs. Of the 13 different regimens, 66.1 % (181/274) of DHs and 64.7 % (277/428) of GHs reported having experienced either improper doses or intervals of drug administration. The median number of improper regimens was 1 at both the DHs (range 0-15) and GHs (range 0-22). We identified two groups of hospitals, those with two or more improper regimens and those with one improper regimen or less. Univariate analysis showed significant differences in the number of DHs (p < 0.01), performance of more than 10 chemotherapies per day (p < 0.05), presence of more than 400 beds (p < 0.01) and the professional qualifications of oncology pharmacists or medical oncologists. From multivariate analysis, significant differences were observed in certifications from the Japanese Society of Pharmacy Healthcare and Sciences certified Senior Oncology Pharmacist (odds ratio 0.29, p < 0.01) and the Japanese Society of Medical Oncology certified oncologist (odds ratio 0.48, p < 0.01). Conclusion Board certification was more prevalent in the designated (cancer specialist) hospitals than general hospitals and adherence to appropriate therapy was better when the DH was involved. Board certification was shown to be beneficial in terms of adherence to adequate chemotherapy.

Evaluation of the anticoagulant effect and timing of the concomitant use of S-1 and warfarin.

Objectives To evaluate the effects of the timing of warfarin (WF) administration in patients with gastric cancer who received S-1 oral chemotherapy. Methods This retrospective chart review collected patient data including the prothrombin time international normalized ratio (PT-INR). Patients were categorized into three groups based on the timing of WF administration in relation to S-1 oral chemotherapy: group A patients received WF before S-1 chemotherapy; group B patients started WF during S-1 chemotherapy; and group C patients started WF after completing S-1 chemotherapy. Results A total of 21 patients with gastric cancer were included in the study; group A ( n = 8), group B ( n = 10) and group C ( n = 3). Seven patients (88%) in group A, seven (70%) in group B and all of the patients (100%) in group C had >2.5 PT-INR. There was no significant difference in the time-to-exceed 2.5 PT-INR between groups A and B. Conclusions These findings suggest that the timing of WF use in relation to S-1 chemotherapy might not be an important factor for PT-INR, although the low patient numbers included in the study should be taken into consideration.

Alpha Linolenic Acid-enriched Diacylglycerol Enhances Postprandial Fat Oxidation in Healthy Subjects: A Randomized Double-blind Controlled Trail.

Alpha linolenic acid-enriched diacylglycerol (ALA-DAG) reduces visceral fat area and body fat in rodents and humans compared to conventional triacylglycerol (TAG). Although ALA-DAG increases dietary fat utilization as energy in rodents, its effects in humans are not known. The present study was a randomized, placebo-controlled, double-blind, crossover intervention trial performed to clarify the effect of ALA-DAG on postprandial energy metabolism in humans. Nineteen healthy subjects participated in this study, and postprandial energy metabolism was evaluated using indirect calorimetry followed by 14-d repeated pre-consumption of TAG (rapeseed oil) as a control or ALA-DAG. As a primary outcome, ALA-DAG induced significantly higher postprandial fat oxidation than TAG. As a secondary outcome, carbohydrate oxidation tended to be decreased. In addition, postprandial energy expenditure was significantly increased by ALA-DAG compared to TAG. These findings suggest that daily ALA-DAG consumption stimulates dietary fat utilization as energy after a meal, as well as greater diet induced thermogenesis in healthy humans. In conclusion, repeated consumption of ALA-DAG enhanced postprandial fat metabolism after a meal, which may partially explain its visceral fat area-reducing effect.