In addition, progression due to NEH (2.42, 1.32-4.44; or EHG 2.39, 1.15-4.96) was added as independent OS predictors in patients with radiologic tumor progression (Table 2). We excluded 23/147 patients from the analysis of PPS because they did not have at least one image evaluation and those 39 who had not presented radiologic

progression at the time of database lock. Median PPS in the 85 patients with radiologic progression was 9.85 months (95% CI: 7.3-12.5). BCLC stage, PS, and Child-Pugh status, which were learn more evaluated at the time of progression, together with progression due to NEH were the independent predictors of PPS (Table 3). The PPS of the previously defined subgroup of patients who would still be fit for second-line treatment was 13.6 months (95% CI: 9-18.2)

(Fig. 3). PPS was significantly different (P = 0.034) according to BCLC stage at progression and according to progression pattern (P = 0.013) (Figs. A2 and A3 in Supporting Material). Thereby, BCLC-C patients with NEH had a significantly worse PPS than those without it (7.1 versus 14.9 months, P = 0.02) (Fig. 4). Systematic review studies in lung,[6, 7] breast,[8] and colorectal[15] cancer have stressed the need to analyze PPS as a potential confounder for OS. Interestingly, no study has established the correlation between progression and survival in patients with HCC, and there are no data about GDC-0449 the predictors of survival after progression. Furthermore, no investigation has focused on the potential outcome differences according to the pattern of progression. As a whole, the current use of TTP as a signal to detect therapeutic efficacy is not supported by robust data gathered using proper statistical

methods that take into account time-dependent covariates. Our results show for the first time that tumor progression at imaging has a significant correlation with OS in patients with HCC and, thus, validate the use of TTP as a valid endpoint in early phase studies to evaluate the potential efficacy of novel molecular agents. Together with this association, we show that survival after progression (PPS) is significantly different according to the progression patterns. Indeed, PPS may correlate better with OS than PFS.[5, 7, 8, 15] The review of www.clinicaltrials.gov and recently MCE published trials in breast, lung, colorectal, and HCC shows that progression pattern is not considered in the evaluation of the patients to define prognosis and/or to stratify patients prior to randomization. Interestingly, a panel of several leading experts in oncology has stressed the need to further dissect the prognostic meaning of the different types of progression that may be encountered and has called for prospective studies to characterize PPS and its outcome predictors,[5] as we have done in our population of HCC patients.

In addition, progression due to NEH (2.42, 1.32-4.44; or EHG 2.39, 1.15-4.96) was added as independent OS predictors in patients with radiologic tumor progression (Table 2). We excluded 23/147 patients from the analysis of PPS because they did not have at least one image evaluation and those 39 who had not presented radiologic

progression at the time of database lock. Median PPS in the 85 patients with radiologic progression was 9.85 months (95% CI: 7.3-12.5). BCLC stage, PS, and Child-Pugh status, which were GSK-3 activation evaluated at the time of progression, together with progression due to NEH were the independent predictors of PPS (Table 3). The PPS of the previously defined subgroup of patients who would still be fit for second-line treatment was 13.6 months (95% CI: 9-18.2)

(Fig. 3). PPS was significantly different (P = 0.034) according to BCLC stage at progression and according to progression pattern (P = 0.013) (Figs. A2 and A3 in Supporting Material). Thereby, BCLC-C patients with NEH had a significantly worse PPS than those without it (7.1 versus 14.9 months, P = 0.02) (Fig. 4). Systematic review studies in lung,[6, 7] breast,[8] and colorectal[15] cancer have stressed the need to analyze PPS as a potential confounder for OS. Interestingly, no study has established the correlation between progression and survival in patients with HCC, and there are no data about find more the predictors of survival after progression. Furthermore, no investigation has focused on the potential outcome differences according to the pattern of progression. As a whole, the current use of TTP as a signal to detect therapeutic efficacy is not supported by robust data gathered using proper statistical

methods that take into account time-dependent covariates. Our results show for the first time that tumor progression at imaging has a significant correlation with OS in patients with HCC and, thus, validate the use of TTP as a valid endpoint in early phase studies to evaluate the potential efficacy of novel molecular agents. Together with this association, we show that survival after progression (PPS) is significantly different according to the progression patterns. Indeed, PPS may correlate better with OS than PFS.[5, 7, 8, 15] The review of www.clinicaltrials.gov and recently 上海皓元医药股份有限公司 published trials in breast, lung, colorectal, and HCC shows that progression pattern is not considered in the evaluation of the patients to define prognosis and/or to stratify patients prior to randomization. Interestingly, a panel of several leading experts in oncology has stressed the need to further dissect the prognostic meaning of the different types of progression that may be encountered and has called for prospective studies to characterize PPS and its outcome predictors,[5] as we have done in our population of HCC patients.

The magnitude of plasma 3-OMG increase was directly related to the rise in post-prandial blood glucose (r = 0.78, P < 0.01), which were significantly higher in the obese than healthy volunteers (P < 0.0001). During fasting, mRNA expression of SGLT-1 but not GLUT2 was higher in obese than healthy subjects (P = 0.05). In the obese, but not the healthy, mRNA

expression of SGLT-1 was reduced after glucose stimulation (P = 0.01). In contrast, the opposite pattern was observed with GLUT2 expression, with a trend for mRNA expression of GLUT2 to be reduced after Z-IETD-FMK research buy glucose exposure in the healthy (P = 0.06), but not the obese. The mRNA expression of SGLT-1 during fasting was related to the peak plasma 3-OMG learn more concentrations (r = 0.60, P = 0.02), whilst expression of GLUT2 30 mins after glucose exposure was positively correlated with integrated 3-OMG concentrations (r = 0.52, P = 0.04) Conclusion: The rate of glucose absorption in the proximal intestine is accelerated in morbid obesity and impacts on glycaemic excursions. This dysregulation of glucose absorption is associated with an increased expression of SGLT-1 during fasting, and is correlated positively with the expression

of GLUT-2 after glucose stimulation. These findings provide novel evidence of a complex dysregulation of intestinal glucose transportation and absorption in morbid obesity, which may mediate the weight gain and type 2 diabetes of obesity. Key Word(s): 1. obesity; 2. glucose transporter; 3. glucose absorption; 4. dysregulation; Presenting Author: FATEMEH HAIDARI Additional Authors: MAJID MOHAMMADSHAHI, MEHRNOUSH ZAKERZADEH, SAMIRA HASHEMI Corresponding Author: FATEMEH HAIDARI, MAJID MOHAMMADSHAHI Affiliations: Ahvaz Jundishapur University of Medical Sciences Objective: There is little information regarding the relationship between maternal dietary pattern and infant anthropometric parameters at birth. So the present study was carried out to determine the association of dietary patterns in pregnancy and infant anthropometric parameters. 上海皓元医药股份有限公司 Methods: In this cross-sectional study, 94 pregnant women (37–40 weeks) referred to Ahvaz Razi hospital were selected. Anthropometric

data were collected by individual questionnaire and dietary intakes were assessed by a semi-quantitative food frequency questionnaire. Factor analysis was used to identify dietary patterns. Statistical analysis was performed by SPSS software. Results: In this study, 3 major dietary patterns were identified: “healthy”, “traditional” and “western” dietary patterns. After adjusting for confounders (age, physical activity, energy intake, pregnancy weight gain and infant sex), the association of dietary patterns with birth weight, height and head circumference was exhibited in 3 models. The relationship between healthy dietary pattern and infant weight, height and head circumference at birth was significantly positive in 3 models (p < 0.05).

LPA levels above 30mg/dL are considered an important risk factor for CVD. Conversely, LPA levels inversely correlate with the incidence of diabetes and HOMA-IR (Cardiovasc Diabetol, 2012). We therefore aimed to assess the impact of an oral 4 week 150g/day FC on hepatic lipid metabolism reflected by total hepatic lipid content (HLC), fatty acid saturation and phosphorous metabolites (PM; indicating hepatic energy metabolism), and

glucose homeostasis. Moreover, we aimed to explore the role of LPA as potential biomarker predicting hepatic sensibility to fructose induced (lipo)toxicity. Methods: Ten healthy volunteers were enrolled in a pilot study (m: f=5: 5; median age 24.5 (21-37)). HLC (CH2 fraction of total signal), unsaturation- (UI), saturation- (SI=1-UI) and polyunsaturation indices (PUI) were determined Selinexor mw by single voxel 3.0-T 1H-, PM by 31P-MRS. BMI was assessed XAV-939 clinically. Blood was collected at days 1, 14 and 28 for routine laboratory analysis, LPA at baseline and fasted glucose. Results: Mean BMI was 21.11 ± 2.68 (SD) kg/m^2 and increased after FC (21.51 ± 2.77; p<0.001). UIs increased from mean 0.175 ± 0.087 to 0.226 ± 0.066 (p=0.034 one-tailed; large effect size r=0.568). Similarly, fasting glucose levels increased (mean 83.2mg/dL ± 8.37 to 88.4 ± 5.48, p=0.035). Notably, total HLC, PUIs, PM, ALT, AST and yGt remained unchanged (p>0.05). Analysis

of responders to FC (FCR; n=6) as reflected by increased total medchemexpress HLC (as potential indicator for lipid partitioning of potentially toxic lipid intermediates as neutral TG) versus non-responders (FCNR; n=4) revealed αATP depletion in FCNR (mean 3.003 ± 2.07 to 1.67 ± 0.413; p=0.034 onetailed). In FCR reflected by increased UI (n=7) γATP depletion was

observed (mean 2.18 ± 0.71 to 1.51 ± 0.4; p=0.036). Notably, baseline LPA levels inversely correlated with total HLC following FC (r=-0.801; p=0.004; r^2=0.652; non-linear fit: r^2=0.594) and delta-αATP (r=-0.652; p=0.039). Conclusions: MRS is feasible to detect slight changes in intrahepatic lipid composition after FC in healthy young volunteers. Changes in fatty acid saturation indices may occur earlier compared to other well established markers of liver damage. Moreover, serum LPA may also serve as a novel biomarker to differentiate between individuals at increased risk for NAFLD, particularly under fructose challenge. Approaches aimed at lowering LPA to counteract CVD risk should also consider potential interactions with hepatic lipid content and partitioning. Disclosures: Michael Trauner – Advisory Committees or Review Panels: MSD, Janssen; Consulting: Falk Pharma, Phenex, Amgen; Grant/Research Support: Intercept; Patent Held/Filed: Med Uni Graz (norUDCA); Speaking and Teaching: Falk Foundation, Roche, Gilead The following people have nothing to disclose: Christian Kienbacher, Martin Gajdosik, Michael Krebs, Stefan Traussnigg, Werner Dolak, Petra E.

Various HNF1β+/HNF4α+ cell types showed phenotypic and analyte expression characteristics SB525334 ic50 intermediate between otherwise typical BEC lining portal bile ducts and hepatocytes (Fig. 4C). For example,

HNF1βhigh/HNF4αlow BEC-type cells showed lower CK19 expression than mature BECs, as expected. CK19-/HNF1βweak/HNF4αstrong hepatocyte-type cells expressed significantly higher HNF1β than mature hepatocytes and significantly higher HNF4α expression than mature BEC (Fig. 4C). Cells most strongly positive for both HNF1β+ and HNF4α+ often showed hepatocyte features with an oval nucleus, but lacked CK19 staining and were close to CH cells or terminal bile ducts, but a direct connection could not always be confirmed in thick sections (Fig. 4D). A graphic reconstruction summarizing our results is shown in Fig. 5. HNF1β28, 29 and HNF4α (reviewed27) are responsible for development and maintenance of mature BEC and hepatocyte phenotypes, respectively. In agreement with previous single marker studies, HNF1β can be expressed by periportal hepatocytes28, 29 and HNF4α can be expressed by occasional BEC.30 A novel workflow with multiplex labeling, however, enabled us to show that the quantitatively

dominant transcription most strongly influenced the routine histopathologic appearance of the cells. Indeed, multiplex labeling, WSI creation, and automated image analysis enabled us to identify and characterize diverse epithelial populations that show transitional cytometric characteristics high throughput screening and analyte expression, including coexpression of HNF1β and HNF4α: (1) CK19+/HNF1βhigh/HNF4αlow BEC-type cells; (2) CK19weak/HNF1βhigh/HNF4αlow BEC/CH-type cells; (3) CK19-/HNF1βweak/HNF4αstrong hepatocyte-type

cells with an oval nucleus; and (4) CK19-/HNF1βweak/HNF4αstrong hepatocyte-type cells with a large round nucleus (identical to mature hepatocytes). This extensive, but difficult to visualize with conventional histology, population of cells with phenotypic and biomarker (including transcription 上海皓元医药股份有限公司 factor) expressions of a hybrid nature between hepatocytes and biliary epithelial cells are positioned over a relatively broad area from small portal-based bile ducts to otherwise typical periportal hepatocytes. Previous studies in rodents show that progenitor cells (i.e., “oval” cells) arise from BEC to provide hepatocytes when regeneration of the liver needs to occur under conditions in which hepatocyte proliferation is inhibited.31 Similar conclusions have been reached in cirrhotic human liver tissue samples where hepatocytes are thought to be derived by terminal bile ducts/CH harboring putative progenitor cells.32-34 Conversely, periportal hepatocytes can give rise to BEC when BECs are incapable of regenerating.