Expression Analysis of Platinum Sensitive and Resistant Epithelial Ovarian Cancer Patient Samples Reveals New Candidates for Targeted Therapies.

Ovarian cancer has the highest mortality rate of all gynecologic malignancies. Identification of new biomarkers is highly needed due to its late diagnosis and high recurrence rate. The objective of this study was to identify mechanisms of therapy resistance and potential biomarkers by analyzing mRNA and protein expression from samples derived from patients with platinum-sensitive and -resistant ovarian cancer (total cohort n = 53). The data revealed new candidates for targeted therapies, such as GREB1 and ROR2. We showed that the development of platinum resistance correlated with upregulation of ROR2, whereas GREB1 was downregulated. Moreover, we demonstrated that high levels of ROR2 in platinum-resistant samples were associated with upregulation of Wnt5a, STAT3 and NF-kB levels, suggesting that a crosstalk between the non-canonical Wnt5a-ROR2 and STAT3/NF-kB signaling pathways. Upregulation of ROR2, Wnt5a, STAT3 and NF-kB was further detected in a platinum-resistant cell-line model. The results of the present study provided insight into molecular mechanisms associated with platinum resistance that could be further investigated to improve treatment strategies in this clinically challenging gynecological cancer.

Freedom Constrained Liner for the Treatment and Prevention of Dislocation in Total Hip Arthroplasty.

BACKGROUND AND PURPOSE: Dislocation is one of the most common complications following total hip arthroplasty. The aim of our study was to assess failure rate of the Biomet Freedom constrained liner (Biomet, Warsaw, IN, USA) either in revision surgery for recurrent dislocation, or as a preventive method in high dislocation risk patients. PATIENTS AND METHODS: We assessed retrospectively 105 consecutive surgical procedures in 103 patients where a Freedom constrained liner or cup was used in Turku University Hospital over a 7-year period from 2007 to 2014. The mechanical failure rate of the device was assessed based on medical records. The average age of the patients was 73.4 years. The number of male patients was 53 (51%). Mean follow-up time was 2.5 years. The association between failure of the device and potential risk factors-age, gender, indication, and approach-was analyzed with logistic regression. Results were expressed by odd ratios and 95% confidence intervals. RESULTS: The mechanical failure rate of the Freedom device was 6 out of 105 (5.7%). None of the 11 preventive primary THAs against dislocation failed, 4 out of 52 (7.7%) preventive revision THAs against dislocation failed, and 2 out of 42 (4.8%) of the treated dislocation cases failed. Four out of six failures were dislocations due to impingement and failure of the locking mechanism. Two liners failed because of loosening. The risk factors assessed were not associated with failure of the device. INTERPRETATION: We found out that the mechanical failure rate of a Freedom constrained device was low. These results encourage us to continue using the device.

Glycemic responses of oat bran products in type 2 diabetic patients.

BACKGROUND AND AIM: Cereal products with low postprandial glycemic response are encouraged in the management of hyperglycemia. In this study, we determined the postprandial glycemic response of two different oat bran products in patients with type 2 diabetes. In addition, we investigated the effects of oat bran flour on postprandial glucose response following an oral glucose load. METHODS AND RESULTS: A randomized, controlled, repeated measures design with two test series was used. Twelve type 2 diabetic patients participated in five 2-h meal glucose tolerance tests on separate occasions. Volunteers were given in random order oat bran flour, oat bran crisp and glucose load providing 12.5 g glycemic carbohydrate (series 1), 25 g glucose load alone and 25 g glucose load with 30 g oat bran flour (series 2). Finger-prick capillary blood analysis was carried out fasting and then 15, 30, 45, 60, 90 and 120 min after the start of the meal. The oat bran flour had a lower 0-120 min area under the glucose response curve (AUC) (47+/-45 mmol min/L) than the glucose load (118+/-40 mmol min/L) (p<0.002), but there was no difference between the oat bran crisp (93+/-41 mmol min/L) and the glucose load in this respect. The oat bran flour decreased the glucose excursion from baseline by 1.6 mmol/l (2.4, 0.8) (mean (95% CI)) and 1.5 mmol/l (2.0, 1.1) at 30 and 45 min after the glucose load, respectively. CONCLUSIONS: Oat bran flour high in beta-glucan had a low glycemic response and acted as an active ingredient decreasing postprandial glycemic response of an oral glucose load in subjects with type 2 diabetes.

Mineral water fortified with folic acid, vitamins B6, B12, D and calcium improves folate status and decreases plasma homocysteine concentration in men and women.

OBJECTIVE: We investigated the effects of mineral water fortified with folic acid, vitamins B(6), B(12), D and calcium on folate concentrations in serum and erythrocytes, serum vitamin B(12) and plasma homocysteine concentrations in free-living subjects. In addition, we investigated the bioavailability of calcium added to mineral water by measuring urinary calcium excretion and serum alkaline phosphatase activity. DESIGN: Randomized, controlled, double-blinded, parallel design. SETTING: Outpatient dietary intervention with free-living subjects in Eastern Finland. SUBJECTS: Altogether, 66 subjects were recruited for the study. In all, 60 subjects completed the study. INTERVENTIONS: The study began with a 2-week run-in period followed by an 8-week intervention period. During the intervention study, subjects consumed mineral water fortified with folic acid (563 microg/day), vitamins B(6) (1 mg/day), B(12) (7.5 microg/day), cholecalciferol (0.6 microg/day) and calcium (563 mg/day) or placebo mineral water. RESULTS: The fortified mineral water increased serum and erythrocyte folate concentrations by 16.1+/-5.6 nmol/l (P<0.001) and 199+/-76 nmol/l (P<0.001), respectively, and decreased plasma homocysteine concentration by 1.6 micromol/l (P<0.001). Urinary calcium excretion and serum alkaline phosphatase activity for 24 h increased significantly (P<0.001 and P=0.01 respectively) in the intervention group. CONCLUSIONS: Mineral water fortified with folic acid, vitamins B(6), B(12) and D and calcium enhanced folate status and reduced plasma homocysteine concentration in normohomocysteinemic subjects without folate deficiency. Indirect measures of calcium and bone metabolism indicated that the calcium used in the fortification of the mineral water was bioavailable.

The effect of vegetable oil-based cheese on serum total and lipoprotein lipids.

OBJECTIVE: To investigate the effect of rapeseed oil-based cheese (milk-fat substituted by rapeseed oil) on serum total and lipoprotein lipid concentrations and blood pressure in reference to ordinary, milk-fat-based cheese in subjects with mildly to moderately elevated serum cholesterol concentration. DESIGN: Randomized, controlled, single-blind, cross-over clinical trial. SETTINGS: Outpatient dietary intervention with free-living subjects in Eastern Finland. INTERVENTIONS: The study began with a 2 week pre-trial period followed by two 4 week intervention periods. During the intervention study subjects replaced their ordinary cheese or cold cuts with 65 g of rapeseed oil-based or milk-fat-based control cheese. The type of test cheese was switched at 4 weeks of intervention. Altogether 31 subjects completed the study. RESULTS: Compared with the control cheese period the mean serum total cholesterol concentration was 6.7% (95% Cl -9.9 to -3.5%) lower after 2 weeks and 5.0% (95% Cl -7.5 to -2.5%) lower after 4 weeks of use of rapeseed oil-based cheese. Respectively, LDL cholesterol concentration was 7.0% (95% Cl -11.7 to -2.6%) lower after 2 weeks use and 6.4% (95% Cl -10.0 to -2.8%) lower after 4 weeks' use of rapeseed oil-based cheese. CONCLUSIONS: The present study showed that the rapeseed oil-based cheese reduces serum total and LDL cholesterol concentrations in mildly to moderately hypercholesterolemic subjects when replacing ordinary milk-fat-based cheese in the diet. SPONSORSHIP: Mildola Ltd, Tuusula, Finland and Kyrönmaan Juustomestarit Ltd, lsokyrö, Finland.