Focal adhesion kinase inhibition synergizes with nab-paclitaxel to target pancreatic ductal adenocarcinoma.

BACKGROUND: Pancreatic ductal adenocarcinoma (PDAC) is a very lethal disease, with minimal therapeutic options. Aberrant tyrosine kinase activity influences tumor growth and is regulated by phosphorylation. We investigated phosphorylated kinases as target in PDAC. METHODS: Mass spectrometry-based phosphotyrosine proteomic analysis on PDAC cell lines was used to evaluate active kinases. Pathway analysis and inferred kinase activity analysis was performed to identify novel targets. Subsequently, we investigated targeting of focal adhesion kinase (FAK) in vitro with drug perturbations in combination with chemotherapeutics used against PDAC. Tyrosine phosphoproteomics upon treatment was performed to evaluate signaling. An orthotopic model of PDAC was used to evaluate the combination of defactinib with nab-paclitaxel. RESULTS: PDAC cell lines portrayed high activity of multiple receptor tyrosine kinases to various degree. The non-receptor kinase, FAK, was identified in all cell lines by our phosphotyrosine proteomic screen and pathway analysis. Targeting of this kinase with defactinib validated reduced phosphorylation profiles. Additionally, FAK inhibition had anti-proliferative and anti-migratory effects. Combination with (nab-)paclitaxel had a synergistic effect on cell proliferation in vitro and reduced tumor growth in vivo. CONCLUSIONS: Our study shows high phosphorylation of several oncogenic receptor tyrosine kinases in PDAC cells and validated FAK inhibition as potential synergistic target with Nab-paclitaxel against this devastating disease.

Bounds on transverse momentum dependent distribution and fragmentation functions

We give bounds on the distribution and fragmentation functions that appear at leading order in deep inelastic one-particle inclusive leptoproduction or in Drell-Yan processes. These bounds simply follow from positivity of the defining matrix elements and are an important guidance in estimating the magnitude of the azimuthal and spin asymmetries in these processes.

Teaching nutritional assessment to nursing students.

A data collection tool was developed to teach nursing students basic principles of nutritional assessment. The tool was used to help nurses coordinate and interpret data they routinely collected so they would be more aware of real and potential nutritional problems. Emphasis was on those aspects of nutritional care relevant to the nurse's advocates in communicating these concerns to the dietitian. Observation and early referral of potential diet-related problems enables the dietitian to more effectively provide for nutritional care.

Strategies for promoting nutrition and dietitians.

To promote nutrition and dietitians, the Nebraska Dietetic Association approached various other associations in the state about featuring articles on nutrition in their newsletters. This public relations strategy permitted greater dissemination of nutritional information to specific target groups through existing channels of communication. Dietitians were presented to other professional groups as nutrition experts. In addition, this activity opened the door to further professional exchanges between dietitians and the various associations.

Nutritional knowledge, attitudes, and food patterns of women athletes.

Nutritional knowledge, attitudes, and food patterns of women athletes at the University of Nebraska at Lincoln were studied. Mean test scores for nutritional knowledge were higher for questions relating to "nutrition for the athlete" than to "general nutrition." Attitudes toward nutrition were generally favorable, with a positive correlation between nutritional knowledge and attitudes. Athletes who had received some form of nutrition education had higher nutritional knowledge and attitude scores than those who had not. Respondents were especially concerned with diet as it relates to weight control; those with higher knowledge scores consistently followed food patterns for weight-control diets similar to those used in training and pre-event diets.

Contribution of foodservice programs in preschool centers to children's nutritional needs.

Seven-day nutrient intakes of 517 Head Start and day care children participating in USDA's Special Food Service Programs for Children in Nebraska, Kansas, and Texas were assessed. Protein, vitamin A, and ascorbic acid levels from diets served at the centers were judged to be adequate, while calories and B vitamins were below recommendations but proportional to each other. Calcium intake from center diets did not increase proportionately as the number of meals and snacks increased. Nutrient contributions were only slightly greater from center diets when two meals and two snacks were provided than when one meal and one snack were served. Home diets made substantial contributions to the diets of all children, resulting in little difference in total nutrient intakes between children receiving fewer or more meals and snacks at the centers. Iron was the nutrient supplied in least amount in relation to recommendations, when intakes from home and center were combined.