Gastrin-releasing peptide (GRP) receptors are overexpressed on several types of human cancer cells, including breast, prostate, small cell lung, and pancreatic cancers. Bombesin (BBN), a 14-amino acid peptide that is an analogue of human GRP, binds to GRP receptors with very high affinity and specificity. The aim of this study was to develop a new fluorescent probe based on BBN having high tumor uptake and optimal pharmacokinetics for specific targeting and optical imaging of human breast cancer tissue. In this study, solid-phase peptide synthesis was used to produce H(2)N-glycylglycylglycine-BBN[7-14]NH(2) peptide with the following general sequence: H(2)N-G-G-G-Q-W-A-V-G-H-L-M-(NH(2)). This conjugate was purified by reversed-phase high-performance liquid chromatography and characterized by electrospray-ionization mass spectra. The fluorescent probe Alexa Fluor 680-G-G-G-BBN[7-14]NH(2) conjugate was prepared by reaction of Alexa Fluor 680 succinimidyl ester to H(2)N-G-G-G-BBN[7-14]NH(2) in dimethylformamide (DMF). In vitro competitive binding assays, using (125)I-Tyr(4)-BBN as the radiolabeling gold standard, demonstrated an inhibitory concentration 50% value of 7.7 +/- 1.4 nM in human T-47D breast cancer cells. Confocal fluorescence microscopy images of Alexa Fluor 680-G-G-G-BBN[7-14]NH(2) in human T-47D breast cancer cells indicated specific uptake, internalization, and receptor blocking of the fluorescent bioprobe in vitro. In vivo investigations in SCID mice bearing xenografted T-47D breast cancer lesions demonstrated the ability of this new conjugate to specifically target tumor tissue with high selectivity and affinity.

Obesity emerges in early childhood and tracks across development. Self-regulation develops rapidly during the toddler years, yet few studies have examined toddlers’ self-regulation in relation to concurrent child weight. Further, few studies compare child responses in food and non-food-related tasks. Our goal was to examine toddlers’ observed behavioral and emotional self-regulation in food and non-food tasks in relation to their body mass index z-score (BMIz) and weight status (overweight/obese vs. not). Observational measures were used to assess self-regulation (SR) in four standardized tasks in 133 low-income children (M age=33.1 months; SD=0.6). Behavioral SR was measured by assessing how well the child could delay gratification for a snack (food-related task) and a gift (non-food-related task). Emotional SR was measured by assessing child intensity of negative affect in two tasks designed to elicit frustration: being shown, then denied a cookie (food-related) or a toy (non-food-related). Task order was counterbalanced. BMIz was measured. Bivariate correlations and regression analyses adjusting for child sex, child race/ethnicity, and maternal education were conducted to examine associations of SR with weight. Results were that better behavioral SR in the snack delay task associated with lower BMIz (β=−0.27, p<.05) and lower odds of overweight/obesity (OR=0.66, 95% CI 0.45, 0.96), but behavioral SR in the gift task did not associate with BMIz or weight status. Better emotional SR in the non-food task associated with lower BMIz (β= −0.27, p<.05), and better emotional SR in food and non-food tasks associated with lower odds of overweight/obesity (OR=0.65, 95% CI 0.45, 0.96 and OR=0.56, 95% CI 0.37, 0.87, respectively). Results are discussed regarding how behavioral SR for food and overall emotional SR relate to weight during toddlerhood, and regarding early childhood obesity prevention implications.

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To identify predictors of eating in the absence of hunger (EAH) in low-income toddlers, describe affect during EAH, test EAH as a predictor of body mass index (BMI), and examine the type of food eaten as a predictor of BMI.METHODS: EAH, indexed as kilocalories (sweet, salty, and total) of palatable foods consumed after a satiating meal, was measured (n = 209) at ages 21, 27, and 33 months. Child gender, age, race/ethnicity, and previous exposure to the foods; maternal education and depressive symptoms; and family chaos, food insecurity, and structure were obtained via questionnaire. Child and mother BMI were measured. Child affect was coded from videotape. Linear regression was used to examine predictors of EAH and the association of kilocalories consumed and affect with 33 month BMI z-score (BMIz). RESULTS:Predictors of greater total kilocalories included the child being a boy (P < .01), being older (P < .001), and greater maternal education (P < .01). Being in the the top quartile of sweet kilocalories consumed at 27 months and showing negative affect at food removal had higher BMIz (β = 0.29 [95% confidence interval 0.10 to 0.48] and β = 0.34 [95% confidence interval, 0.12 to 0.56], respectively).There was no association of salty kilocalories consumed or positive affect with BMIz. CONCLUSIONS:There was little evidence that maternal or family characteristics contribute to EAH. EAH for sweet food predicts higher BMIz in toddlerhood. Studies investigating the etiology of EAH and interventions to reduce EAH in early childhood are needed.

Introduction-Human breast cancer, from which the T-47D cell line was derived, is known to overexpress the gastrin-releasing peptide receptor (GRPR) in some cases. Bombesin (BBN), an agonist for the GRPR, has been appended with a radionuclide capable of positron-emission tomography (PET) imaging and therapy. 64 Cu-NO2A-8-Aoc-BBN(7-14)NH 2 (NO2A=1,4,7-triazacyclononane-1,4-diacetate) has produced high-quality microPET images of GRPR-positive breast cancer xenografted tumors in mice.Methods-The imaging probe was synthesized by solid-phase peptide synthesis followed by manual conjugation of the 1,4,7-triazacyclononane-1,4,7-triacetic acid (NOTA) bifunctional chelator and radiolabeling in aqueous solution. The radiolabeled conjugate was subjected to in vitro and in vivo studies to determine its specificity for the GRPR and its pharmacokinetic profile. A T-47D tumor-bearing mouse was imaged with microPET/CT and microMRI imaging.Results-The 64 Cu-NO2A-8-Aoc-BBN(7-14)NH 2 targeting vector was determined to specifically localize in GRPR-positive tissue. Accumulation was observed in the tumor in sufficient quantities to allow for identification of tumors in microPET imaging procedures. For example, uptake and retention in T-47D xenografts at 1, 4 and 24 h were determined to be 2.27±0.08, 1.35±0.14 and 0.28 ±0.07 % ID/g, respectively. Conclusions-The 64 Cu-NO2A-8-Aoc-BBN(7-14)NH 2 produced high-quality microPET images. The pharmacokinetic profile justifies investigation of this bioconjugate as a potentially useful diagnostic/therapeutic agent. Additionally, the bioconjugate would serve as a good starting point for modification and optimization of similar agents to maximize tumor uptake and minimize nontarget accumulation. NIH Public Access

We provide comprehensive multicenter benchmark data regarding rates of HAIs within dedicated pediatric CICUs. We confirm that although rare, HAIs of all types are associated with significant resource utilization and mortality.

Early stress exposure predicted increases in child eating behaviors known to associate with overweight/obesity. Psychosocial stress may confer overweight/obesity risk through eating behavior pathways. Targeting eating behaviors may be an important prevention strategy for children exposed to stress.