Y 11

Asthma control in adolescents 10 to 11 y after exposure to the World Trade Center disaster.[Pubmed:27656769]

Pediatr Res. 2017 Jan;81(1-1):43-50.

BACKGROUND: Little is known about asthma control in adolescents who were exposed to the World Trade Center (WTC) attacks of 11 September 2001 and diagnosed with asthma after 9/11. This report examines asthma and asthma control 10-11 y after 9/11 among exposed adolescents. METHODS: The WTC Health Registry adolescent Wave 3 survey (2011-2012) collected data on asthma diagnosed by a physician after 11 September 2001, extent of asthma control based on modified National Asthma Education and Prevention Program criteria, probable mental health conditions, and behavior problems. Parents reported healthcare needs and 9/11-exposures. Logistic regression was used to evaluate associations between asthma and level of asthma control and 9/11-exposure, mental health and behavioral problems, and unmet healthcare needs. RESULTS: Poorly/very poorly controlled asthma was significantly associated with a household income of

Profiling movement quality and gait characteristics according to body-mass index in children (9-11 y).[Pubmed:27529450]

Hum Mov Sci. 2016 Oct;49:291-300.

Obese children move less and with greater difficulty than their normal-weight counterparts. Whilst the effect of high BMI on cardiovascular fitness is well known, the effect on movement quality characteristics during a standardised fitness test has not been investigated. The aims of this study were, to characterise the movement quality of children performing the multi-stage fitness test (MSFT), and, report how movement quality characteristics cluster according to weight status. One hundred and three children (10.3+/-0.6 y, 1.42+/-0.08m, 37.8+/-9.3kg, BMI; 18.5+/-3.3kgm(2)) performed the MSFT whilst wearing an ankle mounted accelerometer. BMI groups were used to classify children as underweight (UW), normal weight (NW), overweight (OW) and obese (OB). Characteristics of movement were profiled using a clustering algorithm. Spearman's rho was used to assess relationship with BMI group, and a Mann-Whitney U test was used to assess differences between BMI groups. Obese children had significantly lower spectral purity than every other group and significantly lower time to exhaustion (TTE) than UW and NW children (P<0.05). BMI was clustered with stride profile and TTE with spectral purity. Significant negative correlations (P<0.05) were found between BMI and TTE (r=-0.25), spectral purity (r=-0.24), integrated acceleration (r=-0.22), stride angle (r=-0.23) and stride variability (r=-0.22). This was the first study to report the spectral purity of children's gait. Further analysis unveiled key performance characteristics that differed between BMI groups. These were (i) representative of children's performance during the MSFT and, (ii) significantly negatively correlated with BMI.

A small molecule focal adhesion kinase (FAK) inhibitor, targeting Y397 site: 1-(2-hydroxyethyl)-3, 5, 7-triaza-1-azoniatricyclo [3.3.1.1(3,7)]decane; bromide effectively inhibits FAK autophosphorylation activity and decreases cancer cell viability, clonogenicity and tumor growth in vivo.[Pubmed:22402131]

Carcinogenesis. 2012 May;33(5):1004-13.

Focal adhesion kinase (FAK) is a protein tyrosine kinase that is overexpressed in most solid types of tumors and plays an important role in the survival signaling. Recently, we have developed a novel computer modeling combined with a functional assay approach to target the main autophosphorylation site of FAK (Y397). Using these approaches, we identified 1-(2-hydroxyethyl)-3, 5, 7-triaza-1-azoniatricyclo [3.3.1.1(3,7)]decane; bromide, called Y11, a small molecule inhibitor targeting Y397 site of FAK. Y11 significantly and specifically decreased FAK autophosphorylation, directly bound to the N-terminal domain of FAK. In addition, Y11 decreased Y397-FAK autophosphorylation, inhibited viability and clonogenicity of colon SW620 and breast BT474 cancer cells and increased detachment and apoptosis in vitro. Moreover, Y11 significantly decreased tumor growth in the colon cancer cell mouse xenograft model. Finally, tumors from the Y11-treated mice demonstrated decreased Y397-FAK autophosphorylation and activation of poly (ADP ribose) polymerase and caspase-3. Thus, targeting the major autophosphorylation site of FAK with Y11 inhibitor is critical for development of cancer therapeutics and carcinogenesis field.

A small molecule inhibitor, 1,2,4,5-benzenetetraamine tetrahydrochloride, targeting the y397 site of focal adhesion kinase decreases tumor growth.[Pubmed:18989950]

J Med Chem. 2008 Dec 11;51(23):7405-16.

Focal adhesion kinase (FAK) is a nonreceptor kinase that is overexpressed in many types of tumors. We developed a novel cancer-therapy approach, targeting the main autophosphorylation site of FAK, Y397, by computer modeling and screening of the National Cancer Institute (NCI) small molecule compounds database. More than 140,000 small molecule compounds were docked into the N-terminal domain of the FAK crystal structure in 100 different orientations that identified 35 compounds. One compound, 14 (1,2,4,5-benzenetetraamine tetrahydrochloride), significantly decreased viability in most of the cells to the levels equal to or higher than control FAK inhibitor 1a (2-[5-chloro-2-[2-methoxy-4-(4-morpholinyl)phenylamino]pyrimidin-4-ylamino]-N-met hylbenzamide, TAE226) from Novartis, Inc. Compound 14 specifically and directly blocked phosphorylation of Y397-FAK in a dose- and time-dependent manner. It increased cell detachment and inhibited cell adhesion in a dose-dependent manner. Furthermore, 14 effectively caused breast tumor regression in vivo. Thus, targeting the Y397 site of FAK with 14 inhibitor can be effectively used in cancer therapy.