المؤلفون: Shadick, Nancy A., Zibit, Melanie J., Nardone, Elizabeth, DeMaria, Alfred, Iannaccone, Christine K., Cui, Jing

المصدر: Shadick, Nancy A., Melanie J. Zibit, Elizabeth Nardone, Alfred DeMaria, Christine K. Iannaccone, and Jing Cui. 2016. “A School-Based Intervention to Increase Lyme Disease Preventive Measures Among Elementary School-Aged Children.” Vector Borne and Zoonotic Diseases 16 (8): 507-515. doi:10.1089/vbz.2016.1942. http://dx.doi.org/10.1089/vbz.2016.1942Test.

مصطلحات موضوعية: Ixodes, Lyme disease

الوصف: Purpose: Educational interventions to reduce Lyme disease (LD) among at-risk school children have had little study. The purpose of this study was to evaluate whether a short in-class LD education program based on social learning theory and the Health Belief Model (HBM) impacted a child's knowledge, attitude, and preventive behavior. Methods: Students in grades 2–5 in 19 elementary schools were selected in an area that was highly endemic for LD. The children received an educational intervention or were on a wait list as controls. Their knowledge, attitudes, and self-reported preventive behaviors were surveyed before implementing the program and 1 year later. General linear regression analyses adjusting for age, gender, and baseline variables were used to measure the impact of the intervention. Results: There were 3570 participants in the study: 1562 received the intervention, and 2008 were controls. The mean age for both groups was 9.1 years, with 53% women in the intervention group and 50% women in the control group. The children in the intervention group increased their overall knowledge of LD more than the children in the control group (overall knowledge score improvement, mean difference (SD) 1.38 (1.3) vs. 0.36 (1.3) p < 0.0001). All children in classes receiving the intervention reported an increase in precautionary behavior, positive attitude toward taking precautions, and self-efficacy compared with the wait list controls. Two LD cases were confirmed during the follow-up period, one in the intervention group and one in the controls. Conclusions: These findings demonstrate that a short in-class educational program that includes elements of the HBM, including: (1) awareness and knowledge about the disease, (2) benefits of preventive behavior, and (3) confidence in ability to perform preventive behaviors can improve knowledge, attitude, and self-reported precautionary behavior among at-risk children. www.clinicaltrials.gov: NCT00594997

العلاقة: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4960477/pdfTest/; Vector Borne and Zoonotic Diseases

الوصول الحر: http://nrs.harvard.edu/urn-3:HUL.InstRepos:29002491Test

المؤلفون: Shipitsin, M, Small, C, Choudhury, S, Giladi, E, Friedlander, S, Nardone, J, Hussain, S, Hurley, A D, Ernst, C, Huang, Y E, Chang, H, Nifong, T P, Rimm, D L, Dunyak, J, Loda, M, Berman, D M, Blume-Jensen, P

المصدر: Shipitsin, M., C. Small, S. Choudhury, E. Giladi, S. Friedlander, J. Nardone, S. Hussain, et al. 2014. “Identification of proteomic biomarkers predicting prostate cancer aggressiveness and lethality despite biopsy-sampling error.” British Journal of Cancer 111 (6): 1201-1212. doi:10.1038/bjc.2014.396. http://dx.doi.org/10.1038/bjc.2014.396Test.

مصطلحات موضوعية: prostate cancer, biopsy, biomarkers, prognosis, sampling error, tumour heterogeneity

الوصف: Background: Key challenges of biopsy-based determination of prostate cancer aggressiveness include tumour heterogeneity, biopsy-sampling error, and variations in biopsy interpretation. The resulting uncertainty in risk assessment leads to significant overtreatment, with associated costs and morbidity. We developed a performance-based strategy to identify protein biomarkers predictive of prostate cancer aggressiveness and lethality regardless of biopsy-sampling variation. Methods: Prostatectomy samples from a large patient cohort with long follow-up were blindly assessed by expert pathologists who identified the tissue regions with the highest and lowest Gleason grade from each patient. To simulate biopsy-sampling error, a core from a high- and a low-Gleason area from each patient sample was used to generate a ‘high' and a ‘low' tumour microarray, respectively. Results: Using a quantitative proteomics approach, we identified from 160 candidates 12 biomarkers that predicted prostate cancer aggressiveness (surgical Gleason and TNM stage) and lethal outcome robustly in both high- and low-Gleason areas. Conversely, a previously reported lethal outcome-predictive marker signature for prostatectomy tissue was unable to perform under circumstances of maximal sampling error. Conclusions: Our results have important implications for cancer biomarker discovery in general and development of a sampling error-resistant clinical biopsy test for prediction of prostate cancer aggressiveness.

العلاقة: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4453845/pdfTest/; British Journal of Cancer

الوصول الحر: http://nrs.harvard.edu/urn-3:HUL.InstRepos:17295784Test

المؤلفون: Feng, Qin, Zhang, Zheng, Shea, Martin J, Creighton, Chad J, Coarfa, Cristian, Hilsenbeck, Susan G, Lanz, Rainer, He, Bin, Wang, Lei, Fu, Xiaoyong, Nardone, Agostina, Song, Yongcheng, Bradner, James, Mitsiades, Nicholas, Mitsiades, Constantine S, Osborne, C Kent, Schiff, Rachel, O'Malley, Bert W

المصدر: Feng, Q., Z. Zhang, M. J. Shea, C. J. Creighton, C. Coarfa, S. G. Hilsenbeck, R. Lanz, et al. 2014. “An epigenomic approach to therapy for tamoxifen-resistant breast cancer.” Cell Research 24 (7): 809-819. doi:10.1038/cr.2014.71. http://dx.doi.org/10.1038/cr.2014.71Test.

مصطلحات موضوعية: epigenomic, tamoxifen, breast cancer

الوصف: Tamoxifen has been a frontline treatment for estrogen receptor alpha (ERα)-positive breast tumors in premenopausal women. However, resistance to tamoxifen occurs in many patients. ER still plays a critical role in the growth of breast cancer cells with acquired tamoxifen resistance, suggesting that ERα remains a valid target for treatment of tamoxifen-resistant (Tam-R) breast cancer. In an effort to identify novel regulators of ERα signaling, through a small-scale siRNA screen against histone methyl modifiers, we found WHSC1, a histone H3K36 methyltransferase, as a positive regulator of ERα signaling in breast cancer cells. We demonstrated that WHSC1 is recruited to the ERα gene by the BET protein BRD3/4, and facilitates ERα gene expression. The small-molecule BET protein inhibitor JQ1 potently suppressed the classic ERα signaling pathway and the growth of Tam-R breast cancer cells in culture. Using a Tam-R breast cancer xenograft mouse model, we demonstrated in vivo anti-breast cancer activity by JQ1 and a strong long-lasting effect of combination therapy with JQ1 and the ER degrader fulvestrant. Taken together, we provide evidence that the epigenomic proteins BRD3/4 and WHSC1 are essential regulators of estrogen receptor signaling and are novel therapeutic targets for treatment of Tam-R breast cancer.

العلاقة: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4085766/pdfTest/; Cell Research

الوصول الحر: http://nrs.harvard.edu/urn-3:HUL.InstRepos:12717482Test

المؤلفون: Gu, Ting-lei, Nardone, Julie, Loriaux, Marc, Tucker, Meghan, Kornhauser, Jon, Ren, Jianmin, MacNeill, Joan, Druker, Brian J., Heinrich, Michael C., Rush, John, Polakiewicz, Roberto D., Villén, Judit, Gygi, Steven P., Beausoleil, Sean A, Wang, Yi

المصدر: Gu, Ting-lei, Julie Nardone, Yi Wang, Marc Loriaux, Judit Villén, Sean Beausoleil, Meghan Tucker, et al. 2011. Survey of activated FLT3 signaling in leukemia. PLoS ONE 6(4): e19169.

مصطلحات موضوعية: medicine, hematology, hematologic cancers and related disorders, leukimias, acute lymphoblastic leukemia, oncology, cancers and neoplasms

الوصف: Activating mutations of FMS-like tyrosine kinase-3 (FLT3) are found in approximately 30% of patients with acute myeloid leukemia (AML). FLT3 is therefore an attractive drug target. However, the molecular mechanisms by which FLT3 mutations lead to cell transformation in AML remain unclear. To develop a better understanding of FLT3 signaling as well as its downstream effectors, we performed detailed phosphoproteomic analysis of FLT3 signaling in human leukemia cells. We identified over 1000 tyrosine phosphorylation sites from about 750 proteins in both AML (wild type and mutant FLT3) and B cell acute lymphoblastic leukemia (normal and amplification of FLT3) cell lines. Furthermore, using stable isotope labeling by amino acids in cell culture (SILAC), we were able to quantified over 400 phosphorylation sites (pTyr, pSer, and pThr) that were responsive to FLT3 inhibition in FLT3 driven human leukemia cell lines. We also extended this phosphoproteomic analysis on bone marrow from primary AML patient samples, and identify over 200 tyrosine and 800 serine/threonine phosphorylation sites in vivo. This study showed that oncogenic FLT3 regulates proteins involving diverse cellular processes and affects multiple signaling pathways in human leukemia that we previously appreciated, such as Fc epsilon RI-mediated signaling, BCR, and CD40 signaling pathways. It provides a valuable resource for investigation of oncogenic FLT3 signaling in human leukemia.

العلاقة: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3084268/pdfTest/; PLoS ONE

الوصول الحر: http://nrs.harvard.edu/urn-3:HUL.InstRepos:5089334Test