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Articles 3721 - 3750 of 4180
Full-Text Articles in Entire DC Network
Consumption Of Pornographic Materials Among Hong Kong Early Adolescents: A Replication, Daniel T. L. Shek, Cecilia M. S. Ma
Consumption Of Pornographic Materials Among Hong Kong Early Adolescents: A Replication, Daniel T. L. Shek, Cecilia M. S. Ma
Pediatrics Faculty Publications
Consumption of pornographic materials was examined in 3,638 secondary 2 students in Hong Kong. Results showed that over 80% of the respondents had never consumed pornographic materials in the past year. Internet pornography was the most common medium that adolescents used when viewing pornographic materials. Males reported a higher level of pornography consumption than did females. Participants who were born in mainland China were more likely to consume pornographic materials than their Hong Kong counterparts. Regardless of the types of pornographic materials, the levels of pornography consumption significantly increased over time. Results also showed that higher levels of positive youth …
Autophagy And Senescence In Cancer-Associated Fibroblasts Metabolically Supports Tumor Growth And Metastasis Via Glycolysis And Ketone Production., Claudia Capparelli, Carmela Guido, Diana Whitaker-Menezes, Phd, Gloria Bonuccelli, Renee Balliet, Timothy G Pestell, Allison F Goldberg, Richard Pestell, Anthony Howell, Sharon Sneddon, Ruth Birbe, Aristotelis Tsirigos, Ubaldo E. Martinez-Outshoorn, Federica Sotgia, Michael P. Lisanti
Autophagy And Senescence In Cancer-Associated Fibroblasts Metabolically Supports Tumor Growth And Metastasis Via Glycolysis And Ketone Production., Claudia Capparelli, Carmela Guido, Diana Whitaker-Menezes, Phd, Gloria Bonuccelli, Renee Balliet, Timothy G Pestell, Allison F Goldberg, Richard Pestell, Anthony Howell, Sharon Sneddon, Ruth Birbe, Aristotelis Tsirigos, Ubaldo E. Martinez-Outshoorn, Federica Sotgia, Michael P. Lisanti
Department of Stem Cell Biology and Regenerative Medicine Faculty Papers & Presentations
Senescent fibroblasts are known to promote tumor growth. However, the exact mechanism remains largely unknown. An important clue comes from recent studies linking autophagy with the onset of senescence. Thus, autophagy and senescence may be part of the same physiological process, known as the autophagy-senescence transition (AST). To test this hypothesis, human fibroblasts immortalized with telomerase (hTERT-BJ1) were stably transfected with autophagy genes (BNIP3, CTSB or ATG16L1). Their overexpression was sufficient to induce a constitutive autophagic phenotype, with features of mitophagy, mitochondrial dysfunction and a shift toward aerobic glycolysis, resulting in L-lactate and ketone body production. Autophagic fibroblasts also showed …
Ctgf Drives Autophagy, Glycolysis And Senescence In Cancer-Associated Fibroblasts Via Hif1 Activation, Metabolically Promoting Tumor Growth., Claudia Capparelli, Diana Whitaker-Menezes, Carmela Guido, Renee Balliet, Timothy G Pestell, Anthony Howell, Sharon Sneddon, Richard Pestell, Ubaldo E. Martinez-Outshoorn, Michael P. Lisanti, Federica Sotgia
Ctgf Drives Autophagy, Glycolysis And Senescence In Cancer-Associated Fibroblasts Via Hif1 Activation, Metabolically Promoting Tumor Growth., Claudia Capparelli, Diana Whitaker-Menezes, Carmela Guido, Renee Balliet, Timothy G Pestell, Anthony Howell, Sharon Sneddon, Richard Pestell, Ubaldo E. Martinez-Outshoorn, Michael P. Lisanti, Federica Sotgia
Department of Stem Cell Biology and Regenerative Medicine Faculty Papers & Presentations
Previous studies have demonstrated that loss of caveolin-1 (Cav-1) in stromal cells drives the activation of the TGF-β signaling, with increased transcription of TGF-β target genes, such as connective tissue growth factor (CTGF). In addition, loss of stromal Cav-1 results in the metabolic reprogramming of cancer-associated fibroblasts, with the induction of autophagy and glycolysis. However, it remains unknown if activation of the TGF-β / CTGF pathway regulates the metabolism of cancer-associated fibroblasts. Therefore, we investigated whether CTGF modulates metabolism in the tumor microenvironment. For this purpose, CTGF was overexpressed in normal human fibroblasts or MDA-MB-231 breast cancer cells. Overexpression of …
Selective Impact Of Hiv Disease Progression On The Innate Immune System In The Human Female Reproductive Tract, Timothy Lahey, Mimi Ghosh, John V. Fahey, Zheng Shen, Lucy R. Mukura, Yan Song, Susan Cu-Uvin, Kenneth H. Mayer, Peter F. Wright, John C. Kappes, Christina Ochsenbauer, Charles R. Wira
Selective Impact Of Hiv Disease Progression On The Innate Immune System In The Human Female Reproductive Tract, Timothy Lahey, Mimi Ghosh, John V. Fahey, Zheng Shen, Lucy R. Mukura, Yan Song, Susan Cu-Uvin, Kenneth H. Mayer, Peter F. Wright, John C. Kappes, Christina Ochsenbauer, Charles R. Wira
Dartmouth Scholarship
Background: We have previously demonstrated intrinsic anti-HIV activity in cervicovaginal lavage (CVL) from HIV-infected women with high CD4 counts and not on antiretroviral therapy. However, the impact of HIV disease progression on CVL innate immune responses has not been delineated.
Methods: CVL from 57 HIV-infected women not on antiretroviral therapy were collected by washing the cervicovaginal area with 10 ml of sterile normal saline. We characterized subject HIV disease progression by CD4 count strata: >500 cells/µl, 200-500 cells/µl, or <200 cells/µl of blood. To assess CVL anti-HIV activity, we incubated TZM-bl cells with HIV plus or minus CVL. Antimicrobials, cytokines, chemokines and anti-gp160 HIV IgG antibodies were measured by ELISA and Luminex.
Effect Of Oxidative Stress On Protein Tyrosine Phosphatase 1b In Scleroderma Dermal Fibroblasts., Pei-Suen Tsou, Nadine N. Talia, Adam J. Pinney, Ann Kendzicky, Sonsoles Piera-Velazquez, Sergio A. Jimenez, James R. Seibold, Kristine Phillips, Alisa E Koch
Effect Of Oxidative Stress On Protein Tyrosine Phosphatase 1b In Scleroderma Dermal Fibroblasts., Pei-Suen Tsou, Nadine N. Talia, Adam J. Pinney, Ann Kendzicky, Sonsoles Piera-Velazquez, Sergio A. Jimenez, James R. Seibold, Kristine Phillips, Alisa E Koch
Department of Dermatology and Cutaneous Biology Faculty Papers
OBJECTIVE: Platelet-derived growth factor (PDGF) and its receptor, PDGFR, promote fibrosis in systemic sclerosis (SSc; scleroderma) dermal fibroblasts, and such cells in scleroderma skin lesions produce excessive reactive oxygen species (ROS). PDGFR is phosphorylated upon PDGF stimulation, and is dephosphorylated by protein tyrosine phosphatases (PTPs), including PTP1B. This study was undertaken to determine whether the thiol-sensitive PTP1B is affected by ROS in SSc dermal fibroblasts, thereby enhancing the phosphorylation of PDGFR and synthesis of type I collagen. This study also sought to investigate the effect of a thiol antioxidant, N-acetylcysteine (NAC), in SSc.
METHODS: Fibroblasts were isolated from the skin …
Management Of Hyperglycemia In Type 2 Diabetes: A Patient-Centered Approach: Position Statement Of The American Diabetes Association (Ada) And The European Association For The Study Of Diabetes (Easd)., Silvio E Inzucchi, Richard M Bergenstal, John B Buse, Michaela Diamant, Ele Ferrannini, Michael Nauck, Anne L Peters, Apostolos Tsapas, Richard Wender, David R. Matthews
Management Of Hyperglycemia In Type 2 Diabetes: A Patient-Centered Approach: Position Statement Of The American Diabetes Association (Ada) And The European Association For The Study Of Diabetes (Easd)., Silvio E Inzucchi, Richard M Bergenstal, John B Buse, Michaela Diamant, Ele Ferrannini, Michael Nauck, Anne L Peters, Apostolos Tsapas, Richard Wender, David R. Matthews
Department of Family & Community Medicine Faculty Papers
No abstract provided.
Process Evaluation Of A Positive Youth Development Program In Hong Kong Based On Different Cohorts, Ben M. F. Law, Daniel T. L. Shek
Process Evaluation Of A Positive Youth Development Program In Hong Kong Based On Different Cohorts, Ben M. F. Law, Daniel T. L. Shek
Pediatrics Faculty Publications
There are only a few process evaluation studies on positive youth development programs, particularly in the Chinese context. This study aims to examine the quality of implementation of a positive youth development program (the Project P.A.T.H.S.: Positive Adolescent Training through Holistic Social Programmes) and investigate the relationships among program adherence, process factors, implementation quality, and perceived program success. Process evaluation of 97 classroom-based teaching units was conducted in 62 schools from 2005 to 2009. Findings based on different cohorts generally showed that there were high overall program adherence and implementation quality. Program adherence and implementation process were highly correlated with …
Interim Evaluation Of The Project P.A.T.H.S.: Findings Based On Different Datasets, Daniel T. L. Shek, Lu Yu
Interim Evaluation Of The Project P.A.T.H.S.: Findings Based On Different Datasets, Daniel T. L. Shek, Lu Yu
Pediatrics Faculty Publications
Interim evaluation studies were carried out in order to examine the implementation details of the Tier 1 Program of the Project P.A.T.H.S. (Positive Adolescent Training through Holistic Social Programmes) in Hong Kong. Quantitative results of the interim evaluation findings based on eight datasets collected from 2006 to 2009 are reported in this paper. Three hundred and seventy-eight schools were randomly selected to provide information on the implementation details of the program via face-to-face interviews, telephone interviews, and self-completed questionnaires. Results showed that a majority of the workers perceived that the students had positive responses to the program and the program …
Qualitative Evaluation Of Project P.A.T.H.S.: An Integration Of Findings Based On Program Participants, Daniel T. L. Shek, Rachel C. F. Sun
Qualitative Evaluation Of Project P.A.T.H.S.: An Integration Of Findings Based On Program Participants, Daniel T. L. Shek, Rachel C. F. Sun
Pediatrics Faculty Publications
An integration of the qualitative evaluation findings collected in different cohorts of students who participated in Project P.A.T.H.S. (Positive Adolescent Training through Holistic Social Programmes) (n = 252 students in 29 focus groups) was carried out. With specific focus on how the informants described the program, results showed that the descriptions were mainly positive in nature, suggesting that the program was well received by the program participants. When the informants were invited to name three metaphors that could stand for the program, positive metaphors were commonly used. Beneficial effects of the program in different psychosocial domains were also voiced by …
Shoc2 Is Targeted To Late Endosomes And Required For Erk1/2 Activation In Egf-Stimulated Cells, Emilia Galperin, Lina Abdelmoti, Alexander Sorkin
Shoc2 Is Targeted To Late Endosomes And Required For Erk1/2 Activation In Egf-Stimulated Cells, Emilia Galperin, Lina Abdelmoti, Alexander Sorkin
Molecular and Cellular Biochemistry Faculty Publications
Shoc2 is the putative scaffold protein that interacts with RAS and RAF, and positively regulates signaling to extracellular signal-regulated protein kinases 1 and 2 (ERK1/2). To elucidate the mechanism by which Shoc2 regulates ERK1/2 activation by the epidermal growth factor (EGF) receptor (EGFR), we studied subcellular localization of Shoc2. Upon EGFR activation, endogenous Shoc2 and red fluorescent protein tagged Shoc2 were translocated from the cytosol to a subset of late endosomes containing Rab7. The endosomal recruitment of Shoc2 was blocked by overexpression of a GDP-bound H-RAS (N17S) mutant and RNAi knockdown of clathrin, suggesting the requirement of RAS activity and …
Interleukin-1Β Mediates Metalloproteinase-Dependent Renal Cell Carcinoma Tumor Cell Invasion Through The Activation Of Ccaat Enhancer Binding Protein Β, Brenda L. Petrella, Matthew P. P. Vincenti
Interleukin-1Β Mediates Metalloproteinase-Dependent Renal Cell Carcinoma Tumor Cell Invasion Through The Activation Of Ccaat Enhancer Binding Protein Β, Brenda L. Petrella, Matthew P. P. Vincenti
Dartmouth Scholarship
Effective treatment of metastatic renal cell carcinoma (RCC) remains a major medical concern, as these tumors are refractory to standard therapies and prognosis is poor. Although molecularly targeted therapies have shown some promise in the treatment of this disease, advanced RCC tumors often develop resistance to these drugs. Dissecting the molecular mechanisms underlying the progression to advanced disease is necessary to design alternative and improved treatment strategies. Tumor-associated macrophages (TAMs) found in aggressive RCC tumors produce a variety of inflammatory cytokines, including interleukin-1 b (IL-1b). Moreover, the presence of TAMs and high serum levels of IL-1b in RCC patients correlate …
Dna Methylation Arrays As Surrogate Measures Of Cell Mixture Distribution, Eugene Houseman, William P. Accomando, Devin C. Koestler, Brock C. Christensen, Carmen J. Marsit
Dna Methylation Arrays As Surrogate Measures Of Cell Mixture Distribution, Eugene Houseman, William P. Accomando, Devin C. Koestler, Brock C. Christensen, Carmen J. Marsit
Dartmouth Scholarship
There has been a long-standing need in biomedical research for a method that quantifies the normally mixed composition of leukocytes beyond what is possible by simple histological or flow cytometric assessments. The latter is restricted by the labile nature of protein epitopes, requirements for cell processing, and timely cell analysis. In a diverse array of diseases and following numerous immune-toxic exposures, leukocyte composition will critically inform the underlying immuno-biology to most chronic medical conditions. Emerging research demonstrates that DNA methylation is responsible for cellular differentiation, and when measured in whole peripheral blood, serves to distinguish cancer cases from controls.
Improved Tumor Contrast Achieved By Single Time Point Dual-Reporter Fluorescence Imaging, Kenneth M. Tichauer, Kimberley S. Samkoe, Kristian J. Sexton, Jason R. Gunn, Tayyaba Hasan, Brian W. Pogue
Improved Tumor Contrast Achieved By Single Time Point Dual-Reporter Fluorescence Imaging, Kenneth M. Tichauer, Kimberley S. Samkoe, Kristian J. Sexton, Jason R. Gunn, Tayyaba Hasan, Brian W. Pogue
Dartmouth Scholarship
In this study, we demonstrate a method to quantify biomarker expression that uses an exogenous dual-reporter imaging approach to improve tumor signal detection. The uptake of two fluorophores, one nonspecific and one targeted to the epidermal growth factor receptor (EGFR), were imaged at 1 h in three types of xenograft tumors spanning a range of EGFR expression levels (n = 6 in each group). Using this dual-reporter imaging methodology, tumor contrast-to-noise ratio was amplified by >6 times at 1 h postinjection and >2 times at 24 h. Furthermore, by as early as 20 min postinjection, the dual-reporter imaging signal …
Factor Structure Of A Multidimensional Gender Identity Scale In A Sample Of Chinese Elementary School Children, Lu Yu, Dong Xie, Daniel T. L. Shek
Factor Structure Of A Multidimensional Gender Identity Scale In A Sample Of Chinese Elementary School Children, Lu Yu, Dong Xie, Daniel T. L. Shek
Pediatrics Faculty Publications
This study examined the factor structure of a scale based on the four-dimensional gender identity model (Egan and Perry, 2001) in 726 Chinese elementary school students. Exploratory factor analyses suggested a three-factor model, two of which corresponded to "Felt Pressure" and "Intergroup Bias" in the original model. The third factor "Gender Compatibility" appeared to be a combination of "Gender Typicality" and "Gender Contentment" in the original model. Follow-up confirmatory factor analysis (CFA) indicated that, relative to the initial four-factor structure, the three-factor model fits the current Chinese sample better. These results are discussed in light of cross-cultural similarities and differences …
Pv1 Down-Regulation Via Shrna Inhibits The Growth Of Pancreatic Adenocarcinoma Xenografts, Sophie J. Deharvengt, Dan Tse, Olga Sideleva, Caitlin Mcgarry, Jason R. Gunn, Daniel S. Longnecker, Catherine Carriere, Radu V. Stan
Pv1 Down-Regulation Via Shrna Inhibits The Growth Of Pancreatic Adenocarcinoma Xenografts, Sophie J. Deharvengt, Dan Tse, Olga Sideleva, Caitlin Mcgarry, Jason R. Gunn, Daniel S. Longnecker, Catherine Carriere, Radu V. Stan
Dartmouth Scholarship
PV1 is an endothelial-specific protein with structural roles in the formation of diaphragms in endothelial cells of normal vessels. PV1 is also highly expressed on endothelial cells of many solid tumours. On the basis of in vitro data, PV1 is thought to actively participate in angiogenesis. To test whether or not PV1 has a function in tumour angiogenesis and in tumour growth in vivo, we have treated pancreatic tumour-bearing mice by single-dose intratumoural delivery of lentiviruses encoding for two different shRNAs targeting murine PV1. We find that PV1 down-regulation by shRNAs inhibits the growth of established tumours derived from two …
Relative Telomere Length: A Novel Non-Invasive Biomarker For The Risk Of Non-Cirrhotic Hepatocellular Carcinoma In Patients With Chronic Hepatitis B Infection., Xiaoying Fu, Shaogui Wan, Hie-Won Hann, Md, Ronald E Myers, Phd, Richard S Hann, Jennifer Au, Bicui Chen, Jinliang Xing, Hushan Yang
Relative Telomere Length: A Novel Non-Invasive Biomarker For The Risk Of Non-Cirrhotic Hepatocellular Carcinoma In Patients With Chronic Hepatitis B Infection., Xiaoying Fu, Shaogui Wan, Hie-Won Hann, Md, Ronald E Myers, Phd, Richard S Hann, Jennifer Au, Bicui Chen, Jinliang Xing, Hushan Yang
Division of Gastroenterology and Hepatology Faculty Papers
BACKGROUND AND AIMS: Telomere length has emerged as a promising risk predictor of various cancers including hepatocellular carcinoma (HCC). However, the majority of studies in this area measured telomere length in hepatocytes and one in lymphocytes with conflicting results. Moreover, no studies have been reported on using circulating DNA telomere length as a non-invasive HCC biomarker.
METHODS: We conducted a nested case-control study to determine the relative telomere length (RTL) in serum DNA from 140 hepatitis B virus (HBV)-related HCC cases and 280 frequency-matched cancer-free HBV controls.
RESULTS: Cases had a significantly longer RTL (median, 0.31; range, 0.02-2.31) than controls …
Early Developmental Outcome In Children With Hypoplastic Left Heart Syndrome And Related Anomalies: The Single Ventricle Reconstruction Trial., Jane W. Newburger, Lynn A. Sleeper, David C. Bellinger, Caren S. Goldberg, Sarah Tabbutt, Minmin Lu, Kathleen A. Mussatto, Ismee A. Williams, Kathryn E. Gustafson, Seema Mital, Nancy Pike, Erica Sood, William T. Mahle, David S. Cooper, Carolyn Dunbar-Masterson, Catherine Dent Krawczeski, Alan Lewis, Shaji C. Menon, Victoria L. Pemberton, Chitra Ravishankar, Teresa W. Atz, Richard G. Ohye, J William Gaynor, Pediatric Heart Network Investigators, Girish S. Shirali
Early Developmental Outcome In Children With Hypoplastic Left Heart Syndrome And Related Anomalies: The Single Ventricle Reconstruction Trial., Jane W. Newburger, Lynn A. Sleeper, David C. Bellinger, Caren S. Goldberg, Sarah Tabbutt, Minmin Lu, Kathleen A. Mussatto, Ismee A. Williams, Kathryn E. Gustafson, Seema Mital, Nancy Pike, Erica Sood, William T. Mahle, David S. Cooper, Carolyn Dunbar-Masterson, Catherine Dent Krawczeski, Alan Lewis, Shaji C. Menon, Victoria L. Pemberton, Chitra Ravishankar, Teresa W. Atz, Richard G. Ohye, J William Gaynor, Pediatric Heart Network Investigators, Girish S. Shirali
Manuscripts, Articles, Book Chapters and Other Papers
BACKGROUND: Survivors of the Norwood procedure may experience neurodevelopmental impairment. Clinical trials to improve outcomes have focused primarily on methods of vital organ support during cardiopulmonary bypass.
METHODS AND RESULTS: In the Single Ventricle Reconstruction trial of the Norwood procedure with modified Blalock-Taussig shunt versus right-ventricle-to-pulmonary-artery shunt, 14-month neurodevelopmental outcome was assessed by use of the Psychomotor Development Index (PDI) and Mental Development Index (MDI) of the Bayley Scales of Infant Development-II. We used multivariable regression to identify risk factors for adverse outcome. Among 373 transplant-free survivors, 321 (86%) returned at age 14.3 ± 1.1 (mean ± SD) months. Mean …
Uterine Epithelial Cells Specifically Induce Interferon-Stimulated Genes In Response To Polyinosinic-Polycytidylic Acid Independently Of Estradiol, Mickey V. Patel, Mimi Ghosh, John V. Fahey, Charles R. Wira
Uterine Epithelial Cells Specifically Induce Interferon-Stimulated Genes In Response To Polyinosinic-Polycytidylic Acid Independently Of Estradiol, Mickey V. Patel, Mimi Ghosh, John V. Fahey, Charles R. Wira
Dartmouth Scholarship
Interferon β (IFNβ) is an antiviral cytokine secreted in response to pathogenic exposure that creates a restrictive intracellular environment through the action of downstream interferon-stimulated genes (ISG). The objective of this study was to examine the expression of IFNβ and ISG in both human uterine epithelial cells (UEC) and the ECC-1 uterine epithelial cell line and determine if expression changes with TLR stimulation and hormone exposure. Stimulation of primary uterine epithelial cells and ECC-1 cells with the TLR3 agonist poly (I∶C) induced the mRNA expression of IFNβ, MxA, OAS2 and PKR. Other TLR agonists including imiquimod and CpG had no …
Beliefs In The Future As A Positive Youth Development Construct: A Conceptual Review, Rachel C. F. Sun, Daniel T. L. Shek
Beliefs In The Future As A Positive Youth Development Construct: A Conceptual Review, Rachel C. F. Sun, Daniel T. L. Shek
Pediatrics Faculty Publications
Beliefs in the future are an internalization of hope and optimism about future outcomes. This paper reviews and compares several theories of hope and optimism and highlights the features constituting beliefs in the future. This paper points out that beliefs in the future include a series of goal-directed thoughts and motivation, such as setting up valued and attainable goals, planning pathways, and maintaining self-confidence and mastery, so as to keep adolescents engaged in the pursuit of goals. This kind of personal mastery, together with sociocultural values, family, school, and peers are the antecedents leading to beliefs in the future, which …
Mitochondrial Lysyl-Trna Synthetase Independent Import Of Trna Lysine Into Yeast Mitochondria., Naresh Babu V Sepuri, Madhavi Gorla, Michael P King
Mitochondrial Lysyl-Trna Synthetase Independent Import Of Trna Lysine Into Yeast Mitochondria., Naresh Babu V Sepuri, Madhavi Gorla, Michael P King
Department of Biochemistry and Molecular Biology Faculty Papers
Aminoacyl tRNA synthetases play a central role in protein synthesis by charging tRNAs with amino acids. Yeast mitochondrial lysyl tRNA synthetase (Msk1), in addition to the aminoacylation of mitochondrial tRNA, also functions as a chaperone to facilitate the import of cytosolic lysyl tRNA. In this report, we show that human mitochondrial Kars (lysyl tRNA synthetase) can complement the growth defect associated with the loss of yeast Msk1 and can additionally facilitate the in vitro import of tRNA into mitochondria. Surprisingly, the import of lysyl tRNA can occur independent of Msk1 in vivo. This suggests that an alternative mechanism is present …
Qualitative Evaluation Of The Project P.A.T.H.S.: An Integration Of Findings Based On Program Implementers, Daniel T. L. Shek
Qualitative Evaluation Of The Project P.A.T.H.S.: An Integration Of Findings Based On Program Implementers, Daniel T. L. Shek
Pediatrics Faculty Publications
An integration of the qualitative evaluation findings collected from program implementers conducting the Project P.A.T.H.S. (Positive Adolescent Training through Holistic Social Programmes) in different years (n = 177 participants in 36 focus groups) was carried out. General qualitative data analyses utilizing intra and interrater reliability techniques were performed. Results showed that the descriptors used to describe the program and the metaphors named by the informants that could stand for the program were generally positive in nature. Program participants also perceived the program to be beneficial to the development of the students in different psychosocial domains. The present study further supports …
Chromosomal Instability And Cancer: A Complex Relationship With Therapeutic Potential, Samuel F. Bakhoum, Duane A. Compton
Chromosomal Instability And Cancer: A Complex Relationship With Therapeutic Potential, Samuel F. Bakhoum, Duane A. Compton
Dartmouth Scholarship
Chromosomal instability (CIN) is a hallmark of human neoplasms. Despite its widespread prevalence, knowledge of the mechanisms and contributions of CIN in cancer has been elusive. It is now evident that the role of CIN in tumor initiation and growth is more complex than previously thought. Furthermore, distinguishing CIN, which consists of elevated rates of chromosome missegregation, from aneuploidy, which is a state of abnormal chromosome number, is crucial to understanding their respective contributions in cancer. Collectively, experimental evidence suggests that CIN enables tumor adaptation by allowing tumors to constantly sample the aneuploid fitness landscape. This complex relationship, together with …
Onset Of Alcohol Or Substance Use Disorders Following Treatment For Adolescent Depression., John Curry, Susan Silva, Paul Rohde, Golda Ginsburg, Betsy Kennard, Christopher Kratochvil, Anne Simons, Jerry Kirchner, Diane May, Taryn Mayes, Norah Feeny, Anne Marie Albano, Sarah Lavanier, Mark Reinecke, Rachel Jacobs, Emily Becker-Weidman, Elizabeth Weller, Graham Emslie, John Walkup, Elizabeth Kastelic, Barbara Burns, Karen Wells, John March
Onset Of Alcohol Or Substance Use Disorders Following Treatment For Adolescent Depression., John Curry, Susan Silva, Paul Rohde, Golda Ginsburg, Betsy Kennard, Christopher Kratochvil, Anne Simons, Jerry Kirchner, Diane May, Taryn Mayes, Norah Feeny, Anne Marie Albano, Sarah Lavanier, Mark Reinecke, Rachel Jacobs, Emily Becker-Weidman, Elizabeth Weller, Graham Emslie, John Walkup, Elizabeth Kastelic, Barbara Burns, Karen Wells, John March
Journal Articles: Psychiatry
OBJECTIVE: This study tested whether positive response to short-term treatment for adolescent major depressive disorder (MDD) would have the secondary benefit of preventing subsequent alcohol use disorders (AUD) or substance use disorders (SUD).
METHOD: For 5 years, we followed 192 adolescents (56.2% female; 20.8% minority) who had participated in the Treatment for Adolescents with Depression Study (TADS; TADS Team, 2004) and who had no prior diagnoses of AUD or SUD. TADS initial treatments were cognitive behavior therapy (CBT), fluoxetine alone (FLX), the combination of CBT and FLX (COMB), or clinical management with pill placebo (PBO). We used both the original …
Glycosylation Of Human Cyclooxygenase-2 (Cox-2) Decreases The Efficacy Of Certain Cox-2 Inhibitors., Mary B. Sevigny, Kamara Graham, Esmeralda Ponce, Maggie Louie, Kylie Mitchell
Glycosylation Of Human Cyclooxygenase-2 (Cox-2) Decreases The Efficacy Of Certain Cox-2 Inhibitors., Mary B. Sevigny, Kamara Graham, Esmeralda Ponce, Maggie Louie, Kylie Mitchell
Natural Sciences and Mathematics | Faculty Scholarship
Prostanoids play an important role in a variety of physiological and pathophysiological processes including inflammation and cancer. The rate-limiting step in the prostanoid biosynthesis pathway is catalyzed by cyclooxygenase-2 (COX-2). COX-2 exists as two glycoforms, 72 and 74 kDa, the latter resulting from an additional glycosylation at Asn(580). In this study, Asn(580) was mutated, and the mutant and wild-type COX-2 genes were expressed in COS-1 cells to determine how glycosylation affects the inhibition of COX-2 activity by aspirin, flurbiprofen, ibuprofen, celecoxib, and etoricoxib. Results indicate that certain inhibitors were 2-5 times more effective at inhibiting COX-2 activity when the glycosylation …
Hyccin, The Molecule Mutated In The Leukodystrophy Hypomyelination And Congenital Cataract (Hcc), Is A Neuronal Protein., Elisabetta Gazzerro, Simona Baldassari, Caterina Giacomini, Veronica Musante, Floriana Fruscione, Veronica La Padula, Roberta Biancheri, Sonia Scarfì, Valeria Prada, Federica Sotgia, Ian D Duncan, Federico Zara, Hauke B Werner, Michael P Lisanti, Lucilla Nobbio, Anna Corradi, Carlo Minetti
Hyccin, The Molecule Mutated In The Leukodystrophy Hypomyelination And Congenital Cataract (Hcc), Is A Neuronal Protein., Elisabetta Gazzerro, Simona Baldassari, Caterina Giacomini, Veronica Musante, Floriana Fruscione, Veronica La Padula, Roberta Biancheri, Sonia Scarfì, Valeria Prada, Federica Sotgia, Ian D Duncan, Federico Zara, Hauke B Werner, Michael P Lisanti, Lucilla Nobbio, Anna Corradi, Carlo Minetti
Kimmel Cancer Center Faculty Papers
"Hypomyelination and Congenital Cataract", HCC (MIM #610532), is an autosomal recessive disorder characterized by congenital cataract and diffuse cerebral and peripheral hypomyelination. HCC is caused by deficiency of Hyccin, a protein whose biological role has not been clarified yet. Since the identification of the cell types expressing a protein of unknown function can contribute to define the physiological context in which the molecule is explicating its function, we analyzed the pattern of Hyccin expression in the central and peripheral nervous system (CNS and PNS). Using heterozygous mice expressing the b-galactosidase (LacZ) gene under control of the Hyccin gene regulatory elements, …
Inhibition Of Fatty Acid Synthase Attenuates Cd44-Associated Signaling And Reduces Metastasis In Colorectal Cancer, Yekaterina Y. Zaytseva, Piotr G. Rychahou, Pat Gulhati, Victoria Allison Elliott, William Conan Mustain, Kathleen O'Connor, Andrew J. Morris, Manjula Sunkara, Heidi L. Weiss, Eun Young Lee, B. Mark Evers
Inhibition Of Fatty Acid Synthase Attenuates Cd44-Associated Signaling And Reduces Metastasis In Colorectal Cancer, Yekaterina Y. Zaytseva, Piotr G. Rychahou, Pat Gulhati, Victoria Allison Elliott, William Conan Mustain, Kathleen O'Connor, Andrew J. Morris, Manjula Sunkara, Heidi L. Weiss, Eun Young Lee, B. Mark Evers
Markey Cancer Center Faculty Publications
Fatty acid synthase (FASN) and ATP-citrate lyase, key enzymes of de novo lipogenesis, are significantly upregulated and activated in many cancers and portend poor prognosis. Even though the role of lipogenesis in providing proliferative and survival advantages to cancer cells has been described, the impact of aberrant activation of lipogenic enzymes on cancer progression remains unknown. In this study, we found that elevated expression of FASN is associated with advanced stages of colorectal cancer (CRC) and liver metastasis, suggesting that it may play a role in progression of CRC to metastatic disease. Targeted inhibition of lipogenic enzymes abolished expression of …
Development And Functional Analysis Of Novel Genetic Promoters Using Dna Shuffling, Hybridization And A Combination Thereof, Rajiv Ranjan, Sunita Patro, Bhubaneswar Pradhan, Alok Kumar, Indu B. Maiti, Nrisingha Dey
Development And Functional Analysis Of Novel Genetic Promoters Using Dna Shuffling, Hybridization And A Combination Thereof, Rajiv Ranjan, Sunita Patro, Bhubaneswar Pradhan, Alok Kumar, Indu B. Maiti, Nrisingha Dey
Kentucky Tobacco Research and Development Center Faculty Publications
BACKGROUND: Development of novel synthetic promoters with enhanced regulatory activity is of great value for a diverse range of plant biotechnology applications.
METHODOLOGY: Using the Figwort mosaic virus full-length transcript promoter (F) and the sub-genomic transcript promoter (FS) sequences, we generated two single shuffled promoter libraries (LssF and LssFS), two multiple shuffled promoter libraries (LmsFS-F and LmsF-FS), two hybrid promoters (FuasFScp and FSuasFcp) and two hybrid-shuffled promoter libraries (LhsFuasFScp and LhsFSuasFcp). Transient expression activities of approximately 50 shuffled promoter clones from each of these libraries were assayed in tobacco (Nicotiana tabacum cv. Xanthi) protoplasts. It was observed that most …
Fibrinogen, Chronic Obstructive Pulmonary Disease (Copd) And Outcomes In Two United States Cohorts, Deepa Valvi, David M. Mannino, Hana Müllerova, Ruth Tal-Singer
Fibrinogen, Chronic Obstructive Pulmonary Disease (Copd) And Outcomes In Two United States Cohorts, Deepa Valvi, David M. Mannino, Hana Müllerova, Ruth Tal-Singer
Preventive Medicine and Environmental Health Faculty Publications
BACKGROUND: Fibrinogen is a marker of systemic inflammation and may be important in the pathogenesis and progression of chronic obstructive pulmonary disease (COPD).
METHODS: We used baseline data from Atherosclerosis Risk in Communities and Cardiovascular Health Studies to determine the relation between fibrinogen levels and COPD and to examine how fibrinogen levels at baseline affected outcomes of death, development of COPD, lung function decline, and COPD-hospitalizations.
RESULTS: Our study sample included 20,192 subjects, of whom 2995 died during the follow-up period. The mean fibrinogen level was 307.6 mg/dL and 10% of the sample had levels >393.0 mg/dL. Subjects with Stage …
Krüppel-Like Factor 4 Regulates Intestinal Epithelial Cell Morphology And Polarity, Tianxin Yu, Xi Chen, Wen Zhang, Juan Li, Ren Xu, Timothy C Wang, Walden Ai, Chunming Liu
Krüppel-Like Factor 4 Regulates Intestinal Epithelial Cell Morphology And Polarity, Tianxin Yu, Xi Chen, Wen Zhang, Juan Li, Ren Xu, Timothy C Wang, Walden Ai, Chunming Liu
Markey Cancer Center Faculty Publications
Krüppel-like factor 4 (KLF4) is a zinc finger transcription factor that plays a vital role in regulating cell lineage differentiation during development and maintaining epithelial homeostasis in the intestine. In normal intestine, KLF4 is predominantly expressed in the differentiated epithelial cells. It has been identified as a tumor suppressor in colorectal cancer. KLF4 knockout mice demonstrated a decrease in number of goblet cells in the colon, and conditional ablation of KLF4 from the intestinal epithelium led to altered epithelial homeostasis. However, the role of KLF4 in differentiated intestinal cells and colon cancer cells, as well as the mechanism by which …
Pathobiological Implications Of The Expression Of Egfr, Pakt, Nf-Κb And Mic-1 In Prostate Cancer Stem Cells And Their Progenies., Murielle Mimeault, Sonny L. Johansson, Surinder K. Batra
Pathobiological Implications Of The Expression Of Egfr, Pakt, Nf-Κb And Mic-1 In Prostate Cancer Stem Cells And Their Progenies., Murielle Mimeault, Sonny L. Johansson, Surinder K. Batra
Journal Articles: Biochemistry & Molecular Biology
The progression of prostate cancers (PCs) to locally invasive, androgen-independent and metastatic disease states is generally associated with treatment resistance and disease relapse. The present study was undertaken to establish the possibility of using a combination of specific oncogenic products, including epidermal growth factor receptor (EGFR), pAkt, nuclear factor-kappaB (NF-κB) and macrophage inhibitory cytokine-1 (MIC-1) as biomarkers and therapeutic targets for optimizing the management of patients with localized PC at earlier disease stages. The immunohistochemical and immunofluorescence data have revealed that the expression levels of EGFR, Ser(473)-pAkt, NF-κB p65 and MIC-1 proteins were significantly enhanced in the same subset of …