toggle visibility Search & Display Options

Select All    Deselect All
 |   | 
Details
   print
  Records Links
Author Sareddy, G.R.; Viswanadhapalli, S.; Surapaneni, P.; Suzuki, T.; Brenner, A.; Vadlamudi, R.K. url  doi
openurl 
  Title Novel KDM1A inhibitors induce differentiation and apoptosis of glioma stem cells via unfolded protein response pathway Type Journal Article
  Year 2017 Publication Oncogene Abbreviated Journal Oncogene  
  Volume 36 Issue 17 Pages 2423-2434  
  Keywords Animals; Apoptosis/*drug effects; Cell Differentiation/*drug effects; Cell Line, Tumor; Cell Survival/drug effects; Cell Transformation, Neoplastic; Disease Progression; Enzyme Inhibitors/*pharmacology; Gene Expression Regulation, Neoplastic/drug effects; Glioma/*pathology; Histone Demethylases/*antagonists & inhibitors; Mice; Neoplastic Stem Cells/*drug effects/metabolism/pathology; Signal Transduction/drug effects; Survival Analysis; Transcription, Genetic/drug effects; Unfolded Protein Response/*drug effects  
  Abstract Glioma stem cells (GSCs) have a central role in glioblastoma (GBM) development and chemo/radiation resistance, and their elimination is critical for the development of efficient therapeutic strategies. Recently, we showed that lysine demethylase KDM1A is overexpressed in GBM. In the present study, we determined whether KDM1A modulates GSCs stemness and differentiation and tested the utility of two novel KDM1A-specific inhibitors (NCL-1 and NCD-38) to promote differentiation and apoptosis of GSCs. The efficacy of KDM1A targeting drugs was tested on purified GSCs isolated from established and patient-derived GBMs using both in vitro assays and in vivo orthotopic preclinical models. Our results suggested that KDM1A is highly expressed in GSCs and knockdown of KDM1A using shRNA-reduced GSCs stemness and induced the differentiation. Pharmacological inhibition of KDM1A using NCL-1 and NCD-38 significantly reduced the cell viability, neurosphere formation and induced apoptosis of GSCs with little effect on differentiated cells. In preclinical studies using orthotopic models, NCL-1 and NCD-38 significantly reduced GSCs-driven tumor progression and improved mice survival. RNA-sequencing analysis showed that KDM1A inhibitors modulate several pathways related to stemness, differentiation and apoptosis. Mechanistic studies showed that KDM1A inhibitors induce activation of the unfolded protein response (UPR) pathway. These results strongly suggest that selective targeting of KDM1A using NCL-1 and NCD-38 is a promising therapeutic strategy for elimination of GSCs.  
  Address (up) Cancer Therapy and Research Center, University of Texas Health Science Center at San Antonio, San Antonio, TX, USA  
  Corporate Author Thesis  
  Publisher Place of Publication Editor  
  Language English Summary Language Original Title  
  Series Editor Series Title Abbreviated Series Title  
  Series Volume Series Issue Edition  
  ISSN 0950-9232 ISBN Medium  
  Area Expedition Conference  
  Notes PMID:27893719 Approved no  
  Call Number ref @ user @ Serial 96621  
Permanent link to this record
 

 
Author Yan, H.; Romero-Lopez, M.; Benitez, L.I.; Di, K.; Frieboes, H.B.; Hughes, C.C.W.; Bota, D.A.; Lowengrub, J.S. url  doi
openurl 
  Title 3D Mathematical Modeling of Glioblastoma Suggests That Transdifferentiated Vascular Endothelial Cells Mediate Resistance to Current Standard-of-Care Therapy Type Journal Article
  Year 2017 Publication Cancer Research Abbreviated Journal Cancer Res  
  Volume 77 Issue 15 Pages 4171-4184  
  Keywords Brain Neoplasms/*pathology; Cell Transdifferentiation/physiology; Endothelial Cells/*pathology; Glioblastoma/*pathology; Humans; *Models, Theoretical; Neoplastic Stem Cells/*pathology  
  Abstract Glioblastoma (GBM), the most aggressive brain tumor in human patients, is decidedly heterogeneous and highly vascularized. Glioma stem/initiating cells (GSC) are found to play a crucial role by increasing cancer aggressiveness and promoting resistance to therapy. Recently, cross-talk between GSC and vascular endothelial cells has been shown to significantly promote GSC self-renewal and tumor progression. Furthermore, GSC also transdifferentiate into bona fide vascular endothelial cells (GEC), which inherit mutations present in GSC and are resistant to traditional antiangiogenic therapies. Here we use three-dimensional mathematical modeling to investigate GBM progression and response to therapy. The model predicted that GSCs drive invasive fingering and that GEC spontaneously form a network within the hypoxic core, consistent with published experimental findings. Standard-of-care treatments using DNA-targeted therapy (radiation/chemo) together with antiangiogenic therapies reduced GBM tumor size but increased invasiveness. Anti-GEC treatments blocked the GEC support of GSCs and reduced tumor size but led to increased invasiveness. Anti-GSC therapies that promote differentiation or disturb the stem cell niche effectively reduced tumor invasiveness and size, but were ultimately limited in reducing tumor size because GECs maintain GSCs. Our study suggests that a combinatorial regimen targeting the vasculature, GSCs, and GECs, using drugs already approved by the FDA, can reduce both tumor size and invasiveness and could lead to tumor eradication. Cancer Res; 77(15); 4171-84. (c)2017 AACR.  
  Address (up) Center for Complex Biological Systems, University of California, Irvine, California  
  Corporate Author Thesis  
  Publisher Place of Publication Editor  
  Language English Summary Language Original Title  
  Series Editor Series Title Abbreviated Series Title  
  Series Volume Series Issue Edition  
  ISSN 0008-5472 ISBN Medium  
  Area Expedition Conference  
  Notes PMID:28536277 Approved no  
  Call Number ref @ user @ Serial 96585  
Permanent link to this record
 

 
Author Oliva, C.R.; Zhang, W.; Langford, C.; Suto, M.J.; Griguer, C.E. url  doi
openurl 
  Title Repositioning chlorpromazine for treating chemoresistant glioma through the inhibition of cytochrome c oxidase bearing the COX4-1 regulatory subunit Type Journal Article
  Year 2017 Publication Oncotarget Abbreviated Journal Oncotarget  
  Volume 8 Issue 23 Pages 37568-37583  
  Keywords chlorpromazine; cytochrome c oxidase; glioblastoma; inhibitor; stem cells  
  Abstract Patients with glioblastoma have one of the lowest overall survival rates among patients with cancer. Standard of care for patients with glioblastoma includes temozolomide and radiation therapy, yet 30% of patients do not respond to these treatments and nearly all glioblastoma tumors become resistant. Chlorpromazine is a United States Food and Drug Administration-approved phenothiazine widely used as a psychotropic in clinical practice. Recently, experimental evidence revealed the anti-proliferative activity of chlorpromazine against colon and brain tumors. Here, we used chemoresistant patient-derived glioma stem cells and chemoresistant human glioma cell lines to investigate the effects of chlorpromazine against chemoresistant glioma. Chlorpromazine selectively and significantly inhibited proliferation in chemoresistant glioma cells and glioma stem cells. Mechanistically, chlorpromazine inhibited cytochrome c oxidase (CcO, complex IV) activity from chemoresistant but not chemosensitive cells, without affecting other mitochondrial complexes. Notably, our previous studies revealed that the switch to chemoresistance in glioma cells is accompanied by a switch from the expression of CcO subunit 4 isoform 2 (COX4-2) to COX4-1. In this study, chlorpromazine induced cell cycle arrest selectively in glioma cells expressing COX4-1, and computer-simulated docking studies indicated that chlorpromazine binds more tightly to CcO expressing COX4-1 than to CcO expressing COX4-2. In orthotopic mouse brain tumor models, chlorpromazine treatment significantly increased the median overall survival of mice harboring chemoresistant tumors. These data indicate that chlorpromazine selectively inhibits the growth and proliferation of chemoresistant glioma cells expressing COX4-1. The feasibility of repositioning chlorpromazine for selectively treating chemoresistant glioma tumors should be further explored.  
  Address (up) Center for Free Radical Biology, University of Alabama at Birmingham, Birmingham, 35294 Alabama, USA  
  Corporate Author Thesis  
  Publisher Place of Publication Editor  
  Language English Summary Language Original Title  
  Series Editor Series Title Abbreviated Series Title  
  Series Volume Series Issue Edition  
  ISSN 1949-2553 ISBN Medium  
  Area Expedition Conference  
  Notes PMID:28455961 Approved no  
  Call Number ref @ user @ Serial 96587  
Permanent link to this record
 

 
Author Heydari, N.; Larsen, D.A.; Neira, M.; Beltran Ayala, E.; Fernandez, P.; Adrian, J.; Rochford, R.; Stewart-Ibarra, A.M. url  doi
openurl 
  Title Household Dengue Prevention Interventions, Expenditures, and Barriers to Aedes aegypti Control in Machala, Ecuador Type Journal Article
  Year 2017 Publication International Journal of Environmental Research and Public Health Abbreviated Journal Int J Environ Res Public Health  
  Volume 14 Issue 2 Pages  
  Keywords Aedes/*growth & development; Animals; Dengue/epidemiology/*prevention & control; Ecuador/epidemiology; Housing; Humans; Insect Vectors/*virology; Insecticides/*economics; Mosquito Control/*economics/*methods; Mosquito Nets/*economics; Socioeconomic Factors; Aedes aegypti; Ecuador; Kap; dengue fever; economic cost; mosquito control  
  Abstract The Aedes aegypti mosquito is an efficient vector for the transmission of Zika, chikungunya, and dengue viruses, causing major epidemics and a significant social and economic burden throughout the tropics and subtropics. The primary means of preventing these diseases is household-level mosquito control. However, relatively little is known about the economic burden of Ae. aegypti control in resource-limited communities. We surveyed residents from 40 households in a high-risk community at the urban periphery in the city of Machala, Ecuador, on dengue perceptions, vector control interventions, household expenditures, and factors influencing purchasing decisions. The results of this study show that households spend a monthly median of US$2.00, or 1.90% (range: 0.00%, 9.21%) of their family income on Ae. aegypti control interventions. Households reported employing, on average, five different mosquito control and dengue prevention interventions, including aerosols, liquid sprays, repellents, mosquito coils, and unimpregnated bed nets. We found that effectiveness and cost were the most important factors that influence people's decisions to purchase a mosquito control product. Our findings will inform the development and deployment of new Ae. aegypti control interventions by the public health and private sectors, and add to prior studies that have focused on the economic burden of dengue-like illness.  
  Address (up) Center for Global Health and Translational Science, State University of New York Upstate Medical University, Syracuse, NY 13210, USA. amstew01@gmail.com  
  Corporate Author Thesis  
  Publisher Place of Publication Editor  
  Language English Summary Language Original Title  
  Series Editor Series Title Abbreviated Series Title  
  Series Volume Series Issue Edition  
  ISSN 1660-4601 ISBN Medium  
  Area Expedition Conference  
  Notes PMID:28212349 Approved no  
  Call Number ref @ user @ Serial 97645  
Permanent link to this record
 

 
Author Blitchtein-Winicki, D.; Zevallos, K.; Samolski, M.R.; Requena, D.; Velarde, C.; Briceno, P.; Piazza, M.; Ybarra, M.L. url  doi
openurl 
  Title Feasibility and Acceptability of a Text Message-Based Smoking Cessation Program for Young Adults in Lima, Peru: Pilot Study Type Journal Article
  Year 2017 Publication JMIR MHealth and UHealth Abbreviated Journal JMIR Mhealth Uhealth  
  Volume 5 Issue 8 Pages e116  
  Keywords Pilot Projects, Text Messaging, Smoking Cessation, Young Adult, Cognitive Therapy, Feasibility Studies, Latinos  
  Abstract BACKGROUND: In Peru's urban communities, tobacco smoking generally starts during adolescence and smoking prevalence is highest among young adults. Each year, many attempt to quit, but access to smoking cessation programs is limited. Evidence-based text messaging smoking cessation programs are an alternative that has been successfully implemented in high-income countries, but not yet in middle- and low-income countries with limited tobacco control policies. OBJECTIVE: The objective was to assess the feasibility and acceptability of an short message service (SMS) text message-based cognitive behavioral smoking cessation program for young adults in Lima, Peru. METHODS: Recruitment included using flyers and social media ads to direct young adults interested in quitting smoking to a website where interested participants completed a Google Drive survey. Inclusion criteria were being between ages 18 and 25 years, smoking at least four cigarettes per day at least 6 days per week, willing to quit in the next 30 days, owning a mobile phone, using SMS text messaging at least once in past year, and residing in Lima. Participants joined one of three phases: (1) focus groups and in-depth interviews whose feedback was used to develop the SMS text messages, (2) validating the SMS text messages, and (3) a pilot of the SMS text message-based smoking cessation program to test its feasibility and acceptability among young adults in Lima. The outcome measures included adherence to the SMS text message-based program, acceptability of content, and smoking abstinence self-report on days 2, 7, and 30 after quitting. RESULTS: Of 639 participants who completed initial online surveys, 42 met the inclusion criteria and 35 agreed to participate (focus groups and interviews: n=12; validate SMS text messages: n=8; program pilot: n=15). Common quit practices and beliefs emerged from participants in the focus groups and interviews informed the content, tone, and delivery schedule of the messages used in the SMS text message smoking cessation program. A small randomized controlled pilot trial was performed to test the program's feasibility and acceptability; nine smokers were assigned to the SMS text message smoking cessation program and six to a SMS text message nutrition program. Participant retention was high: 93% (14/15) remained until day 30 after quit day. In all, 56% of participants (5/9) in the SMS text message smoking cessation program reported remaining smoke-free until day 30 after quit day and 17% of participants (1/6) in the SMS text message nutrition program reported remaining smoke-free during the entire program. The 14 participants who completed the pilot reported that they received valuable health information and approved the delivery schedule of the SMS text messages. CONCLUSIONS: This study provides initial evidence that a SMS text message smoking cessation program is feasible and acceptable for young adults residing in Lima.  
  Address (up) Center for Innovative Public Health Research, San Clemente, CA, United States  
  Corporate Author Thesis  
  Publisher Place of Publication Editor  
  Language English Summary Language Original Title  
  Series Editor Series Title Abbreviated Series Title  
  Series Volume Series Issue Edition  
  ISSN 2291-5222 ISBN Medium  
  Area Expedition Conference  
  Notes PMID:28778850 Approved no  
  Call Number ref @ user @ Serial 98009  
Permanent link to this record
Select All    Deselect All
 |   | 
Details
   print

Save Citations:
Export Records: