Generation of an hTERT-restricted, CMV-augmented oncolytic adenovirus capable of tumor-specific transgene expression: Development, characterization, and optimization

Current shortcomings in cancer therapy require the generation of new, broadly applicable, potent, targeted treatments. Here, an adenovirus is engineered to replicate specifically in cells with active human telomerase promotion using a modified hTERT promoter, fused to a CMV promoter element. The virus was also modified to contain a visible reporter transgene, GFP. The virus, Ad/hTC-GFP-E1 was characterized in vitro and demonstrated tumor specific activity both by dose and over time course experiments in a variety of cell lines. In vivo, Ad/hTC-GFP-E1 was affected at suppressing tumor growth and providing a survival benefit without causing any measurable toxicity. To increase the host range of the vector, the fiber region was modified to contain an RGD-motif. The vector, AdRGD/hTC-GFP-E1, was recharacterized in vitro, revealing heightened levels of infectivity and toxicity however maintaining a therapeutic window between cancer and normal cell toxicity. AdRGD/hTC-GFP-E1 was administered in vivo by limb perfusion and was observed to be tumor specific both in expression and replication. To further enhance the efficacy of viral vectors in lung delivery, asthma medications were investigated for their abilities to enhance transgene delivery and expression. A combination of bronchodilators, mast cell inhibitors, and mucolytic agents was devised which demonstrated fold increases in expression in immunocompetent mouse lungs as single agents and more homogenous, intense levels of expression when done in combination of all agents. To characterize the methods in which some cancers are resistant or may become resistant to oncolytic treatments, several small molecule inhibitors of metabolic pathways were applied in combination with oncolytic infection in vitro. SP600125 and PD 98059, respective JNK and ERK inhibitors, successfully suppressed oncolytic toxicity, however did not affect infectivity or transgene expression of Ad/hTC-GFP-E1. JNK and ERK inhibition did significantly suppress viral replication, however, as analyzed by lysate transfer and titration assays. In contrast, SB 203580, an inhibitor for p38, did not demonstrate any protective effects with infected cells. Flow cytometric analysis indicated a possible correlation with G1 arrest and suppressed viral production, however more compounds must be investigated to clarify this observation. ^

Sleep quality and quantity and associated factors among high school students from south Texas

Background. Insufficient and poor quality sleep among adolescents affects not only the cognitive functioning, but overall health of the individual. Existing research suggests that adolescents from varying ethnic groups exhibit differing sleep patterns. However, little research focuses on sleep patterns and associated factors (i.e. tobacco use, mental health indicators) among Hispanic youth. ^ Methods. The study population (n=2,536) included students in grades 9-12 who attended one of the three public high schools along the Texas-Mexico border in 2003. This was a cross sectional study using secondary data collected via a web-based, confidential, self-administered survey. Separate logistic regression models were estimated to identify factors associated with reduced (<9 hours/night) and poor quality sleep on average during weeknights. ^ Results. Of participants, 49.5% reported reduced sleep while 12.8% reported poor quality sleep. Factors significantly (p<0.05) associated with poor quality sleep were: often feeling stressed or anxious (OR=5.49), being born in Mexico (OR=0.65), using a computer/playing video games 15+ hours per week (OR=2.29), working (OR=1.37), being a current smoker (OR=2.16), and being a current alcohol user (OR=1.64). Factors significantly associated with reduced quantity of sleep were: often feeling stressed or anxious (OR=2.74), often having headaches/stomachaches (OR=1.77), being a current marijuana user (OR=1.70), being a current methamphetamine user (OR=4.92), and being a current alcohol user (OR=1.27). ^ Discussion. Previous research suggests that there are several factors that can influence sleep quality and quantity in adolescents. This paper discusses these factors (i.e. work, smoking, alcohol, etc.) found to be associated with poor sleep quality and reduced sleep quantity in the Hispanic adolescent population. A reduced quantity of sleep (81.20% of the participants) and a poor quality of sleep (12.80% of the participants) were also found in high school students from South Texas. ^

New interatheriines (Interatheriidae, notoungulata) from the Paleogene of central Chile and southern Argentina / Ralph B. Hitz -- [et al.].

n.s. no.42(2000)

The royal atlas of England and Wales, reduced from the ordnance survey; a complete series of topographical maps, physical and statistical charts, town plans, and index of 35,000 names ..

Mode of access: Internet.

Heinrichs von Neustadt ʻApollonius von Tyrland ̓nach der Gothaer Handschrift, ʻGottes Zukunft ̓und ʻVisio Philiberti ̓nach der Heidelberger Handschrift,

Mode of access: Internet.

Quartet no. 4 in C minor for two violins, viola and violoncello.

Pl. no. 111942.

A study of English for the advanced grades of deaf pupils /

Cover title: English for advanced grades of deaf pupils, book III.

International adjudications, ancient and modern; history and documents,

Each volume has special t.-p.

Life of Beethoven /

Mode of access: Internet.

Supplement to the Page & Adams' Annotated general code of the state of Ohio, containing all laws of a permanent and general nature enacted by the General assembly of Ohio for the years 1913, 1914, 1915, and contained in volumes of Ohio laws 103, 104, 105, 106 /

Paged continuously.

Chronique de Michel le Syrien : patriarche jacobite d'Antioche (1166-1199) /

Syriac text at the end of each vol. making tome IV.

Essays,

A Jesuit reformer and poet [F. [Spee] (19th cent., August, 1885)--Revelations of the after-world (19th cent., February, 1887)--Savonarola (The Weekly register, September, 1899)--M. Emery, superior of St. Sulpice (1789-1811) (Dub. R., October, 1887)--Auricular confession.--The pope and the Anglican archbishops (19th cent., July, 1897)--Ritualism, Roman Catholicism, and converts (Contemp., February, 1879)--On certain ecclesiastical miracles (19th cent., August 1891)--Irresponsible opinion (Macmil., March, 1885)--The ethics of war (19th cent., May 1899)--The passion of the past (Macmil., September, 1887)--Some memories of a prison chaplain (Macmil., February, 1898)--Purcell's life of Cardinal Manning.--Appendix: Some notes on Fr. Ryder's controversy with Dr. Ward.

For the temple : a tale of the fall of Jerusalem /

32 p. of publisher's advertisements at end.

The story of the International Live Stock Exposition, from its inception in 1900 to the show of 1941.

Mode of access: Internet.