The role of patient-specific variables in protein corona formation and therapeutic efficacy in nanomedicine.

Despite their potential, the adoption of nanotechnology in therapeutics remains limited, with only around eighty nanomedicines approved in the past 30 years. This disparity is partly due to the "one-size-fits-all" approach in medical design, which often overlooks patient-specific variables such as biological sex, genetic ancestry, disease state, environment, and age that influence nanoparticle behavior. Nanoparticles (NPs) must be transported through systemic, microenvironmental, and cellular barriers that vary across heterogeneous patient populations.

Anti-VEGFR2 and anti-IGF-1R-Adnectins inhibit Ewing's sarcoma A673-xenograft growth and normalize tumor vascular architecture.

Increasing experimental evidence suggests that IGF-1 may modulate tumor angiogenesis via activation of the expression of VEGF in Ewing sarcomas and rhabdomyosarcomas. This study investigates the effects of the PEGylated Adnectins™ CT-322, a VEGFR2-inhibitor and AT580Peg40, an IGF-1R inhibitor, as monotherapy and in combination in a murine A673 xenograft tumor model. The combination of Adnectins CT-322 and AT580Peg40 revealed a 83% reduction in tumor growth, a nearly 5 times lower vessel density, less necrotic areas and less appearance of intussusceptive angiogenesis.

Association of SRC-related kinase Lyn with the interleukin-2 receptor and its role in maintaining constitutive phosphorylation of JAK/STAT in human T-cell leukemia virus type 1-transformed T cells.

Human T-cell leukemia virus type 1 (HTLV-1) infection and transformation are associated with an incremental switch in the expression of the Src-related protein tyrosine kinases Lck and Lyn. We examined the physical and functional interactions of Lyn with receptors and signal transduction proteins in HTLV-1-infected T cells. Lyn coimmunoprecipitates with the interleukin-2 beta receptor (IL-2Rβ) and JAK3 proteins; however, the association of Lyn with the IL-2Rβ and Lyn kinase activity was independent of IL-2 stimulation.

Adnectin CT-322 inhibits tumor growth and affects microvascular architecture and function in Colo205 tumor xenografts.

Antiangiogenesis has become a promising pillar in modern cancer therapy. This study investigates the antiangiogenic effects of the PEGylated Adnectin™, CT-322, in a murine Colo-205 xenograft tumor model. CT-322 specifically binds to and blocks vascular endothelial growth factor receptor (VEGFR-2).

A fibronectin scaffold approach to bispecific inhibitors of epidermal growth factor receptor and insulin-like growth factor-I receptor.

Engineered domains of human fibronectin (Adnectins™) were used to generate a bispecific Adnectin targeting epidermal growth factor receptor (EGFR) and insulin-like growth factor-I receptor (IGF-IR), two transmembrane receptors that mediate proliferative and survival cell signaling in cancer. Single-domain Adnectins that specifically bind EGFR or IGF-IR were generated using mRNA display with a library containing as many as 10 ( 13) Adnectin variants. mRNA display was also used to optimize lead Adnectin affinities, resulting in clones that inhibited EGFR phosphorylation at 7 to 38 nM compared to 2.

Anti-tumor effect of CT-322 as an adnectin inhibitor of vascular endothelial growth factor receptor-2.

CT-322 is a new anti-angiogenic therapeutic agent based on an engineered variant of the tenth type III domain of human fibronectin, i.e., an Adnectin™, designed to inhibit vascular endothelial growth factor receptor (VEGFR)-2.

Examining human T-lymphotropic virus type 1 infection and replication by cell-free infection with recombinant virus vectors.

A sensitive and quantitative cell-free infection assay, utilizing recombinant human T-cell leukemia virus type 1 (HTLV-1)-based vectors, was developed in order to analyze early events in the virus replication cycle. Previous difficulties with the low infectivity and restricted expression of the virus have prevented a clear understanding of these events. Virus stocks were generated by transfecting cells with three plasmids: (i) a packaging plasmid encoding HTLV-1 structural and regulatory proteins, (ii) an HTLV-1 transfer vector containing either firefly luciferase or enhanced yellow fluorescent protein genes, and (iii) an envelope expression plasmid.

Reducing complications from alcohol use during pregnancy through screening.

Prenatal providers are reluctant to discuss alcohol use in the clinical setting, even though heavy alcohol use is associated with fetal alcohol syndrome (FAS) and fetal alcohol effects (FAE), sometimes known as alcohol-related neurodevelopmental disorder. Fourteen percent to 20% of pregnant women report drinking some alcohol during pregnancy. Approximately 0.

Development and Psychopathology: Fetal Alcohol Syndrome and Related Conditions.

Prenatal exposure to alcohol, which is a neurobehavioral teratogen, can cause defects in the structure and function of the developing central nervous system and can also impact growth and morphology. These wide-ranging effects occur along a continuum, with the most severe impact known as fetal alcohol syndrome (FAS). As the identified population of alcohol-affected patients grows, because of enhanced societal awareness and increased diagnostic capability, it has become clear that the continuum of fetal alcohol effects can mean lifelong disabilities with serious implications for function in adolescence and adulthood.

Targeting of the visna virus tat protein to AP-1 sites: interactions with the bZIP domains of fos and jun in vitro and in vivo.

The visna virus Tat protein is required for efficient viral transcription from the visna virus long terminal repeat (LTR). AP-1 sites within the visna virus LTR, which can be bound by the cellular transcription factors Fos and Jun, are also necessary for Tat-mediated transcriptional activation. A potential mechanism by which the visna virus Tat protein could target the viral promoter is by protein-protein interactions with Fos and/or Jun bound to AP-1 sites in the visna virus LTR.

The leucine domain of the visna virus Tat protein mediates targeting to an AP-1 site in the viral long terminal repeat.

The visna virus Tat protein is a strong transcriptional activator and is necessary for efficient viral replication. The Tat protein regulates transcription through an AP-1 site proximal to the TATA box within the viral long terminal repeat (LTR). Previous studies from our laboratory using Tat-Gal4 chimeric proteins showed that Tat has a potent acidic activation domain.

Physician awareness of fetal alcohol syndrome: a survey of pediatricians and general practitioners.

Objective: To determine the knowledge, clinical experience and perceived needs for resource materials of Saskatchewan physicians in regard to fetal alcohol syndrome (FAS) and alcohol-related birth defects.

Design: Mailed survey.

Setting: Saskatchewan.

Visna virus Tat protein: a potent transcription factor with both activator and suppressor domains.

Visna virus is a pathogenic lentivirus of sheep tat is distantly related to the primate lentiviruses, including human immunodeficiency virus type 1. The visna virus genome encodes a small regulatory protein, Tat, which is necessary for efficient viral replication and enhanced viral transcription. To investigate the mechanism of action of the visna Tat protein and to localize the protein domain(s) responsible for transcriptional activation, chimeric proteins containing visna virus Tat sequences fused to the DNA binding domain of the yeast transactivation factor GAL4 (residues 1 to 147) were made.

Intervention and the Child With FAS.

Although the research is sparse, it appears that specific interventions may help children with FAS better overcome their cognitive and behavioral problems. Special strategies such as consistency, a structured environment, and attention to learning skills can help these children develop to their highest potential.

Pediatricians' perspectives on fetal alcohol syndrome.

Since the identification of fetal alcohol syndrome (FAS) in 1973, significant inroads have been made towards understanding the effects of alcohol on fetal development. However, it is not clear if these findings are considered clinically relevant by pediatricians. This survey was designed to assess clinical knowledge, practice, and attitudes concerning alcohol-related birth defects.

FAS/FAE: focusing prevention on women at risk.

Consumption of alcohol during pregnancy is well recognized as a risk factor associated with adverse fetal development. While precise safe or dangerous levels of maternal drinking have not been identified, it is clear that the women who drink most heavily are at the greatest risk. Prevention of alcohol-related birth defects requires development of programs directed to the special needs of addicted women and their families.