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Biomedical subjects

Brian Lucas

Publications and source records attributed to Brian Lucas.

8 recordsLinked to original sources
PubMed2004

Targeting wide-range oncogenic transformation via PU24FCl, a specific inhibitor of tumor Hsp90.

Agents that inhibit Hsp90 function hold significant promise in cancer therapy. Here we present PU24FCl, a representative of the first class of designed Hsp90 inhibitors. By specifically and potently inhibiting tumor Hsp90, PU24FCl exhibits wide-ranging anti-cancer activities that occur at similar doses in all tested tumor types. Normal cells are 10- to 50-fold more resistant to these effects. Its Hsp90 inhibition results in multiple anti-tumor-specific effects, such as degradation of Hsp90-client proteins involved in cell growth, survival, and specific transformation, inhibition of cancer cell growth, delay of cell cycle progression, induction of morphological and functional changes, and apoptosis. In concordance with its higher affinity for tumor Hsp90, in vivo PU24FCl accumulates in tumors while being rapidly cleared from normal tissue. Concentrations achieved in vivo in tumors lead to single-agent anti-tumor activity at non-toxic doses.

Adenine↗
PubMed2003

Development of purine-scaffold small molecule inhibitors of Hsp90.

The Hsp90 chaperones play a key role in regulating the physiology of cells exposed to environmental stress and in maintaining the malignant phenotype in tumor cells. Agents that interfere with the function of the chaperone may thus be beneficial in the treatment of cancers. The ansamycins (geldanamycin and herbimycin) and the unrelated natural product radicicol were found to bind to the N-terminal pocket of Hsp90 and inhibit its function. However, translation of these compounds to the clinic was impeded by stability and hepatoxicity issues. 17AAG, a derivative of geldanamycin, was found to be less hepatotoxic and is currently undergoing Phase I clinical trial. Unfortunately, 17AAG is insoluble, difficult to formulate and it is not yet clear if therapeutically effective doses can be administered without escalating non-Hsp90 associated toxicities. Additionally, for reasons not yet completely understood, a subset of tumor cells are insensitive to the action of the drug. The development of novel agents that lack the drawbacks of the natural products is thus necessary. Here we present an overview of such efforts with focus on a new class of purine-scaffold Hsp90 inhibitors developed by rational design.

Animals↗
PubMed2002

Development of a purine-scaffold novel class of Hsp90 binders that inhibit the proliferation of cancer cells and induce the degradation of Her2 tyrosine kinase.

The first published synthesis and characterization of a purine-scaffold library of hsp90 inhibitors is presented. The purine-scaffold represents a platform for the creation of easily synthesizable and derivatizable soluble molecules that are amenable for oral administration. The most active compound of the series (71) exhibits binding to hsp90 comparable to the natural product derivative 17AAG that is now in Phase I clinical trial as a cancer therapeutic. Induces the degradation of Her2 tyrosine kinase and arrests the MCF-7 breast cancer cell line at low micromolar concentrations (IC50=2 microM).

Alkylation↗
PubMed1997

Pressure Dependence Investigation of the Low-Temperature Structure of TlAu(CN)(2) by High-Resolution Neutron Powder Diffraction and Optical Studies.

In contrast to the anomalous increase of the lattice parameter b and associated reorientation of the [Au(3)(CN)(2)](-) ion with decreasing temperature, the unit cell volume and the lattice parameters of TlAu(CN)(2) are found to decrease (at T = 62 K) linearly for external hydrostatic pressures up to 4.5 kbar. The [Au(CN)(2)](-) ions do not essentially change orientation with pressure. The structural results suggest that the change in luminescence energy with pressure is due to changes in Tl.Au as well as in Au.Au interatomic separations, which again illustrates the importance of Tl.Au covalent interactions in this compound.

Journal Article↗
PubMedDate not supplied

Sleep after learning aids memory recall.

In recent years, the effect of sleep on memory consolidation has received considerable attention. In humans, these studies concentrated mainly on procedural types of memory, which are considered to be hippocampus-independent. Here, we show that sleep also has a persisting effect on hippocampus-dependent declarative memory. In two experiments, we examined high school students' ability to remember vocabulary. We show that declarative memory is enhanced when sleep follows within a few hours of learning, independent of time of day, and with equal amounts of interference during retention intervals. Sleep deprivation has a detrimental effect on memory, which was significant after a night of recovery sleep. Thus, fatigue accumulating during wake intervals could be ruled out as a confound.

Adolescent↗
PubMedDate not supplied

Nursing management issues in hip and knee replacement surgery.

Total hip replacement (THR) and total knee replacement (TKR) are carried out for the relief of pain in hip or knee joints usually caused by osteoarthritis. Such replacements last for 10-15 years and therefore many nurses will care for patients with a THR/TKR even if that is not the primary reason for the patient seeking care. The different types of THR/TKR and how patients can be prepared for surgery are discussed. The major long-term complications of loosening or dislocation of the components of the THR/TKR and of infection are explored and the presenting symptoms are highlighted. The article is intended to be useful not only for orthopaedic nurses but also for nurses generally.

Arthroplasty, Replacement, Hip↗
PubMedDate not supplied

Treatment options for patients with osteoarthritis of the knee.

Knee osteoarthritis (OA) affects many older people and may result in pain and loss of function in the knee. The article explores the wide spectrum of treatments available, including education, exercise, pharmacological agents and surgery. The evidence for these treatments is examined so that nurses have a knowledge base on which to build their practice. The importance of individual patient characteristics and available resources when deciding on treatment options is emphasized. The article is intended to be of use for both acute and primary care nurses who care for patients with knee OA.

Activities of Daily Living↗