Current Pharmaceutical Design - Volume 11, Issue 9, 2005

Phospholipid nucleoside conjugates and nucleosides with chemical additions to the hydroxyl and amino moieties have been used since the 1970s in order to increase the biological activity of the parent compound. Previous investigators have found that adding lipid moieties to ara-C or chemically linking ara-C to a phospholipid creates a prodrug that exhibits superior cytotoxic activity compared to ara-C alone when used in animal t Read More

The activity of genes encoded by the highly-condensed DNA in cellular nuclei must be precisely regulated. Regulation of the accessibility of gene promoters to transcription complexes is one level of gene regulation and is influenced by histone tail modifications such as acetylation, methylation, and phosphorylation. Acetylation is a reversible modification catalyzed by histone acetyl transferase (HAT) and histone deacetyltransfer Read More

Oligonucleotide-based therapies have been under investigation for many years, and different antisense oligomers are being tested in clinical trials on patients with cancer and other diseases. Since telomerase reactivation has been defined as one of the six hallmarks of cancer because of the enzyme's ability to provide tumor cells with unlimited proliferative potential, antisense-based approaches, aimed to inhibit the core enzy Read More

Since identifying a transmissible agent responsible for tumorigenesis in chickens, the v-Src oncogene, significant progress has been made in determining the functions of its cellular homologue. c-Src is the product of the SRC gene and has been found both over-expressed and highly activated in a number of human cancers. In fact the relationship between c-Src activation and cancer progression is significant. Further Read More

Geldanamycin, an ansamycin-derivative benzoquinone compound, was originally isolated as a natural product with anti-fungal activity. Later, geldanamycin was found to have anti-proliferative activity on tumor cells transformed by oncogene kinases such as v-Src. Geldanamycin neither bind nor inhibit oncogene kinases directly, but specifically binds and inhibits a major molecular chaperone, Hsp90. Hsp90 is a highly abu Read More

Receptor and non-receptor protein tyrosine kinases (PTKs) are essential enzymes in cellular signaling processes and signal transduction pathways that regulate cell growth, differentiation, migration and metabolism by catalyzing protein phosphorylation and dephosphorylation. In recent years, different tyrosine kinase receptors were identified as regulators of tumor or tumor vessel growth. Their inhibition by specific tyrosine kin Read More

As a treatment modality for malign and certain non-malignant diseases, photodynamic therapy (PDT) involves a two step protocol which consists of the (selective) uptake and accumulation of a photosensitizing agent in target cells and the subsequent irradiation with light in the visible range. Reactive oxygen species (ROS) produced during this process cause cellular damage and, depending on the treatment dose / severity of Read More

Chemotherapy is one of the main modalities in the therapy of cancer. However, an improvement in the efficacy and a reduction in the toxicity of chemotherapeutic agents remains a great challenge to oncologists. A specific delivery of cytotoxic drugs to cancerous cells may help improving both aspects. Peptide hormones, for which receptors have been found in various human cancers, can serve as carriers for a local delive Read More

A novel tumor vaccine consisting of autologous formalin-fixed tumor fragments, cytokine-encapsulated microparticles, and an adjuvant was developed. Although mice experiments revealed mild efficacy, vaccination in a Phase I/IIa clinical trial of patients after resection of hepatocellular carcinoma resulted in significantly longer time before the first recurrence with no problematic adverse effect, than compared to historic Read More

Computational screening of compound databases has become increasingly popular in pharmaceutical research. Virtual screening approaches can roughly be divided into target structure-based screening (often referred to as docking) and screening using active compounds as templates (ligand-based virtual screening). Ligand-based screening techniques essentially focus on comparative molecular similarity analysis of compound Read More

Degeneration of inner ear cells, especially sensory hair cells and associated neurons, results in hearing impairment and balance disorders. These disabilities are incurable because loss of hair cells and associated neurons is currently irreversible. Protection or regeneration of hair cells and associated neurons is an important area of research for developing an effective treatment for inner ear diseases. Cell therapy is a rapidl Read More