Natural antisense transcripts are endogenous transcripts that contain sequences that are complementary to other transcripts. Such complementary transcripts may be transcribed from opposing DNA strands at the same genomic locus (cis), or from different loci (trans), for example, pseudogenes. Notably, both types of antisense RNAs are genome-encoded and transcribed by DNA-directed RNA polymerases. A third putative source of antisense RNAs is transcription of the sense mRNA by an RNA-dependent RNA polymerase (Volloch et al., 1996).

Although only a few examples have been studied in detail (reviewed in Kumar and Carmichael, 1998; Lavorgna et al., 2004), a significant number of naturally occurring ... Read more

A major obstacle to the development of gene therapy for cancer has been the inability to specifically and systemically deliver gene therapy vectors throughout the body to primary and/or metastasized tumor cells. Although intratumor injections of gene therapy vectors have sometimes been possible, no viral vector has been available that could be administered systemically and would selectively and efficiently target tumors without infection of normal tissues. Furthermore, even when locally injected, many viral vectors end up at high concentrations in the liver, because many cells of the body have low receptor numbers for some of the vectors in current use, ... Read more

All screening approaches rely on ways of compartmentalizing assay reactions, and means of rapidly screening various molecules imbedded in these compartments. Miniaturization, which has become the hallmark of modern science and technology, has also been applied to screening, thus leading to a variety of high-throughput screening (HTS) technologies that aim at the smallest possible reaction volumes and the most sensitive and rapid means of detection. These demands are general and do not depend on the type of molecules (genes, proteins, small molecules, etc.) or activity (enzymatic, binding, inhibitory, etc.) that are being screened for, nor on the target of screening ... Read more

Current methodologies for single nucleotide polymorphism (SNP) screening often require amplification, followed by time-consuming enzymatic manipulation (e.g., digestion or extension) and separation of the resultant products. Advancements in real-time PCR methods (Walker, 2002) permit simultaneous amplification and quantification. Unfortunately, the ability to provide quantitative determinations can be made difficult by factors such as non-specific amplification and alterations in amplification efficiency owing to secondary-structure and sample matrix effects. Newer sensor and microarray technologies attempt to facilitate SNP analysis but usually require several hours for hybridization and data analysis. Furthermore, microarrays often cannot be reused as a result of limitations in the ... Read more

By identifying the proteins (normal or oncogenic), which participate in the development of malignant diseases, we can identify novel targeted therapies to either stabilize or treat the disease. The approach is common to all: identification of targets, establishment of models, definition of pre-requisites for clinical transfer and surrogate markers for evaluation of in vivo efficacy. We have used animal models of myeloid leukemia using a genetic approach in order to understand the biology of leukemogenesis and to develop targeted approaches to therapy. These models are now developed and are ready for testing various different therapeutic strategies. There are good molecular ... Read more

The Human Genome Project has produced a map detailing a vast genetic frontier that will continue to provide useful insights for the treatment of human diseases. The large number of uncharacterized genes reflects the degree of our progress and the wealth of opportunity. Functional genomics will broadly impact our understanding of disease and illuminate the path to better therapeutics.

One of the most definitive ways to determine gene function is to specifically inactivate a gene through knockout approaches, thereby permitting comparisons between genetically matched (i.e., isogenic) knockout and wild-type controls. Gene knockout technologies have been performed in a variety of model ... Read more

Problems associated with conventional cancer therapy are numerous, but two stand out: lack of specificity and the inability to totally eradicate all cancerous cells. The former leads to severe, sometimes intolerable, adverse effects, whereas the latter contributes to the dismal prognosis for a variety of cancer types.

Effective cancer therapy should consist of components targeting both normoxic and hypoxic tumor tissues.

The progression of solid tumors requires a sufficient blood supply to deliver both nutrients and oxygen. However, the growth rate of malignant tumors often outpaces angiogenesis. In addition, the tumor vasculature is often poorly organized and leaky in nature. Consequently, the ... Read more

The holy grail of drug development is to design a magic bullet that will deliver a therapeutic agent only to the site of disease with minimal side effects. This is of great importance in particular when it refers to biological agents such as cytokines that have pleiotropic actions in different tissues.

Cytokines are local mediators of cell-to-cell communication. Their expression is transient and they have a short half-life. Therefore, to overcome the pharmacokinetic limitations of cytokines, they are given subcutaneously to reduce side effects. However, by this route they lose their potency. In order to use cytokines for therapeutic purposes they ... Read more

The tumor suppressor protein p53 is crucial in preventing cancer as well as for achieving the therapeutic effects of both radiotherapy and much of chemotherapy. p53 responds to oncogene activation, DNA damage, hypoxia and other stresses by activating the expression of factors that trigger cell cycle arrest or programmed cell death (Vogelstein et al., 2000). Strong evidence that inactivation of p53 is required for cancer cell survival comes from accumulated data that p53 is inactivated by mutations in some 50% of all human tumors, regardless of patient age or tumor type. This makes p53 the most frequently mutated gene in ... Read more

Other Names: abarelix.

Maker: Praecis Pharmaceuticals.

Disease Treated: Men with advanced prostate cancer who refuse surgical castration and yet for whom treatment with gonadotropin-releasing hormone (GnRH) agonist is not appropriate.

Approval Status: Approved by the U.S. FDA on November 25, 2003.

Chemical/Biological Nature: PLENAXIS is a synthetic decapeptide, consisting of both natural and artificial amino acids, of 1,416 daltons. It is supplied as a sterile powder which, when mixed with a 0.9% sodium chloride solution, becomes a depot suspension ready for intramuscular injections.

Administration: The single-dose vial of PLENAXIS contains 113 mg of anhydrous peptide and is reconstituted with 2.2 ml of sodium chloride solution. ... Read more