Current Drug Targets - Volume 6, Issue 6, 2005

Although the hematological malignancies constitute a minor fraction of the total number of newly diagnosed cancers per year, they pose a substantial burden to the individual patient. In general neoplasias affecting the lymphohematopoietic system carry a poor prognosis with median 5- year survival rates usually below 50-60%, and some are still considered incurable, like chronic lymphoid leukemia and multiple myeloma Read More

Enduring efforts into determination of the molecular biological status of acute myelogenous leukaemia (AML), a stem cell disease characterised by distinct blastic differentiation blocks and their extensive growth, continue to provide us with prognostically important information for more than half of all patients. In subsets of AML, molecular diagnostics rigorously guide the clinician toward the choice of optimal therapy. The in-depth Read More

Selective gene silencing by nucleic acid enzymes has provided researchers with a new strategy to block gene expression and drug target validation. Ribozymes, DNAzymes and small interfering RNAs (siRNAs) are being explored as genetic inhibitors of gene expression as well as potential therapeutics against viral infections, inflammatory disorders, haematological diseases and cancers. We review the mode of action of the Read More

In several cases of immunodeficiency and autoimmunity, the dysfunctional immune system is associated with either hypo- or hyperactive T and B cells. In autoimmune conditions such as systemic lupus erythematosus (SLE) and immunodeficiencies such as acquired immunodeficiency syndrome (AIDS), it has been demonstrated that the regulatory effect of the signaling pathway of cyclic 3', 5' adenosine monophosphate Read More

The heterogeneity of proteoglycans (PG)s contributes to their functional diversity. Many functions depend on their ability to bind and modulate the activity of components of the extracellular matrix (ECM). The ability of PGs to interact with other molecules, such as growth factors, is largely determined by the fine structure of the glycosaminoglycan (GAG) chains. Tumorigenesis is associated with changes in the PG synthesis. Read More

Angiogenesis is essential for tumor growth and metastasis. This is firmly established in solid tumors, but accumulating evidence suggests that this is also an important event in hematological neoplasias. Angiogenesis is therefore a putative target for therapy. The potential application of different angiogenesis inhibitors is currently under intense clinical investigation, and we will here review a number of these trials. The association Read More

One of the most characteristic features of multiple myeloma is the development of osteolytic bone lesions. Myeloma-associated bone disease is caused by an increase in osteoclastic bone resorption and a decrease in osteoblastic new bone formation. Insight into the molecular mechanisms of osteoclastogenesis has been provided by the detection of receptor activator of NF-kB ligand (RANKL), its specific receptor (RANK) and Read More

The myelodysplastic syndromes (MDS) constitute a group of clonal stem cell disorders characterized by cytopenia, ineffective hematopoiesis, bone marrow dysplasia, and a risk of progression to acute myeloid leukemia (AML). Disease mechanisms can be divided into two main groups; those underlying the increased apoptosis of bone marrow progenitors, and those associated with progressive blast proliferation, and transfor Read More