Current Medicinal Chemistry - Volume 15, Issue 29, 2008

The inhibition of protein degradation through the ubiquitin-proteasome pathway is a recently developed approach to cancer treatment which extends the range of cellular targets for chemotherapy. This therapeutic strategy is very interesting since the proteasomes carry out the regulated degradation of unnecessary or damaged cellular proteins, a process that is dysregulated in many cancer cells. Based on this hypothesis, Read More

Chronic myeloid leukemia (CML) is characterized by the presence of the Philadelphia (Ph) chromosome, which results from a reciprocal translocation between the long arms of the chromosomes 9 and 22 t(9;22)(q34;q11). This translocation creates two new genes, BCR-ABL on the 22q- (Ph chromosome) and the reciprocal ABL-BCR on 9q-. The BCR-ABL gene encodes for a 210-kD protein with deregulated tyrosine ki Read More

Cancer immunotherapy targeting tumor-associated antigens is now being developed. Wilms' tumor gene WT1-encoding protein is one of the promising target antigens for cancer immunotherapy, because the gene has an oncogenic function and is expressed in many kinds of malignancies. Furthermore, a series of investigations indicated that WT1 protein was highly immunogenic in cancer patients. Based on t Read More

Recent advances in tumor biology have identified the stroma as an important regulator of carcinogenesis and potentially a valuable therapeutic target. While however the fact that by targeting the stromal component of a tumor represents a potential therapeutic strategy has been established, the knowledge for specific regulators for such interactions remains poor. The latter is largely due to the fact that appropriat Read More

Oxidative stress is implicated in the pathogenesis of a number of neurological disorders such as Alzheimer's disease (AD), Parkinson's disease (PD), multiple sclerosis and stroke in the adult as well as in conditions such as periventricular white matter damage in the neonatal brain. It has also been linked to the disruption of blood brain barrier (BBB) in hypoxic-ischemic injury. Both experimental and clinical results have shown that an Read More

Chemotherapy-induced neurotoxicity is a significant complication in the successful treatment of many cancers. Neurotoxicity may develop as a consequence of treatment with platinum analogues (cisplatin, oxaliplatin, carboplatin), taxanes (paclitaxel, docetaxel), vinca alkaloids (vincristine) and more recently, thalidomide and bortezomib. Typically, the clinical presentation reflects an axonal peripheral neuropathy with glove- Read More

Insulin-like growth factor-I (IGF-I) plays various important roles in cellular proliferation, differentiation, survival and functions of the cell, thereby contributing to the maintenance of tissue integrity. Although it is well known that growth hormone (GH) increases serum IGF-I levels by stimulating the hepatic production, little is known about the mechanism by which local production of IGF-I in individual tissues is regulated. Stimulati Read More

FLT3 is a tyrosine kinase (TK), member of the class III TK receptor family, normally expressed in hematopoietic, immune and neural systems, also playing an important role in the pathogenesis of acute leukemias, particularly acute myeloid leukemia (AML), where it is present in constitutively activated mutated forms, correlated with poor prognosis, in a notable percentage of patients. For these reasons FLT3 soon appeared as Read More

Mucous epithelia and their glands represent vital surfaces of the body which are topologically in direct contact and communicate with the environment. These highly specialized epithelia are protected by several lines of defence, such as mucous gels, regeneration and repair mechanisms, and acute inflammatory processes. Pathologically, chronic inflammation is associated with cancer. There are two different Read More