Current Cancer Drug Targets - Volume 10, Issue 2, 2010

Sarcomas are malignant mesenchymal tumors of variable aggressiveness characterized by a substantial invasive and metastatic potential. In this review we discuss current results of pharmacological targeting of Rho/ROCK signaling in tumor cells, and the growing evidence supporting the hypothesis that Rho/ROCK dependent amoeboid mode of invasion could play a substantial role in metastatic potential of cells of maligna Read More

FOXO proteins are evolutionarily conserved transcription factors implicated in several fundamental cellular processes, functioning as end-point for transcriptional programs involved in apoptosis, stress response and longevity. Abrogation of FOXO function is very frequent in human cancer, therefore the mechanisms of regulation of the FOXO proteins are receiving increasing attention in cancer research. The FOXO proteins i Read More

Among endocrine disruptors, the xenoestrogen bisphenol A (BPA) is of particular interest due to the very high production and widespread environmental contamination. We recently demonstrated that the oral administration of BPA to mice results in the formation of DNA adducts not only in liver but also in mammary tissue. The present study aimed at evaluating the modulation of BPA-related DNA adducts and proteo Read More

To determine the effect of dexamethasone on the antimyeloma effects of lenalidomide, we tested in vitro proliferation, tumor suppressor gene expression, caspase activity, cell cycling, and apoptosis levels in a series of multiple myeloma (MM) and plasma cell leukemia cell lines treated with lenalidomide and dexamethasone, alone or in combination. The effect of dexamethasone on the immunomodulatory activities of lenalid Read More

Lapatinib, a dual HER2 and EGFR tyrosine kinase inhibitor is highly active in HER2+ breast cancer. However, its efficacy is limited by either primary or acquired resistance. Although mutations in ras genes are rarely found in breast cancer, H-ras overexpression is frequently observed. Moreover, genetic alterations that do not directly involve ras such as Brk amplification, ultimately result in increased ras signaling. Using SKBR3 cell Read More

Altered EGFR activity is a causal factor for human tumor development, including malignant pleural mesotheliomas. The aim of the present study was the evaluation of the effects of Gefitinib on EGF-induced mesothelioma cell proliferation and the intracellular mechanisms involved. Cell proliferation, DNA synthesis and apoptosis were measured by MTT, thymidine incorporation and FACS analysis; EGFR, ERK1/2 and Akt ex Read More

This paper reports the synthesis of a panel of small molecules with arylamides and arylsulfonamides groups and their biological activity in inhibiting nucleotide exchange on human Ras. The design of these molecules was guided by experimental and molecular modelling data previously collected on similar compounds. Aim of this work is the validation of the hypothesis that a phenyl hydroxylamine group linked to a second aromati Read More

In the development of novel immune therapies for high-risk cancers, one goal is to find tumor targets that are not widely shared by normal cells. One such target is the surface disialoganglioside GD2. This antigen is expressed on the surface of a variety of tumors for which no curative therapies exist for patients with advanced disease. In childhood, the most common GD2-expressing tumor is neuroblastoma. GD2 is also Read More

Alterations in genomic and non-genomic mechanisms can disturb homeostasis and cause severe human diseases. Histone deacetylases (HDACs) are epigenetic regulators which catalyze the removal of acetyl moieties from histones and non-histone proteins. Aberrant histone deacetylation, due to increased HDAC activity and expression, often correlates with pathological gene repression and neoplastic transformation. There Read More

Whole unfractionated heparin can modestly decrease tumor growth, but the dose of heparin is limited by its anticoagulant properties. To overcome this limitation, we modified the chemical structure of heparin and have prepared a heparin derivative by O-acylating low molecular weight heparin with butyric anhydride, producing a more potent antiproliferative compound, which is only weakly anticoagulant so that the dose may b Read More

The sodium iodide symporter (NIS) is responsible for thyroidal, salivary, gastric, intestinal and mammary iodide uptake. It was first cloned from the rat in 1996 and shortly thereafter from human and mouse tissue. In the intervening years, we have learned a great deal about the biology of NIS. Detailed knowledge of its genomic structure, transcriptional and post-transcriptional regulation and pharmacological modulation has un Read More