Over the last decade, the advances in the high-throughput omic technologies have given the possibility to profile tumor cells at different levels, fostering the discovery of new biological data and the proliferation of a large number of bio-technological databases. In this paper we describe a framework for enabling the interoperability among different biological data sources and for ultimately supporting expert users in the complex process of extraction, navigation and visualization of the precious knowledge hidden in a such huge quantity of data. In this framework, a key role is played by the Connectivity Map, a databank which relates diseases, physiological processes, and the action of drugs. The system will be used in a pilot study on the Multiple Myeloma (MM).

Biological targets, such as proteins and nucleic acids, are chiral, therefore stereoisomers of chiral molecules interact with these targets differently and, indeed, the antitumor drug oxaliplatin contains only one enantiomer (R,R) of its 1,2-cyclohexanediamine (DACH) ligand. In this review article we illustrate the effect of chirality in platinum drugs in relation to different aspects spanning from cytotoxicity to mutagenicity, from differences in the reaction with DNA and processing of DNA lesions to gene expression and proteomic profile, to conclude with a section on the use of platinum compounds with chiral amines to investigate non-covalent interactions in adducts of platinum drugs with nucleotides and DNA. Unlike the deep understanding of the interactions at a molecular level which has allowed us to interpret the different antitumor activity and mutagenicity of DACH enantiomers and to propose an explanation for the particularly high efficacy of cisplatin toward the testis tumor, it is noted that “omics” investigations are still scanty and a reassessment of chirality effects, through molecular profiling technologies, would be timely as well as appropriate.

BACKGROUND: Multiple myeloma (MM) is a cancer of terminally differentiated plasma that is part of a spectrum of blood diseases. The role of the micro-environment is crucial for MM clonal evolution. METHODS: This paper describes the analysis carried out on a limited number of genes automatically extracted by a nonnegative matrix factorization (NMF) based approach from gene expression profiles of bone marrow fibroblasts of patients with monoclonal gammopathy of undetermined significance (MGUS) and MM. RESULTS: Automatic exploration through NMF, combined with a motivated post-processing procedure and a pathways analysis of extracted genes, allowed to infer that a functional switch is required to lead fibroblasts to acquire pro-tumorigenic activity in the progression of the disease from MGUS to MM. CONCLUSION: The extracted biologically relevant genes may be representative of the considered clinical conditions and may contribute to a deeper understanding of tumor behavior.

IntroductionTumor Cell Growth Inhibition and Cell Death Screening AssaysMetal-Based Anticancer Compounds and Gene Expression Microarray TechnologiesMetal-Based Anticancer Compounds and the Proteomic ApproachConcluding Remarks

Advances of high throughput technologies have yielded the possibility to investigate human cells of healthy and morbid ones at different levels. Consequently, this has made possible the discovery of new biological and biomedical data and the proliferation of a large number of databases. In this paper, we describe the IS-BioBank (Integrated Semantic Biological Data Bank) proposal. It consists of the realization of a framework for enabling the interoperability among different biological data sources and for ultimately supporting expert users in the complex process of extraction, navigation and visualization of the precious knowledge hidden in such a huge quantity of data. In this framework, a key role has been played by the Connectivity Map, a databank which relates diseases, physiological processes, and the action of drugs. The system will be used in a pilot study on the Multiple Myeloma (MM).