Monica Borgatti

Plants with antitumor properties: from biologically active molecules to drugs

Abstract Medicinal plants are of great interest as starting material for identification of new biologically active compounds. A large number of low-molecular-weight compounds isolated from plants or microorganisms have already been identified as effective in diseases as diverse as HIV infection, herpes simplex, neuroblastoma, and breast cancer. Some drugs that emerged from this process are already in the late-phase clinical trials. The first step for the identification of bioactive compounds in the biomedical field is the screening of extracts from different tissues of several medicinal plants for a given activity (for instance, in vitro antiproliferative activity). To this aim, the method of extraction of bioactive compounds is crucial. The second step is the fractionation and the characterization of the plant extracts exhibiting the desired biological activity. This step takes advantage from several analytical and preparative procedures, among which preparative and analytic high-performance liquid chromatography (HPLC), several HPLC-based methods, such as HPLC/MS, gas chromatography/mass spectrometry (GC/MS), surface plasmon resonance (SPR)-based biospecific interaction analysis (BIA) employing biosensors. Applications of these methodologies to the screening, identification, purification, and characterization of bioactive compounds from medicinal plants are described in this review.

Therapy for Cystic Fibrosis Caused by Nonsense Mutations

Nonsense mutations cover about 10% of cystic fibrosis (CF) patients and generate premature termination codons (PTCs) leading to premature translational termination and causing the synthesis of truncated non-functional or partially functional CFTR (cystic fibrosis transmembrane conductance regulator) protein. The read-through approach is the suppression of translation terminations at PTCs and it has been developed as a therapeutic strategy to restore full-length protein using aminoglyco‐ side antibiotics or PTC124. Phenotypic consequences of PTCs can be exacerbated by the nonsense-mediated mRNA decay (NMD) pathway, which detects and degrades mRNA containing PTC. Therefore, modulation of NMD is also of interest as a potential target for suppression therapy. Not all PTCs are susceptible to the read-through treatment alone, especially where the nonsense mutations are combined with other CFTR mutations. For example, many CF patients present the highly frequent F508del CF mutation, causing an alteration of the cell membrane positioning of the CFTR channel. Pharmacological correctors that rescue the trafficking of F508del CFTR may overcome this defect. A combined administration of correctors/potentiators, readthrough molecules, and/or NMD inhibitors, depending on the genotype of the CF patients, could be the basis for the design of a personalized therapeutic approach.

Genetic Analyses in Health Laboratories: Current Status and Expectations

Genetic analyses performed in health laboratories involve adult patients, newborns, embryos/fetuses, pre-implanted pre-embryos, pre-fertilized oocytes and should meet the major medical needs of hospitals and pharmaceutical companies. Recent data support the concept that, in addition to diagnosis and prognosis, genetic analyses might lead to development of personalized therapy. Novel frontiers in genetic testing involve the development of single cell analyses and non-invasive assays, including those able to predict outcome of cancer pathologies by looking at circulating tumor cells, DNA, mRNA and microRNAs. In this respect, PCR-free diagnostics appears to be one of the most interesting and appealing approaches.