Si113-prodrugs selectively activated by plasmin against hepatocellular and ovarian carcinoma.

Si113, a pyrazolo[3,4-d]pyrimidine derivative, gained more attention as an anticancer agent due to its potent anticancer activity on both in vitro and in vivo hepatocellular carcinomas (HCC) and ovarian carcinoma models. But the drawback is the low water solubility which prevents its further development. In this context, we successfully overcame this limitation by synthesizing two novel prodrugs introducing the amino acid sequence D-Ala-Leu-Lys (TP).

Efficient optimization of pyrazolo[3,4-d]pyrimidines derivatives as c-Src kinase inhibitors in neuroblastoma treatment.

The proto-oncogene c-Src is a non-receptor tyrosine kinase which is involved in the regulation of many cellular processes, such as differentiation, adhesion and survival. c-Src hyperactivation has been detected in many tumors, including neuroblastoma (NB), one of the major causes of death from neoplasia in infancy. We already reported a large family of pyrazolo[3,4-d]pyrimidines active as c-Src inhibitors.

Pyrazolo[3,4-d]pyrimidines-loaded human serum albumin (HSA) nanoparticles: Preparation, characterization and cytotoxicity evaluation against neuroblastoma cell line.

Pyrazolo[3,4-d]pyrimidine derivatives 1-5, active as c-Src inhibitors, have been selected to be formulated as drug-loaded human serum albumin (HSA) nanoparticles, with the aim of improving their solubility and pharmacokinetic properties. The present study includes the optimization of a desolvation method-based procedure for preparing HSA nanoparticles. First, characterization by HPLC-MS and Dynamic Light Scattering (DLS) showed a good entrapment efficacy, a controllable particle size (between 100 and 200nm) and an optimal stability over time, confirmed by an in vitro drug release assay.

Metformin and breast cancer: basic knowledge in clinical context.

Although preclinical work is vital in unraveling the molecular tenets which apply to metformin action in breast cancer, it is by nature unable to capture the host's response to metformin in terms of insulin-mediated effects and related changes in the hormonal and metabolic asset at the systemic level. The latter might sound seemingly paradoxical when considering the inveterate use of metformin in dysmetabolisms and pathologic conditions with underlying hormonal disruption. Bridging the gap between the molecular target and characteristics of breast cancer patients may help lab-based experiments and clinical work converge into one or more well characterized sub-populations instead of a sub optimally selected one.

p53 status as effect modifier of the association between pre-treatment fasting glucose and breast cancer outcomes in non diabetic, HER2 positive patients treated with trastuzumab.

Mounting evidence supports the role of p53 in metabolic processes involved in breast carcinogenesis. We investigated whether p53 status affects the association of pre-treatment fasting glucose with treatment outcomes in 106 non diabetic, HER2 positive breast cancer patients treated with trastuzumab. p53 status was validated against gene sequencing of selected codons in 49 patients.

A novel dual signaling axis for NSP 5a3a induced apoptosis in head and neck carcinoma.

NSP 5a3a is a novel structural protein found to be over-expressed in certain cancer cell lines in-vitro such as Hela, Saos-2, and MCF-7 while barely detectable levels in normal body tissues except for Testis. This particular isoform has been known to interact with cyto- nuclear proteins B23, known to be involved in multi-faceted cellular processes such as cell division, apoptosis, ribosome biogenesis, and rRNA processing, as well as with hnRNP-L, known to be involved with RNA metabolism and rRNA processing. A previous preliminary investigation of NSP 5a3a as a potential target in Head and Neck Carcinoma revealed a novel p73 dependent mechanism through which NSP 5a3a induced apoptosis in Head and Neck cell lines when over-expressed in-vitro.

Possible functional role of NSPs in cancer.

Since the discovery of several distinct yet similar cDNA clones encoding novel structural proteins an initiative was taken to investigate their role in tumorigenesis. Sequence analysis revealed that these cDNAs correspond to locus HCMOGT-1 located at chromosome 17p11.2.

MyoD recruits the cdk9/cyclin T2 complex on myogenic-genes regulatory regions.

During skeletal myogenesis, muscle-regulatory factors bHLH and MEF2 promote the expression of muscle-specific genes by recruiting several chromatin-modifying complexes on specific DNA regulatory sequences. A number of MyoD-interacting proteins have been reported, but whether they are recruited to the chromatin of myogenic loci, and the relationship with other chromatin bound proteins is unknown. We show that MyoD recruits cdk9/cyclin T2, together with the histone acetyltransferases p300 and PCAF, and the chromatin remodeling complex SWI/SNF, on promoters and enhancers of muscle-specific genes, and that this event correlates with the acetylation of histone tails, remodeling of chromatin, and phosphorylation of the C-terminal domain (CTD) of the RNA polymerase II at these elements.