Previous studies from this laboratory have demonstrated that down-regulation of the standard CD44 isoform at the mRNA and protein level is associated with the acquisition of high metastatic ability within the Dunning R-3327 system of rat prostate cancers. Additional studies demonstrated that transfection-induced enhanced expression of the standard CD44 isoform suppresses the metastatic ability ...

Abnormal myelination underlies the pathology of white matter diseases such as preterm injury and multiple sclerosis. Osteopontin (OPN) has been suggested to play a role in myelination. Murine OPN mRNA is translated into secreted isoform (sOPN) or an intracellular (iOPN). Whether there isoform-specific involvement unknown. Here we generated mouse models that either lacked both isoforms all cells...

The AKT kinase family is a high-profile target for cancer therapy. Despite their high degree of homology the three isoforms (AKT1, AKT2 and AKT3) are non-redundant can even have opposing functions. Small-molecule inhibitors affect all which severely limits usefulness as research tool or therapeutic. Using AKT2-specific nanobodies we examined function endogenous in breast cells. Two (Nb8 Nb9) mo...

Recent studies have shown that the RNA binding protein Musashi 2 (Msi2) plays important roles during development. Msi2 has also been shown to be elevated in several leukemias and its elevated expression has been linked with poorer prognosis in these cancers. Additionally, in embryonic stem cells (ESC) undergoing the early stages of differentiation, Msi2 has been shown to associate with the tran...

The μ-opioid receptor (MOR) is the primary target for opioid analgesics. MOR induces analgesia through the inhibition of second messenger pathways and the modulation of ion channels activity. Nevertheless, cellular excitation has also been demonstrated, and proposed to mediate reduction of therapeutic efficacy and opioid-induced hyperalgesia upon prolonged exposure to opioids. In this mini-pers...

We have studied a new sample of 276 NIDDM patients from the population of Penne (Italy). Comparison of the new data with those of 214 diabetic pregnant women from the population of Rome reported in a previous paper has shown that the pattern of association between low molecular weight acid phosphatase genotype and degree of glycemic control is similar in the two classes of diabetic patients. Am...

Deoxyguanosine kinase (dGK) is a nuclear gene product that catalyzes the phosphorylation of purine deoxyribonucleosides and their analogues. The human enzyme is located predominantly in the mitochondria, as shown by biochemical fractionation studies and in situ localization of the overexpressed recombinant protein. Here we describe the cloning of mouse dGK cDNA and the identification of a novel...

Abstract Phosphorylated H2A.X is a critical chromatin marker of DNA damage repair (DDR) in higher eukaryotes. However, gene expression remains relatively uncharacterised. Replication-dependent (RD) histone genes generate poly(A)- mRNA encoding new histones to package during replication. In contrast, replication-independent (RI) synthesise poly(A)+ throughout the cell cycle, translated into vari...

Enzymes AKR1C regulate the action of oestrogens, androgens, and progesterone at pre-receptor level are also associated with chemo-resistance. The activities these oestrone halides were investigated on recombinant enzymes. halogen atoms both C-2 C-4 positions (13?-, 13?-methyl-17-keto derivatives) most potent inhibitors AKR1C1. lowest IC50 values for 13?-epimers 2_2I,4Br 2_2I,4Cl (IC50, 0.7 ?M, ...