Ewa Wasilewska

Diadenylated polyols as new non-isopolar analogues of diadenosine tri- and tetraphosphates

Abstract A series of diadenosine polyphosphate-mimics were prepared based upon phosphorothioylation of the hydroxyl functions of polyols 1 and 1,3,2-oxathiaphospholane ring-opening condensation methodology.

NEW APPROACH TO THE SOLID PHASE SYNTHESIS OF N3'P5' PHOSPHORAMIDATE OLIGONUCLEOTIDES

Abstract LCA-CPG-nucleoside 5′-O-(O-β-cyanoethyl-H-phosphonates) react with 3′-amino-2′,3′-dideoxynucleoside in the presence of iodine giving in a high yield N3′→P5′ phosphoramidate oligonucleotides.

Stereochemical analysis of diastereomeric 1,3-bis(adenosine-5'-O-phosphorothioyl)glycerols.

We have published recently that 1,3-bis(adenosine-50-phosphorothioyl)glycerol (1), prepared according to the oxathiaphospholane methodology possesses stronger inhibitory activity towards FHIT protein, as compared with all known inhibitors. Fhit protein is the Ap3A hydrolase which binds and cleaves diadenosine polyphosphates and acts as a tumor suppressor. Loss of Fhit protein is among the earliest known events in the development of a variety of the most common and lethal human malignancies. Function of Fhit in tumor suppression does not require diadenosine polyphosphates cleavage but correlates with the ability to form enzyme-substrate complexes. If Fhit-substrate complexes promote tumor suppression by stimulating a pro-apoptotic effector, then Fhit inhibitors, that resemble natural substrates, may promote or antagonize Fhit function, depending on their features, in Fhit þ cells. NUCLEOSIDES, NUCLEOTIDES & NUCLEIC ACIDS Vol. 22, Nos. 5–8, pp. 797–799, 2003

The role of intestinal microflora and probiotic bacteria in prophylactic and development of colorectal cancer

The gut microbiota comprises a large and diverse range of microorganisms whose activities have a significant impact on health. It interacts with its host at both the local and systemic level, resulting in a broad range of beneficial or detrimental outcomes for nutrition, infections, xenobiotic metabolism, and cancer. The current paper reviews research on the role of intestinal microflora in colorectal cancer development. Especially a protective effect of beneficial bacteria and probiotics on the risk of cancer development is highly discussed. There is substantial experimental evidence that the beneficial gut bacteria and their metabolism have the potential to inhibit the development and progression of neoplasia in the large intestine. Most of the data derive, however, from experimental and animal trials. Over a dozen well-documented animal studies have been published, wherein it has been clearly revealed that some lactic acid bacteria, especially lactobacilli and bifidobacteria, inhibit initiation and progression of colorectal cancer. Studies on cancer suppression in humans as a result of the consumption of probiotics are still sparse. Nevertheless, some epidemiological and interventional studies seem to confirm the bacterial anticancerogenic activity also in human gut. The mechanism by which probiotics may inhibit cancer development is unknown. Probiotics increase the amount of beneficial bacteria and decrease the pathogen level in the gut, consequently altering metabolic, enzymatic and carcinogenic activity in the intestine, decreasing inflammation and enhancing immune function, which may contribute to cancer defense.

Immunomodulatory potential of probiotics oraly delivered with β- LG to Balb/C mice

Two commercial probiotics preparations were analysed regarding the possibility to induce different T cells population. Determining CD4+, CD4+CD8+ and CD8+ expression (Tab.1) one was subjected to further experiments and delivered it together with milk allergen β-LG to Balb/C mice. 14, 21, 28 and 35d from the beginning of experiments specific serum IgG&IgA, sIgA and copro-IgA were checked. We found significant decrease of humoral response in group fed with β-LG with probiotic compared to group with β-LG only, the same time increase specific copro-IgA by 35 days of experiments was observed (Fig. ​(Fig.1).1). Flow cytometry analysis of T cells subsets show significant decreased in percentage of CD8+ population in head and neck lymph nodes (HNLN) and spleen (SPL) when probiotic was delivered. In Peyers Patches elevated number of CD4+CD8+ and CD8+ T cell subsets was observed in the same group. During in vitro studies lymphocytes isolated from group β-LG+probiotic show significant increased CD8+, CD8+CD4+ compare to B-LG group. Results show that probiotics has potential to modulate immune answer to food allergens. Figure 1 Specific antibodies titer Table 1