IFN-alpha 2B enhances Th1 cytokine responses in bladder cancer patients receiving Mycobacterium bovis bacillus Calmette-Guérin immunotherapy

Combination therapy with intravesical bacillus Calmette-Guérin (BCG) plus IFN-alpha for superficial bladder cancer has been demonstrated to be more effective than either single agent alone in animal studies and of suggested greater efficacy in clinical studies. However, the mechanism by which IFN-alpha enhances BCG-mediated antitumor activity is poorly understood. Using PBMCs from bladder cancer patients, IFN-alpha was found to substantially enhance the efficacy of BCG to induce IFN-gamma production. Among 34 patients tested, 80% showed >4-fold increase. This effect of IFN-alpha was observed in both initial and memory responses to BCG. In addition, IFN-alpha up-regulated BCG-induced IL-12 and TNF-alpha and down-regulated BCG-induced IL-10. Neutralizing endogenous IL-10 or adding exogenous IL-12 provided further synergy for IFN-gamma production. In clinical practice, intravesical IFN-alpha 2B (50 million units (MU)/dose) was observed to accelerate urinary IFN-gamma production to low-dose BCG (one-tenth or one-third of a full dose) in patients treated with combination therapy compared with BCG alone. These results suggest that IFN-alpha is a potent BCG enhancer that polarizes the BCG-induced immune response toward the cellular immune pathway by promoting Th1 cytokine expression and reducing Th2 cytokine expression. This study provides an immunological basis for future rational use of IFN-alpha in conjunction with intravesical BCG for bladder cancer immunotherapy.     

Microstructure and chemical degradation of adobe and clay bricks

The environmental degradation of adobe and fired clay brick was studied. Leaching media based on Na₂S₂O₅ solution and deionized water were used. The microstructure of the samples was evaluated by X-ray powder diffraction, nitrogen adsorption–desorption (BET method), Fourier transform infrared spectroscopy and scanning electron microscopy. The predominant phases detected were kaolinite and quartz for both the adobe and fired brick samples. The high surface reactivity, associated with a large amount of OH groups, contributes to the significant degradation of adobe. The fired clay brick showed a significant decrease in the average pore diameter after the first day of the leaching process; its specific surface area exhibited a reduction of about three orders of magnitude. The results of the present investigation contribute to a better understanding of the correlation between structure and leaching behaviour in adobe and clay brick, attending the renewed interest in these materials as environmentally attractive building blocks.     

Measurement of distributions of small-scale energy depositions from low-linear energy transfer particles using the superheated drop detector

We have developed a new detection method for measuring distributions of energy depositions from particles characterized by low linear energy transfers (LETs). In particular, we have developed a detection system to measure energy depositions produced by electrons and photons on nanometer scales. The detector is based upon the operational principles of the superheated drop detector (SDD). SDDs consist of tiny droplets of superheated liquid suspended within a gel-like emulsion. The SDDs in this study are fabricated using Freon-115 and a glycerol-based gel as the superheated liquid and host medium. This SDD configuration is operated as a threshold temperature-dependent detector for measuring nanoscopic distributions of energy depositions from low-LET particles. Measured results are compared to the calculated distributions of energy depositions along an electron track. A new electron track code, ESLOW3.1, is used to perform the computational study. Measurements show good agreement with computational results in the energy deposition range of 40-200 eV.     

Expression of the Evi-1 gene in haemopoietic cells of children with juvenile myelomonocytic leukaemia and normal donors

Activation of the Evi-1 gene was first described to be associated with the transformation of murine myeloid leukaemias and has previously been detected in cases of human acute myeloid leukaemia (AML) and chronic myeloid leukaemia (CML) in blast crises and in myelodysplastic syndromes. In this study we determined the frequency and the level of Evi-1 expression in juvenile myelomonocytic leukaemia (JMML) and in normal haemopoiesis. Using RT-PCR and Southern blot hybridization mRNA of Evi-1 could be detected in bone marrow (BM) and peripheral blood (PB) mononuclear cells (MNC) of normal donors. In JMML 12/20 patients examined expressed elevated levels of Evi-1 compared to normal controls. In these samples over-expression of the gene was correlated with a higher percentage of blasts (P = 0.02). Expression levels in BFU-E and CFU-GM derived colonies from BM of JMML patients were lower than those in the corresponding MNC samples. Analysis of CD34+ and CD34- cells demonstrated that Evi-1 is primarily expressed in the CD34+ cell population of both JMML and normal donors. These findings suggest that Evi-1 expression is linked to the early stages of haemopoiesis. Studies on the regulation of Evi-1 expression in CD34+ cells will elucidate its function in progenitor cells and clarify its possible role in the pathogenesis of JMML.     

Stereochemical influence on the stability of radio-metal complexes in vivo. Synthesis and evaluation of the four stereoisomers of 2-(p-nitrobenzyl)-trans-CyDTPA

Distinct differences in in vivo stability of the two diastereomeric C-Functionalized CyDTPA chelating agents, (CHX-A DTPA and CHX-B DTPA, both racemates), as recently reported prompted further investigation as to why differences in configuration produced striking effects on the in vivo stability of their yttrium complexes. To this end, the four individual component stereoisomers of CHX-A and CHX-B were synthesized and ability to bind yttrium was investigated both in vitro and in vivo.