Bortezomib inhibits nuclear factor-kappaB dependent survival and has potent in vivo activity in mesothelioma.

Purpose: Purpose of this study has been the assessment of nuclear factor-kappaB (NF-kappaB) as a survival factor in human mesothelial cells (HMC), transformed HMC and malignant mesothelioma (MMe) cells. We aimed at verifying whether the proteasome inhibitor Bortezomib could abrogate NF-kappaB activity in MMe cells, leading to tumor cell death and may be established as a novel treatment for this aggressive neoplasm.

Experimental Design: In HMC and MMe cells, NF-kappaB nuclear translocation and DNA binding were studied by electrophoretic mobility shift assay, following treatment with tumor necrosis factor-alpha (TNF-alpha).

Renal cell carcinoma-induced immunosuppression: an immunophenotypic study of lymphocyte subpopulations and circulating dendritic cells.

Background: Renal cell carcinoma (RCC)-induced immune dysfunction in patients at first diagnosis was investigated.

Patients And Methods: The main circulating lymphocyte subsets, the total number of circulating and intratumor dendritic cells and the titers of circulating VEGF were quantified in 47 RCC patients, using flow cytometric, immunohistochemical and ELISA assays.

Results: Despite a significant activation of CD3/HLA-DR+ lymphocytes and of the CD56+ NK subset, RCC patients presented a marked immunosuppression of CD4/CD45RA naïve T-cells, CD4/CD45RO memory T-cells, CD16+ NK-cells, and total circulating dendritic cells, as well as a significant increase of lymphocytes co-expressing the CD4 and CD8 antigens.

Survivin expression, apoptosis and proliferation in chronic myelomonocytic leukemia.

We analyzed the expression of the inhibitor of apoptosis survivin by immunocytochemistry in bone marrow cells from patients with chronic myelomonocytic leukemia (CMML) to evaluate possible abnormalities in comparison with other myelodysplastic (MDS) and myeloproliferative syndromes, and to investigate a possible correlation between survivin expression and altered apoptosis or proliferation, or relevant laboratory and clinical findings. Thirty-four patients with CMML [18 MDS-CMML and 16 myeloproliferative disorder (MPD)-CMML], 90 with MDS, 41 with acute myeloid leukemia (AML), 19 with chronic MPD and 25 control subjects were studied. In normal samples survivin was never detectable.

Autoimmunity in thrombotic thrombocytopenic purpura.

In the last few years, an autoimmune hypothesis for the pathogenesis of thrombotic thrombocytopenic purpura (TTP) has been proposed often, with variable success because of inconsistent supporting data. We are now aware that at least one subgroup of TTP patients does present with pathogenic autoantibodies (i.e, anti-ADAMTS13); this group consequently is a putative candidate for a curative treatment including plasma exchange (still the cornerstone of TTP treatment), together with corticosteroids or other immunosuppressants.

Interleukin-2 induces cell cycle perturbations leading to cell growth inhibition and death in malignant mesothelioma cells in vitro.

Previous report indicated that Interleukin-2 (IL-2) is able to inhibit the growth of IL-2-receptor-positive cancer cell lines without any involvement of the immune system, through IL-2-induced alterations of the cell cycle kinetics. In this study we provide evidence that IL-2 exerts anti-proliferative effect on three human malignant mesothelioma (MMe) cells in vitro, while no effects were observed on normal human mesothelial cell (HMC) primary cultures. The growth inhibitory effect of IL-2 on neoplastic cells appeared to depend on the baseline proliferative status of these cells.

Circulating progenitor cell release and functional characterization after topotecan plus G-CSF and erythropoietin in small cell lung cancer patients.

Topotecan is a new antineoplastic agent active in ovarian cancer, with promising activity in small cell lung cancer and predictable toxicity. As a part of our ongoing attempt to optimize the use of disease-specific drugs as circulating progenitor cell (CPC) priming in solid tumors, we have evaluated the effects on CPC release of single-agent Topotecan followed by granulocyte colony-stimulating factor (G-CSF) + human recombinant erythropoietin (rhEPO), together with the cell cycle status of the collected CD34+ cells. Ten pretreated patients with small cell lung cancer received Topotecan (1 mg/m2, i.

Relationship between size and thiazole orange fluorescence of platelets in patients undergoing high-dose chemotherapy.

The reticulated platelet count relies upon the assumption that newly formed platelets contain a residual amount of RNA which selectively binds the dye thiazole orange (TO) and greatly enhances its fluorescence signal. It has, however, recently been shown that almost half of the platelet TO-signal is derived from the labelling of dense-granule nucleotides. It is therefore possible that the higher TO fluorescence of young platelets partially derives from the higher granule content due to their larger volume.

The myelodysplastic syndromes: predictive value of eight prognostic systems in 143 cases from a single institution.

Background And Objective: Despite the fact that several prognostic systems for myelodysplastic syndromes (MDS) have been proposed, few studies have been designed to test their effectiveness in independent patient populations. The aim of this study was to compare the prognostic value of 8 previously described prognostic systems in a series of consecutive MDS patients observed at a single institution over a 10-year period.

Design And Methods: One hundred and forty-three patients were diagnosed as having myelodysplastic syndrome (MDS) according to the French-American-British (FAB) criteria.