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CAF-1 is a proliferation marker in various malignant tumours with prognostic value in renal, endometrial and cervical carcinomas, which supports the value of CAF-1 as a clinical marker of cancer progression.

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These results suggest a positive association between the most reactive and palest skin types and NHL or HL in men and do not rule out a slight negative relationship between UV exposure and LM.

Many children with steroid-dependent nephrotic syndrome (NS) have significant sequelae despite steroid-sparing therapies. Levamisole may reduce short-term relapse frequency (RF) with minimal side effects. Little data exist, however, as to its long-term effect. To assess both short- and long-term efficacy in NS, RF and cumulative annual steroid burden were quantified in ten consecutive children with steroid-dependent NS treated with levamisole. Data were analyzed for three time periods: 1 year prior to levamisole therapy (Pre-Lev), during 1 year of levamisole therapy (During-Lev), and the year after cessation of all levamisole therapy (Off-Lev). Median RF fell from 6.0 (4.0-9.0) relapses/patient per year Pre-Lev to 0.0 (0.0-4.0) During-Lev (p = 0.002) with 6/10 patients having no relapse and 0.5 (0.0-8.0) Off-Lev (p = 0.01) with 5/10 patients without relapse. Concurrently, cumulative annual steroid burden fell from 6,067 (1,660-8,691) mg/m(2) per year Pre-Lev to 2,920 (782-5,271) During-Lev (p = 0.002) and 716 (0-3,637) Off-Lev (p = 0.002). In 4/5 hypertensive children, blood pressure normalized During-Lev. Somatic indices also improved: height Z scores, which fell from 0.8 (-2.4 to 3.6) at diagnosis to -0.6 (-2.7 to 0.4) Pre-Lev (p = 0.004), remained stable at -0.6 (-3.0 to 0.6) after 1 year of therapy and -0.5 (-2.6 to 0.2) Off-Lev. Height velocity improved from 3.0 (0.3-6.0) cm/year Pre-Lev to 3.7 (0.0-8.0) cm/year During-Lev and 5.4 (0.0-9.1) Off-Lev. We conclude that levamisole is an effective short- and long-term steroid-sparing agent in pediatric NS.

Progressive restriction to a differentiation pathway results from both activation and silencing of particular gene expression programs. To identify the coexpression and the expression levels of regulatory genes during hematopoietic stem cell (HSC) differentiation toward the T cell branch, we applied a new single-cell RT-PCR technique to analyze the simultaneous expression of 13 genes in 9 functionally purified populations from the bone marrow and the thymus. We report in this paper that Lin−Sca1+ckit+ HSCs display, at the single-cell level, a homogeneous and high transcriptional activity as do early thymic progenitors. Moreover, the coexpression of lymphoid and myeloid genes is an early event detected in ∼30% of short-term HSC and most multipotent progenitors, suggesting novel sources for the generation of early thymic progenitors, common lymphoid progenitors (CLPs), and common myeloid progenitors. Loss of multipotency in Lin−Sca1+ckit+ cells directed to the lymphoid branch is characterized by Lmo2 and Gata2 gene expression downregulation. Indeed, highest levels of Gata2 expression are detected only in long-term and short-term HSC populations. Complete shutdown of Pu1 gene expression in all triple-negative (TN)3 stage thymic pre-T cells is indicative of total T cell commitment. Interestingly, this is also observed in 30% of TN2 cells and 25% of CLP in the bone marrow, suggesting a possible initiation of T cell engagement in TN2 and CLP. Also, our strategy highlights similar gene patterns among HSCs and intrathymic progenitors, proposing, therefore, that identical activation signals are maintained until further maturation and generation of CD4 and CD8 coreceptors bearing thymocytes.

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