Local lymph node involvement in pediatric renal cell carcinoma: A report from the Italian TREP project

Background. One of the most important adverse prognostic factors for adult renal cell carcinoma (RCC) is the retroperitoneal lymph node involvement. The aim of this article is to study the prognostic significance of local lymph node involvement in pediatric RCC and the role of retroperitoneal lymph node dissection (RLND) at diagnosis. Procedure. The series included 16 patients with RCC and lymph nodes involvement registered in the Italian Rare Tumors Pediatric Age (TREP) project, accounting for 26.2% of 61 pediatric RCC observed at AIEOP centers. Results. A radical nephrectomy was performed in all cases: at diagnosis in 12 cases, after preoperative chemotherapy (CT) in 4 cases. As a part of the same procedure 9 patients underwent RLND, and 7 received a more limited lymph nodes resection. Five (31.2%) developed disease recurrence 2-34 months after diagnosis (median, 6 months) plus 1 developed progression; 6 patients died, 1 of them from secondary leukemia. Among the nine patients receiving RLND, eight are alive and disease free. This compares with only one patient surviving among the seven receiving a more limited lymph nodes resection. The estimated 25-year PFS and OS rates for all patients were 61.4% (95% CI 33.2-80.5) and 50.8% (95% CI 16.5-77.5), respectively. Conclusions. Lymph node involvement is an unfavorable prognostic factor in children with RCC. RLND appears to be a critical factor to improve the outcome. However, when compared to similar adult patients, the outcome in children appears to be better, suggesting that pediatric RCC, or the host, may be critical differences. © 2008 Wiley-Liss, Inc

Artificial Antigen Presenting Cells With Preclustered anti-CD28/-CD3/-LFA-1 Monoclonal Antibodies Are Highly Effective To Induce The Ex-Vivo Expansion Of Functional Human Antitumor T Cells

Effective adoptive T cell therapy requires the _ex vivo_ generation of functional T lymphocytes with a long lifespan _in vivo_. We evaluated _in vitro_ T cell expansion by artificial antigen presenting cells (aAPC) generated with activating (human anti-CD3), co-stimulating (human anti-CD28) and adhesion (human anti-LFA-1) monoclonal antibodies pre-clustered in microdomains (MDs) held by a liposome scaffold. The co-localization of T cell ligands in MDs and the targeting of an adhesion protein, increasing the efficiency of immunological synapse formations, represent the novelties of our system. These aAPCs allowed increased expansion of polyclonal CD4^+^ and CD8^+^ T cells and of tumor antigen-specific CD8^+^ T cells compared to anti-CD28- and anti-CD3-coated microbeads and to immobilized anti-CD3. These aAPCs allowed the generation of T cells displaying an immunophenotype consistent with long-term _in vivo_ persistence, without increasing the frequency of regulatory T cells. Finally, our aAPCs proved to be suitable for large scale T cell expansion required in immunotherapy trials

Linking crop yields in Tuscany, Italy, to large-scale atmospheric variability, circulation regimes and weather types

AbstractThe paper presents results from a study examining the relationship between large-scale modes of climate variability with the fluctuations in the yield of barley, durum wheat, olives and sunflower crops in Tuscany, Italy. In particular, the blocking circulation over the growing season, with associated hot and dry conditions, decreased yield for olive crops, barley and durum wheat. The teleconnections analysed in this study are the winter North Atlantic Oscillation (NAO) and the Summer North Atlantic Oscillation (SNAO); the West African Monsoon (WAM) and the Intertropical Front (ITF); and although NAO, SNAO, ITF and WAM are not strictly related to each other, the values of these indices are strongly related to the atmospheric circulation regimes and related weather types. Thus, they have an impact on precipitation and temperature patterns in Italy and on yields of important crops in Tuscany. Results show that the large-scale temperate and tropical variability directly influences the crop yield through three main circulation regimes. These patterns illustrate the importance of the large-scale modes, which, together with the associated weather types, have an impact directly on Tuscan crop yields; both barley and olive yields decline significantly when the ITF is further north with warmer and drier conditions in Italy

An Expanded Peripheral T Cell Population to a Cytotoxic T Lymphocyte (Ctl)-Defined, Melanocyte-Specific Antigen in Metastatic Melanoma Patients Impacts on Generation of Peptide-Specific Ctls but Does Not Overcome Tumor Escape from Immune Surveillance in Metastatic Lesions

It is not known if immune response to T cell–defined human histocompatibility leukocyte antigen (HLA) class I–restricted melanoma antigens leads to an expanded peripheral pool of T cells in all patients, affects cytotoxic T lymphocyte (CTL) generation, and correlates with anti-tumor response in metastatic lesions. To this end, a limiting dilution analysis technique was developed that allowed us to evaluate the same frequency of peptide-specific T cells as by staining T cells with HLA–peptide tetrameric complexes. In four out of nine patients, Melan-A/Mart-127–35–specific CTL precursors (CTLp) were ≥1/2,000 peripheral blood lymphocytes and found mostly or only in the CD45RO+ memory T cell subset. In the remaining five patients, a low (<1/40,000) peptide-specific CTLp frequency was measured, and the precursors were only in the CD45RA+ naive T cell subset. Evaluation of CTL effector frequency after bulk culture indicated that peptide-specific CTLs could be activated in all patients by using professional antigen-presenting cells as dendritic cells, but CTLp frequency determined the kinetics of generation of specificity and the final number of effectors as evaluated by both limiting dilution analysis and staining with HLA-A*0201–Melan-A/Mart-1 tetrameric complexes. Immunohistochemical analysis of 26 neoplastic lesions from the nine patients indicated absence of tumor regression in most instances, even in patients with an expanded peripheral T cell pool to Melan-A/Mart-1 and whose neoplastic lesions contained a high frequency of tetramer-positive Melan-A/Mart-1–specific T cells. Furthermore, frequent lack of a “brisk” or “nonbrisk” CD3+CD8+ T cell infiltrate or reduced/absent Melan-A/Mart-1 expression in several lesions and lack of HLA class I antigens were found in some instances. Thus, expansion of peripheral immune repertoire to Melan-A/Mart-1 takes place in some metastatic patients and leads to enhanced CTL induction after antigen-presenting cell–mediated selection, but, in most metastatic lesions, it does not overcome tumor escape from immune surveillance

Upfront intensive chemo-immunotherapy with autograft in 199 adult mantle cell lymphoma patients : prolonged survival and cure potentiality at long term

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Human neural stem cell transplantation in ALS: initial results from a phase I trial

We report the initial results from a phase I clinical trial for ALS. We transplanted GMP-grade, fetal human neural stem cells from natural in utero death (hNSCs) into the anterior horns of the spinal cord to test for the safety of both cells and neurosurgical procedures in these patients. The trial was approved by the Istituto Superiore di Sanit\ue0 and the competent Ethics Committees and was monitored by an external Safety Board