Caspase 3 and 8 deficiency in human neuroblastoma

An altered apoptotic response represents a pivotal feature of cancer and is involved in cancerogenesis and resistance to chemotherapy. So far, however, only a few studies have been devoted to survey caspase content in malignant cell lines and primary tumor specimens. In this report, we investigated the expression of two pivotal caspases, 3 and 8, in 63 neuroblastoma specimens by three complementary techniques (i.e., reverse transcriptase polymerase chain reaction, immunoblotting, and immunohistochemistry). We confirmed the frequent absence of caspase 8 expression. Moreover and most important, we demonstrated, for the first time to our knowledge, that a significant percentage of neuroblastomas lack caspase 3 mRNA and protein. Both caspase alterations do not show any correlation with tumor stage and MYCN status. Immunohistochemistry showed a large number of caspase-negative cell islets also present in positive samples. Our findings suggest that the absence of caspases might play an important role in neuroblastoma development and resistance to apoptosisbased treatments

Infant hypervitaminosis A causes severe anemia and thrombocytopenia: evidence of a retinol-dependent bone marrow cell growth inhibition

Vitamin A is a pivotal biochemical factor required for normal proliferation and differentiation as well as for specialized functions, such as vision. The dietary intake of 1500 IU/day is recommended in the first year of life. Here, we report the case of an infant who had been given 62 000 IU/day for 80 days. The infant showed several clinical signs of retinol intoxication, including severe anemia and thrombocytopenia. Bone marrow showed a remarkably reduced number of erythroid and megakaryocytic cells. The interruption of vitamin A treatment was immediately followed by clinical and biochemical recovery. To clarify whether the effects of retinol are due to a direct action on bone marrow cell proliferation, we investigated the activity of retinol (both the drug and the pure molecule) on the growth of K-562, a multipotent hematopoietic cell line, and on bone marrow mesenchymal stem cells. We observed that vitamin A strongly inhibited the proliferation of the cells at concentrations similar to those reached in vivo. Subsequent biochemical analyses of the cell cycle suggested that the effect was mediated by the up-regulation of cyclin-dependent kinase inhibitors, p21(Cip1) and p27(Kip1). These are the first findings to demonstrate that infant hypervitaminosis A causes a severe anemia and thrombocytopenia and that this is probably due to the direct effect of the molecule on the growth of all bone marrow cellular components. Our data also suggest potential bone marrow functional alterations after excessive vitamin A intake because of emerging social habits

Ex vivo expansion of bone marrow stromal cells by platelet-rich plasma: a promising strategy in maxillo-facial surgery

The aim of our study is to evaluate in vitro the response of bone marrow stromal cells (BMSCs) to platelet-rich plasma (PRP), in order to clarify the potential role of their combined use in a preclinical phase preceding BMSCs transplantation for bone repair and regeneration procedures.Thus PRP represents a valid preclinical tool for obtaining an effective, rapid and safe ex vivo expansion of BMSCs prior to their clinical utilization in bone engineering

A novel Leu153Ser mutation of the Fanconi anemia FANCD2 gene is associated with severe chemotherapy toxicity in a pediatric T-cell acute lymphoblastic leukemia.

13nonenoneBORRIELLO A; LOCASCIULLI A; BIANCO AM; CRISCUOLO M; CONTI V; GRAMMATICO P; CAPPELLACCI S; ZATTERALE A; MORGESE F; CUCCIOLLA V; DELIA D; DELLA RAGIONE F; SAVOIA A.Borriello, A; Locasciulli, A; Bianco, Am; Criscuolo, M; Conti, V; Grammatico, P; Cappellacci, S; Zatterale, A; Morgese, F; Cucciolla, V; Delia, D; DELLA RAGIONE, F; Savoia, Ann