Long-term treatment with high-dose of sildenafil in a thalassemic patient with pulmonary hypertension

We report a case of a 37-years-old man, affected by thalassemia major, hypogonadotropic hypogonadism, chronic HCV-hepatitis, diabetes mellitus, severe osteoporosis, prior septic pulmonary embolism and pulmonary artery hypertension was performed a long-term treatment with highdose of sildenafil (120 mg/die) with reduction of pulmonary arterial systolic pressure and of the dyspnea

Heme oxygenase-1 in central nervous system malignancies

Central nervous system tumors are the most common pediatric solid tumors and account for 20%-25% of all childhood malignancies. Several lines of evidence suggest that brain tumors show altered redox homeostasis that triggers the activation of various survival pathways, leading to disease progression and chemoresistance. Among these pathways, heme oxygenase-1 (HO-1) plays an important role. HO-1 catalyzes the enzymatic degradation of heme with the simultaneous release of carbon monoxide (CO), ferrous iron (Fe2+), and biliverdin. The biological effects of HO-1 in tumor cells have been shown to be cell-specific since, in some tumors, its upregulation promotes cell cycle arrest and cellular death, whereas, in other neoplasms, it is associated with tumor survival and progression. This review focuses on the role of HO-1 in central nervous system malignancies and the possibility of exploiting such a target to improve the outcome of well-established therapeutic regimens. Finally, several studies show that HO-1 overexpression is involved in the development and resistance of brain tumors to chemotherapy and radiotherapy, suggesting the use of HO-1 as an innovative therapeutic target to overcome drug resistance. The following keywords were used to search the literature related to this topic: nuclear factor erythroid 2 p45-related factor 2, heme oxygenase, neuroblastoma, medulloblastoma, meningioma, astrocytoma, oligodendroglioma, glioblastoma multiforme, and gliomas

Bortezomib modulates CHIT1 and YKL40 in monocyte-derived osteoclast and in myeloma cells

Osteolytic bone disease is a common manifestation of multiple myeloma (MM) that leads to progressive skeleton destruction and is the most severe cause of morbidity in MM patients.It results from increased osteolytic activity and decrease osteoblastic function. Activation of mammalian chitinases CHIT1 and YKL40 is associated with osteoclast (OCs) differentiation and bone digestion. In the current study, we investigated the effect of two Bortezomib’s concentration (BO) (2.5 nM and 5nM) on osteoclastogenesis by analyzing regulation of chitinase expression. OCs exposition to BO was able to inhibit the expression of different OCs markers such as RANK, CTSK, TRAP and MMP9. In addition BO-treatment reduced CHIT1 enzymatic activity and both CHIT1 and YKL40 mRNA expression levels and cytoplasmatic and secreted protein. Moreover, immunofluorescence evaluation of mature OCs showed that BO was able to translocate YKL40 into the nucleus, while CHIT1 remained into the cytoplasm. Since MM cell lines such as U266, SKM-M1 and MM1 showed high levels of CHIT1 activity, we analyzed bone resorption ability of U266 using dentin disc assay resorption pits. Silencing chitinase proteins in U266 cell line with specific siRNAs, resulted in pits number reduction on dentine discs. In conclusion, we showed that BO decreases osteoclastogenesis and reduces bone resorption in OCs and U266 cell line by modulating the chitinases CHIT1 and YKL40. These results indicate that chitinases may be a therapeutic target for bone disease in MM patients

Microstructural and Optical Properties of MgAl2O4 Spinel: Effects of Mechanical Activation, Y2O3 and Graphene Additions

Magnesium aluminate and other alumina-based spinels attract attention due to their high hardness, high mechanical strength, and low dielectric constant. MgAl2O4 was produced by a solid-state reaction between MgO and α-Al2O3 powders. Mechanical activation for 30 min in a planetary ball mill was used to increase the reactivity of powders. Yttrium oxide and graphene were added to prevent abnormal grain growth during sintering. Samples were sintered by hot pressing under vacuum at 1450 °C. Phase composition and microstructure of sintered specimens were characterized by X-ray powder diffraction and scanning electron microscopy. Rietveld analysis revealed 100% pure spinel phase in all sintered specimens, and a decrease in crystallite size with the addition of yttria or graphene. Density measurements indicated that the mechanically activated specimen reached 99.6% relative density. Furthermore, the highest solar absorbance and highest spectral selectivity as a function of temperature were detected for the mechanically activated specimen with graphene addition. Mechanical activation is an efficient method to improve densification of MgAl2O4 prepared from mixed oxide powders, while additives improve microstructure and optical properties

The ability of lumbar spine DXA and phalanx QUS to detect previous fractures in young thalassemic patients with hypogonadism, hypothyroidism, diabetes, and hepatitis-B: A 2-year subgroup analysis from the Taranto Area of Apulia Region.

BACKGROUND: Osteoporosis is a leading cause of morbidity in patients affected by β-thalassemia major or intermediate; we aimed to assess the association between demineralization observed in young thalassemic patients. METHODS: A total of 88 patients with β-thalassemia were recruited at Microcitemia Center of Taranto Hospital under the Prevention Osteoporosis and Fractures research project from 2008 to 2010. All the patients were screened with both dual energy x-ray absorptiometry (DXA) and quantitative ultrasound (QUS). T score and Z score values were obtained for each subject. RESULTS: The overall prevalence of demineralization was 84% with DXA and 70% with QUS, whereas normality was found in 16% of patients screened with DXA and in 30% of cases with QUS. Hypogonadism, hypothyroidism, diabetes mellitus, hepatitis-B, and the presence of previous fragility fractures were significantly associated with the demineralization status (lower T scores values) both with DXA and QUS. CONCLUSION: Our data confirm that DXA and QUS examinations are both useful for detecting bone demineralization in thalassemic patients

Genetic and molecular characterization of the human osteosarcoma 3AB-OS cancer stem cell line: a possible model for studying osteosarcoma origin and stemness.

Finding new treatments targeting cancer stem cells (CSCs) within a tumor seems to be critical to halt cancer and improve patient survival. Osteosarcoma is an aggressive tumor affecting adolescents, for which there is no second-line chemotherapy. Uncovering new molecular mechanisms underlying the development of osteosarcoma and origin of CSCs is crucial to identify new possible therapeutic strategies. Here, we aimed to characterize genetically and molecularly the human osteosarcoma 3AB-OS CSC line, previously selected from MG63 cells and which proved to have both in vitro and in vivo features of CSCs. Classic cytogenetic studies demonstrated that 3AB-OS cells have hypertriploid karyotype with 71–82 chromosomes. By comparing 3AB-OS CSCs to the parental cells, array CGH, Affymetrix microarray, and TaqMan1 Human MicroRNA array analyses identified 49 copy number variations (CNV), 3,512 dysregulated genes and 189 differentially expressed miRNAs. Some of the chromosomal abnormalities and mRNA/miRNA expression profiles appeared to be congruent with those reported in human osteosarcomas. Bioinformatic analyses selected 196 genes and 46 anticorrelated miRNAs involved in carcinogenesis and stemness. For the first time, a predictive network is also described for two miRNA family (let-7/98 and miR-29a,b,c) and their anticorrelated mRNAs (MSTN, CCND2, Lin28B, MEST, HMGA2, and GHR), which may represent new biomarkers for osteosarcoma and may pave the way for the identification of new potential therapeutic targets