Antioxidant effects of potassium ascorbate with ribose in costello syndrome.

BACKGROUND: Costello syndrome is a rare genetic condition characterized by coarse facies, short stature, loose folds of skin especially on hands and feet, severe feeding difficulties and failure to thrive. Other features include cardiac anomalies, developmental disability and increased risk of neoplasms. Given the link between oxidative stress (OS) and carcinogenesis, we tested the hypothesis that OS occurs in this syndrome, supposing its role both in cancer development and in other clinical features. PATIENTS AND METHODS: We describe four cases with Costello syndrome in which we verified the presence of OS by measuring a redox biomarker profile including total hydroperoxides, non-protein-bound iron, advanced oxidation protein products, thyols, carbonyl groups and isoprostanes. Thus, we introduced an antioxidant agent, namely potassium ascorbate with ribose (PAR) into the therapy and monitored the redox profile every three months to verify its efficacy. RESULTS: A progressive decrease in OS biomarkers occurred, together with an improvement in the clinical features of the patients. CONCLUSION: OS was proven in all four cases of Costello syndrome. The antioxidant therapy with PAR demonstrated positive effects. These promising results need further research to confirm the relevance of OS and the efficacy of PAR therapy in Costello syndrome.

Impressive activity of lenalidomide monotherapy in refractory angioimmunoblastic T-cell lymphoma: report of a case with long-term follow-up.

Angioimmunoblastic T-cell lymphoma (AITL) is characterized by an aggressive clinical course and unfavourable prognosis. Refractory AITL patients have very few treatment options. Lenalidomide has previously been reported to have clinical efficacy in this setting; however, long-term reports are limited. A 59-year-old man was referred to the hospital with fatigue, skin rash, weight loss and generalized lymphadenopathy and was diagnosed with AITL; clinical stage was IV B with bone marrow involvement. The patient had an unsatisfactory response despite three lines of conventional chemotherapy and radiotherapy. The patient received lenalidomide monotherapy (25 mg once daily) on days 1 to 21 of every 28-day cycle for six cycles, followed by maintenance therapy with six cycles of lenalidomide 15 mg once daily on days 1 to 21 of every 28-day cycle. A computed tomography scan was assessed before lenalidomide treatment, after the third cycle, at disease restaging 2 months after completion of the induction phase, every 3 months during the maintenance phase and every 6 months during the follow-up period. At the last evaluation, after a follow-up of 30 months, the patient maintained a clinical and radiological complete response. The treatment was well tolerated with manageable toxicity. Lenalidomide treatment demonstrated for the first time in the literature impressive and long-term clinical efficacy in a heavily pretreated chemorefractory AITL patient.

Identification of a novel p190-derived breakpoint Peptide suitable for Peptide vaccine therapeutic approach in ph+ acute lymphoblastic leukemia patients.

Ph+ acute lymphoblastic leukemia (Ph+ ALL) is a high-risk acute leukemia with poor prognosis, in which the specific t(9;22)(q34;q11) translocation results in a chimeric bcr-abl (e1a2 breakpoint) and in a 190 KD protein (p190) with constitutive tyrosine kinase activity. The advent of first- and second-generation tyrosine kinase inhibitors (TKIs) improved the short-term outcome of Ph+ ALL patients not eligible for allo-SCT; yet disease recurrence is almost inevitable. Peptides derived from p190-breakpoint area are leukemia-specific antigens that may mediate an antitumor response toward p190+ leukemia cells. We identified one peptide named p190-13 able to induce in vitro peptide-specific CD4+ T cell proliferation in Ph+ ALL patients in complete remission during TKIs. Thus this peptide appears a good candidate for developing an immune target vaccine strategy possibly synergizing with TKIs for remission maintenance.