BACKGROUND Following their previous report on the activity of vinorelbine in the treatment of rhabdomyosarcoma, the authors report the results of a pilot study aimed at defining the optimal dose of vinorelbine when this agent is used in conjunction with continuous, orally administered low‐dose cyclophosphamide to treat patients with refractory or recurrent sarcoma. It is hoped that the combination of vinorelbine and low‐dose cyclophosphamide can be used as a maintenance regimen in an upcoming European trial involving high‐risk patients with rhabdomyosarcoma. METHODS In the current pilot study, the cyclophosphamide dose was fixed at 25 mg/m2 per day for 28 days. Vinorelbine was administered intravenously on Days 1, 8, and 15, with trial doses escalated from an initial level of 15 mg/m2 in steps of 5 mg/m2; intrapatient dose escalation was not allowed. RESULTS Between April 2002 and November 2003, 18 patients ages 2–23 years were treated with the study regimen after having received 1–4 (median, 2) other regimens previously. Ninety cycles were administered in total (median, 5 cycles per patient; range, 1–10 cycles per patient). Two cases of dose‐limiting toxicity (Grade 4 neutropenia in both cases) were observed among the 5 patients who received vinorelbine at a dose of 30 mg/m2. Of the 41 cycles in which vinorelbine was administered at a dose of 25 mg/m2, Grade ≥ 3 neutropenia was observed in 15 (37%); no other major toxicity was documented in association with these cycles. One complete remission and 6 partial remissions were noted among the 17 patients who had measurable disease. Three of the eight assessable patients with rhabdomyosarcoma (which was embryonal in two cases and alveolar in one) had responses to treatment. CONCLUSIONS Combination therapy involving vinorelbine and low‐dose cyclophosphamide was found to be feasible and to possess activity against recurrent sarcomas. The maintenance therapy doses recommended for use in the upcoming European trial are cyclophosphamide 25 mg/m2 per day for 28 days and vinorelbine 25 mg/m2 on Days 1, 8, and 15. Cancer 2004. © 2004 American Cancer Society.

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Citropin 1.1, maculatin 1.1, and caerin 1.1 are short antibacterial cationic peptides from the skin glands of the Australian tree frog Litoria species. Several analogues have been synthesized to give a better insight into the relationship between the structure of the peptides and their antibacterial and haemolytic activity. Binding studies using a surface plasmon resonance (SPR) biosensor together with a vesicle‐capture sensor chip have been used to investigate selectivity of the peptides and their analogues for 1,2‐dimyristoyl‐sn‐glycero‐3‐phosphoglycerol (DMPG) and 1,2‐dimyristoyl‐sn‐glycero‐3‐phosphocholine (DMPC) vesicles, as well as for vesicles made from lipid extracts from Escherichia coli and bovine brain. Data obtained for membrane selectivity using natural lipid extracts show better correlation with minimum inhibitory concentration (MIC) values against Gram‐positive bacteria and haemolytic activity than that obtained using synthetic DMPG and DMPC. Electron microscopy and membrane leakage studies using Gram‐positive bacteria gave further insight into the membrane disruption properties of the peptides. For maculatin 1.1, it was found that the central proline residue, which is responsible for a bend in the α‐helical structure, is essential not only for the antibacterial activity but also for binding, and perturbation of membranes. The caerin analogues showed only small variations in their MIC values and membrane binding. In contrast, for citropin 1.1, the analogue replacing the aspartate with a lysine showed the lowest MIC against Gram‐positive bacteria and best membrane binding to E. coli lipid extracts, coinciding with an increased hydrophobic moment of the peptide. These data give further insight into these antimicrobial natural products, toward the development and evaluation of these and other analogues as potential antibiotics. © 2010 Wiley Periodicals, Inc. Biopolymers (Pept Sci) 96:147–157, 2011.

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BMT is curative in almost 75% of children affected by severe primary immunodeficiencies (PIDs). Recently, the chance of cure has increased thanks to the availability of matched unrelated donors (MUDs). Nevertheless, besides the conventional indications to BMT (profound or absent T-cell function, profound or absent natural killer function, known syndromes with T-cell deficiencies), indications to BMT for PIDs affecting the quality of life or having an expectation of life that does not exceed the third-fourth decade remain unclear. Infact, if it is evident that the survival rate in an infant grafted for a PID with a MUD is expected to be more than 80%, alternative treatments such as gene therapy are now available.