The efficacy and safety of intracavernosal alprostadil was evaluated for the treatment of erectile dysfunction in men with type I or type II diabetes mellitus. This was an open-label, flexible doseescalating study involving 336 men (77% of whom were Asian=Oriental) enrolled by 15 centres in Australia, Canada and seven countries in Asia. The effective alprostadil dose, ie the dose producing penile rigidity adequate for intercourse and lasting up to 60 min, was established by titration at the clinic prior to entry into the 6 month self-treatment home phase. All men were fully trained in the self-injection technique before entry into the home phase. Efficacy and safety were assessed using patient and partner diaries and by interview at clinic visits during the titration phase and after 1, 3 and 6 months of treatment. An effective home dose was established by titration for 94% of the 336 men (median dose 20 mg, range 2.5 -60 mg). Of 278 (83%) men who entered the home phase, 277 men (247 with type II diabetes and 30 with type I diabetes) had evaluable data for alprostadil dosage and clinical response. During the home phase, a satisfactory erectile response was achieved after 99% of injections, and the median alprostadil dose remained unchanged. The initial home dose and clinical response were similar in type I and type II diabetic men. Treatment was generally well tolerated with a low incidence of penile pain (24%) In conclusion, intracavernosal alprostadil was effective and well tolerated in type I and type II diabetic men with erectile dysfunction of mixed aetiology.

Let-7 was one of the earliest discovered miRNAs and while it reportedly acts as a tumor suppressor in various solid tumors, its function in breast cancer has not been fully studied. Therefore, we examined let-7a and MAGE-A1 expression in breast tissues by qRT-PCR and found that let-7a expression significantly correlates with larger tumor size, higher histological grade (p<0.05) and is significantly lower in patients with Her-2-positive cancers and Ki-67 >14% (p=0.028 and p=0.023). MAGE-A1 expression incidence is 50.8% (33/65) and it inversely correlates with let-7a expression (p=0.008). let-7a inhibition of breast cancer cell proliferation, migration and invasion was also observed in in vitro cell culture experiments, and dual-luciferase reporter assays showed that melanoma-associated antigen A1 (MAGE-A1) was its target gene; the target comprised bases 451-457 of the 3'UTR region of the MAGE-A1 mRNA. RT-qPCR and Western blot analyses showed that let-7a inhibited MAGE-A1 expression at both the nucleic acid and protein levels. In our final co-transfection experiment, we targeted MAGE-A1 in a breast cancer cell line and observed that let-7a inhibited cell proliferation, migration and invasion. These combined results confirm that let-7a functions as a tumor suppressor by targeting MAGE-A1 in breast cancer and it therefore provides a novel target in breast cancer clinical treatment.