PURPOSE: Even though hypospadias is one of the most common congenital anomalies, the cause of hypospadias is largely unknown. With regard to molecular biology and microarray technology, it appears that hypospadias is potentially related to disrupted gene expression. Genomic analysis of hypospadiac tissue indicated a potential role for activating transcription factor 3 (ATF3) in the development of this anomaly. This study prospectively examined the expression of ATF3 in tissues from 20 children with hypospadias compared with 26 normal penile skin tissue samples from elective circumcision. MATERIALS AND METHODS: Prepucial tissue was obtained from children who underwent repair of hypospadias for comparison with tissue samples from children who underwent elective circumcision. Skin specimens were evaluated for the expression of ATF3 protein by immunohistochemical staining. RESULTS: Immunohistochemical staining for ATF3 in samples from children who underwent repair of hypospadias was significantly greater than in samples from children who underwent elective circumcision (80% vs. 11%, respectively; p<0.05). CONCLUSIONS: Our results indicate that ATF3 is up-regulated in the penile skin tissue of boys with hypospadias, which suggests a role for this transcription factor in the development of this abnormality.
Activating Transcription Factor 3 ; Child ; Circumcision, Male ; Estrogens ; Female ; Gene Expression ; Humans ; Hypospadias ; Male ; Molecular Biology ; Prospective Studies ; Skin ; Transcription Factors ; Urogenital Abnormalities

Sunitinib is a multiple tyrosine kinase receptor inhibitor that is approved for the treatment of metastatic renal cell carcinoma (RCC). However, neither an appropriate dose nor dosing schedule of sunitinib has yet been established for patients with metastatic RCC who are on hemodialysis. Here, we report on two hemodialysis patients who received sunitinib to treat metastatic RCC. Sunitinib was planned to be administered at a dosage of 25 mg/d for 4 of every 6 weeks. Although sunitinib toxicity was manageable in one patient, disease progression occurred after 4 months of treatment. In the second patient, acute pulmonary edema, caused by uncontrolled hypertension, developed on the 15th day of sunitinib therapy and the drug had to be discontinued. Sunitinib is thus not well tolerated in a hemodialysis setting. Close monitoring of toxicity and dose manipulation may be required if such therapy is attempted.
Appointments and Schedules ; Carcinoma, Renal Cell* ; Disease Progression ; Humans ; Hypertension ; Protein-Tyrosine Kinases ; Pulmonary Edema ; Renal Dialysis*