A systematic evaluation of the influence of sex on transduction by recombinant adeno-associated viral vector (rAAV) indicated that transgene expression after liver-targeted delivery of vector particles was between 5- to 13-fold higher in male mice compared with female mice, irrespective of the proviral promoter or cDNA and mouse strain. Molecular analysis revealed that the rAAV genome was stably retained in male liver at levels that were 7-fold higher than those observed in females. Further, the sex difference in transduction was observed with AAV-2– and AAV-5–based vectors, which use distinct receptor complexes for infection. In concordance with the differences in AAV transduction, gel shift analysis with nuclear extracts derived from the liver of mice and humans revealed substantially higher binding of host nuclear protein to the rep-binding site (RBS) of AAV inverted terminal repeat (ITR) in males compared with females. Transduction efficiency and binding of nuclear protein to RBS was dramatically reduced in male mice by castration. In contrast, although oophorectomy did not significantly influence rAAV transduction, administration of 5α dihydrotestosterone, prior to gene transfer, increased stable hepatocyte gene transfer in females to levels observed in male mice, implying that androgens significantly influence hepatocyte gene transfer. Interestingly, sex did not have a significant effect on AAV gene transfer into nonhepatic tissue, indicating that there are distinct tissue- and sex-specific differences in the mechanisms responsible for efficient transduction with this vector. These results have significant implications for gene therapy of autosomal and acquired disorders affecting the liver.

Purpose of review Wilms' tumor accounts for nearly 6% of all pediatric cancers and more than 95% of all kidney tumors in children. Fortunately, survival for patients with Wilms' tumor is generally excellent. This review will outline the results of prior clinical trials that have led to this excellent outcome and how information gleaned from these trials has led to the development of the current series of clinical trials for the management of children with Wilms' tumor. Recent findings Tumor stage and histologic subtype have long been recognized as important prognostic factors in Wilms' tumor. More recent evidence suggests that, in certain instances, patient age, tumor size, response to therapy, and genetic abnormalities, specifically the loss of genetic material on chromosomes 1p and 16q, provide additional prognostic information. These factors have, therefore, been incorporated into a new risk stratification system that is currently being used to assign patients with Wilms' tumor to specific protocol-based therapies. Summary Survival for patients with Wilms' tumor when considered as a whole, once less than 30%, is currently greater than 90%, with this dramatic improvement being due, in part, to the systematic manner in which the approach to therapy has evolved. Further refinement in therapy is being undertaken, with the current trials aiming to maintain the excellent survival for children being treated for Wilms' tumor, while minimizing therapy-related toxicity.

BACKGROUND.: Approximately 5% of children with Wilms tumor present with bilateral disease. The treatment challenge is to achieve a high cure rate while maintaining adequate long‐term renal function. The authors of this report assessed the feasibility and outcome of nephron‐sparing surgery in patients with bilateral Wilms tumor who were treated at a single institution.METHODS.: A retrospective review was performed of all children who were treated at St. Jude Children's Research Hospital for synchronous, bilateral Wilms tumors from 1999 through 2006. Imaging studies, surgical techniques, and pathology reports were reviewed. The outcomes evaluated included surgical complications, tumor recurrence, renal function, and patient survival.RESULTS.: Twelve patients with synchronous, bilateral Wilms tumors were identified, including 10 patients who underwent successful bilateral nephron‐sparing procedures. One patient who presented with renal failure and anaplastic histology underwent bilateral nephrectomies, and 1 patient with intra‐atrial tumor extension underwent an ipsilateral nephrectomy/thrombectomy and subsequent contralateral partial nephrectomy. Postoperative complications included persistent urine leak in 3 patients, macroscopic residual tumor in 2 patients, and pyelonephritis in 1 patient. Long‐term complications included local tumor recurrence in 2 patients, intestinal obstruction in 2 patients, ureteropelvic junction obstruction in 1 patient, and renal failure in 1 patient. The overall survival rate was 83% (mean follow‐up, 3.9 years); both patients who died had bilateral, diffuse, anaplastic histology.CONCLUSIONS.: All patients who had bilateral Wilms tumors with favorable histology, except for 1 patient who had extensive tumor thrombus, underwent successful bilateral partial nephrectomies. Complications were minimal, and long‐term renal function and survival were excellent. From this experience, the authors concluded that bilateral nephron‐sparing surgery should be considered for all patients who have bilateral Wilms tumor with favorable histology, even if preoperative imaging studies suggest that the lesions are unresectable.Cancer 2008. © 2008 American Cancer Society.