The histone deacetylase inhibitor valproic acid alters growth properties of renal cell carcinoma in vitro and in vivo

Histone deacetylase (HDAC) inhibitors represent a promising class of antineoplastic agents which affect tumour growth, differentiation and invasion. The effects of the HDAC inhibitor valproic acid (VPA) were tested in vitro and in vivo on pre-clinical renal cell carcinoma (RCC) models. Caki-1, KTC-26 or A498 cells were treated with various concentrations of VPA during in vitro cell proliferation 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assays and to evaluate cell cycle manipulation. In vivo tumour growth was conducted in subcutaneous xenograft mouse models. The anti-tumoural potential of VPA combined with low-dosed interferon-α (IFN-α) was also investigated. VPA significantly and dose-dependently up-regulated histones H3 and H4 acetylation and caused growth arrest in RCC cells. VPA altered cell cycle regulating proteins, in particular CDK2, cyclin B, cyclin D3, p21 and Rb. In vivo, VPA significantly inhibited the growth of Caki-1 in subcutaneous xenografts, accompanied by a strong accumulation of p21 and bax in tissue specimens of VPA-treated animals. VPA–IFN-α combination markedly enhanced the effects of VPA monotherapy on RCC proliferation in vitro, but did not further enhance the anti-tumoural potential of VPA in vivo. VPA was found to have profound effects on RCC cell growth, lending support to the initiation of clinical testing of VPA for treating advanced RCC

Long-term results of simple enucleation for the treatment of small renal cell carcinoma

OBJECTIVE: We have analyzed our institutional experience with simple enucleation for the treatment of small renal tumors for elective indications. MATERIALS AND METHODS: A total of 30 patients underwent elective nephron-sparing surgery (NSS) from May 1997 to January 2001. All patients underwent NSS by means of enucleation. The tumor bed was coagulated carefully for haemostatic and partly for oncological reasons. Median follow-up was 71 months (range: 49-91 months). RESULTS: Pathological review according to the 2002 TNM classification showed that 70 % (21 of 30) of tumors were pT1a, 26.7 % (8 of 30) pT1b and 3.3 % (1 of 30) pT3a. Median tumor size was 3.7 cm. (range: 3.0 - 5.5 cm). There was no perioperative mortality (within the first 30 days). Bleeding had not been recorded during perioperative period. Urinary leakage was observed in 1 patient (3.3%). No case of local recurrence was observed. Five and 7-year cumulative survival was 96.6% and 93.3%, respectively. Five and 7-year cancer specific survival was 100% and 96.5%, respectively. CONCLUSIONS: Simple tumor enucleation is a safe and acceptable approach for elective NSS. It provides excellent long-term progression-free and cancer specific survival rates, and is not associated with an increased risk of local recurrence compared to partial nephrectomy