Dose-dense and dose-intense chemotherapy for small cell ovarian cancer: 2 cases and review of literature

Small cell carcinomas of the ovary (SCCO) are rare and aggressive malignant neoplasms carrying a poor prognosis. Although multi-modality treatment including chemotherapy leads to a high initial response rate, the majority of these patients relapse quickly and die within 2 years of diagnosis. Because these tumours are rare, there is no consensus to support any particular approach to management. We present 2 cases and review the relevant literature to make a number of recommendations. The treatment of these unusual cases should to be individually discussed in a multi-disciplinary team and multi-modality treatment including surgery, chemotherapy and radiotherapy should be considered for patients with limited disease. Conservative, fertility-preserving surgery may be considered in younger women with early-stage disease. Induction chemotherapy with weekly dose-dense and dose-intense carboplatin and taxane is useful. Prophylactic cranial irradiation (PCI) may be considered in patients in remission after primary treatment with chemotherapy or surgery

The selenocysteine tRNA STAF-binding region is essential for adequate selenocysteine tRNA status, selenoprotein expression and early age survival of mice.

STAF [Sec (selenocysteine) tRNA gene transcription activating factor] is a transcription activating factor for a number of RNA Pol III- and RNA Pol II-dependent genes including the Trsp [Sec tRNA gene], which in turn controls the expression of all selenoproteins. Here, the role of STAF in regulating expression of Sec tRNA and selenoproteins was examined. We generated transgenic mice expressing the Trsp transgene lacking the STAF-binding site and made these mice dependent on the transgene for survival by removing the wild-type Trsp. The level of Sec tRNA was unaffected or slightly elevated in heart and testis, but reduced similar to 60% in liver and kidney, similar to 70% in lung and spleen and similar to 80% in brain and muscle compared with the corresponding organs in control mice. Moreover, the ratio of the two isoforms of Sec tRNA that differ by methylation at position 34 (Um34) was altered significantly, and the Um34-containing form was substantially reduced in all tissues examined. Selenoprotein expression in these animals was most affected in tissues in which the Sec tRNA levels were most severely reduced. Importantly, mice had a neurological phenotype strikingly similar to that of mice in which the selenoprotein P gene had been removed and their life span was substantially reduced. The results indicate that STAF influences selenoprotein expression by enhancing Trsp synthesis in an organ-specific manner and by controlling Sec tRNA modification in each tissue examined