In our analy sis, however, hsa miR 125b appeared to be up to 5 fold down regulated in NCCIT R NCCIT and 2102EP R 2102EP cell line pairs, thus making an inhibition of apoptosis through this micro RNA species unlikely. According to our analysis, further micro RNA species appeared either about 8 fold up regulated or about 10 fold down regulated in both NTERA 2 R NTERA any other enquiries 2 and NCCIT R NCCIT cell line pairs. Literature results describing a role of these micro RNAs in cisplatin resis tance are missing, warranting further studies to elucidate their potential role in development of resistance. Recently, a role of the miR 106b seed family members in cisplatin resistance of testicular cancer has been described by another group. Although detectable, neither miRNA 106b, nor miRNA 106a, miRNA 17 5, miRNA 93, and miRNA 20 were differentially expressed in our model.
In our view, this points at the multifactor ial nature of cisplatin resistance in germ cell tumors. Conclusions Inhibitors,Modulators,Libraries In summary, our approach, simultaneously examining almost all known human micro RNA species, confirms that the miR 371 373 cluster seems to be involved in cisplatin resistance in germ cell tumors in vitro and could be an interesting target for interference with drug resistance. Inhibitors,Modulators,Libraries Moreover, new micro RNA species such as hsa miR 512 3p 515 517 518 525 or hsa miR 99a 100 145, also potentially involved in cisplatin resistance, could be identified in the germ cell tumor cell lines stu died here. It will be of interest to examine tumor sam ples of patients with both cisplatin sensitive and cisplatin resistant germ cell tumors to analyse whether the changes described here are also found in vivo.
Furthermore, functional analyses, e. g. by employing si RNA and Inhibitors,Modulators,Libraries simultaneous whole genome microarrays, can help to examine the causal link with cisplatin resistance and to get insight into the mRNA species controlled by the micro RNAs. Introduction Inhibitors,Modulators,Libraries Renal cell carcinoma is a highly vascularized tumor which accounts for 3% of all malignancies in adults. Most symptomatic patients Inhibitors,Modulators,Libraries present with advanced metastatic disease, which has a poor prog nosis. Traditional chemotherapy, hormonal therapy or radiation are not effective in the treatment of advanced RCC, and immunotherapy provides only limited benefit. Nevertheless, based on the molecular biology of RCC, new therapeutic strategies have recently emerged in the management of advanced disease.
Indeed, a characteristic of RCC is the frequent inactivation of the Von Hippel Lindau protein, which occurs in 50 to 60 percent of patients with sporadic RCC. The molecular consequences of pVHL mutations result in the upregulation of Hypoxia Inducible Factor 1a which induces the tran scription of hypoxia responsive Tubacin MM genes such as Vascular Endothelial Growth Factor.