Liver metastases from UMs have a distinct gene expression pattern compared with the primary tumor while sharing similarities with gene expression patterns of normal liver. Several candidate genes for involvement in UM metastasis have been identified -- among them several in the NFKB pathway.

Purpose. To examine the involvement of nuclear factor-kappa B (NFkappaB) pathways in uveal melanoma (UM) and to assess their potential as a therapeutic target for metastatic UM. Methods. Samples from primary (n = 7) and metastatic (n = 7) UM were evaluated for NFkappaB transcription factor family expression by quantitative PCR (QPCR), immunofluorescent staining, and Western blot analysis. The effect of two NFkappaB inhibitors, DHMEQ and BMS-345541, on two cell lines derived from UM liver metastases was assessed. Cell proliferation was examined by MTT [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide] assay, methylene blue assay, and immunostaining for Ki-67. Apoptosis was assessed by immunostaining for activated caspase 3. Results. NFkappaB1, NFkappaB2, RelA, RelB, and NIK were expressed in primary UM and in its liver metastases. NFkappaB2, RelB, and NIK showed significantly higher mRNA levels in metastases from UM compared with primary tumors (3.4-fold, P = 0.03; 3.6-fold, P = 0.05; 3.5-fold, P = 0.03; respectively). NFkappaB2 protein activation was 3.9-fold higher in metastases (P = 0.03). NFkappaB inhibition reduced metastatic cell proliferation by 9.2-fold and 1.9-fold according to Ki67 staining (P = 0.04) and methylene blue assay (P = 6 x 10(-7)), respectively. Both NFkappaB inhibitors achieved dose-dependent reductions of UM cell proliferation in both cell lines (P < 0.001). NFkappaB inhibition resulted in a 6.3-fold increase of apoptosis (P = 7 x 10(-7)). Conclusions. These data indicate that the NFkappaB1 and NFkappaB2 pathways are active in both primary and metastatic UM and that these pathways regulate metastatic cell proliferation and apoptosis. The role of NFkappaB as a therapeutic target for UM should be further evaluated.

One of the challenges in developing plant-beneficial bacterial agents for agricultural application is ensuring that an effective selection and screening procedure is in place. The sporadic success of using bacterial agents in the field is usually due to the inability of added bacteria to compete with the local microorganisms. In the present study, the effectiveness of Paenibacillus dendritiformis, a unique pattern-forming, Gram-positive, soil bacterium, to reduce disease indices and increase yield in potato crops was examined. This bacterium was chosen as a potential agent based on genome analysis carried out in previous studies. In vitro laboratory experiments, as well as three greenhouse and one field experiment, were conducted. The results show that, in agreement with the hypothesis, P. dendritiformis significantly reduced the maceration area of tuber slices infected by Pectobacterium carotovorum subsp. carotovorum, significantly reduced disease indices in greenhouse experiments and significantly increased tuber yield of infected plants in the field. This work demonstrates the potential of preliminary screening based on genome analysis to identify effective biocontrol agents.