IL-6 signaling by STAT3 participates in the change from hyperplasia to neoplasia in NRP-152 and NRP-154 rat prostatic epithelial cells

BACKGROUND: STAT3 phosphorylation is associated with the neoplastic state in many types of cancer, including prostate cancer. We investigated the role of IL-6 signaling and phosphorylation of STAT3 in 2 rat prostatic epithelial lines. NRP-152 and NRP-154 cells were derived from the same rat prostate, yet the NRP-152 cells are not tumorigenic while the NRP-154 cells are tumorigenic. These lines are believed to represent 2 of the stages in the development of prostate cancer, hyperplasia and neoplasia. Differences in signaling pathways should play a role in the 2 phenotypes, hyperplastic and neoplastic. METHODS: We looked at the phosphorylation state of STAT3 by intracellular flow cytometry, using phospho-specific antibodies to STAT3. We used the same method to examine IL-6 production by the cell lines. We also measured apoptosis by binding of fluorescent annexin V to the cells. RESULTS: Although both cells lines made IL-6 constitutively, phosphorylated-STAT3 was present in untreated NRP-154 cells, but not in NRP-152 cells. Treatment with dexamethasone inhibited the IL-6 production of NRP-152 cells, but enhanced that of NRP-154 cells. Treatment with the JAK2 inhibitor AG490 induced apoptosis in NRP-152, but not NRP-154 cells. CONCLUSIONS: We conclude from these experiments that STAT3 activity plays a role in the phenotype of NRP-154 cell, but not NRP-152 cells. The significance of alternative IL-6 signaling pathways in the different phenotypes of the 2 cell lines is discussed

Optimizing radiotherapy for locally advanced prostate cancer with IMRT and image-guided tumor localization

Intensity modulated radiotherapy (IMRT) combined with recently developed non, invasive image-guided targeting techniques for tumor localization/repositioning provide a means to further improve on conformal radiotherapy of prostate cancer by optimally sparing the rectum. This refined approach may potentially improve treatment results for locally advanced prostate cancer while reducing side effects. This review summarizes the clinical requirements for effective prostate radiotherapy and describes the new technology that helps to better fulfil these requirements. These noninvasive developments, their potential benefit as well as their limitations; together with new data on fractionation sensitivity of prostate cancer that may lead to shortened overall treatment times may be of interest for all physicians treating patients with prostate cancer

Prevalence, emergence and factors associated with a Viral Papillomatosis and Carcinomatosis Syndrome in wild, reintroduced and captive Western Barred Bandicoots (Perameles Bougainville)

Once widespread across western and southern Australia, wild populations of the western barred bandicoot (WBB) are now only found on Bernier and Dorre Islands, Western Australia. Conservation efforts to prevent the extinction of the WBB are presently hampered by a papillomatosis and carcinomatosis syndrome identified in captive and wild bandicoots, associated with infection with the bandicoot papillomatosis carcinomatosis virus type 1 (BPCV1). This study examined the prevalence and distribution of BPCV1 and the associated syndrome in two island and four mainland (reintroduced and captive) WBB populations in Western Australia, and factors that may be associated with susceptibility to this syndrome. BPCV1 and the syndrome were found in the wild WBB population at Red Cliff on Bernier Island, and in mainland populations established from all or a proportion of founder WBBs from Red Cliff. BPCV1 and the syndrome were not found in the wild population on Dorre Island or in the mainland population founded by animals exexclusively from Dorre Island. Findings suggested that BPCV1 and the syndrome were disseminated into mainland WBB populations through the introduction of affected WBBs from Red Cliff. No difference in susceptibility to the syndrome was found between Dorre Island, Bernier Island, and island-cross individuals. Severity of lesions and the number of affected animals observed in captivity was greater than that observed in wild populations. This study provided epidemiological evidence to support the pathological and molecular association between BPCV1 infection and the papillomatosis and carcinomatosis syndrome and revealed increasing age as an additional risk factor for this disease