Background and PurposeThe phosphatidylinositol-3-kinase (PI3K)/Akt pathway is frequently deregulated in prostate cancer and associated with neoplastic transformation, malignant progression, and enhanced resistance to classical chemotherapy and radiotherapy. Thus, it is a promising target for therapeutic intervention. In the present study, the cytotoxic action of the Akt inhibitor Erufosine (ErPC3) was analyzed in prostate cancer cells and compared to the cytotoxicity of the PI3K inhibitor LY294002. Moreover, the efficacy of combined treatment with Akt inhibitors and ionizing radiation in prostate cancer cells was examined.Materials and methodsProstate cancer cell lines PC3, DU145, and LNCaP were treated with ErPC3 (1-100 µM), LY294002 (25-100 µM), irradiated (0-10 Gy), or subjected to combined treatments. Cell viability was determined by the WST-1 assay. Apoptosis induction was analyzed by flow cytometry after staining with propidium iodide in a hypotonic citrate buffer, and by Western blotting using antibodies against caspase-3 and its substrate PARP. Akt activity and regulation of the expression of Bcl-2 family members and key downstream effectors involved in apoptosis regulation were examined by Western blot analysis.ResultsThe Akt inhibitor ErPC3 exerted anti-neoplastic effects in prostate cancer cells, however with different potency. The anti-neoplastic action of ErPC3 was associated with reduced phosphoserine 473-Akt levels and induction of apoptosis. PC3 and LNCaP prostate cancer cells were also sensitive to treatment with the PI3K inhibitor LY294002. However, the ErPC3-sensitive PC3-cells were less susceptible to LY294002 than the ErPC3-refractory LNCaP cells. Although both cell lines were largely resistant to radiation-induced apoptosis, both cell lines showed higher levels of apoptotic cell death when ErPC3 was combined with radiotherapy.ConclusionsOur data suggest that constitutive Akt activation and survival are controlled by different different molecular mechanisms in the two prostate cancer cell lines - one which is sensitive to the Akt-inhibitor ErPC3 and one which is more sensitive to the PI3K-inhibitor LY294002. Our findings underline the importance for the definition of predictive biomarkers that allow the selection patients that may benefit from the treatment with a specific signal transduction modifier.

Health-care professionals should be aware of the interaction between levodopa and protein content of enteral nutrition to avoid the occurrence of NMLS in patients with PD.

Fecal microbiota transplantation has gathered much attention due to its high efficacy in resolving recurrent infection. Until today, it is recognized as a safe procedure without any severe side effects. Patients with impaired conscious states suffering from recurrent episodes of aspiration are at increased risk by endoscopic interventions needed during standard approaches for fecal microbiota transplantation application.Here, we illustrate the case of a tetraplegic patient undergoing fecal microbiota transplantation due to his fifth recurrent episode of infection using a self-advancing nasal jejunal feeding tube as effective minimal-invasive option of fecal microbiota transplantation application. Persistent aggravation of arterial hypertension, which developed post-intervention in this patient, could be interpreted as a hitherto unknown side effect of fecal microbiota transplantation in this setting. Moreover, this is a further hint for a link between the intestinal microbiome and arterial hypertension in general.

No abstract

No abstract