Search

PDF file, 42KB, Pharmacokinetic profiles of plasma and OCI-LY19-Luc tumor tissue in mice treated with a single oral dose of MLN0905.

PDF file, 45KB, MLN0905 yields significant anti-tumor responses in mice bearing subcutaneous OCI LY-19-Luc tumors.

PDF file, 43KB, Evaluating pHisH3 in OCI LY-19-Luc and OCI LY-10 cells following MLN0905 treatment.

Diffuse large B-cell lymphoma (DLBCL) is the most common of the non–Hodgkin lymphomas, accounting for up to 30% of all newly diagnosed lymphoma cases. Current treatment options for this disease are effective, but not always curative; therefore, experimental therapies continue to be investigated. We have discovered an experimental, potent, and selective small-molecule inhibitor of PLK1, MLN0905, which inhibits cell proliferation in a broad range of human tumor cells including DLBCL cell lines. In our report, we explored the pharmacokinetic, pharmacodynamic, and antitumor properties of MLN0905 in DLBCL xenograft models grown in mice. These studies indicate that MLN0905 modulates the pharmacodynamic biomarker phosphorylated histone H3 (pHisH3) in tumor tissue. The antitumor activity of MLN0905 was evaluated in three human subcutaneous DLBCL xenograft models, OCI LY-10, OCI LY-19, and PHTX-22L (primary lymphoma). In each model, MLN0905 yielded significant antitumor activity on both a continuous (daily) and intermittent dosing schedule, underscoring dosing flexibility. The antitumor activity of MLN0905 was also evaluated in a disseminated xenograft (OCI LY-19) model to better mimic human DLBCL disease. In the disseminated model, MLN0905 induced a highly significant survival advantage. Finally, MLN0905 was combined with a standard-of-care agent, rituximab, in the disseminated OCI LY-19 xenograft model. Combining rituximab and MLN0905 provided both a synergistic antitumor effect and a synergistic survival advantage. Our findings indicate that PLK1 inhibition leads to pharmacodynamic pHisH3 modulation and significant antitumor activity in multiple DLBCL models. These data strongly suggest evaluating PLK1 inhibitors as DLBCL anticancer agents in the clinic. Mol Cancer Ther; 11(9); 2045–53. ©2012 AACR.

PDF file, 59KB.

PDF file, 44KB, Evaluating cell viability in DLBCL cell lines following MLN0905 treatment.

PDF file, 53KB, MLN0905 yields significant anti-tumor responses in mice bearing subcutaneous OCI LY-10 tumors.

PDF file, 48KB, Plasma and OCI LY-19-Luc tumor pharmacokinetic parameters following a single oral dose of MLN0905 in CB-17 SCID mice.

The purpose of this non-experimental descriptive study was to measure psychiatric clinical nurses' ( N = 25) perceptions of the Edmonson Psychiatric Falls Risk Assessment Tool © (EPFRAT) compared to the Morse Fall Scale (MFS) and to evaluate patient falls with injury rates 12 months before and after the study. The setting was a 27-bed, adult psychiatric unit in a community-based teaching hospital located in the Northeast region of the United States. The EPFRAT and MFS were used to assess fall risk in 216 patients over 3 months. Findings indicated that the EPFRAT was more user-friendly and relevant; improved nurses' clinical judgment in identifying high-risk patients; and nurses were supportive toward changing practice from using the MFS to EPFRAT for fall risk assessment. Falls with injury rates decreased by 0.52 per 1,000 patient care days post-implementation of the EPFRAT. [ Journal of Psychosocial Nursing and Mental Health Services, 58 (2), 21–26.]

In this library-nursing initiative, the goal was to identify any changes in stigmatic perceptions among public library staff regarding mental health and substance abuse, post 3-day educational sessions. A total of n = 37 library staff participated in this project and attended all three educational sessions and completed a pre- and postquestionnaire designed to address common mental health and substance abuse-related stigmatic perceptions among public library staff. Upon analysis of the pre- and postresponses, we identified that there were statistically significant changes in two perceptions, namely; "embarrassed to disclose mental illness" and "commonality of substance abuse" (p ≤ .05). Therefore, it is essential that behavioral health nurses engage and collaborate with local public libraries to educate and build a safe environment for vulnerable populations like those affected with mental illness and substance abuse in the community settings.

BACKGROUND: Research has shown that animal-assisted activity (AAA) effectively improves physiological, psychological, emotional, and social well-being in various environments. AIMS: To identify how AAA affects mood states and feelings among both patients and staff on inpatient psychiatric units. METHODS: This study used a quasi-experimental, pre-/posttest design with nonequivalent comparison groups. Quantitative data were collected using the Visual Analog Mood Scale. Demographic data, with an open-ended question, were obtained postsessions. RESULTS: Significant changes were observed pre- and postexposure to AAA sessions with a therapy dog. Negative moods decreased, and positive moods increased as measured by the Visual Analog Mood Scale. Content analysis identified themes of feeling happy, feeling relaxed, and feeling calm. CONCLUSIONS: This research expands scientific evidence associated with AAA by identifying changes in mood states and feelings among individuals in a psychiatric setting.

Angiogenesis, the formation of new blood vessels from an existing vasculature, is requisite for tumor growth. It entails intercellular coordination of endothelial and tumor cells through angiogenic growth factor signaling. Interruption of these events has implications in the suppression of tumor growth. PD166285, a broad-spectrum receptor tyrosine kinase (RTK) inhibitor, and PD173074, a selective FGFR1TK inhibitor, were evaluated for their anti-angiogenic activity and anti-tumor efficacy in combination with photodynamic therapy (PDT). To evaluate the anti-angiogenic and anti-tumor activities of these compounds, RTK assays, in vitro tumor cell growth and microcapillary formation assays, in vivo murine angiogenesis and anti-tumor efficacy studies utilizing RTK inhibitors in combination with photodynamic therapy were performed. PD166285 inhibited PDGFR-beta-, EGFR-, and FGFR1TKs and c-src TK by 50% (IC50) at concentrations between 7-85 nM. PD173074 displayed selective inhibitory activity towards FGFR1TK at 26 nM. PD173074 demonstrated (>100 fold) selective growth inhibitory action towards human umbilical vein endothelial cells compared with a panel of tumor cell lines. Both PD166285 and PD173074 (at 10 nM) inhibited the formation of microcapillaries on Matrigel-coated plastic. In vivo anti-angiogenesis studies in mice revealed that oral administration (p.o.) of either PD166285 (1-25 mg/kg) or PD173074 (25-100 mg/kg) generated dose dependent inhibition of angiogenesis. Against a murine mammary 16c tumor, significantly prolonged tumor regressions were achieved with daily p.o. doses of PD166285 (5-10 mg/kg) or PD173074 (30-60 mg/kg) following PDT compared with PDT alone (p

Stout and colleagues [ Proc Am Assoc Cancer Res 1993, 34, p. 298] previously reported that both hydrocortisone and tamoxifen increased the free fraction of suramin in human plasma. We examined several corticosteroids as well as tamoxifen for their effects on suramin protein binding and also evaluated hydrocortisone for its ability to modulate suramin activity in PC-3 and MCF-7 cells. Greater than 99% of the suramin was protein bound in undiluted human plasma. However, the free fraction of suramin was increased with the reduced plasma protein levels and increased suramin concentrations. At concentrations ranging from 1 to 30 μM, neither tamoxifen, hydrocortisone, prednisone nor dexamethasone had any effect on the binding of suramin to human plasma, regardless of protein concentrations. Similar results were observed with fetal calf serum. Hydrocortisone also had no effect on suramin activity against PC-3 and MCF-7 cell in vitro . We conclude from these studies that neither corticosteroids nor tamoxifen affect suramin protein binding or its cytotoxic activity.