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Surprisingly scant research has adequately examined directional influences between different perceptions of managerial leadership behaviors and different types of work motivation, and even fewer studies have examined contextual moderators of these influences. The present study investigated longitudinal and multilevel autoregressive cross-lagged relations between perceptions of transformational, transactional, and passive-avoidant leadership with autonomous motivation, controlled motivation, and amotivation. Multilevel longitudinal models were estimated on data from 788 employees, nested under 108 distinct supervisors, from six Canadian organizations. Results revealed that perceptions of leadership behaviors predicted changes in motivation mostly at the collective level and that some of these relations changed as a function of whether organizations had recently faced a crisis. Collective perceptions of transformational leadership were related to increased collective autonomous and controlled motivation, while individual controlled motivation was related to increased individual perceptions of transactional leadership. In organizations facing a crisis, individual perceptions of transactional leadership were related to decreased individual controlled motivation, while collective perceptions of transactional leadership were related to increased collective autonomous motivation and decreased collective amotivation. In organizations not facing a crisis, collective perceptions of transactional leadership were related to decreased collective autonomous motivation. Implications for theory and practice are discussed. [ABSTRACT FROM AUTHOR]

Background: Tail vein injection under short anesthesia is the most commonly used route for administering radiopharmaceuticals. However, the small caliber of the vein in rodents may lead to tracer extravasation and thereby compromise quantitative accuracy of PET. We aimed to evaluate a method for correction of interstitial radiotracer leakage in the context of pre-clinical therapeutic response assessment. Methods: In two separate studies involving 16 nude rats, a model of human ovarian cancer was xenografted and each was treated with a Phosphoinositide 3-kinase/mammalian target of rapamycin inhibitor or used as a control. Tracer injections were performed via the tail vein by a single operator. Two observers qualitatively evaluated the resulting images and if appropriate drew a volume of interest (VOI) over the injection site to record extravasated activities. Uncorrected and corrected tumors' mean standardized uptake value (SUV)mean was computed (corrected injected activity = calibrated activity - decay corrected residual syringe activity - decay corrected tail extravasated activity). Molecular analyses were taken as a gold standard. The frequency and magnitude of extravasation were analyzed, as well as the inter-observer agreement and the impact of the correction method on tumor uptake quantification. Results: Extravasation never exceeded 20 % of the injected dose but occurred in more than 50 % of injections. It was independent of groups of animals and protocol time points with p values of 1.00 and 0.61, respectively, in the first experiment and 0.47 and 0.13, respectively, in the second experiment. There was a good inter-observer agreement for qualitative analysis (kappa = 0.72) and a moderate agreement when using quantitative analysis (?c= 0.94). In both experiments, there was significant difference between uncorrected and corrected SUVmean. Despite this significant difference, mean percent differences between uncorrected and corrected SUVmean in the first and the second experiments were -3.61 and -1.78, respectively. Concerning therapy assessment, in both experiments, significant differences in median %SUVmean between control and treated groups were observed over all time points with either uncorrected and corrected data (p < 0.05). Conclusions: Although extravasation is common and can be reproducibly corrected, this is probably not required for validation of response to drugs that induce large SUV changes. However, further studies are required to evaluate the impact of extravasation in situations where less marked metabolic responses are observed or important extravasations occur. [ABSTRACT FROM AUTHOR]

Purpose: We compared conventional filtered back-projection (FBP), two-dimensional-ordered subsets expectation maximization (OSEM) and maximum a posteriori (MAP) NEMA NU 4-optimized reconstructions for therapy assessment. Procedures: Varying reconstruction settings were used to determine the parameters for optimal image quality with two NEMA NU 4 phantom acquisitions. Subsequently, data from two experiments in which nude rats bearing subcutaneous tumors had received a dual PI3K/mTOR inhibitor were reconstructed with the NEMA NU 4-optimized parameters. Mann-Whitney tests were used to compare mean standardized uptake value (SUV) variations among groups. Results: All NEMA NU 4-optimized reconstructions showed the same 2-deoxy-2-[F]fluoro- d-glucose ([F]FDG) kinetic patterns and detected a significant difference in SUV relative to day 0 between controls and treated groups for all time points with comparable p values. Conclusion: In the framework of therapy assessment in rats bearing subcutaneous tumors, all algorithms available on the Inveon system performed equally. [ABSTRACT FROM AUTHOR]

Ovarian cancer is the leading cause of death from gynecological cancer. The anti-apoptotic protein Bcl-x is frequently overexpressed in ovarian carcinoma which correlates with chemotherapy resistance. It has been demonstrated that Bcl-x cooperates with another anti-apoptotic protein, Mcl-1, to protect ovarian cancer cells against apoptosis, and that their concomitant inhibition induces massive cell death. Here, we examined the interest of ABT-737, a potent BH3-mimetic molecule targeting Bcl-x, both alone and in combination with Mcl-1 modulators, in ovarian cancer cell lines. As a single agent, ABT-737 was ineffective at promoting cell death in the four cell lines we tested in vitro. However, the specific inhibition of Mcl-1 by siRNA dramatically increased the sensitivity of chemoresistant cells to ABT-737. Platinum compounds also sensitize to ABT-737 by dose-dependently decreasing Mcl-1 expression or by increasing the expression of pro-apoptotic BH3-only proteins Noxa and, to a lower extent, Bim. Furthermore, we demonstrated that Noxa accumulation was involved in apoptosis occurring in response to the combination of ABT-737 and platinum compounds, since cells were protected from apoptosis by its silencing. Moreover, the combination was also highly cytotoxic ex vivo in sliced SKOV3 tumor nodes. However we observed in these slices a strong basal expression of Noxa and apoptotic cell death in response to ABT-737 alone. Therefore, we have revealed that the modulation of the Mcl-1/Noxa axis by platinum compounds results in a strong sensitization of chemoresistant ovarian carcinoma cells to ABT-737, which could constitute a promising therapeutic in these cancers. [ABSTRACT FROM AUTHOR]

PurposeWe assessed whether imaging αvβ3 integrin could distinguish mature teratoma from necrosis in human non-seminomatous germ cell tumour (NSGCT) post-chemotherapy residual masses.MethodsHuman embryonal carcinoma xenografts (six/rat) were untreated (controls) or treated to form mature teratomas with low-dose cisplatin and all-trans retinoic acid (ATRA) over a period of 8 weeks. In another group, necrosis was induced in xenografts with high-dose cisplatin plus etoposide (two cycles).18F-Fluorodeoxyglucose (18F-FDG) small animal positron emission tomography (SA PET) imaging was performed in three rats (one control and two treated for 4 and 8 weeks with cisplatin+ATRA). Imaging of αvβ3 expression was performed in six rats bearing mature teratomas and two rats with necrotic lesions on a microSPECT/CT device after injection of the tracer [99mTc]HYNIC-RGD [6-hydrazinonicotinic acid conjugated to cyclo(Arg-Gly-Asp-D-Phe-Lys)]. Correlative immunohistochemistry studies of human and mouse αvβ3 expression were performed.ResultsCisplatin+ATRA induced differentiation of the xenografts. After 8 weeks, some glandular structures and mesenchymal cells were visible; in contrast, control tumours showed undifferentiated tissues. SA PET imaging showed that mature teratoma had very low avidity for 18F-FDG [mean standardised uptake value (SUVmean) = 0.48 ± 0.05] compared to untreated embryonal carcinoma (SUVmean = 0.92 ± 0.13) (p = 0.005). αvβ3 imaging accurately distinguished mature teratoma (tumour to muscle ratio = 4.29 ± 1.57) from necrosis (tumour to muscle ratio = 1.3 ± 0.26) (p = 0.0002). Immunohistochemistry studies showed that αvβ3 integrin expression was strong in the glandular structures of mature teratoma lesions and negative in host stroma.ConclusionImaging αvβ3 integrin accurately distinguished mature teratoma from necrosis following cisplatin-based treatment in human NSGCT xenografts. [ABSTRACT FROM AUTHOR]

We aimed to evaluate the usefulness of FDG PET in the early prediction of the effects of chemotherapy on human testicular cancer xenografts. Nude rats bearing subcutaneous human embryonal carcinoma xenografts received either cisplatin (5 mg/kg) or saline serum. Small-animal PET studies were performed on days 0, 2, 4 and 7 and compared to immunochemistry studies, flow cytometry studies and hexokinase assays. Cisplatin treatment resulted in biphasic FDG uptake evolution: a peak was observed on day 2, followed by a marked decrease on day 7 despite an insignificant change in tumour volume. Similarly, a peak in cyclin A immunostaining was observed on days 2 and 4), followed by a significant decrease on day 7. Flow cytometry showed that the cyclin A peak was not related to increased cell proliferation but was due to a transient S and G2/M cell cycle arrest. A marked increase in cell apoptosis was observed from day 2 to day 7. GLUT-1 showed a significant decrease on day 7. Macrophagic infiltrate remained stable except for an increase observed on day 7. In control tumours, continuous growth was observed, all immunostaining markers remaining stable over time. Hexokinase activity was significantly lower on day 7 in treated tumours than in controls. FDG PET may be useful in the early evaluation of treatment in patients with testicular cancer. In our model, a very early increased [18F]-FDG uptake was related to a transient cell cycle arrest and early stage apoptosis but did not reveal refractory disease. [ABSTRACT FROM AUTHOR]