42 research outputs found

    Evaluation of neuroendocrine markers in renal cell carcinoma

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    <p>Abstract</p> <p>Background</p> <p>The purpose of the study was to examine serotonin, CD56, neurone-specific enolase (NSE), chromogranin A and synaptophysin by immunohistochemistry in renal cell carcinomas (RCCs) with special emphasis on patient outcome.</p> <p>Methods</p> <p>We studied 152 patients with primary RCCs who underwent surgery for the removal of kidney tumours between 1990 and 1999. The mean follow-up was 90 months. The expression of neuroendocrine (NE) markers was determined by immunohistochemical staining using commercially available monoclonal antibodies. Results were correlated with patient age, clinical stage, Fuhrman grade and patient outcome.</p> <p>Results</p> <p>Eight percent of tumours were positive for serotonin, 18% for CD56 and 48% for NSE. Chromogranin A immunostaining was negative and only 1% of the tumours were synaptophysin immunopositive. The NSE immunopositivity was more common in clear cell RCCs than in other subtypes (<it>p </it>= 0.01). The other NE markers did not show any association with the histological subtype. Tumours with an immunopositivity for serotonin had a longer RCC-specific survival and tumours with an immunopositivity for CD56 and NSE had a shorter RCC-specific survival but the difference was not significant. There was no relationship between stage or Fuhrman grade and immunoreactivity for serotonin, CD56 and NSE.</p> <p>Conclusions</p> <p>Serotonin, CD56 and NSE but not synaptophysin and chromogranin A are expressed in RCCs. However, the prognostic potential of these markers remains obscure.</p

    Development of an improved blood-stage malaria vaccine targeting the essential RH5-CyRPA-RIPR invasion complex

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    Reticulocyte-binding protein homologue 5 (RH5), a leading blood-stage Plasmodium falciparum malaria vaccine target, interacts with cysteine-rich protective antigen (CyRPA) and RH5-interacting protein (RIPR) to form an essential heterotrimeric “RCR-complex”. We investigate whether RCR-complex vaccination can improve upon RH5 alone. Using monoclonal antibodies (mAbs) we show that parasite growth-inhibitory epitopes on each antigen are surface-exposed on the RCR-complex and that mAb pairs targeting different antigens can function additively or synergistically. However, immunisation of female rats with the RCR-complex fails to outperform RH5 alone due to immuno-dominance of RIPR coupled with inferior potency of anti-RIPR polyclonal IgG. We identify that all growth-inhibitory antibody epitopes of RIPR cluster within the C-terminal EGF-like domains and that a fusion of these domains to CyRPA, called “R78C”, combined with RH5, improves the level of in vitro parasite growth inhibition compared to RH5 alone. These preclinical data justify the advancement of the RH5.1 + R78C/Matrix-M™ vaccine candidate to Phase 1 clinical trial

    Nuclear Kaiso Expression Is Associated with High Grade and Triple-Negative Invasive Breast Cancer

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    Kaiso is a BTB/POZ transcription factor that is ubiquitously expressed in multiple cell types and functions as a transcriptional repressor and activator. Little is known about Kaiso expression and localization in breast cancer. Here, we have related pathological features and molecular subtypes to Kaiso expression in 477 cases of human invasive breast cancer. Nuclear Kaiso was predominantly found in invasive ductal carcinoma (IDC) (p = 0.007), while cytoplasmic Kaiso expression was linked to invasive lobular carcinoma (ILC) (p = 0.006). Although cytoplasmic Kaiso did not correlate to clinicopathological features, we found a significant correlation between nuclear Kaiso, high histological grade (p = 0.023), ERα negativity (p = 0.001), and the HER2-driven and basal/triple-negative breast cancers (p = 0.018). Interestingly, nuclear Kaiso was also abundant in BRCA1-associated breast cancer (p<0.001) and invasive breast cancer overexpressing EGFR (p = 0.019). We observed a correlation between nuclear Kaiso and membrane-localized E-cadherin and p120-catenin (p120) (p<0.01). In contrast, cytoplasmic p120 strongly correlated with loss of E-cadherin and low nuclear Kaiso (p = 0.005). We could confirm these findings in human ILC cells and cell lines derived from conditional mouse models of ILC. Moreover, we present functional data that substantiate a mechanism whereby E-cadherin controls p120-mediated relief of Kaiso-dependent gene repression. In conclusion, our data indicate that nuclear Kaiso is common in clinically aggressive ductal breast cancer, while cytoplasmic Kaiso and a p120-mediated relief of Kaiso-dependent transcriptional repression characterize ILC

    Safer Sex as the Bolder Choice: Testosterone Is Positively Correlated with Safer Sex Behaviorally Relevant Attitudes in Young Men

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    Introduction.  Higher testosterone (T) is tied to risk‐taking, especially in financial domains but also in health domains relevant to acquiring sexually transmitted infections (STIs). However, safer sex constructs could themselves carry the possibility of “social risk” due to sexual stigma or embarrassment, or could involve boldness or confidence because they could represent status displays of frequent sexual activity. Aim.  To determine how T and behaviorally relevant attitudes about sexual risk‐taking are linked, to better understand biopsychosocial aspects of sexual health related to STIs. Methods.  In 78 first‐year male college students, we examined correlations between salivary T and behaviorally relevant safer sex attitudes assessed via questionnaires. Main Outcome Measures.  T, via saliva; safer sex attitudes, via a composite and the University of California, Los Angeles Multidimensional Condom Attitudes Scale (MCAS). Results.  Higher T was significantly correlated with higher scores on the following: safer sex likelihood composite, r (73) = 0.33, P  = 0.003; the MCAS safer sex resilience, r (32) = 0.36, P  = 0.037; and the MCAS condom purchase comfort, r (32) = 0.37, P  = 0.031. Associations between T and safer sex likelihood and resilience were still robust after controlling for potential confounds, though the association between T and purchase comfort diminished to a trend. Conclusions.  Higher T was positively linked with safer sex attitudes, especially those most closely tied to STI risk avoidance. Thus, future research and interventions for STI prevention should address the possibility that safer sex may be paradoxically perceived as a “bold” or “risky” choice even as it decreases STI risk. van Anders SM, Goldey KL, Conley TD, Snipes DJ, and Patel DA. Safer sex as the bolder choice: Testosterone is positively correlated with safer sex behaviorally relevant attitudes in young men. J Sex Med 2012;9:727–734.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/90413/1/j.1743-6109.2011.02544.x.pd
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