MRP3: a molecular target for human glioblastoma multiforme immunotherapy.

<p>Abstract</p> <p>Background</p> <p>Glioblastoma multiforme (GBM) is refractory to conventional therapies. To overcome the problem of heterogeneity, more brain tumor markers are required for prognosis and targeted therapy. We have identified and validated a promising molecular therapeutic target that is expressed by GBM: human multidrug-resistance protein 3 (MRP3).</p> <p>Methods</p> <p>We investigated MRP3 by genetic and immunohistochemical (IHC) analysis of human gliomas to determine the incidence, distribution, and localization of MRP3 antigens in GBM and their potential correlation with survival. To determine MRP3 mRNA transcript and protein expression levels, we performed quantitative RT-PCR, raising MRP3-specific antibodies, and IHC analysis with biopsies of newly diagnosed GBM patients. We used univariate and multivariate analyses to assess the correlation of RNA expression and IHC of MRP3 with patient survival, with and without adjustment for age, extent of resection, and KPS.</p> <p>Results</p> <p>Real-time PCR results from 67 GBM biopsies indicated that 59/67 (88%) samples highly expressed <it>MRP3 </it>mRNA transcripts, in contrast with minimal expression in normal brain samples. Rabbit polyvalent and murine monoclonal antibodies generated against an extracellular span of MRP3 protein demonstrated reactivity with defined <it>MRP3</it>-expressing cell lines and GBM patient biopsies by Western blotting and FACS analyses, the latter establishing cell surface MRP3 protein expression. IHC evaluation of 46 GBM biopsy samples with anti-MRP3 IgG revealed MRP3 in a primarily membranous and cytoplasmic pattern in 42 (91%) of the 46 samples. Relative RNA expression was a strong predictor of survival for newly diagnosed GBM patients. Hazard of death for GBM patients with high levels of <it>MRP3 </it>RNA expression was 2.71 (95% CI: 1.54-4.80) times that of patients with low/moderate levels (p = 0.002).</p> <p>Conclusions</p> <p>Human GBMs overexpress MRP3 at both mRNA and protein levels, and elevated MRP3 mRNA levels in GBM biopsy samples correlated with a higher risk of death. These data suggest that the tumor-associated antigen MRP3 has potential use for prognosis and as a target for malignant glioma immunotherapy.</p

Calf health from birth to weaning. I. General aspects of disease prevention

Calfhood diseases have a major impact on the economic viability of cattle operations. This is the first in a three part review series on calf health from birth to weaning, focusing on preventive measures. The review considers both pre- and periparturient management factors influencing calf health, colostrum management in beef and dairy calves and further nutrition and weaning in dairy calves

Calcium - a life and death signal

One of the most versatile and universal signalling agents in the human body is the calcium ion, Ca2+. How does this simple ion act during cell birth, life and death, and how does it regulate so many different cellular processes

Parasexuality in genitourinary investigations: a qualitative study

BACKGROUND: Genitourinary investigations are performed on a large proportion of middle-aged and older men and the majority undergo investigations for prostate issues. The effects that genitourinary disease can have on men depend on the type of problem, investigations required and treatment including impotence, gynaecomastia and urinary incontinence that have lasting devastating physical, social and psychological effects. The aim was to explore older men’s experience and views of intimate and intrusive genitourinary investigations and specifically to develop hypotheses and theories concerning gender and sexuality issues in intimate genitourinary investigations. METHODS: Written informed consent was obtained for this qualitative study. Data were collected through one-off, semi-structured interviews involving 15 men in the first year following patient’s last urological procedure. Initially, multiple themes were identified and when analysed further concepts were repeatedly present. As the urological investigations were limited to men, gender and sexuality became prominent issues in the data. RESULTS: On analysis, the term parasexuality appeared to explain the dynamic of the situation. Parasexuality is a modified form of sexuality which is channelled and limited to maintain propriety. This was not expressed as sexuality in its overt, explicit sense, but instead a type of covert sexuality where professional boundaries are maintained but nonetheless undercurrents remain. This managed version of sexuality created a common currency by which interactions between staff and patients could take place safely. Feeding into parasexuality were gender role stereotypes and for some of the participants this reflected their own experience, context, historical and cultural norms. Intimate contact in the form of exposure and handling of the participants' genitalia during the investigations particularly challenged the boundaries of parasexuality. In order to remain parasexual, many of the participants suppressed their sexuality. Viewing staff as professional was an additional strategy used by participants to limit any sexuality as parasexuality. CONCLUSION: This study has contributed towards the appeal for more studies to examine privacy perceptions of patients in genitalia-related care, however, it is by no means definitive. Parasexuality goes some way to explain the dynamics of communication between older men and health care professionals during genitourinary investigations