Cryptosporidium, a waterborne enteric parasite, is a frequent cause of diarrheal disease outbreaks worldwide. Thus far, the few antigens shown to be important for attachment to and invasion of the host cell by Cryptosporidium are all mucin-like glycoproteins. In order to investigate other antigens that could be important for Cryptosporidium host-parasite interactions, the Cryptosporidium genome databases were mined for other mucinlike genes. A single locus of seven small mucin sequences was identified on chromosome 2 (CpMuc1 to -7). Reverse transcriptase PCR analysis demonstrated that all seven CpMucs were expressed throughout intracellular development. CpMuc4 and CpMuc5 were selected for further investigation because of the significant sequence divergence between Cryptosporidium parvum and C. hominis alleles. Rabbit anti-CpMuc5 and -CpMuc4 antibodies identified several polypeptides in C. parvum lysates, suggestive of proteolytic processing of the mucins. All polypeptides were larger than the predicted molecular weight, which is suggestive of posttranslational processing, most likely O-glycosylation. In immunofluorescence assays, both anti-CpMuc4 and -CpMuc5 antibodies reacted with the apical region of sporozoites and revealed surface-exposed epitopes. The antigens were not shed during excystation but did partition into the aqueous phase of Triton X-114 extractions. Consistent with a role in attachment and invasion, CpMuc4 and CpMuc5 could be detected binding to fixed Caco-2A cells, and anti-CpMuc4 peptide antibodies inhibited Cryptosporidium infection in vitro. Sequencing of CpMuc4 and CpMuc5 from C. hominis clinical isolates identified several polymorphic alleles. The data suggest that these antigens are integral for Cryptosporidium infection in vitro and may be potential vaccine candidates.

Macrophage migratory inhibitory factor (MIF) is a proinflammatory cytokine shown to promote tumorigenesis. Using the N-butyl-N-(4-hydroxybutyl)-nitrosamine (BBN) model of bladder cancer, we previously showed that MIF knockout mice display decreased angiogenesis and invasion compared with wild-type. This study examines the role of MIF in bladder cancer via use of oral inhibitors of MIF. In vitro, high-grade bladder cancer cells were treated with recombinant human MIF +/- (rhMIF+/-) inhibitor. Measurements included cell counts, proliferation by (3)H-thymidine incorporation (TdR), extracellular signal-regulated kinase (ERK) phosphorylation by western blot analysis, messenger RNA (mRNA) expression by quantitative PCR and protein secretion by enzyme-linked immunosorbent assay. Treatment with rhMIF increased ERK phosphorylation, cell counts, TdR and mRNA expression and protein secretion of vascular endothelial growth factor, which were blocked by specific inhibitors of ERK and MIF. In vivo, 3-month-old male C57Bl/6 mice were given BBN for 22 and 16 weeks in study 1 and study 2, respectively. Mice (n = 8-10 per group) were gavaged with vehicle or doses of MIF inhibitors daily from weeks 16-22 in both studies. Average bladder weights, reflecting tumor mass, tumor stage/burden, mitotic rate and proliferation indices, and microvessel densities were reduced in inhibitor groups versus controls. In summary, MIF promotes bladder cancer via increasing cell proliferation and angiogenesis and oral inhibitors of MIF may prove useful in treatment of this disease.

Health literacy is the ability to obtain, comprehend and act on medical information and is an independent predictor of health outcomes in patients with chronic health conditions. However, there is little reported regarding the potential association of health literacy and surgical outcomes. We hypothesized that patient complications after radical cystectomy (RC) are associated with health literacy. In a sample of 368 patients, we found that higher health literacy scores (as determined by the Brief Health Literacy Screen) are associated with decreased odds of developing minor complications (OR=0.90, 95% CI: 0.83,0.97). Health literacy should be considered when caring for patients undergoing radical cystectomy and serve as a potential indicator of the need for additional resources to improve post-operative outcomes.

No abstract

The advent of multiparametric magnetic resonance imaging (mpMRI) has ushered in a new era for urologists who perform prostate needle biopsies. The fusion of MRI with transrectal ultrasound (TRUS) allows the direct targeting of suspicious lesions, which has been shown to improve the performance of conventional random biopsy techniques by increasing detection of clinically relevant disease while also decreasing detection of low-risk cancer. However, as with any new technology, many questions regarding effectiveness, reproducibility, and generalizability still remain. In this review, we 1) provide a summary of the various sequences that comprise a MRI of the prostate; 2) evaluate the three different ways of incorporating MRI into targeted biopsies of the prostate including in-bore MRI-guided biopsy, cognitive fusion, and device-mediated fusion; 3) review the sensitivity of MR-US fusion in the detection of clinically significant and clinically insignificant disease; and 4) review the barriers to the widespread implementation of MR-US fusion into everyday practice. While other articles in this issue of Urologic Oncology Seminars will discuss other aspects of MRI in the management of prostate cancer, the purpose of this article is to provide an overview of MR-US fusion biopsies in the diagnosis of prostate cancer.