Multiple Endocrine Neoplasia 2a Presenting with Pheochromocytoma and Pituitary Macroadenoma

Multiple Endocrine Neoplasia type 2A (MEN-2a) is a rare disease associated with tumors of endocrine organs. Presentation most commonly is with medullary thyroid cancer and infrequently with other complaints. Pituitary adenoma has been seen coincidentally with this disease very rarely. Presented is a case of coincident MEN-2a with a symptomatic pituitary adenoma and an asymptomatic pheochromocytoma. A brief review is also provided

Xanthogranulomatous Cystitis Presenting as Urinary Incontinence and a Vesicovaginal Fistula: A Case Report and Review of the Literature

Abstract Anthogranulomatous cystitis (XC) is an inflammatory condition of the urinary bladder that is benign and rarely seen. XC is a unique disease in which there have been only 26 cases described in the literature, including our case. Patients with XC often present with lower urinary tract symptoms, hematuria, abdominal pain, or abdominal mass. We present the unusual case of an 81 year old female who presents with urinary incontinence, which was later diagnosed as a vesicovaginal fistula. After describing the treatment of this patient, a review of the literature is detailed including presentation, possible etiologies, and treatment of XC

Screening and identification of differentially expressed transcripts in circulating cells of prostate cancer patients using suppression subtractive hybridization

BACKGROUND: Tumor metastasis and changes in host immunosurveillance are important components in cancer development. Tumor cell invasion into the bloodstream is an essential step for systemic metastasis. Currently, the detection of tumor cells in the circulation is mainly dependent upon the utilization of known epithelial cell markers. However, expression of these molecules is not limited to cancer patients; healthy people also have a small number of epithelial cells in their circulation. Utilizing these markers to detect circulating tumor cells (CTCs) cannot adequately explain the mechanisms of tumor cell survival or their development of metastatic potential in peripheral blood. The immune system can also evolve along with the cancer, actually promoting or selecting the outgrowth of tumor variants. Unfortunately, both metastasis and immunosurveillance remain mysterious and are debatable because we have yet to define the molecules that participate in these processes. We are interested in identifying the existence of expressed genes, or mRNA species, that are specifically associated with circulating cells of cancer-bearing patients using prostate cancer (PCa) as a model. RESULTS: We established two comprehensive subtracted cDNA libraries using a molecular technique called suppression subtractive hybridization. This technique selectively amplifies transcripts that are specifically expressed in circulating cells of either PCa patients or healthy men. Following sequencing reaction, we showed that 17 out of 23 (73.9%) sequenced clones did not match any mRNAs in the GenBank database. This result suggests that genes associated with alterations in circulating cells of cancer-bearing patients are largely unknown. Semi-quantitative RT-PCR confirmed that two genes are up-regulated in circulating cells of PCa patients, whereas another two genes are down-regulated in the same patients. CONCLUSION: The comprehensive gene expression analysis is capable of identifying differentially expressed genes in circulating cells of healthy men and PCa patients. We did not attempt to enrich specific cell types in this study because phenotypes of CTCs and subsets of leukocytes participating in immunosurveillance remain largely unknown. Continuous studies of these differentially expressed genes will eventually lead us to understand the mechanisms involved in tumor metastasis and immune modulation during cancer development

Comparison of a New Length Measurement Technique for Inflatable Penile Prosthesis Implantation to Standard Techniques: Outcomes and Patient Satisfaction

Introduction.  Within a study evaluating the redesigned AMS 700MS inflatable penile prosthesis (IPP) (American Medical Systems, Minnetonka, MN, USA), one site used new length measurement technique (NLMT), a more aggressive dilation and measurement of the corpora cavernosa on a stretched penis, to address penile shortening. Aim.  To compare cylinder size and patient satisfaction, between a NLMT and traditional sizing for IPP implantation. Methods.  Fourteen men received IPPs using NLMT, and 55 with traditional sizing. Nationwide sales data from 2005 to 2008 for AMS 700 IPPs was obtained from AMS for comparison; additional surveys captured patient satisfaction. Main Outcome Measure.  Demographic data, cylinder sizes, and patient satisfaction were compared between the NLMT and standard techniques. Results.  The Fisher's exact test ( P  21 cm long and 28.6% (4) received cylinders <21 cm long, as compared with 12.7% (7) and 87.3% (48), respectively, for patients implanted by traditional techniques. There were ethnic differences between the samples: 42.9% (6) NLMT patients were of African‐American descent, as compared with 10.9% (6) in the standard technique group. However, longer cylinders were utilized more often, with 83.3% (5) of African‐Americans treated using the NLMT; as compared with 33.3% (2) of the standard technique group. Nationwide data reveal 12.3% of patients routinely receive 21 cm cylinders. At 6 months postimplantation, patient satisfaction with NLMT was no different than standard techniques. There were no distal erosions, complications, infections, or pain concerns reported through 24 months among the NLMT patients. Conclusions.  The NLMT resulted in a larger number of subjects implanted with larger cylinders. Satisfaction with performance and complication rates for NLMT patients was comparable to those implanted using standard techniques. Henry G, Houghton L, Culkin D, Otheguy J, Shabsigh R, and Ohl DA. Comparison of a new length measurement technique for inflatable penile prosthesis implantation to standard techniques: Outcomes and patient satisfaction. J Sex Med 2011;8:2640–2646.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/86820/1/j.1743-6109.2011.02340.x.pd

From microarray to biology: an integrated experimental, statistical and in silico analysis of how the extracellular matrix modulates the phenotype of cancer cells

A statistically robust and biologically-based approach for analysis of microarray data is described that integrates independent biological knowledge and data with a global F-test for finding genes of interest that minimizes the need for replicates when used for hypothesis generation. First, each microarray is normalized to its noise level around zero. The microarray dataset is then globally adjusted by robust linear regression. Second, genes of interest that capture significant responses to experimental conditions are selected by finding those that express significantly higher variance than those expressing only technical variability. Clustering expression data and identifying expression-independent properties of genes of interest including upstream transcriptional regulatory elements (TREs), ontologies and networks or pathways organizes the data into a biologically meaningful system. We demonstrate that when the number of genes of interest is inconveniently large, identifying a subset of "beacon genes" representing the largest changes will identify pathways or networks altered by biological manipulation. The entire dataset is then used to complete the picture outlined by the "beacon genes." This allow construction of a structured model of a system that can generate biologically testable hypotheses. We illustrate this approach by comparing cells cultured on plastic or an extracellular matrix which organizes a dataset of over 2,000 genes of interest from a genome wide scan of transcription. The resulting model was confirmed by comparing the predicted pattern of TREs with experimental determination of active transcription factors

Elevated AKR1C3 expression promotes prostate cancer cell survival and prostate cell-mediated endothelial cell tube formation: implications for prostate cancer progressioan

<p>Abstract</p> <p>Background</p> <p>Aldo-keto reductase (AKR) 1C family member 3 (AKR1C3), one of four identified human AKR1C enzymes, catalyzes steroid, prostaglandin, and xenobiotic metabolism. In the prostate, AKR1C3 is up-regulated in localized and advanced prostate adenocarcinoma, and is associated with prostate cancer (PCa) aggressiveness. Here we propose a novel pathological function of AKR1C3 in tumor angiogenesis and its potential role in promoting PCa progression.</p> <p>Methods</p> <p>To recapitulate elevated AKR1C3 expression in cancerous prostate, the human PCa PC-3 cell line was stably transfected with an AKR1C3 expression construct to establish PC3-AKR1C3 transfectants. Microarray and bioinformatics analysis were performed to identify AKR1C3-mediated pathways of activation and their potential biological consequences in PC-3 cells. Western blot analysis, reverse transcription-polymerase chain reaction (RT-PCR), enzyme-linked immunosorbent assay (ELISA), and an <it>in vitro </it>Matrigel angiogenesis assays were applied to validate the pro-angiogenic activity of PC3-AKR1C3 transfectants identified by bioinformatics analysis.</p> <p>Results</p> <p>Microarray and bioinformatics analysis suggested that overexpression of AKR1C3 in PC-3 cells modulates estrogen and androgen metabolism, activates insulin-like growth factor (IGF)-1 and Akt signaling pathways, as well as promotes tumor angiogenesis and aggressiveness. Levels of IGF-1 receptor (IGF-1R) and Akt activation as well as vascular endothelial growth factor (VEGF) expression and secretion were significantly elevated in PC3-AKR1C3 transfectants in comparison to PC3-mock transfectants. PC3-AKR1C3 transfectants also promoted endothelial cell (EC) tube formation on Matrigel as compared to the AKR1C3-negative parental PC-3 cells and PC3-mock transfectants. Pre-treatment of PC3-AKR1C3 transfectants with a selective IGF-1R kinase inhibitor (AG1024) or a non-selective phosphoinositide 3-kinases (PI3K) inhibitor (LY294002) abolished ability of the cells to promote EC tube formation.</p> <p>Conclusions</p> <p>Bioinformatics analysis followed by functional genomics demonstrated that AKR1C3 overexpression promotes angiogenesis and aggressiveness of PC-3 cells. These results also suggest that AKR1C3-mediated tumor angiogenesis is regulated by estrogen and androgen metabolism with subsequent IGF-1R and Akt activation followed by VEGF expression in PCa cells.</p