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

Successful Removal of a Penile Constriction Ring in a 14-Year-Old Male

Penile strangulation is a rarely described medical emergency, especially in the adolescent population. This case demonstrates the successful removal of a constricting metal ring from the penis of a 14-year-old male with a diamond blade equipped orthopedic oscillating saw while under ketamine anesthesia in the emergency department

Suppression and activation of the malignant phenotype by extracellular matrix in xenograft models of bladder cancer: a model for tumor cell "dormancy".

A major problem in cancer research is the lack of a tractable model for delayed metastasis. Herein we show that cancer cells suppressed by SISgel, a gel-forming normal ECM material derived from Small Intestine Submucosa (SIS), in flank xenografts show properties of suppression and re-activation that are very similar to normal delayed metastasis and suggest these suppressed cells can serve as a novel model for developing therapeutics to target micrometastases or suppressed cancer cells. Co-injection with SISgel suppressed the malignant phenotype of highly invasive J82 bladder cancer cells and highly metastatic JB-V bladder cancer cells in nude mouse flank xenografts. Cells could remain viable up to 120 days without forming tumors and appeared much more highly differentiated and less atypical than tumors from cells co-injected with Matrigel. In 40% of SISgel xenografts, growth resumed in the malignant phenotype after a period of suppression or dormancy for at least 30 days and was more likely with implantation of 3 million or more cells. Ordinary Type I collagen did not suppress malignant growth, and tumors developed about as well with collagen as with Matrigel. A clear signal in gene expression over different cell lines was not seen by transcriptome microarray analysis, but in contrast, Reverse Phase Protein Analysis of 250 proteins across 4 cell lines identified Integrin Linked Kinase (ILK) signaling that was functionally confirmed by an ILK inhibitor. We suggest that cancer cells suppressed on SISgel could serve as a model for dormancy and re-awakening to allow for the identification of therapeutic targets for treating micrometastases

Tumor growth at 28 days from 3 million cells as a function of ECM preparation on which J82 bladder cancer cells were grown and ECM preparation co-injected with J82 bladder cancer cells.

<p>Tumor growth at 28 days from 3 million cells as a function of ECM preparation on which J82 bladder cancer cells were grown and ECM preparation co-injected with J82 bladder cancer cells.</p

Comparison of the phenotypes of J82 bladder cancer cell lines grown on (A) Matrigel, (B) collagen or (C) SISgel in 3-D culture.

<p>Note the loss of invasion and of the more orderly appearance of the cells grown on SISgel. All magnifications are 200X. Images are representative of a minimum of 4 experiments.</p

Kaplan-Meier analysis with the endpoint of beginning active growth of a tumor, i.e. survival is defined as the absence of active growth.

<p>(A) SISgel vs Matrigel. (B) Three or more million cells implanted vs. fewer than three million cells.</p

Signature of proteins that are statistically significantly differentially expressed comparing cells from 4 lines grown on plastic, SISgel and Matrigel.

<p>The symbol (V) indicates the antibody was validated to show a single band by Western blot. A “p” indicates that the antibody is against a phosphorylated form of the protein, with the amino acid position and identity provided. The two mTOR entries represent duplicates. A complete list of the antibodies used at the time of the analysis is provided as <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0064181#pone.0064181.s001" target="_blank">Table S1</a>.</p

Functional role of ILK signaling in SISgel suppressed cells in culture.

<p>J82 cells grown on Matrigel for five days with no ILK inhibitor (top) or with 10 µM QLT0267 ILK inhibitor (bottom panel). Note suppression of invasion. All magnifications are 200X. Images are representative of 3 experiments.</p