VAV3 Overexpressed in Cancer Stem Cells Is a Poor Prognostic Indicator in Ovarian Cancer Patients.

Ovarian carcinoma is a highly lethal malignancy due to frequent relapse and drug resistance. Cancer stem cells (CSCs) are thought to contribute significantly to disease relapse and drug resistance. In this study, a subpopulation of CSCs of ovarian carcinoma was isolated and the genes differentially expressed in these cells were identified to characterize CSCs and to find candidate biomarkers. Ovarian carcinoma cells from patients were primarily cultured, and spheroid-forming cells (SFCs) were isolated. The characteristic genes of SFCs were identified through cDNA microarray and validation by quantitative real-time polymerase chain reaction and immunohistochemistry, and the association of their expression with clinicopathologic parameters was analyzed. GSC (4.26-fold), VAV3 (7.05-fold), FOXA2 (12.06-fold), LEF1 (17.26-fold), COMP (21.33-fold), GRIN2A (9.36-fold), CD86 (23.14-fold), PYY (4.18-fold), NKX3-2 (10.35-fold), and PDK4 (74.26-fold) were significantly upregulated in SFCs compared with parental cancer cells. With validation for human ovarian carcinomas, LEF1, PYY, NKX3-2, and WNT3A were significantly upregulated in chemoresistant cancers compared with chemosensitive cancers. Overexpression of LEF1, VAV3, and NKX3-2 was significantly associated with distant metastasis by immunohistochemistry. VAV3 overexpression was an independent poor survival indicator (hazard ratio=15.27, P<0.05) by multivariate Cox analysis. The further functional assay revealed that VAV3 knockdown regulated CSC activation and ovarian cancer cell proliferation and sensitized paclitaxel (PTX)-resistant cancer cells to PTX treatment. Taken together, we identified by high-throughput analysis of CSCs that VAV3 overexpression is a novel biomarker for poor prognosis and survival in ovarian carcinoma.

Concordant or discordant? Imaging-pathology correlation in a sonography-guided core needle biopsy of a breast lesion.

An imaging-guided core needle biopsy has been proven to be reliable and accurate for the diagnosis of both benign and malignant diseases of the breast, and has replaced surgical biopsy. However, the possibility of a false-negative biopsy still remains. Imaging-pathology correlation is of critical importance in imaging-guided breast biopsies to detect such a possible sampling error and avoid a delay in diagnosis. We will review five possible categories and corresponding management after performing an imaging-pathology correlation in a sonography-guided core needle biopsy of a breast lesion, as well as illustrate the selected images for each category in conjunction with the pathologic finding. Radiologists should be familiar with the imaging features of various breast pathologies and be able to appropriately correlate imaging findings with pathologic results after a core needle biopsy.

Assessment of musculoskeletal infection in rats to determine usefulness of SPIO-enhanced MRI.

OBJECTIVE: The objective of our study was to evaluate the usefulness of superparamagnetic iron oxide (SPIO)-enhanced MRI in experimental models of infectious disease and to analyze the intracellular uptake of SPIO. MATERIALS AND METHODS: Nine rats with infectious arthritis of the knee or soft-tissue infection were imaged on an MRI unit on days 4-6 after i.v. injection of a bacterial suspension. All animals were imaged on a T2-weighted fast spin-echo sequence before and 24 hours after administration of SPIO. The nine rats were classified into two groups according to the dose of SPIO. We calculated the relative signal-to-noise ratio (SNR) change and compared the relative SNR change with the histologic findings. We analyzed iron-loaded cells and the intracellular uptake of iron particles according to the dose of SPIO. RESULTS: The SNR value decreased in proportion to the increase in the number of iron-laden macrophages or fibroblasts in the wall of the soft-tissue abscess (p < 0.01). The intracellular uptake of iron particles was shown in fibroblasts as well as in macrophages, and their uptake in the fibroblasts was greater than that in the macrophages (p < 0.05). There was no statistically significant difference in the intracellular uptake of iron particles according to the dose of SPIO (p > 0.1). CONCLUSION: SPIO-enhanced MRI can be useful in evaluating infectious disease of the joint or soft tissue and is influenced by the uptake of iron particles in fibroblasts as well as macrophages.

[Effects of octreotide on small bowel obstructions in rats].

BACKGROUNDS/AIMS: Gastrointestinal decompression by nasogastric or intestinal tubes developed in 1930s has been the only treatment modality for inoperable intestinal obstruction. We hypothesized that the octreotide, a potent inhibitor of intestinal secretion, has a therapeutic potential in intestinal obstruction. METHODS: Forty Sprague-Dawley rats were randomly assigned to four groups. The rats were subjected to complete or partial ileal obstruction. The treated rats received octreotide (100 microgram/kg) while the controls received the same quantity of saline every 12 hours for 24 or 48 hours. After 24 or 48 hours, the volumes of the small bowel contents were measured. The volumes of supernatant and the concentrations of electrolytes in the small bowel contents after centrifugation were also analyzed. The ileal segments proximal to obstruction were harvested, fixed, and stained, and the pathological changes were evaluated with mucosal damage scores. RESULTS: There were no statistical differences in the volume and the electrolyte composition of intestinal fluid among the 4 groups. In the 48 hour complete obstruction group, the octreotide-treated rats showed statistically lower mucosal damage scores than the control rats (p<0.05). CONCLUSIONS: Octreotide exerts mucosal protecting effect on the complete intestinal obstruction rat model.

Intranuclear cytoplasmic pseudoinclusions in pituitary adenomas.

Intranuclear pseudoinclusions are well known in papillary carcinomas of the thyroid gland, hepatocellular carcinomas, meningiomas, paragangliomas, pheochromocytomas, and melanomas. Only two papers on the intranuclear inclusions of adenohypophyseal cells in humans have been reported. This study found that intranuclear cytoplasmic pseudoinclusions occur frequently in pituitary adenoma cases (70.3%, 97 of 138 pituitary adenomas) and are uncommon in normal pituitary tissue (11.1%, 1 of 9 normal pituitary tissues). In addition, the frequency of intranuclear cytoplasmic pseudoinclusions between the functional and non-functional pituitary adenomas was found to be similar. Electron microscopy and immunostaining was used to reveal the entity of the intranuclear inclusion. These intranuclear inclusions are due to cytoplasmic invagination because 1) the inclusions are continuous with the cytoplasm, 2) all cytoplasmic organelles, such as the endoplasmic reticulum, the Golgi apparatus, and the secretory granules are found in the inclusions, 3) immunoreactivity of the intranuclear inclusion is the same as that of the cytoplasm. In conclusion, intranuclear cytoplasmic pseudoinclusions in pituitary adenomas occur frequently (70.3%) and are formed by cytoplasmic invagination. This study suggests that pituitary intranuclear inclusions caused by cytoplasmic invagination be called "intranuclear cytoplasmic pseudoinclusions".