CRK SH3N Domain Diminishes Cell Invasiveness of Non-Small Cell Lung Cancer.

CRK (c-Crk) as an adaptor protein is involved in several oncogenic signal transduction pathways, conveying oncogenic signals to its downstream effectors and thereby affecting multiple cellular processes including proliferation, differentiation, and migration. For example, we have observed that CRK expression and phosphorylation influence the invasiveness of non-small cell lung cancer (NSCLC) cells. To intervene in CRK signaling pathway, we examined whether CRK protein domains can be used as therapeutic tools to interrupt CRK signaling, thus influencing the biological behavior of NSCLC cells.

PAK1 kinase promotes cell motility and invasiveness through CRK-II serine phosphorylation in non-small cell lung cancer cells.

The role of c-Crk (CRK) in promoting metastasis is well described however the role of CRK phosphorylation and the corresponding signaling events are not well explained. We have observed CRK-II serine 41 phosphorylation is inversely correlated with p120-catenin and E-cadherin expressions in non-small cell lung cancer (NSCLC) cells. Therefore, we investigated the role of CRK-II serine 41 phosphorylation in the down-regulation of p120-catenin, cell motility and cell invasiveness in NSCLC cells.

Exclusion of the uniform tetraploid cells significantly improves specificity of the urine FISH assay.

The urine fluorescence in situ hybridization (FISH) assay (UroVysion™), with the current scoring criteria, has a higher sensitivity than routine cytopathology but a lower specificity. Among 215 urine FISH tests we performed, 45 had associated histopathology and clinical follow up. In this study, a cell with four signals for each probe was classified as a uniform tetraploid cell (UTC); a presumed reparative cell which is currently classified as an abnormal cell in the FDA approved assay.

Iron deposition in duodenal mucosa; a review and report of three cases in pediatric age group.

Background: Ferrous sulfate drops are routinely used in Iran in infants older than 6 months of age. Effect of ferrous sulfate drops in preventive or therapeutic doses on gastrointestinal mucosa of infants is not studied as yet. Upper gastrointestinal complications due to acute iron poisoning are well known in this age group.

A novel role for Niemann-Pick disease type 2C protein in papillae formation.

Background: Despite the presence of papillary structures and papillary tumors in humans, the mechanism of papillae formation is unknown. We describe herein a novel role for Niemann-Pick disease type 2C (NPC2) protein, a cholesterol binding protein in the lysosome, in papillae formation.

Methodology/principal Finding: We examined NPC2 protein expression in surgical samples of papillary tissues by immunohistochemical stain, and all papillary tissues expressed NPC2 protein in the epithelium.

Indomethacin inhibits cell growth of medullary thyroid carcinoma by reducing cell cycle progression into S phase.

Indomethacin, a non-steroidal anti-inflammatory drug (NSAID), has been reported to inhibit the growth of medullary thyroid carcinoma (MTC) cells in vitro. However, the mechanism of inhibition of MTC cell growth by indomethacin and its potency have yet to be revealed. We examined the effect of indomethacin on three different MTC cell lines (TT cells, DRO 81-1 cells and HRO 85-1 cells) and two non-MTC cells.

Breastfeeding: a potential protective factor against ventriculoperitoneal shunt infection in young infants.

Object: Previous studies have shown nutritional benefits of breastfeeding for a child's health, especially for protection against infection. Protective factors in human milk locally and systemically prevent infections in the gastrointestinal as well as upper and lower respiratory tracts. It remains unclear whether breastfeeding protects infants against ventriculoperitoneal (VP) shunt infection.

A mutant thyroid hormone receptor alpha antagonizes peroxisome proliferator-activated receptor alpha signaling in vivo and impairs fatty acid oxidation.

Thyroid hormone regulates the balance between lipolysis and lipogenesis. We previously reported that male mice with a dominant-negative P398H mutation introduced into the TRalpha gene have visceral obesity, hyperleptinemia, and reduced catecholamine-stimulated lipolysis in white adipose tissue. Based on our observation of hepatic steatosis in the TRalpha P398H male mice, we used in vitro and in vivo models to investigate the influence of the TRalpha P398H mutant on peroxisome proliferator-activated receptor-alpha (PPARalpha) signaling.

In vivo antitumor effects of the mTOR inhibitor CCI-779 against human multiple myeloma cells in a xenograft model.

In vitro studies indicate the therapeutic potential of mTOR inhibitors in treating multiple myeloma. To provide further support for this potential, we used the rapamycin analog CCI-779 in a myeloma xenograft model. CCI-779, given as 10 intraperitoneal injections, induced significant dose-dependent, antitumor responses against subcutaneous growth of 8226, OPM-2, and U266 cell lines.

Systemic retinoic acid treatment induces sodium/iodide symporter expression and radioiodide uptake in mouse breast cancer models.

Lactating breast tissue and some breast cancers express the sodium/iodide symporter (NIS) and concentrate iodide. We recently demonstrated that all-trans retinoic acid (tRA) induces both NIS gene expression and iodide accumulation in vitro in well-differentiated human breast cancer cells (MCF-7). In the present study, we investigated the in vivo efficacy and specificity of tRA-stimulated iodide accumulation in mouse breast cancer models.

Enhanced expression of nicotinamide N-methyltransferase in human papillary thyroid carcinoma cells.

To gain an understanding of the molecular pathogenesis of thyroid cancer, we used DNA microarray to study the expression profiles of 10 different human thyroid carcinoma cell lines. These included papillary lines BHP 2-7, BHP 7-13, BHP 10-3, BHP 18-21, NPA 87, and TPC1; anaplastic lines ARO 81-1 and DRO 90-1; follicular line WRO 82-1; and medullary line HRO 85-1. Among the genes with increased expression in the cancer cell lines, a gene coding for nicotinamide N-methyltransferase (NNMT) was identified for being highly expressed only in the papillary cell lines.

Frequent overexpression of cyclin D1 in sporadic pancreatic endocrine tumours.

Pancreatic endocrine tumours (PETs) occur sporadically or are inherited as part of the multiple endocrine neoplasia type-1 syndrome. Little is known about the molecular events leading to these tumours. Cyclin D1, a key regulator of the G1/S transition of the cell cycle, is overexpressed in a variety of human cancers as well as certain endocrine tumours.

Intestinal polyp formation in the Apcmin mouse: effects of levels of dietary calcium and altered vitamin D homeostasis.

This study evaluated the effects of various levels of dietary calcium on polyp formation, vitamin D homeostasis, and fecal bile acids in the Apcmin mouse. Female Apcmin mice were randomized to three groups and fed a purified diet with either half or double the level of calcium in control AIN-93G. Serum 25-OH-D and fecal bile acids were measured at weeks 0 and 12 of treatment.

Excessive survivin expression in thyroid lymphomas.

Thyroid lymphoma occurs most commonly in the thyroid glands with a background of Hashimoto's thyroiditis. Therefore, it is occasionally difficult to distinguish lymphoma from Hashimoto's thyroiditis because of some cellular and histologic similarities. We have examined whether survivin or human telomerase reverse transcriptase (hTERT) expression can differentiate between the 2 disorders.

Alternative mRNA splicing in colon cancer causes loss of expression of neural cell adhesion molecule.

Background: The neural cell adhesion molecule (NCAM) has numerous isoforms resulting from alternative splicing of mRNA. The 3 major isoforms found in adult tissue are (1) a 120-kDa protein that is linked to the plasma membrane by glycosylphosphatidylinositol; (2) a 140-kDa form that has a transmembrane component and a cytoplasmic tail with unknown function; and (3) a 180-kDa isoform that has an intracellular protein that binds the cytoskeleton. NCAM is capable of homotypic binding and therefore plays a role in cell-cell adhesion for cells expressing the 180-kDa isoform by anchoring groups of cells into epithelial sheets.

Detection of chromosome 11q13 amplification in head and neck cancer using fluorescence in situ hybridization.

Background: Head and neck squamous cell carcinoma (HNSCC) remains a cancer with one of the lowest five-year survival rates. Despite a better understanding of the disease and recent advances in diagnosis and treatment, survival rates for HNSCC patients have not improved. Chromosomal abnormalities are common in HNSCC, and aberrations of chromosome 11q13 have been correlated with a poor prognosis.

Phosphate depletion in the rat: effect of bisphosphonates and the calcemic response to PTH.

Background: The removal of phosphate from the diet of the growing rat rapidly produces hypercalcemia, hypophosphatemia, hypercalciuria, and hypophosphaturia. Increased calcium efflux from bone has been shown to be the important cause of the hypercalcemia and hypercalciuria. It has been proposed that the increased calcium efflux from bone is osteoclast mediated.

Fractal dimension of the bone marrow in metastatic lesions.

We previously reported that the distribution of the cells in normal bone marrow is fractal and self-similar. The purpose of this study was to determine whether the same is true in metastatic tumors. Thirty-two bone marrow biopsy sections (3 to 5 microm thick) of 28 patients were used to measure the fractal dimensions of the metastatic tumor cells' distribution.

Tumor suppressor activity of neural cell adhesion molecule in colon carcinoma.

Background And Aims: Neural Cell Adhesion Molecule (NCAM) is a well-characterized member of the immunoglobin superfamily. The structure of NCAM is similar to the tumor suppressor Deleted in Colon Carcinoma (DCC). NCAM has been found in some epithelial tissues and plays a role in tumorigenesis of some cancers.

Morphogenesis of the bone marrow: fractal structures and diffusion-limited growth.

Bone marrow (BM) provides a particular spatial organization that allows interaction between its various components. Characterization of the spatial patterns in the BM and understanding the mechanisms that give rise to them may play a role in better understanding of the BM pathologic processes. Morphometric analyses were performed in BM biopsy samples from 30 patients (16 men and 14 women) with an average age of 46 years, ranging from 17 to 77 years.

Pulmonary reaction to an aspirated balanced liquid diet in a cancer patient.

A 60-year-old man with pharyngeal carcinoma developed spontaneous pneumothorax. A biopsied lung tissue revealed an extensive granulomatous reaction to some yellow material. Because of the patient's frequent aspirations of the liquid diet which was mixed with an artificial lemon flavor, it is considered that the aspirated material provoked the pulmonary reaction and possibly the pneumothorax.

Fiber contamination of vermiculites: a potential occupational and environmental health hazard.

Vermiculite ores from Montana, Virginia, and South Africa have been analyzed for the presence of amphibole contamination. Fibrous actinolite was found in unexpanded Montana vermiculite ore at a maximum concentration of 2.0%.

Identification and significance of magnetite in human tissues.

Magnetite or iron oxide has been identified in humans as well as certain animals and bacteria. With the current popularity of magnetic resonance imaging, the presence of these ferromagnetic particles in the tissues may impose biological significance. So far, identification of magnetite in tissue has been mainly based on magnetometry.