CytoGTA: A cytoscape plugin for identifying discriminative subnetwork markers using a game theoretic approach.

In recent years, analyzing genome-wide expression profiles to find genetic markers has received much attention as a challenging field of research aiming at unveiling biological mechanisms behind complex disorders. The identification of reliable and reproducible markers has lately been achieved by integrating genome-scale functional relationships and transcriptome datasets, and a number of algorithms have been developed to support this strategy. In this paper, we present a promising and easily applicable tool to accomplish this goal, namely CytoGTA, which is a Cytoscape plug-in that relies on an optimistic game theoretic approach (GTA) for identifying subnetwork markers. Given transcriptomic data of two phenotype classes and interactome data, this plug-in offers discriminative markers for the two classes. The high performance of CytoGTA would not have been achieved if the strategy of GTA was not implemented in Cytoscape. This plug-in provides a simple-to-use platform, convenient for biological researchers to interactively work with and visualize the structure of subnetwork markers. CytoGTA is one of the few available Cytoscape plug-ins for marker identification, which shows superior performance to existing methods.

GTA: a game theoretic approach to identifying cancer subnetwork markers.

The identification of genetic markers (e.g. genes, pathways and subnetworks) for cancer has been one of the most challenging research areas in recent years. A subset of these studies attempt to analyze genome-wide expression profiles to identify markers with high reliability and reusability across independent whole-transcriptome microarray datasets. Therefore, the functional relationships of genes are integrated with their expression data. However, for a more accurate representation of the functional relationships among genes, utilization of the protein-protein interaction network (PPIN) seems to be necessary. Herein, a novel game theoretic approach (GTA) is proposed for the identification of cancer subnetwork markers by integrating genome-wide expression profiles and PPIN. The GTA method was applied to three distinct whole-transcriptome breast cancer datasets to identify the subnetwork markers associated with metastasis. To evaluate the performance of our approach, the identified subnetwork markers were compared with gene-based, pathway-based and network-based markers. We show that GTA is not only capable of identifying robust metastatic markers, it also provides a higher classification performance. In addition, based on these GTA-based subnetworks, we identified a new bonafide candidate gene for breast cancer susceptibility.

Formulation and evaluation of a vitamin C multiple emulsion.

Multiple phase emulsions are increasingly used as alternatives to simple emulsions in personal care products. One of the major advantages of these emulsions over simple emulsions is slow and controlled release of their ingredients. Other favorite cosmetic characteristics of multiple emulsions include occlusivity (in O/W/O emulsions), esthetics and consumer acceptance. Vitamin C (ascorbic acid) has been widely used in formulations of skin care products. Due to its effects on collagen biosynthesis, it is considered as moisturizing and anti-aging active ingredient. Instability problems such as oxidation susceptibility have made incorporating vitamin C in topical formulations a challenging issue. The O/W/O emulsions have been formulated using two-step procedure, to investigate vitamin C stability and its release profile. By using different surfactant types and ratios, volume ratio of phases, multiple emulsions containing vitamin C were prepared. Different parameters and formulation factors such as temperature of phases, duration and speed of mixing were evaluated. Based on our results, more stable emulsions were prepared from non-ionic siliconized surfactants, sorbitan derivatives and co-surfactants such as polyglyceryl derivatives. Physical stability was determined by microscopic examination, centrifugation and incubating emulsions in different temperatures. Vitamin C in vitro release studies from O/W and O/W/O emulsions were conducted using Franz diffusion cell (at room temperature) and UV spectrophotometry. The results showed that in the first four-hour period, about 14% of vitamin C released from O/W/O emulsions. It appears that in multiple emulsions the profile of release follows zero-order kinetics. Our data indicate that incorporating vitamin C in multiple emulsions significantly increased its stability possibly attributed to the formation of reverse micelles of surfactants (and/or co-surfactants), which entrapped vitamin C inside the micelles surrounded by hydrophilic heads of surfactant. Moreover, vitamin C was released from multiple emulsions in a zero order slow and controlled release manner.

p53 immunostaining as a significant adjunct diagnostic method for uterine surface carcinoma: precursor of uterine papillary serous carcinoma.

Uterine papillary serous carcinoma (UPSC) is a biologically aggressive carcinoma that causes a disproportionate number of endometrial cancer deaths because of its dismal clinical outcome. Although the precursor lesion of UPSC has been suggested both morphologically and molecularly, diagnosis continues to represent a challenge to surgical pathologists, particularly in biopsy specimens, largely in part because of its multiple histologic patterns and many benign morphologic mimics. In this study, we used p53 immunohistochemical staining as an adjunct test to correctly identify six cases of uterine surface carcinoma (USC) prospectively and three cases retrospectively. Both sensitivity and specificity for this immunostaining method approached 100% when the cutoff score of p53 overexpression was 7 or higher. The precision estimated by receiving operating characteristic curve was 100%, indicating that the diagnostic value of the score for p53 overexpression was very high. p53 immunohistochemical staining was considered a significant adjunct diagnostic method for the probable precursor lesion of UPSC. The probable precursor lesion of UPSC, previously referred to as endometrial intraepithelial carcinoma or endometrial carcinoma in situ, appears to represent the early phase of UPSC. However, unlike its names would suggest, this lesion is often multicentric and behaves in a more aggressive fashion than regular in situ carcinomas. For this reason, we prefer the term uterine surface carcinoma, a term that is more descriptive and less restrictive, to emphasize the unique aggressive nature of the UPSC precursor lesion. The reason we postulate using the term uterine surface carcinoma rather than endometrial intraepithelial carcinoma or endometrial carcinoma in situ is that the latter terms would seem define a neoplastic process confined to the endometrial epithelium without potential for metastasis. In reality, the precursor lesion of UPSC has a tendency to stromal and vascular space involvement as seen by the presence of stromal and vascular invasion in one of the prospectively identified USC cases. Therefore, the term uterine surface carcinoma is selected to alert clinicians that this early carcinoma has features of carcinoma in situ, but still carries a potential for metastasis.

Sarcoidosis manifesting as uveitis and menometrorrhagia.

PURPOSE: To report a rare systemic manifestation of sarcoidosis identified in a 47-year-old white woman while she was undergoing evaluation for bilateral recurrent uveitis. METHODS: The patient underwent clinical and laboratory evaluation for bilateral recurrent uveitis including serologic and radiologic testing, a gallium scan, and an endometrial biopsy. RESULTS: Although the serologic tests and chest x-ray were normal, the gallium scan was consistent with sarcoidosis, and the endometrial biopsy provided a tissue diagnosis. CONCLUSION: Sarcoidosis involving the female reproductive tract is rare. A thorough review of systems is crucial in the evaluation of any patient with recurrent uveitis.

Endometrial glandular proliferation and estrogen receptor content during the normal menstrual cycle.

Hysterectomy specimens from 35 normally cycling premenopausal women were examined to determine the relationship of endometrial glandular proliferation to estrogen receptor content. The cases were divided into follicular phase (n = 20), early luteal phase, days 1-5 post ovulation (n = 5) and mid to late luteal phase (n = 10). Proliferation rates, as determined by MIB-1 expression, were maximal in the endometrial functionalis during the follicular phase (701 cells/1000), decreased by half during the early luteal phase (327 cells/1000), and virtually ceased during the mid to late luteal phase (8 cells/1000) (p < 0.001). Estrogen receptor status, determined immunohistochemically and graded on a scale of 0 to 4+, averaged 3.4+, 2.2+ and 0.5+ during the follicular, early luteal, and mid to late luteal phases, respectively, in the endometrial functionalis (p < 0.001). Proliferation rates in the endometrial basalis paralleled those in the functionalis, but at a lower rate, whereas estrogen receptor expression underwent considerably less cyclical variation. We conclude that estrogen receptor status shows a highly significant correlation with glandular proliferation rates and are predictive of endometrial proliferative changes during the normal menstrual cycle.

Elastosis in the normal aging breast. A histopathologic study of 140 cases.

The incidence and pattern of elastosis of the breast was studied in tissue specimens taken at autopsy from 140 women with clinically normal breasts, ranging in age from 19 through 101 years. Elastosis, presence of excess elastic fibers, while less common in younger women, may be found in nearly half of all women over age 50 years with no breast disease. Elastosis occurs in three sites: diffusely in the stroma, around vessels, and around ducts. In the first two sites, it bears little relationship to age, while periductal elastic tissue appears to accumulate with age, probably reflecting parity, until about age 50 years. Thereafter, it is found at a more or less constant incidence and degree. While it may be associated with breast cancer, periductal elastosis by itself is not a cause for concern. Marked perivascular elastosis is, however, uncommon at any age, and its presence should suggest a special search for carcinoma, if not already evident.

Polyclonal gammopathy with marked increase in serum viscosity.

A 45-year-old man with polyclonal hypergammaglobulinemia (gamma globulins, 102 g/L) had a serum relative viscosity of 13 nu but did not manifest clinical signs of hyperviscosity syndrome (e.g., retinopathy, bleeding diathesis, and neurological alterations), except for fatigue and anorexia. In contrast with other patients with polyclonal hyperviscosity reported so far, this patient did not have detectable rheumatoid factor in serum. Analytical ultracentrifugation of his serum showed aggregates of polyclonal IgG3 of various sizes (between 10 and 36 S). The serum also contained immune complex-like material, as demonstrated by the Raji cell immunoradiometric assay and the C1q solid-phase enzyme immunoassay.

Ovarian endodermal sinus tumor associated with pregnancy: review of the literature.

Endodermal sinus tumor is the second most common malignant germ cell tumor of the ovary and its reported concurrence with pregnancy is extremely rare. This report is the 10th case of endodermal sinus tumor associated with pregnancy and also reviews the previous literature regarding the subject.