Transitional cell carcinoma of the ovary: A rare case and review of literature

Goblet cell carcinoid of the large intestine is a rare neoplasm, usually located in ascending colon and rectum. A 60-year-old male patient underwent surgery after the diagnosis of acute abdomen. Exploratory laparotomy revealed perforation with a diameter of 1 cm at the site of the previously performed gastroenterostomy and dilatation of the right colic flexure, secondary to a solid obstructive mass located in the mid-portion of transverse colon. Histopathological investigation of the biopsies, taken from the gastroenterostomy site and the tumor, revealed mixed carcinoid-adenocarcinoma with carcinoid component, predominantly composed of goblet cells. Three cycles of FOLFOX-4 protocol was administered. Following respiratory distress secondary to pulmonary metastasis, the patient's condition deteriorated and subsequently died in the fourth postoperative month. Our aim with this paper is to point out that more cases should be reported for more effective diagnosis, histopathological study, clinical investigation, treatment and prognosis of this specific neoplasm.     

Prospective cohort studies on risk factors for cardiovascular events in systemic lupus erythematosus: a major challenge

Cardiovascular disease (CVD) has been identified as a major contributor to morbidity and mortality in patients with systemic lupus erythematosus (SLE). The etiology of premature CVD in SLE is supposed to have many factors, including traditional coronary artery disease (CAD) risk factors, antiphospholipid antibodies, and metabolic and inflammatory factors. Despite the overwhelming interest in CVD in SLE research, prospective studies evaluating risk factors for hard endpoints (that is, cardiovascular events) are relatively scarce. The article by Gustafsson and colleagues suggests that prothrombotic factors play an important role in SLE-related CVD and that the influence of traditional CAD risk factors might be limited.     

CXCR6, a newly defined biomarker of tissue-specific stem cell asymmetric self-renewal, identifies more aggressive human melanoma cancer stem cells

Background

A fundamental problem in cancer research is identifying the cell type that is capable of sustaining neoplastic growth and its origin from normal tissue cells. Recent investigations of a variety of tumor types have shown that phenotypically identifiable and isolable subfractions of cells possess the tumor-forming ability. In the present paper, using two lineage-related human melanoma cell lines, primary melanoma line IGR39 and its metastatic derivative line IGR37, two main observations are reported. The first one is the first phenotypic evidence to support the origin of melanoma cancer stem cells (CSCs) from mutated tissue-specific stem cells; and the second one is the identification of a more aggressive subpopulation of CSCs in melanoma that are CXCR6+.

Methods/Findings

We defined CXCR6 as a new biomarker for tissue-specific stem cell asymmetric self-renewal. Thus, the relationship between melanoma formation and ABCG2 and CXCR6 expression was investigated. Consistent with their non-metastatic character, unsorted IGR39 cells formed significantly smaller tumors than unsorted IGR37 cells. In addition, ABCG2+ cells produced tumors that had a 2-fold greater mass than tumors produced by unsorted cells or ABCG2- cells. CXCR6+ cells produced more aggressive tumors. CXCR6 identifies a more discrete subpopulation of cultured human melanoma cells with a more aggressive MCSC phenotype than cells selected on the basis of the ABCG2+ phenotype alone.

Conclusions/Significance

The association of a more aggressive tumor phenotype with asymmetric self-renewal phenotype reveals a previously unrecognized aspect of tumor cell physiology. Namely, the retention of some tissue-specific stem cell attributes, like the ability to asymmetrically self-renew, impacts the natural history of human tumor development. Knowledge of this new aspect of tumor development and progression may provide new targets for cancer prevention and treatment.     

Inductin of neuron-derived orphan receptor-1 in the dentate gyrus of the hippocampal formation following transient global ischemia in the rat

Neuron-derived orphan receptor (NOR-1) is a member of the thyroid/steroid receptor superfamily that was originally identified in forebrain neuronal cells undergoing apoptosis. In addition to apoptotic stimuli, activation of several signal transduction pathways including direct neuronal depolarization regulates the expression of NOR-1. In this study we tested whether the expression of NOR-1 is changed following transient ischemic injury in the adult rat brain. NOR-1 mRNA increased rapidly in the dentate gyrus of the hippocampal formation and piriform cortex 3 h after transient global ischemia and returned to basal level at 6 h. On the other hand, oxygen-glucose deprivation of cultured cerebral cortical neurons did not alter the expression of NOR-1. These results suggest that expression of NOR-1 is differentially regulated in different brain regions in response to globally applied brain ischemia, but that hypoxia is not sufficient to induce its expression.     

Rapid upregulation ofDehyrin3 andDehydrin4 in response to dehydration is a characteristic of drought-tolerant genotypes in barley

The identification of molecular markers and marker-aided selection are essential to the efficient breeding of drought-tolerant plants. However, because that characteristic is controlled by many quantitative trait loci, such markers that can screen and trace desirable barley genotypes in a segregating population or germplasm have not yet been determined. Relative water content has been used to estimate drought tolerance in plants because it is highly correlated with the drought index of yield. To develop reliable gene-specific markers for identifying tolerant versus susceptible genotypes, we performed suppression subtractive hybridization to identify candidate genes. We used two domestic barley cultivars, one having the highest RWC (drought-tolerant ‘Chalbori’) and the other having the lowest (drought-susceptible ‘Daebaekbori’). In response to dehydration at the early seedling stage, rapid upregulation ofDehydrin3 (Dhn3) andDhn4 occurred in the drought-tolerant genotypes, but not in the susceptible ones. Similar results were obtained with mature plants growing under frequent drought stress in the greenhouse. In addition,Dhn3 andDhn4 conferred higher drought tolerance when they were over-expressed in transgenicArabidopsis. Thus, in addition to using assessments of RWC, we propose thatDhn3 andDhn4 expressions can serve as drought-induced gene-specific markers to determine drought-tolerant barley genotypes at the seedling stage.     

Prevention of ginsenoside-induced desensitization of Ca2+-activated Cl- current by microinjection of inositol hexakisphosphate in Xenopus laevis oocytes: involvement of GRK2 and beta-arrestin I

We demonstrated that ginsenosides, the active ingredient of Panax ginseng, enhance endogenous Ca(2+)-activated Cl(-) currents via Galpha(q/11)-phospholipase C-beta3 pathway in Xenopus laevis oocytes. Moreover, prolonged treatment of ginsenosides induced Cl(-) channel desensitization. However, the molecular mechanisms involved in ginsenoside-induced Cl(-) channel desensitization have not yet been determined precisely. To provide answers to these questions, we investigated the changes in ginsenoside-induced Cl(-) channel desensitization after intraoocyte injection of inositol hexakisphosphate (InsP(6)), which is known to bind beta-arrestins and interfere with beta-arrestin-induced receptor down-regulation, and cRNAs coding beta-arrestin I/II and G-protein receptor kinase 2 (GRK2), which is known to phosphorylate G protein-coupled receptors and attenuate agonist stimulations. When control oocytes were stimulated with ginsenosides, the second, third, and fourth responses to ginsenosides were 69.6 +/- 4.1, 9.2 +/- 2.3, and 2.6 +/- 2.2% of the first responses, respectively. Preintraoocyte injection of InsP(6) before ginsenoside treatment restored ginsenoside effect to initial response levels in a concentration-, time-, and structurally specific manner, in that inositol hexasulfate had no effect. The EC(50) was 13.9 +/- 8.7 microM. Injection of cRNA coding beta-arrestin I but not beta-arrestin II blocked InsP(6) effect on prevention of ginsenoside-induced Cl(-) channel desensitization. Injection of cRNA coding GRK2 abolished ginsenoside effect enhancing Cl(-) current. However, the GRK2-caused loss of ginsenoside effect on Cl(-) current was prevented by coinjection of GRK2 with GRK2-K220R, a dominant-negative mutant of GRK. These results indicate that ginsenoside-induced Cl(-) channel desensitization is mediated via activation of GRK2 and beta-arrestin I.     

Low zinc intake decreases the lymphatic output of retinol in rats infused intraduodenally with beta-carotene

Previously, we have shown that the lymphatic absorption of retinol is significantly decreased in rats fed a low zinc diet. This study was conducted to determine whether the absorption of beta-carotene also is altered in zinc-deficient male rats. The absorption of beta-carotene was estimated by determining the amount of retinol appearing in the mesenteric lymph during intraduodenal infusion of beta-carotene. One group of rats was fed the AIN-93G diet but low in zinc (LZ; 3 mg/kg) and the other was fed the same diet adequate in zinc (AZ; 30 mg/kg). The LZ and AZ rats were trained to meal feed equal amounts of the diets twice daily. At 6 weeks, each rat with lymph cannula was infused via an intraduodenal catheter at 3 ml/h for 8 h with a lipid emulsion containing 65.0 nM beta-carotene, 565.1 microM triolein, 27.8 kBq 14C-triolein (14C-OA), 72 mg albumin, and 396 microM Na-taurocholate in 24 ml PBS (pH 6.7). The lymphatic output of retinol over the 8-h period was significantly lower in LZ rats than in AZ rats. The absorption of 14C-OA also was significantly lower in LZ rats. No significant differences were observed between groups in intestinal beta-carotene 15,15'-dioxygenase, retinal reductase, and retinal oxidase activities. The findings demonstrate that low zinc intake or marginal zinc deficiency significantly lowers the absorption of beta-carotene as estimated by lymphatic retinol output. The results also indicate that the decrease in retinol output in LZ rats is not linked to defects in beta-carotene cleavage and subsequent conversion of retinal to retinol in the intestinal mucosa. This study suggests that zinc status is an important factor determining the intestinal absorption of beta-carotene and hence the nutritional status of vitamin A.