Expression and clinical significance of retinoid X receptor α in esophageal carcinoma.

PURPOSE: Esophageal carcinoma (EC) is one of the most aggressive type cancers and dysregulation of retinoid X receptor α (RXRα) involves various tumors. However, the relationship of RXRα with the clinicopathological factors of EC, particularly prognostic characteristics, remains unclear. This present study was to evaluate the effect of RXRα expression in the development of EC. METHODS: The mRNA and protein expression level of RXRα in EC and normal esophageal tissues using reverse transcription-polymerase chain reaction (RT-PCR) and Western blot, respectively. The subcellular localization was detected by immunohistochemistry (IHC) analysis. The clinicopathological parameters were included age, sex, tumor size, differentiation, TNM stages and lymph node metastasis. Kaplan-Meier method and Cox's regression analyses were performed to evaluate the prognosis of 60 patients with EC. RESULTS: RXRα was elevated in EC tissues comparing with normal esophageal tissues at both mRNA and protein levels. The overexpression level of RXRα was closely associated to the tumor differentiation, TNM stage and lymph node metastasis of patients with EC. In addition, EC patients with RXRα high expression had significantly lower disease-free survival (DFS) and overall survival (OS). Multivariate analysis showed RXRα expression as an independent predictor for the DFS and OS rate of patients with EC. CONCLUSIONS: Our results showed that overexpression of RXRα was correlated with unfavorable prognosis, suggesting that RXRα may serve as a potential targeted therapeutic marker in the treatment of EC.

Fetal gene defects precipitate platelet-mediated pregnancy failure in factor V Leiden mothers.

We describe a mouse model of fetal loss in factor V Leiden (FvL) mothers in which fetal loss is triggered when the maternal prothrombotic state coincides with fetal gene defects that reduce activation of the protein C anticoagulant pathway within the placenta. Fetal loss is caused by disruption of placental morphogenesis at the stage of labyrinth layer formation and occurs in the absence of overt placental thrombosis, infarction, or perfusion defects. Platelet depletion or elimination of protease-activated receptor 4 (Par4) from the mother allows normal placentation and prevents fetal loss. These findings establish a cause-effect relationship for the observed epidemiologic association between maternal FvL status and fetal loss and identify fetal gene defects as risk modifiers of pregnancy failure in prothrombotic mothers. Pregnancy failure is mediated by Par4-dependent activation of maternal platelets at the fetomaternal interface and likely involves a pathogenic pathway independent of occlusive thrombosis. Our results further demonstrate that the interaction of two given thrombosis risk factors produces markedly disparate consequences on disease manifestation (i.e., thrombosis or pregnancy loss), depending on the vascular bed in which this interaction occurs.

Caveolin-1-dependent apoptosis induced by fibrin degradation products.

In mice lacking the blood coagulation regulator thrombomodulin, fibrinolytic degradation products (FDP) of fibrin induce apoptotic cell death of a specialized cell type in the placenta, polyploid trophoblast giant cells. Here, we document that this bioactivity of FDP is conserved in human FDP, is not limited to trophoblast cells, and is associated with an Aalpha-chain segment of fibrin fragment E (FnE). The majority of proapoptotic activity is arginine-glycine-aspartic acid (RGD)-independent and requires caveolin-1-dependent cellular internalization of FnE. Internalization through caveoli is mediated by an epitope contained within Aalpha52-81 that is necessary and sufficient for cellular uptake of FnE. Aalpha52-81 does not cause apoptosis itself, and competitively inhibits FnE internalization and apoptosis induction. Apoptotic activity per se resides within Aalpha17-37 and requires the N-terminal neoepitope generated by release of fibrinopeptide A. Cellular internalization of FnE elicits depression of mitochondrial function and consequent apoptosis that is strictly dependent on the activity of caspases 9 and 3. These findings describe the molecular details of a novel mechanism linking fibrin degradation to cell death in the placenta, which may also contribute to pathologic alterations in nonplacental vascular beds that are associated with fibrinolysis.

Novel self-adaptive boat-shaped complexes with a tetraphosphine ligand.

A series of novel boat-shaped host-guest complexes were designed and synthesized by the combination of a new calixarene fragment-based tetraphosphine ligand L with group 11 metal salts Cu(MeCN)4ClO4 and AgNO3 in a self-assembly process, and by the following anion exchange reactions of complex 1 with sodium p-toluenesulfonate, AcONa, PhCO2Na and sodium 9-anthrylcarboxylate. The host with a novel boat-shaped cavity is capable of self-adaptive encapsulation of various anions of different sizes through M(i)-O coordinations and CHπ interactions between the host and guest anion. The DFT calculations confirmed that the CHπ interaction played a vital role in the self-adaptive phenomenon in complexes 4-6.

Primary small cell carcinoma of the lesser omentum.

Although pulmonary small cell carcinoma (SCC) is seen frequently, SCC that originates from the extrapulmonary organs is extremely rare. We herein report a case of a SCC located in the lesser omentum. A 61-year-old male was admitted to our department due to intermittent epigastralgia for 2 months. Ultrasonography (US) revealed an irregular hypoechoic mass measuring about 58 mm × 50 mm × 45 mm under the left lobe of the liver. Magnetic resonance imaging (MRI) was performed to verify the irregular mass with T1- and T2- weighted images between the left lobe of liver and the stomach. At laparotomy, the well-circumscribed neoplasm was found in the lesser omentum, and the fundus of the neoplasm was located in the root of left gastric artery. Intraoperative microscopic evaluation of frozen sections revealed malignancy of the lesser omentum. Resection of the neoplasm was performed, and the combined resection of the vagal nerve was also performed for the partial adhesion. Pyloroplasty was performed for avoiding delayed gastric emptying caused by combined resection of vagal nerve. The lymph nodes dissection at lesser curvature and right cardia was also performed with a negative result. Based on the histological findings, the final diagnosis of primary lesser omental SCC was confirmed. The pathologic staging showed locoregional disease.

[Nonalcoholic steatohepatitis: a clinicopathological analysis of liver biopsy in 32 cases].

OBJECTIVE: To investigate the clinicopathological features of nonalcoholic steatohepatitis (NASH) and elucidate its diagnosis and differential diagnosis. METHODS: Liver biopsy tissues and clinical data of 32 patients with NASH were collected and the clinicopathological findings by HE and Masson staining were evaluated for NASH grading. RESULTS: Ballooning degeneration of the liver cells and fibrosis around hepatic sinusoid was scarce in mild NASH cases and increased in moderate to severe cases. Steatotic and inflammatory cells in the liver lobes decrease in liver cirrhosis related to seatohepatitis. CONCLUSION: Ballooning degeneration of the liver cells and fibrosis around the hepatic sinusoid have important value in differential diagnosis of mild from moderate to severe NASH, and correct histological grading benefits clinical intervention and prognostic evaluation of NASH.

[Expression of IGF-I and IGF-IR in bladder cancer].

BACKGROUND & OBJECTIVE: Insulin-like growth factors (IGF) is one of polypeptide growth factors that stimulate proliferation, survival, and differentiation in many cell types; their signal pathways implicate development and progression of many kinds of malignant tumor, while less study were undergone on the roles of IGF-I and IGF-IR in bladder cancer genesis. This study was designed to investigate the expression of IGF-I and IGF-IR and proliferation cell nuclear antigen (PCNA) in human normal and carcinomatous bladder cancer, and to explore the mechanism of IGF-I and IGF-IR in cellular proliferation and tumorigenesis of bladder cancer. METHODS: Immunohistochemical methods were adopted to examine expression of IGF-I, IGF-IR, and PCNA in 88 cases with bladder cancer and 12 cases with normal bladder tissues. The relationship of expression of IGF-I and IGF-IR with various clinicopathological parameters and PCNA were analyzed. RESULTS: The protein expression rates of IGF-I and IGF-IR in bladder cancer were 73.9% and 59.1%, significantly higher than 33.3% and 16.7% in normal tissues, respectively(P< 0.05). Both two protein expression were association with PCNA indexes in bladder cancer (P< 0.05). There were close relationship among IGF-I expression and tumor recurrence (P< 0.05), IGF-IR and tumor grade, stage and recurrence (P< 0.05). CONCLUSION: Abnormality of IGF-I-IGF-IR autocrine loop play an important role in development and progression of bladder cancer by promoting abnormal cellular proliferation. IGF-IR may be a marker for evaluating tumor biological behaviors.