RNA-binding proteins: Underestimated contributors in tumorigenesis.

mRNA export, translation, splicing, cleavage or capping determine mRNA stability, which represents one of the primary aspects regulating gene expression and function. RNA-binding proteins (RBPs) bind to their target mRNAs to regulate multiple cell functions by increasing or reducing their stability. In recent decades, studies of the role of RBPs in tumorigenesis have revealed an increasing number of proteins impacting the prognosis, diagnosis and cancer treatment. Several RBPs have been identified based on their interactions with oncogenes or tumor suppressor genes in human cancers, which are involved in apoptosis, the epithelial-mesenchymal transition (EMT), DNA repair, autophagy, cell proliferation, immune response, metabolism, and the regulation of noncoding RNAs. In this review, we propose a model showing how RBP mutations influence tumorigenesis, and we update the current knowledge regarding the molecular mechanism by which RBPs regulate cancer. Special attention is being devoted to RBPs that represent prognostic and diagnostic factors in cancer patients.

Ambient pressure phase transitions over Ir(1 1 1): at the onset of CO oxidation.

In this study we report on the adsorbate structures on an Ir(1 1 1) surface during the phase transition from the inactive to the active state during CO oxidation. The CO oxidation over Pt(1 1 1) is used as a reference case. Where Pt(1 1 1) either is inactive and CO covered or active and O covered, Ir(1 1 1) exhibits a transition state with co-existing chemisorbed O and CO. The observed structural differences are explained in terms of DFT-calculated adsorption energies. For Pt(1 1 1) the repulsive CO-O interaction makes co-existing chemisorbed CO and O unfavourable, while for Ir(1 1 1) the stronger O and CO adsorption allows for overcoming the repulsive interaction. At the onset of CO oxidation over Ir(1 1 1), a CO structure containing defects forms, which enables O2 to dissociatively adsorb on the Ir(1 1 1) surface, thus enabling the CO oxidation reaction. At the mass transfer limit, the Ir(1 1 1) surface is covered by a chemisorbed O structure with defects; hence, the active surface is predominately chemisorbed O covered at a total pressure of 0.5 mbar and no oxide formation is observed.

Semi-allogeneic dendritic cells injected via the intratumoural injection route show efficient antitumour effects in cooperation with host-derived professional antigen-presenting cells.

Dendritic cells (DC)-based immunotherapy is a potent anticancer modality. In DC-based immunotherapy, allogeneic DC may be an alternative source, but the usefulness of allogeneic DC in DC-based immunotherapy is still controversial. When used for immunotherapy, three factors may affect the efficiency of an allogeneic DC-driven antitumour response: (1) survival time, which is affected by T-cell alloresponses; (2) major histocompatibility complex incompatibility with the host cells in the context of antigen presentation; and (3) the role of host-derived professional antigen-presenting cells (pAPC). In addition, it is unclear which injection route is preferable when using allogeneic DC. In this study, we demonstrate that semi-allogeneic DC, which share half of the genes of the recipient, are more effective when used via the intratumoural (i.t.) injection route, rather than the subcutaneous (s.c.) injection route, for the induction of efficient antitumour effects and the generation of a significant tumour-specific CD8(+) T-cell response. The i.t. route has the advantage of not requiring ex vivo pulsation with tumour lysates or tumour antigens, because the i.t.-injected DC can engulf tumour antigens in situ. Allogeneic bone marrow transplantation (BMT) models, which permit us to separately assess the three factors described previously, show that while all three factors are important for efficient antitumour effects, the control of the alloresponse to injected DC is the most crucial for host-derived pAPC to function well when DC are administered intratumourally. This information may be useful for DC-based cancer immunotherapy under circumstances that do not allow for the use of autologous DC.

Acute methemoglobinemia associated with ochronotic valvular heart disease: report of a case.

We describe the first reported case of acute methemoglobinemia associated with ochronotic valvular heart disease. A 79-year-old man with ochronotic valvular heart disease experienced decreased urinary output starting 9 days after an operation. Thereafter, the patient's methemoglobin concentration acutely increased, indicating systemic cyanosis, while the arterial partial oxygen pressure (PaO (2)) was maintained at around 200 mmHg. In patients with ochronotic valvular heart disease, acute methemoglobinemia may occur, as in cases of renal failure or oliguresis.

Simultaneous treatment of pulmonary AV malformation with rheumatic heart disease.

Only 13 cases of pulmonary arteriovenous malformation (PAVM) combined with rheumatic heart disease have been reported, and only 3 have been treated simultaneously by surgery. Transcatheter embolotherapy, the first-line treatment of PAVM, avoids major surgery, general anesthesia, and the loss of pulmonary parenchyma, but the subsequent PAVM reperfusion can occur through recanalization of the embolized arteries. We report a case of PAVM with rheumatic heart disease, in which both diseases were simultaneously treated by surgery.

Rplp1 bypasses replicative senescence and contributes to transformation.

To determine whether genes expressed by embryonic stem cells have a proliferative effect in primary cells, primary mouse embryonic fibroblasts were infected with an ES cell cDNA library. This led to identification of the ribosomal protein, Rplp1, a member of the P group of ribosomal proteins, whose putative role for bypassing replicative senescence in MEFs was investigated. Our results show that Rplp1 produces a two-fold increase in the expression of an E2F1 promoter and upregulation of cyclin E in MEFs. Therefore, this study is the first to show that overexpression of a single ribosomal protein, Rplp1, is a cause and not a consequence of cell proliferation. In addition, co-expression of Rplp1 with mutant rasVal12 contributed to transformation in NIH3T3 cells, as was evidenced by colony production in soft-agar assays. Moreover, the Rplp1 protein was upregulated in MEFs and NIH3T3 cells upon expression of a p53 dominant negative mutant gene designated p53R175H. Hence, mutation of p53 may facilitate immortalization in vitro by upregulating Rplp1. Lastly, Rplp1 mRNA was found to be upregulated in 16 of 26 human colon cancer biopsy specimens, a finding that may be of relevance to cancer research.

Proton transfer in a two-dimensional hydrogen-bonding network: water and hydroxyl on a pt(111) surface.

The time scale of proton transfer between H(2)O and OH adsorbed on a Pt(111) surface was determined by a combination of laser-induced thermal desorption (LITD) and microscale x-ray photoelectron spectroscopy (micro-XPS). The patterned distribution OH+H(2)O/H(2)O/OH + H(2)O was initially prepared on the Pt(111) surface by the LITD method and the time evolution of the spatial distribution of H(2)O and OH was observed by the micro-XPS technique. From quantitative analyses based on a diffusion equation, we found two proton-transfer pathways with different time scales of 5.2+/-0.9 ns and 48+/-12 ns at 140 K, which were attributed to direct proton transfer to the neighbor site and H(3)O(+)-mediated transfer to the next-nearest site, respectively.

Acute renal infarction in a patient with left atrial myxoma.

A 24-year-old male first attended our hospital with acute onset of right flank pain radiating to the right lower quadrant of the abdomen. A contrast-enhanced computer tomography (CT) scan showed renal infarction, and he was admitted immediately for treatment. On admission, the right lower abdominal pain diminished gradually. On the second day in hospital, a left atrial echogenic mass was detected which filled the left atrial cavity; it appeared to be a left atrial myxoma measuring 3.9+/-4.9 cm. The patient was immediately transferred and underwent emergency surgery. Histologic examination confirmed the diagnosis of myxoma. Post-operatively, he recovered well and was discharged from hospital without any further specific treatment.

Protection from oxidative stress by enhanced glycolysis; a possible mechanism of cellular immortalization.

Reactive oxygen species (ROS) play a crucial role not only in the physiological signal transduction but also in the pathogenesis of several human diseases such as atherosclerosis, neuro-degenerative diseases, metabolic disorders, aging or cancer amongst others. Oxidative stress is also responsible for cellular and organism senescence, in accordance with what Harman initially proposed in the free radical theory of aging. Recent findings support the notion that protection from oxidative stress can increase life span significantly. We reported that enhanced glycolysis could modulate cellular life span with reduction of oxidative stress. Moreover, the tumor suppressor gene p53 controls post-transcriptionally the level of the glycolytic enzyme, phosphoglycerate mutase (PGM). As enhanced glycolysis is a distinctive and prominent feature of cancer cells (termed the Warburg effect), our findings disclosed a novel aspect of the Warburg effect: the connection between senescence and oxidative stress.

New p53 related genes in human tumors: significant downregulation in colon and lung carcinomas.

Human epithelial tumors need to accumulate multiple genetic alterations to form invasive carcinomas. These genetic alterations are related with growth factor receptors, cell signalling, the cell cycle and cell invasiveness. Importantly, cells need to avoid senescence and become immortalized for this process. Recently, five genes: RPS6KA6, HDAC4, KIAA0828, TCP1 and Tip60, which modulate p53-dependent function and avoid senescence were identified in a large-scale RNA interference screen. Twenty colon, 20 prostate and 20 lung carcinomas were studied to investigate whether these genes might be related with human tumors. RNA was extracted from both normal and tumor tissue from each patient. Real-time RT-PCR was performed using TaqMan probes corresponding to the RPS6KA6, HDAC4, KIAA0828, TCP1, Tip60 and p53 genes. In colon carcinomas, the RPS6KA6, HDAC4, KIAA0828 and Tip60 genes were downregulated in tumor tissue as compared with normal tissue (P < 0.001 for all genes). In lung carcinomas, HDAC4, KIAA0820 and Tip60 were downregulated (P < 0.01, P < 0.001 and P < 0.001 respectively). Whereas no significant differences were observed in prostate carcinomas, striking downregulation of the RPS6KA6 and KIAA0828 genes was observed in colon carcinomas and KIAA0828 in a subset of lung carcinomas. mRNA expression of these genes may control p53 function as well as the ras-MAPK pathway, methylation and transcriptional cellular programs. These results could unravel a novel set of regulatory suppressor genes involved in human colon and lung tumors.

Mechanism of the CO oxidation reaction on O-precovered Pt(111) surfaces studied with near-edge x-ray absorption fine structure spectroscopy.

The mechanism of CO oxidation reaction on oxygen-precovered Pt(111) surfaces has been studied by using time-resolved near-edge x-ray absorption fine structure spectroscopy. The whole reaction process is composed of two distinct paths: (1) a reaction of isolated oxygen atoms with adsorbed CO, and (2) a reaction of island-periphery oxygen atoms after the CO saturation. CO coadsorption plays a role to induce the dynamic change in spatial distribution of O atoms, which switches over the two reaction paths. These mechanisms were confirmed by kinetic Monte Carlo simulations. The effect of coadsorbed water in the reaction mechanism was also examined.

Expression of DCC and netrin-1 in normal human endometrium and its implication in endometrial carcinogenesis.

OBJECTIVE: Although DCC has been considered as a candidate tumor suppressor, the roles it plays in the uterine endometrium and in the carcinogenic process remains unclear. To define these roles more clearly, we examined the expression of DCC and its ligand, netrin-1, in the normal endometrium and in endometrial cancer. METHODS: The expression of DCC and netrin-1 in normal endometrial glands and in cancer cell lines was examined by RT-PCR and immunohistochemistry. The effects of exogenous DCC and netrin-1 expression were observed together with the respective expression vector transfection. RESULTS: Endometrial glands in the proliferative and early secretory phase expressed both DCC and netrin-1, but glands in the late-secretory phase tended to silence DCC expression. In addition, all of the endometrial cancer cell lines lost normal DCC expression. Restored DCC expression in the cancer cell lines in the absence of netrin-1 induced apoptosis. However, no changes were observed in the presence of netrin-1. CONCLUSION: Our observations suggest that DCC/netrin-1 signaling may commit cells to the transition of endometrial gland architecture or function from a proliferating to a secretory phase. In addition, the silencing of DCC expression may contribute to the escape of endometrial cancer cells from a DCC-regulated apoptotic program, thereby promoting malignant phenotypes.

Reaction-path switching induced by spatial-distribution change of reactants: CO oxidation on Pt(111).

We studied the mechanism of CO oxidation on O-covered Pt(111) surfaces during CO exposure by means of time-resolved near edge x-ray absorption fine structure spectroscopy. Two distinct reaction processes were found to occur sequentially; isolated O atoms and island-periphery O atoms contribute to each process. Combination of in situ monitoring of the reaction kinetics and Monte Carlo simulations revealed that CO coadsorption plays a role of inducing the dynamic change in spatial distribution of O atoms, which switches over the two reaction paths.

Adsorption of thiolates to singly coordinated sites on Au111 evidenced by photoelectron diffraction.

The adsorption structure of methylthiolate (CH3S) adsorbed on Au(111), a long-standing controversial issue, has been unambiguously determined by scanned-energy and scanned-angle S 2p photoelectron diffraction. The methylthiolate molecules are found to occupy atop sites with a S-Au distance of 2.42 +/- 0.03 A. The angular distribution of the S 2p photoelectrons due to forward scattering reveals that the S-C bond is inclined by approximately 50 degrees from the surface normal towards both the [211] and [121] (nearest-neighbor thiolate) directions.

Protein levels of genes encoded on chromosome 21 in fetal Down syndrome brain: challenging the gene dosage effect hypothesis (Part II).

Down syndrome (DS) is the most common genetic cause of mental retardation. To explain the impact of extra chromosome 21 in the pathology of DS, gene dosage effect hypothesis has been proposed, but several investigators including our group have challenged this hypothesis. Although analysis of the sequence of chromosome 21 has been essentially completed, the molecular and biochemical mechanisms underlying the pathology are still unknown. We therefore investigated expression levels of six proteins encoded on chromosome 21 (HACS1, DYRK1A, alphaA-crystallin, FTCD, GARS-AIRS-GART, and CBS) in fetal cerebral cortex from DS and controls at 18-19 weeks of gestational age using Western blot analysis. Protein expression of HACS1 was significantly and remarkably decreased in DS, and the expression levels of five proteins were comparable between DS and controls suggesting that the gene dosage effect hypothesis is not sufficient to fully explain the DS phenotype. We are continuing to quantify proteins whose genes are encoded on chromosome 21 in order to provide a better understanding of the pathobiochemistry of DS at the protein level.

The effect of basic fibroblast growth factor on the regeneration of guinea pig olfactory epithelium.

Olfactory receptor cells are widely thought to regenerate after degeneration and also thought to show turnover in normal circumstances in animal olfactory epithelium. The identity of the factor that controls proliferation and differentiation of olfactory receptor cells is a very important problem that has yet to be resolved. In this study, the mitogenic effects of epidermal growth factor (EGF) and basic fibroblast growth factor (bFGF) on olfactory receptor cells in guinea pig olfactory epithelium was examined. The intraperitoneal injection of 1,000 ng bFGF/day for 14 days increased the cells in proliferation detected by immunostaining with proliferating cell nuclear antigen (PCNA), while neither EGF nor low-dose bFGF had any effect. These results support the idea that an adequate dose of bFGF plays an important role in the neurogenesis in the olfactory epithelium. Further study is needed to clarify the efficacy of bFGF in the damaged olfactory epithelium, but bFGF may provide a therapeutic option for olfactory disturbances caused by complete or partial loss of olfactory receptor cells.

Chromosome assignment of eight SOX family genes in chicken.

Chromosome locations of the eight SOX family genes, SOX1, SOX2, SOX3, SOX5, SOX9, SOX10, SOX14 and SOX21, were determined in the chicken by fluorescence in situ hybridization. The SOX1 and SOX21 genes were localized to chicken chromosome 1q3.1-->q3.2, SOX5 to chromosome 1p1.6-->p1.4, SOX10 to chromosome 1p1.6, and SOX3 to chromosome 4p1.2-->p1.1. The SOX2 and SOX14 genes were shown to be linked to chromosome 9 using two-colored FISH and chromosome painting, and the SOX9 gene was assigned to a pair of microchromosomes. These results suggest that these SOX genes form at least three clusters on chicken chromosomes. The seven SOX genes, SOX1, SOX2, SOX3, SOX5, SOX10, SOX14 and SOX21 were localized to chromosome segments with homologies to human chromosomes, indicating that the chromosome locations of SOX family genes are highly conserved between chicken and human.

PACS linked to EPR.

We developed a new PACS linked to Electronic Patient Record system (EPR). It was a hospital-wide PACS storing all the radiological examinations. The images and reports were linked on EPR. The concept of navigation servers and segment servers was introduced for prefetchig and quick displaying. After the start of operation, increasing retrieval indicated its effectiveness on practical work in spite of remaining delivery of radiographs.

Complete response of a stage IV mucinous cystadenocarcinoma of the ovary to systemic chemotherapy employing paclitaxel and carboplatin.

BACKGROUND: The survival rate of patients with advanced-stage mucinous cystadenocarcinoma of the ovary is dismal and no best treatment is known. We report a case of complete response of a stage IV mucinous cystadenocarcinoma of the ovary to systemic chemotherapy employing paclitaxel and carboplatin. CASE: A 51-year-old nullipara diagnosed with International Federation of Gynecology and Obstetrics stage IV mucinous cystadenocarcinoma of the ovary underwent cytoreductive surgery followed by systemic chemotherapy employing paclitaxel and carboplatin every 4 weeks for 3 courses. The patient tolerated chemotherapy well, demonstrated a remarkable response showing no evidence of malignancy at a second-look laparotomy. As a consolidation chemotherapy after negative second-look laparotomy, she underwent another three courses of chemotherapy of the same regimen, and is showing no evidence of disease. CONCLUSION: Paclitaxel and carboplatin may be effective in treating mucinous cystadenocarcinoma of the ovary.

Characterization of ruthenium-dinitrogen tetraamine complexes by XAFS spectroscopy.

A reaction between N2 and trans-Ru(II)Cl2L (L=2,5,9,12-tetramethyl-2.5,9,12-tetraazatridecane) in aqueous solutions has been investigated by XAFS spectroscopy. Ru K-edge EXAFS clearly revealed that there exists an N2-bridged binuclear complex and that the Ru-Ru distance is 4.96 A with the coordination number of 0.5. The Ru K-edge energies of the N2 complexes are closer to that of Ru(III)Cl2L+ rather than that of Ru(II)Cl2L, indicating back donation from the Ru dpi to the N2 pi* orbitals.