A Cystic Lymphangioma of the Colon Seen in a Patient with Early Gastric Cancer

Lymphangiomas are very rare benign neoplasms of the gastrointestinal tract. A case of cystic lymphangioma in the hepatic flexure of the colon seen in patient with early gastric cancer is reported and the literature is reviewed

Lymphangioma of the Small Intestine : A Case Report

Lymphangiomas of the small intestine are rare tumors arising from masses of dilated lymphatic vessels in the submucosa. There are 11 cases of lymphangioma of the small intestine in the Japanese literature. We report a case of lymphangioma of the jejunum seen in a 76-year-old female and discuss with clinical feature

大腸3D-CT検査(CT-colonography)における腸管外病変の検出

大腸疾患患者を対象に大腸3D-CT検査(CT-colonography)を施行し,腸管外病変の検出率,検出された腸管外病変の臨床的重要性の分類および大腸疾患の有無と腸管外病変の関係の3項目について検討した.その結果,対象者112例のうち84.8%の症例に少なくとも1つ以上の腸管外病変を認めた.また,対象例のうち33例(29.5%)にカテゴリーE4(臨床上重要な所見を有する)群に分類される腸管外病変を認めた.そして,カテゴリーE4群のうち大腸内視鏡検査で24例(72.7%)が大腸癌と,4例(12.1%,全例に対する比率:3.6%)が所見なしと診断された.これらのことから,大腸疾患およびその疑いを有する症例にCT-colonographyを施行することは,大腸疾患を有する症例はもとより内視鏡検査で所見なしと診断された症例においても,重大な腸管外病変の早期発見に有用である

Evidence for mitochondrial localization of a novel human sialidase (NEU4)

Based on the human cDNA sequence predicted to represent the NEU4 sialidase gene in public databases, a cDNA covering the entire coding sequence was isolated from human brain and expressed in mammalian cells. The cDNA encodes two isoforms: one possessing an N-terminal 12-amino-acid sequence that is predicted to be a mitochondrial targeting sequence, and the other lacking these amino acids. Expression of the isoforms is tissuespecific, as assessed by reverse transcription–PCR. Brain, muscle and kidney contained both isoforms; liver showed the highest expression, and the short form was predominant in this organ. In transiently transfected COS-1 cells, enzyme activity was markedly increased with gangliosides as well as with glycoproteins and oligosaccharides as substrates compared with the control levels. This differs from findings with other human sialidases. Although the isoforms were not distinguishable with regard to substrate specificity, they exhibited differential subcellular localizations. Immunofluorescence microscopy and biochemical fractionation demonstrated that an exogenously expressed haemagglutinin-tagged long form of NEU4 was concentrated in mitochondria in several human culture cell types, whereas the short form was present in intracellular membranes, indicating that the sequence comprising the N-terminal 12 amino acid residues acts as a targeting signal for mitochondria. Co-localization of the long form to mitochondria was further supported by efficient targeting of the N-terminal region fused to enhanced green fluorescent protein, and by the targeting failure of a mutant with an amino acid substitution in this region. NEU4 is possibly involved in regulation of apoptosis by modulation of ganglioside G(D3), which accumulates in mitochondria during apoptosis and is the best substrate for the sialidase

Reduced susceptibility to colitis-associated colon carcinogenesis in mice lacking plasma membrane-associated sialidase.

Sialic acids are acidic monosaccharides that bind to the sugar chains of glycoconjugates and change their conformation, intermolecular interactions, and/or half-life. Thus, sialidases are believed to modulate the function of sialoglycoconjugates by desialylation. We previously reported that the membrane-associated mammalian sialidase NEU3, which preferentially acts on gangliosides, is involved in cell differentiation, motility, and tumorigenesis. The NEU3 gene expression is aberrantly elevated in several human cancers, including colon, renal, prostate, and ovarian cancers. The small interfering RNA-mediated knock-down of NEU3 in cancer cell lines, but not in normal cell-derived primary cultures, downregulates EGFR signaling and induces apoptosis. Here, to investigate the physiological role of NEU3 in tumorigenesis, we established Neu3-deficient mice and then subjected them to carcinogen-induced tumorigenesis, using a sporadic and a colitis-associated colon cancer models. The Neu3-deficient mice showed no conspicuous accumulation of gangliosides in the brain or colon mucosa, or overt abnormalities in their growth, development, behavior, or fertility. In dimethylhydrazine-induced colon carcinogenesis, there were no differences in the incidence or growth of tumors between the Neu3-deficient and wild-type mice. On the other hand, the Neu3-deficient mice were less susceptible than wild-type mice to the colitis-associated colon carcinogenesis induced by azoxymethane and dextran sodium sulfate. These results suggest that NEU3 plays an important role in inflammation-dependent tumor development

Limited Inhibitory Effects of Oseltamivir and Zanamivir on Human Sialidases▿

Oseltamivir (Tamiflu) and zanamivir (Relenza), two extensively used clinically effective anti-influenza drugs, are viral sialidase (also known as neuraminidase) inhibitors that prevent the release of progeny virions and thereby limit the spread of infection. Recently mortalities and neuropsychiatric events have been reported with the use of oseltamivir, especially in pediatric cases in Japan, suggesting that these drugs might also inhibit endogenous enzymes involved in sialic acid metabolism, including sialidase, sialyltransferase, and CMP-synthase, in addition to their inhibitory effects on the viral sialidase. The possible inhibition could account for some of the rare side effects of oseltamivir. However, there has been little direct evidence in regard to the sensitivities of animal sialidases to these drugs. Here, we examined whether these inhibitors might indeed affect the activities of human sialidases, which differ in primary structures and enzyme properties but possess tertiary structures similar to those of the viral enzymes. Using recombinant enzymes corresponding to the four human sialidases identified so far, we found that oseltamivir carboxylate scarcely affected the activities of any of the sialidases, even at 1 mM, while zanamivir significantly inhibited the human sialidases NEU3 and NEU2 in the micromolar range (Ki, 3.7 ± 0.48 and 12.9 ± 0.07 μM, respectively), providing a contrast to the low nanomolar concentrations at which these drugs block the activity of the viral sialidases

NEU3-mediated potentiation of cell growth assessed by MTT assays and colony formation assays.

<p>(A) The cell growth curves of NEU3-transfected cells were compared with those of vector controls in the absence and presence of murine EGF (20 ng/ml). Three independent experiments were performed (mean ±SD). (B) The cell growth curves of EGFR- and EGFR/NEU3-transfected cells are shown with or without EGF in independent experiments performed in triplicate (mean ±SD). (C) Colony formation assays in the transfectants. The cells were plated at 1000 cells/well in six-well dishes with or without EGF, and the colonies were quantified after 7–14 days of culture. Representative images are shown. (D) Values represent means with standard deviations obtained from three independent experiments. In the right graph, the number of colonies over 3.0 mm in size was counted in independent experiments performed in triplicate (mean ±SD).</p

NEU3-mediated potentiation of cell growth assessed by MTT assays and colony formation assays.

<p>(A) The cell growth curves of NEU3-transfected cells were compared with those of vector controls in the absence and presence of murine EGF (20 ng/ml). Three independent experiments were performed (mean ±SD). (B) The cell growth curves of EGFR- and EGFR/NEU3-transfected cells are shown with or without EGF in independent experiments performed in triplicate (mean ±SD). (C) Colony formation assays in the transfectants. The cells were plated at 1000 cells/well in six-well dishes with or without EGF, and the colonies were quantified after 7–14 days of culture. Representative images are shown. (D) Values represent means with standard deviations obtained from three independent experiments. In the right graph, the number of colonies over 3.0 mm in size was counted in independent experiments performed in triplicate (mean ±SD).</p