Tumor location and patient characteristics of colon and rectal adenocarcinomas in relation to survival and TNM classes

<p>Abstract</p> <p>Background</p> <p>Old age at diagnosis is associated with poor survival in colorectal cancer (CRC) for unknown reasons. Recent data show that colonoscopy is efficient in preventing left-sided cancers only. We examine the association of Tumor Node Metastasis (TNM) classes with diagnostic age and patient characteristics.</p> <p>Methods</p> <p>The Swedish Family-Cancer Database has data on TNM classes on 6,105 CRC adenocarcinoma patients. Ordinal logistic regression analysis was performed to model tumor characteristics according to age at diagnosis, tumor localization, gender, socioeconomic status, medical region and family history. The results were compared to results from survival analysis.</p> <p>Results</p> <p>The only parameters systematically associated with TNM classes were age and tumor localization. Young age at diagnosis was a risk factor for aggressive CRC, according to stage, N and M with odds ratios (ORs) ranging from 1.80 to 1.93 for diagnosis before age 50 years compared to diagnosis at 80+ years. All tumor characteristics, particularly T, were worse for colon compared to rectal tumors. Right-sided tumors showed worse characteristics for all classifiers but M. The survival analysis on patients diagnosed since 2000 showed a hazard ratio of 0.55 for diagnosis before age 50 years compared to diagnosis at over 80 years and a modestly better prognosis for left-sided compared to right-sided tumors.</p> <p>Conclusions</p> <p>The results showed systematically more aggressive tumors in young compared to old patients. The poorer survival of old patients in colon cancer was not related to the available tumor characteristics. However, these partially agreed with the limited colonoscopic success with right-sided tumors.</p

Chinese herb mix Tiáo-Gēng-Tāng possesses antiaging and antioxidative effects and upregulates expression of estrogen receptors alpha and beta in ovariectomized rats

<p>Abstract</p> <p>Background</p> <p>Herb mixtures are widely used as an alternative to hormonal therapy in China for treatment of the menopausal syndrome. However, composition of these herb mixtures are complex and their working mechanism is often unknown. This study investigated the effect of Tiáo-Gēng-Tāng (TG-decoction), a Chinese herbal mixture extract, in balancing female hormones, regulating expression of estrogen receptors (ERs), and preventing aging-related tissue damage.</p> <p>Methods</p> <p>Ovariectomized 5-month-old female rats were used to model menopause and treated with either TG-decoction or conjugated estrogen for 8 weeks. Estradiol (E₂), luteinizing hormone (LH) and follicle-stimulating hormone (FSH) were measured in serum and in the hypothalamus. Hypothalamic expression of estrogen receptor (ER) alpha and beta were studied by real-time PCR and western blotting. Total antioxidant capacity (T-AOC), oxidation indicator superoxide dismutase (SOD) activity and tissue damage parameter malondialdehyde (MDA) were measured using standard assays. Aging-related ultrastructural alterations in mitochondria were studied in all animals by transmission electron microscopy.</p> <p>Results</p> <p>TG-decoction-treatment elevated E₂and lowered FSH in serum of ovariectomized rats. The potency and efficacy of TG-decoction on the hypothalamus was generally weaker than that of conjugated estrogens. However, TG-decoction was superior in upregulating expression of ERα and β. TG-decoction increased hypothalamic SOD and T-AOC levels and decreased MDAlevels and mitochondrial damage in hypothalamic neurons.</p> <p>Conclusions</p> <p>TG-decoction balances female hormones similarly to conjugated estrogens but less effectively. However, it is superior in up regulating ERα and β and exhibits antioxidative antiaging activities. Whilst it shares similar effects with estrogen, TG-decoction also seems to have distinctive and more complex functions and activities.</p

Hyper-IgG4 disease: report and characterisation of a new disease

BACKGROUND: We highlight a chronic inflammatory disease we call 'hyper-IgG4 disease', which has many synonyms depending on the organ involved, the country of origin and the year of the report. It is characterized histologically by a lymphoplasmacytic inflammation with IgG4-positive cells and exuberant fibrosis, which leaves dense fibrosis on resolution. A typical example is idiopathic retroperitoneal fibrosis, but the initial report in 2001 was of sclerosing pancreatitis. METHODS: We report an index case with fever and severe systemic disease. We have also reviewed the histology of 11 further patients with idiopathic retroperitoneal fibrosis for evidence of IgG4-expressing plasma cells, and examined a wide range of other inflammatory conditions and fibrotic diseases as organ-specific controls. We have reviewed the published literature for disease associations with idiopathic, systemic fibrosing conditions and the synonyms: pseudotumour, myofibroblastic tumour, plasma cell granuloma, systemic fibrosis, xanthofibrogranulomatosis, and multifocal fibrosclerosis. RESULTS: Histology from all 12 patients showed, to varying degrees, fibrosis, intense inflammatory cell infiltration with lymphocytes, plasma cells, scattered neutrophils, and sometimes eosinophilic aggregates, with venulitis and obliterative arteritis. The majority of lymphocytes were T cells that expressed CD8 and CD4, with scattered B-cell-rich small lymphoid follicles. In all cases, there was a significant increase in IgG4-positive plasma cells compared with controls. In two cases, biopsies before and after steroid treatment were available, and only scattered plasma cells were seen after treatment, none of them expressing IgG4. Review of the literature shows that although pathology commonly appears confined to one organ, patients can have systemic symptoms and fever. In the active period, there is an acute phase response with a high serum concentration of IgG, and during this phase, there is a rapid clinical response to glucocorticoid steroid treatment. CONCLUSION: We believe that hyper-IgG4 disease is an important condition to recognise, as the diagnosis can be readily verified and the outcome with treatment is very good

Notes for genera: basal clades of Fungi (including Aphelidiomycota, Basidiobolomycota, Blastocladiomycota, Calcarisporiellomycota, Caulochytriomycota, Chytridiomycota, Entomophthoromycota, Glomeromycota, Kickxellomycota, Monoblepharomycota, Mortierellomycota, Mucoromycota, Neocallimastigomycota, Olpidiomycota, Rozellomycota and Zoopagomycota)

Compared to the higher fungi (Dikarya), taxonomic and evolutionary studies on the basal clades of fungi are fewer in number. Thus, the generic boundaries and higher ranks in the basal clades of fungi are poorly known. Recent DNA based taxonomic studies have provided reliable and accurate information. It is therefore necessary to compile all available information since basal clades genera lack updated checklists or outlines. Recently, Tedersoo et al. (MycoKeys 13:1--20, 2016) accepted Aphelidiomycota and Rozellomycota in Fungal clade. Thus, we regard both these phyla as members in Kingdom Fungi. We accept 16 phyla in basal clades viz. Aphelidiomycota, Basidiobolomycota, Blastocladiomycota, Calcarisporiellomycota, Caulochytriomycota, Chytridiomycota, Entomophthoromycota, Glomeromycota, Kickxellomycota, Monoblepharomycota, Mortierellomycota, Mucoromycota, Neocallimastigomycota, Olpidiomycota, Rozellomycota and Zoopagomycota. Thus, 611 genera in 153 families, 43 orders and 18 classes are provided with details of classification, synonyms, life modes, distribution, recent literature and genomic data. Moreover, Catenariaceae Couch is proposed to be conserved, Cladochytriales Mozl.-Standr. is emended and the family Nephridiophagaceae is introduced

15 years of reuse experience in evolutionary prototyping for the defense industry

International audienceAt Thales Defense Mission Systems, software products first go through an industrial prototyping phase. We elaborate evolutionary prototypes which implement complete business behavior and fulfill functional requirements. We elaborate and evolve our solutions directly with end-users who act as stake-holders in the products' design. Prototypes also serve as models for the final products development. Because software products in the defense industry are developed over many years, this prototyping phase is crucial. Therefore, reusing software is a high-stakes issue in our activities. Component-oriented development helps us to foster reuse throughout the life cycle of our products. The work presented in this paper stems from 15 years of experience in developing prototypes for the defense industry. We directly reuse component implementations to build new prototypes from existing ones. We reuse component interfaces transparently in multiple prototypes, whatever the underlying implementation solutions. This kind of reuse spans prototypes and final products which are deployed on different execution platforms. We reuse non-component legacy software that we integrate in our component architectures. In this case, we seamlessly augment standard classes with component behavior, while preserving legacy code. In this paper, we present our component programming framework with a focus on component reuse in the context of evolutionary prototyping. We report three scenarios of reuse that we encounter regularly in our prototyping activity

Growth inhibitory activity of a novel lectin from Cliona varians against K562 human erythroleukemia cells

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)Purpose In this study, the antitumoral potential of a novel lectin (CvL) purified from the marine sponge Cliona varians was studied in different cancer cell lines. Methods CvL cytotoxicity was evaluated in mammalian tumor cells and in normal human peripheral blood lymphocytes by the MTT assay using the same range of concentrations (1 - 150 mu g ml(-1)). The mechanisms involved in K562 cell death were investigated by confocal fluorescence microscopy, flow cytometry and immunoblot. Results CvL inhibited the growth of human leukemia cells, with IC(50) values of 70 and 100 mu g ml(-1) for K562 and JURKAT cells, respectively, but it was ineffective on blood lymphocytes and solid tumor cell lines. K562 cell death occurred 72 h after exposure to the lectin and with signs of apoptosis, as analyzed by DAPI and annexin V/PI staining. Investigation of the possible mediators of this process showed that cell death occurred via a caspase-independent pathway. Confocal fluorescence microscopy indicated a pivotal role for the lysosomal protease cathepsin B in mediating cell death. Accordingly, pre-incubation of K562 cells with the cathepsin inhibitor L-trans-epoxysuccinyl-L-leucylamido-(4-guanidino) butane (E-64) abolished CvL cytotoxic eVect. Furthermore, we found upregulation of tumor necrosis factor receptor 1 (TNFR1) and down-modulation of p65 subunit of nuclear factor kappa B ( NF kappa B) expression in CvL-treated cells. These effects were accompanied by increased levels of p21 and reduced expression of pRb, suggesting that CvL can induce cell cycle arrest. Conclusions Collectively, these findings indicate an anti-leukemic eVect for CvL and suggest that cathepsin B acts as a death mediator in CvL-induced cytotoxicity possibly in an uncharacterized connection with the membrane death receptor pathway.63610231033Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Financiadora de Estudos e Projetos (FINEP)Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)FAPESP [06/07315-3