346 research outputs found

    L’an zéro du monde contemporain à la Biennale de Venise: de Aperto à une Strada Novissima

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    La question de l’année 1980, envisagée comme «an zéro du monde contemporain», se cristallise dans le domaine artistique lors de la Biennale de Venise, et plus précisément à travers deux expositions qui ont écrit cette année-là l’histoire de la discipline, et a fortiori l’histoire de la Biennale elle-même: Aperto, organisée par le curateur suisse Harald Szeemann, et La Presenza del Passato (La Présence du Passé), avec sa partie principale, La Strada Novissima, dirigée par l’architecte italien ..

    MLH1-deficient HCT116 colon tumor cells exhibit resistance to the cytostatic and cytotoxic effect of the poly(A) polymerase inhibitor cordycepin (3'-deoxyadenosine) in vitro

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    Cordycepin (3'-deoxyadenosine) is an inhibitor of poly(A) polymerase (PAP), an enzyme crucial to mRNA 3'-end processing, which produces the shortening of poly(A) tails, leading to the destabilization of mRNAs. Cordycepin inhibits proliferation and induces apoptosis in tumor cells, indicating its antitumor activity. Defective 3'-end processing is associated with hypersensitivity to UV treatment. We investigated the effects of cordycepin on proliferation and apoptosis in MLH1-deficient and MLH1-proficient HCT116 colon tumor cells. MLH1 is a DNA mismatch repair (MMR) protein involved in the processing of damaged DNA. Cells with defective MMR show resistance to certain anticancer drugs. The results showed that MLH1-deficient HCT116 cells are 2-fold less sensitive to the cytostatic effect of cordycepin, as compared to MLH1-proficient cells. This reduced sensitivity to cordycepin in MLH1-deficient cells was associated with reduced upregulation of the cell cycle inhibitor p21. MLH1-deficient cells also exhibited reduced susceptibility to apoptosis upon treatment with cordycepin, as demonstrated by the reduced PARP-1 cleavage. Our findings showed that MLH1-deficient HCT116 colon tumor cells are resistant to the cytostatic and cytotoxic effect of cordycepin, indicating a possible involvement of MMR in mRNA polyadenylation. The findings also suggest that cordycepin is not suitable to therapeutically encounter tumor cells lacking MLH1 expression

    The antibody-mediated targeted delivery of interleukin-10 inhibits endometriosis in a syngeneic mouse model

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    BACKGROUND Endometriosis is still a highly underdiagnosed disease, and the current medical and surgical treatment of endometriosis is associated with a high recurrence rate. This study investigates the use of derivatives of the human antibody F8, specific to the alternatively spliced extra-domain A of fibronectin (Fn), for the imaging and treatment of endometriosis. METHODS Immunohistochemistry and immunofluorescence was used to evaluate antigen expression in endometriotic tissue of human endometriosis and of a syngeneic mouse model of the disease. The in vivo targeting performance of a fluorescent derivative of the F8 antibody was assessed by imaging mice with endometriosis using a near-infrared fluorescence imager, 24 h following i.v. injection of the antibody conjugate. Furthermore, the mouse model was used for therapy experiments using two recombinant F8-based immunocytokines [F8-interleukin-10 (IL10) and F8-IL2] or saline for the treatment groups. RESULTS A very strong vascular expression of splice isoforms of Fn and of tenascin-C was observed in human endometriotic lesions by immunohistochemistry and immunofluorescence techniques. After i.v. administration, a selective accumulation of the F8 antibody in endometriotic lesions could be observed in a syngeneic mouse model. These targeting data were used as a basis for therapy experiments with a pro-inflammatory (F8-IL2) and an anti-inflammatory (F8-IL10) cytokine fusion protein of the F8 antibody. The average lesion size in the F8-IL10 treatment group was clearly reduced compared with the saline control group and with the F8-IL2 group, for which no therapeutic effects were observed. CONCLUSIONS The F8 antibody targets endometriotic lesions in vivo in a mouse model of endometriosis and may be used for the non-invasive imaging of the disease and for the pharmacodelivery of anti-inflammatory cytokines, such as IL1

    Inpatient and outpatient loop electrosurgery excision procedure for cervical intraepithelial neoplasia: a retrospective analysis

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    Purpose: To determine whether the outpatient loop electrosurgical excision procedure (LEEP) conization (out-LEEP) is as effective and safe as inpatient LEEP conization (in-LEEP) with regard to the complete removal of cervical dysplasia, recurrence-free survival and post-operative morbidity. Methods: 233 patients were included in this retrospective cohort study from January 2002 to December 2007. 181 had outpatient treatment and 52 inpatient treatment. We used Mann-Whitney U test, two-sided Fisher's exact test, Chi-square test, log rank test and Kaplan-Meier curve. Results: Incomplete excision was found in 16/52 (30.8%) cases in the inpatient group and 46/181 (25.4%) in the outpatient group (P=0.48). Six patients had post-operative complications: two cases of secondary haemorrhage in each group (in-LEEP 3.8%, out-LEEP 1.1%, P=0.22) and two cases of cervical stenosis amongst inpatients (3.8%, P=0.049). Alteration of specimen by thermal artifact were reported in 4/52 (7.7%) of in-LEEP cones and 10/181 (5.5%) of out-LEEP cones (P=0.52). Measurements of cones in both groups were comparable with a mean depth of 9.35mm (±5.5mm) and 8.4mm (±3.4mm), respectively. Conclusion: Our results suggest that efficacy and safety of ambulatory LEEP conization is comparable as in inpatient procedur

    Popularity of endocrine endometriosis drugs and limited alternatives in the present and foreseeable future: A survey among 1420 affected women

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    Objectives: Endocrine drugs represent an important cornerstone of endometriosis therapy. Pharmaceutical alternatives with similar efficacy remain out of sight in the near future. Aim of this study is to investigate attitudes and perceptions concerning endocrine therapies among affected women. Study design: An online survey was distributed via social media in Austria, Germany, and Switzerland. Primary endpoints were satisfaction, attitudes and perceptions towards endocrine endometriosis drugs and secondary outcomes differences regarding demographic variables. Results: Of 1420 respondents, 63.5 % (n = 901) described their own attitude towards these drugs as rather negative. The most frequently reported unfavorable associations and experiences were sideeffects in general (85.5 %, n = 1181), change in libido (67.5 %, n = 932), hormone cycle disruptions (65.9 %, n = 910), and inefficiency at alleviating symptoms (38.2 %, n = 527). In total, 66.1 % (n = 935) were not satisfied with endocrine drugs for endometriosis. Age ≤ 30 years, living in a large city, and having an academic degree were significantly correlated to a more negative perception of these drugs and greater dissatisfaction with current endocrine endometriosis drugs. Conclusions: Among women with endometriosis - and particularly among those aged ≤30 years, being large-city residents, or holding an academic degree - there appears to be a relevant degree of rejection and wariness towards endocrine endometriosis drugs. Given the prevalence of endometriosis and the few pharmaceutical alternatives on the horizon, these data point a growing need for further research and development of non-hormonal drugs for the treatment of endometriosis. Keywords: Endometriosis; Endometriosis drug therapy; Endometriosis social media; Endometriosis survey
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