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Einfluss von Krüppel-Like Factor 4 auf die Entwicklung und Progression des Magenkarzinoms sowie Vergleich der unterschiedlichen Funktionen von KLF4 und KLF5 in der Karzinogese
No full textThe work presented in this thesis, which is based on our publication in Cancer Research in 2005: “Drastic Down-regulation of Krüppel-Like Factor 4 Expression Is Critical in Human Gastric Cancer Development and Progression” provides new insights of the role of KLF4 in human gastric cancer.
First, we discovered the distinct KLF4 expression patterns in normal gastric and gastric tumor tissues. Specifically, we found that KLF4 protein was expressed in the cytoplasm and nuclei of cells localized predominantly in the glandular epithelium (glandular differentiation), suggesting that KLF4 plays an important role in the homeostasis and maintenance of gastric mucosa. In contrast, we observed a substantially decreased or lost KLF4 expression in both gastric tumor specimens and tumor cell lines. Second, restored expression of KLF4 significantly inhibited gastric cancer growth in vitro and tumorigenicity in animal models. Third, mechanism study showed that promoter hypermethylation and hemizygous deletion were found in a subset of gastric cancer tissues and cell lines and restoration of KLF4 expression induced typical apoptosis in gastric cancer cells. Finally, we observed an inverse correlation between decreased KLF4 expression and survival, and the expression of KLF4 was an independent prognostic factor to predict the outcome of patients. These results show that KLF4 plays an important role in the regulation of homeostasis and maintenance of gastric mucosa and functions as a tumor suppressor in gastric carcinogenesis and progression and that KLF4 pathway is both prognostic marker and potential therapeutic target for human gastric cancer treatment. Comparison with KLF5 revealed that both, KLF4 and KLF5 can act as either tumor suppressor or as promoter of tumorigenesis, depending on the cellular, tissue and genetic context. Further investigations of KLF4 and KLF5 may advance the understanding of the physiological and pathophysiological roles of KLF4 and KLF5 in regulating cellular proliferation and tumor formation in diverse tissues.Der Transkriptionsfaktor Krüppel-Like Factor 4 (KLF 4) spielt eine wichtige Rolle in der Differenzierung und Aufrechterhaltung der gesunden Magenschleimhaut. KLF 4 zeigt unterschiedliche Expressionsmuster in gesunder Magenschleimhaut bzw. im Magenkarzinom. KLF4 ist in Proben von Magenkarzinomen bzw. in unterschiedlichen Magenkarzinomzelllinien geringer oder nicht exprimiert. Durch Wiedereinbringung des Transkriptionsfaktors KLF4 über einen Adenovirus in die Karzinomzellen wurde in vitro wie in vivo das Tumorwachstum unterdrückt. Hypermethylation des Promoters sowie hemizygote Deletion sind Ursache der verminderten Expression in einer Untergruppe von
Karzinomgeweben- bzw. Zelllinien.Zudem konnte gezeigt werden, dass eine verminderte KLF-4 Expression bei Magenkarzinomen mit einer verminderten Überlebensrate einherging.
Vergleiche zwischen KLF-4 und KLF-5 zeigen das beide Transkriptionsfaktoren abhängig von unterschiedlichen Faktoren sowohl begünstigend bezüglich der Karzinogenese wie auch hemmend auf diese einwirken können
Going Beyond Counting First Authors in Author Co-citation Analysis
Full text linkThe present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation
counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings
are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that
only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into
account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed
Variations on the Author
Full text link“Variations on the Author” discusses two of Eduardo Coutinho’s recent films (Um Dia na Vida, from 2010, and Últimas Conversas, posthumously released in 2015) and their contribution to the general question of documentary authorship. The director’s filmography is characterized by a consistent yet self-effacing form of authorial self-inscription: Coutinho often features as an interviewer that rather than express opinions propels discourses; an interviewer that is good at listening. This mode of self-inscription characterizes him as an author who is not expressive but who is nonetheless markedly present on the screen. In Um Dia na Vida, however, Coutinho is completely absent form the image, while Últimas Conversas, on the contrary, includes a confessional prologue that moves the director from the margins to the center of his films. This article examines the ways in which these works stand out in the filmography of a director who offers new insights into the notion of cinematic authorship
Appropriate Similarity Measures for Author Cocitation Analysis
Full text linkWe provide a number of new insights into the methodological discussion about author cocitation analysis. We first argue that the use of the Pearson correlation for measuring the similarity between authors’ cocitation profiles is not very satisfactory. We then discuss what kind of similarity measures may be used as an alternative to the Pearson correlation. We consider three similarity measures in particular. One is the well-known cosine. The other two similarity measures have not been used before in the bibliometric literature. Finally, we show by means of an example that our findings have a high practical relevance.information science;Pearson correlation;cosine;similarity measure;author cocitation analysis
Irinotecan in patients with relapsed or cisplatin-refractory germ cell cancer: a phase II study of the German Testicular Cancer Study Group
No full textDespite generally high cure rates in patients with metastatic germ cell cancer, patients with progressive disease on first-line cisplatin-based chemotherapy or with relapsed disease following high-dose salvage therapy exhibit a very poor prognosis. Irinotecan has shown antitumour activity in human testicular tumour xenografts in nude mice. We have performed a phase 11 study examining the single agent activity of irinotecan in patients with metastatic relapsed or cisplatin-refractory germ cell cancer. Refractory disease was defined as progression or relapse within 4 weeks after cisplatin-based chemotherapy or relapse after salvage high-dose chemotherapy with autologous stem cell support. Irinotecan was administered at a dose of (-350) mg m(-2) every 3 weeks. Response was evaluated every 4 weeks. Fifteen patients have been enrolled. Median age was 35 (19-53) years. Primary tumour localisation was gonadal/mediastinal in 12/3 patients. Patients had been pretreated with a median of six (4-12) cisplatin-containing cycles and 13 out of 15 patients had previously failed high-dose chemotherapy with blood stem cell support. Median number of irinotecan applications was two (1-3). Fourteen patients are assessable for response and all for toxicity. In one patient, no adequate response evaluation was performed. Toxicity was generally acceptable and consisted mainly of haematological side effects with common toxicity criteria 3degrees anaemia (two patients), common toxicity criteria 3degrees leukocytopenia (one patient) and common toxicity criteria 3degrees thrombocytopenia (three patients). Common toxicity criteria 3/4degrees non-haematological toxicity occurred in five patients (33%): 1 x diarrhoea, 2 x alopecia, I x fever and in one patient worsening of pre-existing peripheral polyneuropathy from 1degrees to 4degrees. No response was observed to irinotecan therapy. Currently, 13 patients have died of the disease and two patients are alive with the disease. The patients included in our study exhibit similar prognostic characteristics as patients treated in previous trials evaluating new drugs in this setting. Irinotecan at a dose of 300-350 mg m(-2) every 3 weeks appears to have no antitumour activity in patients with cisplatin-refractory germ cell cancer and, thus, further investigation in this disease is not justified. (C) 2002 Cancer Research UK
Combination chemotherapy with gemcitabine plus oxaliplatin in patients with intensively pretreated or refractory germ cell cancer: A study of the German Testicular Cancer Study Group
No full textPurpose Long-term survival is rarely achieved in patients with cisplatin-refractory germ cell cancer (GCT). Both single-agent gemcitabine and oxaliplatin have shown activity in patients who experience relapse or are refractory to cisplatin treatment. This study investigates the activity of a gemcitabine plus oxaliplatin regimen in these patients. Patients and Methods Gemcitabine was administered at a dose of 1,000 mg/m(2) on days 1 and 8, oxaliplatin was administered at a dose of 130 mg/m(2) on day 1. Response was evaluated every 4 weeks. Results Thirty-five patients with a median age of 37 years (range, 21 to 54 years) were enrolled onto the study. Primary tumor localization was gonadal, retroperitoneal, or mediastinal in 30, one, and four patients, respectively. Patients had been pretreated with a median of six platinum-containing cycles (range, four to 13 cycles) and 89% of patients previously had experienced treatment failure after high-dose chemotherapy with peripheral-blood stem-cell transplantation. Sixty-three percent of patients were considered absolutely cisplatin-refractory or cisplatin-refractory. A median of two cycles (range, I to 6 cycles) per patient were applied. Toxicity consisted mainly of myelosuppression, with Common Toxicity Criteria grade 3 occurring in 54% of patients. Only 9% of patients developed neutropenic fever. Three patients attained a complete remission (CR), two patients attained a marker-negative partial remission, and 11 patients attained a marker-positive partial remission, resulting in an overall response rate of 46% (95% Cl, 30% to 64%). All three patients with CR and one patient with a marker-negative partial remission remained disease free at 16+, 12+, 4+, and 2+ months of follow-up. Seven (44%) of these 16 responses, including one CR, occurred in cisplatin-refractory patients. Conclusion Gemcitabine plus oxaliplatin demonstrates antitumor activity with acceptable toxicity in heavily pretreated patients with relapsed or cisplatin-refractory GCT, and may offer a chance of long-term survival for selected patients
Choroidal metastases from thymic carcinoma during pregnancy: Case Report
Full text linkAbstract Background Rare sites of metastases, atypical symptoms and paraneoplastic syndromes are often neglected or misinterpreted, especially when they represent early symptoms of an underlying malignant disease. Hence, an interdisciplinary approach to these patients is essential to avoid tumor progression and metastatic spread in order to provide curative treatment options to the patients. We here report the case of a young woman presenting with visual loss which led to diagnosis of a thymic carcinoma. Case presentation A 28-year old white woman presented with subacute loss of vision in the last trimester of her first pregnancy which was first interpreted as an exacerbation of a pre-existing dermatomyositis and treated with steroids. After failure of steroid therapy choroidal metastases from an undifferentiated thymic carcinoma were diagnosed. This also shed a new light on the dermatomyositis the patient had been suffering from for seven years possibly representing a paraneoplastic syndrome from the tumor. Despite aggressive chemotherapy, the patient died from progressive disease eight years after first onset of dermatomyositis and 14 months after initial diagnosis of the thymic carcinoma. Conclusions Choroidal metastases from a thymic carcinoma have never been reported before but should be included into the differential diagnosis of choroidal masses
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