Search

Your search keyword '"Sattler, Martin"' showing total 759 results
Start Over Author "Sattler, Martin"
759 results on '"Sattler, Martin"'

101. Effects of the multi‐kinase inhibitor midostaurin in combination with chemotherapy in models of acute myeloid leukaemia

Author

Weisberg, Ellen, primary, Meng, Chengcheng, additional, Case, Abigail E., additional, Tiv, Hong L., additional, Gokhale, Prafulla C., additional, Buhrlage, Sara J., additional, Yang, Jing, additional, Liu, Xiaoxi, additional, Wang, Jinhua, additional, Gray, Nathanael, additional, Adamia, Sophia, additional, Sattler, Martin, additional, Stone, Richard, additional, and Griffin, James D., additional

Published
2020
Full Text
View/download PDF

102. The combination of FLT3 and SYK kinase inhibitors is toxic to leukaemia cells with CBL mutations

Author

Weisberg, Ellen, primary, Meng, Chengcheng, additional, Case, Abigail E., additional, Tiv, Hong L., additional, Gokhale, Prafulla C., additional, Toure, Anthia A., additional, Buhrlage, Sara, additional, Liu, Xiaoxi, additional, Wang, Jinhua, additional, Gray, Nathanael, additional, Stone, Richard, additional, Adamia, Sophia, additional, Winer, Eric, additional, Sattler, Martin, additional, and Griffin, James D., additional

Published
2020
Full Text
View/download PDF

103. Fascist Files

Author

Sattler, Martin

Subjects
Ethnic, cultural, racial issues/studies, Literature/writing, Philosophy and religion
Abstract

To the Editor:IN HIS REVIEW of How Fascism Works, by Jason Stanley, Oliver Traldi counters Stanley's claims effectively but does not address the larger historical context of the book ('Not [...]

Published
2019

108. Comparison of effects of midostaurin, crenolanib, quizartinib, gilteritinib, sorafenib and BLU-285 on oncogenic mutants of KIT and FLT3 in hematologic malignancies: Mutant KIT and FLT3 response to Tyrosine Kinase Inhibitors

Author

Weisberg, Ellen, Meng, Chengcheng, Case, Abigail, Sattler, Martin, Tiv, Hong L., Gokhale, Prafulla C., Buhrlage, Sara, Liu, Xiaoxi, Yang, Jing, Wang, Jinhua, Gray, Nathanael, Stone, Richard, Adamia, Sophia, Dubreuil, Patrice, Letard, Sebastien, and Griffin, James D.

Subjects
Antineoplastic Agents, Article, fluids and secretions, Piperidines, hemic and lymphatic diseases, Cell Line, Tumor, Humans, Pyrroles, Benzothiazoles, Proto-Oncogene Proteins c-cbl, Protein Kinase Inhibitors, Aniline Compounds, Triazines, Phenylurea Compounds, hemic and immune systems, Sorafenib, Staurosporine, Proto-Oncogene Proteins c-kit, fms-Like Tyrosine Kinase 3, Hematologic Neoplasms, Pyrazines, embryonic structures, Pyrazoles, Benzimidazoles, Mutant Proteins, Drug Screening Assays, Antitumor
Abstract

Mutations in two type-3 receptor tyrosine kinases (RTKs), KIT and FLT3, are common in both acute myeloid leukaemia (AML) and systemic mastocytosis (SM) and lead to hyperactivation of key signalling pathways. A large number of tyrosine kinase inhibitors (TKIs) have been developed that target either FLT3 or KIT and significant clinical benefit has been demonstrated in multiple clinical trials. Given the structural similarity of FLT3 and KIT, it is not surprising that some of these TKIs inhibit both of these receptors. This is typified by midostaurin, which has been approved by the US Food and Drug Administration for mutant FLT3-positive AML and for KIT D816V-positive SM. Here, we compare the in vitro activities of the clinically available FLT3 and KIT inhibitors with those of midostaurin against a panel of cells expressing a variety of oncogenic FLT3 or KIT receptors, including wild-type (wt) FLT3, FLT3-internal tandem duplication (ITD), FLT3 D835Y, the resistance mutant FLT3-ITD+ F691L, KIT D816V, and KIT N822K. We also examined the effects of these inhibitors in vitro and in vivo on cells expressing mutations in c-CBL found in AML that result in hypersensitization of RTKs, such as FLT3 and KIT. The results show a wide spectrum of activity of these various mutations to these clinically available TKIs.

Published
2019

109. Patient Characteristics and General Practitioners' Advice to Stop Statins in Oldest-Old Patients: a Survey Study Across 30 Countries

Author

van der Ploeg, Milly A, Streit, Sven, Achterberg, Wilco P, Beers, Erna, Bohnen, Arthur M, Burman, Robert A, Collins, Claire, Franco, Fabio G, Gerasimovska-Kitanovska, Biljana, Gintere, Sandra, Gomez Bravo, Raquel, Hoffmann, Kathryn, Iftode, Claudia, Peštić, Sanda Kreitmayer, Koskela, Tuomas H, Kurpas, Donata, Maisonneuve, Hubert, Mallen, Christan D, Merlo, Christoph, Mueller, Yolanda, Muth, Christiane, Petrazzuoli, Ferdinando, Rodondi, Nicolas, Rosemann, Thomas, Sattler, Martin, Schermer, Tjard, Šter, Marija Petek, Švadlenková, Zuzana, Tatsioni, Athina, Thulesius, Hans, et al, and University of Zurich

Subjects
11035 Institute of General Practice, 2724 Internal Medicine, 610 Medicine & health
Published
2019
Full Text
View/download PDF

112. Multi‐wavelength, handheld laser speckle imaging for skin evaluation.

Author

Zieger, Michael, Kaatz, Martin, Springer, Steffen, Riesenberg, Rainer, Wuttig, Andreas, Kanka, Mario, Stanca, Sarmiza, Reble, Carina, Khazaka, Georg, Sieg, Robin, De Gregorio, Marco, Sattler, Martin, and Fischer, Frank

Subjects
SPECKLE interference, SKIN imaging, SPECKLE interferometry, BASAL cell carcinoma, SKIN aging, FRACTAL dimensions
Abstract

Objective: A handheld device was developed and qualified for in vivo human skin evaluation using laser speckle imaging technology. Methods: Each laser speckle device prototype allows the choice of up to three different laser wavelengths in the range of 400 nm to 800 nm in total. Speckle pattern analysis gives various speckle parameters, for example, speckle contrast, speckle size, speckle modulation or fractal dimension. The developed laser speckle device prototypes were evaluated investigating three skin issues. Results: We receive reproducible results from the speckle imaging device. For skin ageing, we found significant changes within three age groups. The effect of a methyl nicotinate treatment was clearly visible and quantifiable using a moorFLPI device as well as our speckle imaging device. In terms of basal cell carcinoma diagnosis, we found significant differences between normal and diseased skin, even though the number of samples was limited. Conclusion: As shown with first application examples, it was possible to demonstrate the potential of the method for skin evaluation in vivo. [ABSTRACT FROM AUTHOR]

Published
2021
Full Text
View/download PDF

114. Multiple Myeloma Pathogenesis: The Role of Junb in Bone Marrow Angiogenesis

Author

Fan, Fengjuan, primary, Malvestiti, Stefano, additional, Shen, Yujia, additional, Morelli, Eugenio, additional, Mishima, Yuji, additional, Seckinger, Anja, additional, Hose, Dirk, additional, Bakiri, Latifa, additional, Vallet, Sonia, additional, Sattler, Martin, additional, Roccaro, Aldo M., additional, Goldschmidt, Hartmut, additional, Percherstorfer, Martin, additional, Sun, Chunyan, additional, Hu, Yu, additional, Wagner, Erwin F, additional, Tassone, Piefrancesco, additional, Ghobrial, Irene M., additional, Jaeger, Dirk, additional, and Podar, Klaus, additional

Published
2019
Full Text
View/download PDF

115. Phenotypic Switching of Naïve T cells to Immune-suppressive Treg-like Cells by Mutant KRAS

Author

Kalvala, Arjun, primary, Wallet, Pierre, additional, Yang, Lu, additional, Wang, Chongkai, additional, Li, Haiqing, additional, Nam, Arin, additional, Nathan, Anusha, additional, Mambetsariev, Isa, additional, Poroyko, Valeriy, additional, Gao, Hanlin, additional, Chu, Peiguo, additional, Sattler, Martin, additional, Bild, Andrea, additional, Manuel, Edwin R., additional, Lee, Peter P., additional, Jolly, Mohit Kumar, additional, Kulkarni, Prakash, additional, and Salgia, Ravi, additional

Published
2019
Full Text
View/download PDF

116. Evaluation of ERK as a therapeutic target in acute myelogenous leukemia

Author

Weisberg, Ellen, primary, Meng, Chengcheng, additional, Case, Abigail, additional, Sattler, Martin, additional, Tiv, Hong L., additional, Gokhale, Prafulla C., additional, Buhrlage, Sara, additional, Wang, Jinhua, additional, Gray, Nathanael, additional, Stone, Richard, additional, Liu, Suiyang, additional, Bhagwat, Shripad V., additional, Tiu, Ramon V., additional, Adamia, Sophia, additional, and Griffin, James D., additional

Published
2019
Full Text
View/download PDF

117. Comparison of effects of midostaurin, crenolanib, quizartinib, gilteritinib, sorafenib and BLU‐285 on oncogenic mutants of KIT, CBL and FLT3 in haematological malignancies

Author

Weisberg, Ellen, primary, Meng, Chengcheng, additional, Case, Abigail E., additional, Sattler, Martin, additional, Tiv, Hong L., additional, Gokhale, Prafulla C., additional, Buhrlage, Sara J., additional, Liu, Xiaoxi, additional, Yang, Jing, additional, Wang, Jinhua, additional, Gray, Nathanael, additional, Stone, Richard M., additional, Adamia, Sophia, additional, Dubreuil, Patrice, additional, Letard, Sebastien, additional, and Griffin, James D., additional

Published
2019
Full Text
View/download PDF

120. Materialien

Author

Höffken, Heinz-Werner, Sattler, Martin, Höffken, Heinz-Werner, and Sattler, Martin

Published
1980
Full Text
View/download PDF

122. An international case-vignette study to assess general practitioners’ willingness to deprescribe (LESS)

Author

Tabea Jungo, Katharina, Mantelli, Sophie, Rozsnyai, Zsofia, Missiou, Aristea, Gerasimovska Kitanovska, Biljana, Weltermann, Birgitta, Tuz, Canan, Mallen, Christian, Collins, Claire, Kurpas, Donata, De Mello Franco, Fabio Gazelato, Petrazzuoli, Ferdinando, Thulesius, Hans, Lingner, Heidrun, Johansen, Kasper Lorenz, Wallis, Katharine, Hoffmann, Kathryn, Peremans, Lieve, Pilv, Liina, Petek Šter, Marija, Sattler, Martin, Van Der Ploeg, Milly, Torzsa, Péter, Kánská, Petra, Vinker, Shlomo, Assenova, Radost, Gomez Bravo, Raquel, Viegas, Rita, Tsopra, Rosy, Kreitmayer Pestić, Sanda, Gintere, Sandra, Koskela, Tuomas, Lazic, Vanja, Tkachenko, Victoria, Reeve, Emily, Luymes, Clare, Poortvliet, Rosalinde, Chiolero, Arnaud, Rodondi, Nicolas, Gussekloo, Jacobijn, Streit, Sven, Tabea Jungo, Katharina, Mantelli, Sophie, Rozsnyai, Zsofia, Missiou, Aristea, Gerasimovska Kitanovska, Biljana, Weltermann, Birgitta, Tuz, Canan, Mallen, Christian, Collins, Claire, Kurpas, Donata, De Mello Franco, Fabio Gazelato, Petrazzuoli, Ferdinando, Thulesius, Hans, Lingner, Heidrun, Johansen, Kasper Lorenz, Wallis, Katharine, Hoffmann, Kathryn, Peremans, Lieve, Pilv, Liina, Petek Šter, Marija, Sattler, Martin, Van Der Ploeg, Milly, Torzsa, Péter, Kánská, Petra, Vinker, Shlomo, Assenova, Radost, Gomez Bravo, Raquel, Viegas, Rita, Tsopra, Rosy, Kreitmayer Pestić, Sanda, Gintere, Sandra, Koskela, Tuomas, Lazic, Vanja, Tkachenko, Victoria, Reeve, Emily, Luymes, Clare, Poortvliet, Rosalinde, Chiolero, Arnaud, Rodondi, Nicolas, Gussekloo, Jacobijn, and Streit, Sven

Abstract

Background: Globally, many oldest-old (>80 years of age) suffer from several chronic conditions and take multiple medications. Ideally, their general practitioners (GPs) regularly and systematically search for inappropriate medications and, if necessary, deprescribe those. However, deprescribing is challenging due to numerous barriers not only within patients, but also within GPs. Research questions: How does the willingness to deprescribe in oldest-old with polypharmacy differ in GPs from different countries? What factors do GPs in different contexts perceive as important for deprescribing? Method: We assess GPs' willingness to deprescribe and the factors GPs perceive to influence their deprescribing decisions in a cross-sectional survey using case-vignettes of oldest-old patients with polypharmacy. We approach GPs in 28 European countries as well as in Israel, Brazil and New Zealand through national coordinators, who administer the survey in their GP network. The case vignettes differ in how dependent patients are and whether or not they have a history of cardiovascular disease (CVD). For each case vignette, GPs are asked if and which medication they would deprescribe. GPs further rate to what extent pre-defined factors influence their deprescribe decisions. We will compare the willingness to deprescribe and the factors influencing deprescribing across countries. Multilevel models will be used to analyze the proportions of the deprescribed medications per case along the continuum of dependency and history of CVD and to analyze the factors perceived as influencing deprescribing decisions. Results: As of early-July 2018, the survey has been distributed in 14 countries and >650 responses have been returned. We will present first results at the conference. Conclusions: First, assessing GPs’ willingness to deprescribe and comparing the factors influencing GPs’ deprescribing decisions across countries will allow an understanding of the expected variation in the willingn

Published
2018

123. Burden of cardiovascular disease across 29 countries and GPs’ decision to treat hypertension in oldest-old

Author

Streit, Sven, Gussekloo, Jacobijn, Burman, Robert A., Collins, Claire, Gerasimovska Kitanovska, Biljana, Gintere, Sandra, Gomez Bravo, Raquel, Hoffmann, Kathryn, Iftode, Claudia, Johansen, Kasper L., Kerse, Ngaire, Koskela, Tuomas H., Kreitmayer Pe"sti!c, Sanda, Kurpas, Donata, Mallen, Christian D., Maisonneuve, Hubert, Merlo, Christoph, Mueller, Yolanda, Muth, Christiane, Ornelas, Rafael H., Petek Ster, Marija, Petrazzuoli, Ferdinando, Rosemann, Thomas, Sattler, Martin, Svadlenkova, Zuzana, Tatsioni, Athina, Thulesius, Hans, Tkachenko, Victoria, Torzsa, Peter, Tsopra, Rosy, Tuz, Canan, Verschoor, Marjolein, Viegas, Rita P. A., Vinker, Shlomo, de Waal, Margot W. M., Zeller, Andreas, Rodondi, Nicolas, Poortvliet, Rosalinde K. E., Streit, Sven, Gussekloo, Jacobijn, Burman, Robert A., Collins, Claire, Gerasimovska Kitanovska, Biljana, Gintere, Sandra, Gomez Bravo, Raquel, Hoffmann, Kathryn, Iftode, Claudia, Johansen, Kasper L., Kerse, Ngaire, Koskela, Tuomas H., Kreitmayer Pe"sti!c, Sanda, Kurpas, Donata, Mallen, Christian D., Maisonneuve, Hubert, Merlo, Christoph, Mueller, Yolanda, Muth, Christiane, Ornelas, Rafael H., Petek Ster, Marija, Petrazzuoli, Ferdinando, Rosemann, Thomas, Sattler, Martin, Svadlenkova, Zuzana, Tatsioni, Athina, Thulesius, Hans, Tkachenko, Victoria, Torzsa, Peter, Tsopra, Rosy, Tuz, Canan, Verschoor, Marjolein, Viegas, Rita P. A., Vinker, Shlomo, de Waal, Margot W. M., Zeller, Andreas, Rodondi, Nicolas, and Poortvliet, Rosalinde K. E.

Abstract

Objectives: We previously found large variations in general practitioner (GP) hypertension treatment probability in oldest-old (>80 years) between countries. We wanted to explore whether differences in country-specific cardiovascular disease (CVD) burden and life expectancy could explain the differences. Design: This is a survey study using case-vignettes of oldest-old patients with different comorbidities and blood pressure levels. An ecological multilevel model analysis was performed. Setting: GP respondents from European General Practice Research Network (EGPRN) countries, Brazil and New Zeeland. Subjects: This study included 2543 GPs from 29 countries. Main outcome measures: GP treatment probability to start or not start antihypertensive treatment based on responses to case-vignettes; either low (<50% started treatment) or high (!50% started treatment). CVD burden is defined as ratio of disability-adjusted life years (DALYs) lost due to ischemic heart disease and/or stroke and total DALYs lost per country; life expectancy at age 60 and prevalence of oldest-old per country. Results: Of 1947 GPs (76%) responding to all vignettes, 787 (40%) scored high treatment probability and 1160 (60%) scored low. GPs in high CVD burden countries had higher odds of treatment probability (OR 3.70; 95% confidence interval (CI) 3.00–4.57); in countries with low life expectancy at 60, CVD was associated with high treatment probability (OR 2.18, 95% CI 1.12–4.25); but not in countries with high life expectancy (OR 1.06, 95% CI 0.56–1.98). Conclusions: GPs’ choice to treat/not treat hypertension in oldest-old was explained by differences in country-specific health characteristics. GPs in countries with high CVD

Published
2018

125. Spotlight on midostaurin in the treatment of FLT3-mutated acute myeloid leukemia and systemic mastocytosis: design, development, and potential place in therapy

Author

Weisberg,Ellen, Sattler,Martin, Manley,Paul W, and Griffin,James D

Subjects
hemic and lymphatic diseases, embryonic structures, hemic and immune systems, OncoTargets and Therapy
Abstract

Ellen Weisberg,1,2 Martin Sattler,1,2 Paul W Manley,3 James D Griffin1,2 1Department of Medical Oncology, Dana-Farber Cancer Institute, 2Department of Medicine, Harvard Medical School, Boston, MA, USA; 3Department of Oncology, Novartis Institutes of Biomedical Research, Basel, Switzerland Abstract: The Fms-like tyrosine kinase-3 (FLT3; fetal liver kinase-2; human stem cell tyrosine kinase-1; CD135) is a class III receptor tyrosine kinase that is normally involved in regulating the proliferation, differentiation, and survival of both hematopoietic cells and dendritic cells. Mutations leading it to be constitutively activated make it an oncogenic driver in ~30% of acute myeloid leukemia (AML) patients where it is associated with poor prognosis. The prevalence of oncogenic FLT3 and the dependency on its constitutively activated kinase activity for leukemia growth make this protein an attractive target for therapeutic intervention. Of the numerous small molecule inhibitors under clinical investigation for the treatment of oncogenic FLT3-positive AML, the N-benzoyl-staurosporine, midostaurin (CGP41251; PKC412; Rydapt®; Novartis Pharma AG, Basel, Switzerland), is the first to be approved by the US Food and Drug Administration for the treatment, in combination with standard chemotherapy, of newly diagnosed adult AML patients who harbor mutations in FLT3. Here, we describe the early design of midostaurin, the preclinical discovery of its activity against oncogenic FLT3, and its subsequent clinical development as a therapeutic agent for FLT3 mutant-positive AML. Keywords: AML, acute myeloid leukemia, PKC412, midostaurin, FLT3-ITD, oncogenic FLT3, targeted therapy

Published
2017

127. Additional file 2: of Variation in GP decisions on antihypertensive treatment in oldest-old and frail individuals across 29 countries

Author

Streit, Sven, Verschoor, Marjolein, Rodondi, Nicolas, Bonfim, Daiana, Burman, Robert, Collins, Claire, Gerasimovska Biljana, Gintere, Sandra, Bravo, Raquel Gómez, Hoffmann, Kathryn, Iftode, Claudia, Johansen, Kasper, Ngaire Kerse, Koskela, Tuomas, Peštić, Sanda, Kurpas, Donata, Mallen, Christian, Maisoneuve, Hubert, Merlo, Christoph, Mueller, Yolanda, Muth, Christiane, Šter, Marija, Petrazzuoli, Ferdinando, Rosemann, Thomas, Sattler, Martin, Švadlenková, Zuzana, Tatsioni, Athina, Thulesius, Hans, Tkachenko, Victoria, Torzsa, Peter, Tsopra, Rosy, Tuz Canan, Viegas, Rita, Vinker, Shlomo, Waal, Margot, Zeller, Andreas, Jacobijn Gussekloo, and Poortvliet, Rosalinde

Abstract

Characteristics of the eight case vignettes used in this survey. (DOCX 18 kb)

Published
2017
Full Text
View/download PDF

129. A messy world

Author

Andrea, Sattler, Martin, and Canes, Michael

Subjects
Ethnic, cultural, racial issues/studies, Literature/writing, Philosophy and religion
Abstract

To the Editor: BARACK OBAMA has created something much larger and more problematic than a mess in regard to American foreign policy ('Cleaning Up Obama's Foreign Policy Mess,' November, 2016). [...]

Published
2017

132. Burden of cardiovascular disease across 29 countries and GPs’ decision to treat hypertension in oldest-old

Author

Streit, Sven, primary, Gussekloo, Jacobijn, additional, Burman, Robert A., additional, Collins, Claire, additional, Kitanovska, Biljana Gerasimovska, additional, Gintere, Sandra, additional, Gómez Bravo, Raquel, additional, Hoffmann, Kathryn, additional, Iftode, Claudia, additional, Johansen, Kasper L., additional, Kerse, Ngaire, additional, Koskela, Tuomas H., additional, Peštić, Sanda Kreitmayer, additional, Kurpas, Donata, additional, Mallen, Christian D., additional, Maisonneuve, Hubert, additional, Merlo, Christoph, additional, Mueller, Yolanda, additional, Muth, Christiane, additional, Ornelas, Rafael H., additional, Šter, Marija Petek, additional, Petrazzuoli, Ferdinando, additional, Rosemann, Thomas, additional, Sattler, Martin, additional, Švadlenková, Zuzana, additional, Tatsioni, Athina, additional, Thulesius, Hans, additional, Tkachenko, Victoria, additional, Torzsa, Peter, additional, Tsopra, Rosy, additional, Tuz, Canan, additional, Verschoor, Marjolein, additional, Viegas, Rita P. A., additional, Vinker, Shlomo, additional, de Waal, Margot W. M., additional, Zeller, Andreas, additional, Rodondi, Nicolas, additional, and Poortvliet, Rosalinde K. E., additional

Published
2018
Full Text
View/download PDF

136. Variation in GP decisions on antihypertensive treatment in oldest-old and frail individuals across 29 countries

Author

Streit, Sven, Verschoor, Marjolein, Rodondi, Nicolas, Bonfim, Daiana, Burman, Robert A., Collins, Claire, Kitanovska Biljana, Gerasimovska, Gintere, Sandra, Gomez Bravo, Raquel, Hoffmann, Kathryn, Iftode, Claudia, Johansen, Kasper L., Kerse, Ngaire, Koskela, Tuomas H., Kreitmayer Peštić, Sanda, Kurpas, Donata, Mallen, Christian D., Maisoneuve, Hubert, Merlo, Christoph, Mueller, Yolanda, Muth, Christiane, Petek Šter, Marija, Petrazzuoli, Ferdinando, Rosemann, Thomas, Sattler, Martin, Švadlenková, Zuzana, Tatsioni, Athina, Thulesius, Hans, Tkachenko, Victoria, Torzsa, Peter, Tsopra, Rosy, Canan, Tuz, Viegas, Rita P. A., Vinker, Shlomo, de Waal, Margot W. M., Zeller, Andreas, Gussekloo, Jacobijn, Poortvliet, Rosalinde K. E., Streit, Sven, Verschoor, Marjolein, Rodondi, Nicolas, Bonfim, Daiana, Burman, Robert A., Collins, Claire, Kitanovska Biljana, Gerasimovska, Gintere, Sandra, Gomez Bravo, Raquel, Hoffmann, Kathryn, Iftode, Claudia, Johansen, Kasper L., Kerse, Ngaire, Koskela, Tuomas H., Kreitmayer Peštić, Sanda, Kurpas, Donata, Mallen, Christian D., Maisoneuve, Hubert, Merlo, Christoph, Mueller, Yolanda, Muth, Christiane, Petek Šter, Marija, Petrazzuoli, Ferdinando, Rosemann, Thomas, Sattler, Martin, Švadlenková, Zuzana, Tatsioni, Athina, Thulesius, Hans, Tkachenko, Victoria, Torzsa, Peter, Tsopra, Rosy, Canan, Tuz, Viegas, Rita P. A., Vinker, Shlomo, de Waal, Margot W. M., Zeller, Andreas, Gussekloo, Jacobijn, and Poortvliet, Rosalinde K. E.

Abstract

Background In oldest-old patients (>80), few trials showed efficacy of treating hypertension and they included mostly the healthiest elderly. The resulting lack of knowledge has led to inconsistent guidelines, mainly based on systolic blood pressure (SBP), cardiovascular disease (CVD) but not on frailty despite the high prevalence in oldest-old. This may lead to variation how General Practitioners (GPs) treat hypertension. Our aim was to investigate treatment variation of GPs in oldest-olds across countries and to identify the role of frailty in that decision. Methods Using a survey, we compared treatment decisions in cases of oldest-old varying in SBP, CVD, and frailty. GPs were asked if they would start antihypertensive treatment in each case. In 2016, we invited GPs in Europe, Brazil, Israel, and New Zealand. We compared the percentage of cases that would be treated per countries. A logistic mixed-effects model was used to derive odds ratio (OR) for frailty with 95% confidence intervals (CI), adjusted for SBP, CVD, and GP characteristics (sex, location and prevalence of oldest-old per GP office, and years of experience). The mixed-effects model was used to account for the multiple assessments per GP. Results The 29 countries yielded 2543 participating GPs: 52% were female, 51% located in a city, 71% reported a high prevalence of oldest-old in their offices, 38% and had >20 years of experience. Across countries, considerable variation was found in the decision to start antihypertensive treatment in the oldest-old ranging from 34 to 88%. In 24/29 (83%) countries, frailty was associated with GPs’ decision not to start treatment even after adjustment for SBP, CVD, and GP characteristics (OR 0.53, 95%CI 0.48–0.59; ORs per country 0.11–1.78). Conclusions Across countries, we found considerable variation in starting antihypertensive medication in oldest-old. The frail oldest-old had an odds ratio of 0.53 of receiving antihypertensive treatment. Future hypertension trial

Published
2017

137. Additional file 1: Figure S1. of Mcl-1 confers protection of Her2-positive breast cancer cells to hypoxia: therapeutic implications

Author

Bashari, Muhammad, Fengjuan Fan, Vallet, Sonia, Sattler, Martin, Arn, Melissa, Luckner-Minden, Claudia, Schulze-Bergkamen, Henning, ZÜrnig, Inka, Marme, Frederik, Schneeweiss, Andreas, Cardone, Michael, Opferman, Joseph, JäGer, Dirk, and Podar, Klaus

Subjects
hemic and lymphatic diseases, skin and connective tissue diseases, neoplasms
Abstract

Showing MCL-1 mRNA levels do not change in Her2-positive BC cells under hypoxic conditions. Figure S2 showing a Bcl-2 is expressed in both Mcl-1wt/wt and Mcl-1Î /null MEFs. Whole-cell extracts were analyzed by immunoblotting with indicated antibodies. Immunoblotting for Erk2 confirmed equal protein loading. b EU-5346 does not change Mcl-1 mRNA expression in Her2-positive BC cells under hypoxic conditions. Figure S3 showing Mcl-1 is a potential therapeutic target not only in Her2-positive, but also in Luminal A-like and TNBC cells under hypoxic conditions. (PDF 1580 kb)

Published
2016
Full Text
View/download PDF

138. JunB is a key regulator of multiple myeloma bone marrow angiogenesis

Author

Fan, Fengjuan, Malvestiti, Stefano, Vallet, Sonia, Lind, Judith, Garcia-Manteiga, Jose Manuel, Morelli, Eugenio, Jiang, Qinyue, Seckinger, Anja, Hose, Dirk, Goldschmidt, Hartmut, Stadlbauer, Andreas, Sun, Chunyan, Mei, Heng, Pecherstorfer, Martin, Bakiri, Latifa, Wagner, Erwin F., Tonon, Giovanni, Sattler, Martin, Hu, Yu, Tassone, Pierfrancesco, Jaeger, Dirk, and Podar, Klaus

Abstract

Bone marrow (BM) angiogenesis significantly influences disease progression in multiple myeloma (MM) patients and correlates with adverse prognosis. The present study shows a statistically significant correlation of the AP-1 family member JunB with VEGF, VEGFB, and IGF1 expression levels in MM. In contrast to the angiogenic master regulator Hif-1α, JunB protein levels were independent of hypoxia. Results in tumor-cell models that allow the induction of JunB knockdown or JunB activation, respectively, corroborated the functional role of JunB in the production and secretion of these angiogenic factors (AFs). Consequently, conditioned media derived from MM cells after JunB knockdown or JunB activation either inhibited or stimulated in vitro angiogenesis. The impact of JunB on MM BM angiogenesis was finally confirmed in a dynamic 3D model of the BM microenvironment, a xenograft mouse model as well as in patient-derived BM sections. In summary, in continuation of our previous study (Fan et al., 2017), the present report reveals for the first time that JunB is not only a mediator of MM cell survival, proliferation, and drug resistance, but also a promoter of AF transcription and consequently of MM BM angiogenesis. Our results thereby underscore worldwide efforts to target AP-1 transcription factors such as JunB as a promising strategy in MM therapy.

Published
2021
Full Text
View/download PDF

139. Formação (Bildung): entre o sagrado e o profano = Education (Bildung): between the sacred and the profane

Author

Sattler, Martin

Subjects
SOCIOLOGIA EDUCACIONAL, Education (General), L7-991, lcsh:L7-991, lcsh:Education (General)
Abstract

O artigo parte do reconhecimento que a formação (Bildung) encontra-se em crise, gerando transformações em todo o sistema educacional. A crise, de natureza sócio-política, projeta novas perguntas sobre as condições de possibilidade da formação e a relação homem-natureza (crise ecológica). Na análise dessa crise, assume relevância o processo de secularização, suas metamorfoses simbólicas (o deslocamento do sagrado ao profano) e as repercussões na política, em especial, para o Estado nacional. Conclui pela impossibilidade de pensar a formação sem a autocompreensão dos profundos efeitos causados pelos laços internos gerados em tal processo de secularização, que desloca elementos do sagrado ao profano, como um modo de manter vínculo social

Published
2011

140. Abstract PR04: Degradation of leukemia oncogenes: A novel approach to therapy of leukemia

Author

Buhrlage, Sara, primary, Weisberg, Ellen, additional, Lamberto, Ilaria, additional, Yang, Jing, additional, Schauer, Nathan, additional, Sattler, Martin, additional, Nonami, Atushi, additional, Christie, Amanda, additional, Weinstock, David, additional, Ritorto, Stella, additional, DeCesare, Virginia, additional, Trost, Matthias, additional, Stone, Richard, additional, Gray, Nathanael, additional, and Griffin, James, additional

Published
2017
Full Text
View/download PDF

143. Inhibition of USP10 induces degradation of oncogenic FLT3

Author

Weisberg, Ellen L, primary, Schauer, Nathan J, additional, Yang, Jing, additional, Lamberto, Ilaria, additional, Doherty, Laura, additional, Bhatt, Shruti, additional, Nonami, Atsushi, additional, Meng, Chengcheng, additional, Letai, Anthony, additional, Wright, Renee, additional, Tiv, Hong, additional, Gokhale, Prafulla C, additional, Ritorto, Maria Stella, additional, De Cesare, Virginia, additional, Trost, Matthias, additional, Christodoulou, Alexandra, additional, Christie, Amanda, additional, Weinstock, David M, additional, Adamia, Sophia, additional, Stone, Richard, additional, Chauhan, Dharminder, additional, Anderson, Kenneth C, additional, Seo, Hyuk-Soo, additional, Dhe-Paganon, Sirano, additional, Sattler, Martin, additional, Gray, Nathanael S, additional, Griffin, James D, additional, and Buhrlage, Sara J, additional

Published
2017
Full Text
View/download PDF

144. Characterization of midostaurin as a dual inhibitor of FLT3 and SYK and potentiation of FLT3 inhibition against FLT3-ITD-driven leukemia harboring activated SYK kinase

Author

Weisberg, Ellen L., primary, Puissant, Alexandre, additional, Stone, Richard, additional, Sattler, Martin, additional, Buhrlage, Sara J., additional, Yang, Jing, additional, Manley, Paul W., additional, Meng, Chengcheng, additional, Buonopane, Michael, additional, Daley, John F., additional, Lazo, Suzan, additional, Wright, Renee, additional, Weinstock, David M., additional, Christie, Amanda L., additional, Stegmaier, Kimberly, additional, and Griffin, James D., additional

Published
2017
Full Text
View/download PDF

147. Variation in GP decisions on antihypertensive treatment in oldest-old and frail individuals across 29 countries

Author

Streit, Sven, primary, Verschoor, Marjolein, additional, Rodondi, Nicolas, additional, Bonfim, Daiana, additional, Burman, Robert A., additional, Collins, Claire, additional, Biljana, Gerasimovska Kitanovska, additional, Gintere, Sandra, additional, Gómez Bravo, Raquel, additional, Hoffmann, Kathryn, additional, Iftode, Claudia, additional, Johansen, Kasper L., additional, Kerse, Ngaire, additional, Koskela, Tuomas H., additional, Peštić, Sanda Kreitmayer, additional, Kurpas, Donata, additional, Mallen, Christian D., additional, Maisoneuve, Hubert, additional, Merlo, Christoph, additional, Mueller, Yolanda, additional, Muth, Christiane, additional, Šter, Marija Petek, additional, Petrazzuoli, Ferdinando, additional, Rosemann, Thomas, additional, Sattler, Martin, additional, Švadlenková, Zuzana, additional, Tatsioni, Athina, additional, Thulesius, Hans, additional, Tkachenko, Victoria, additional, Torzsa, Peter, additional, Tsopra, Rosy, additional, Canan, Tuz, additional, Viegas, Rita P. A., additional, Vinker, Shlomo, additional, de Waal, Margot W. M., additional, Zeller, Andreas, additional, Gussekloo, Jacobijn, additional, and Poortvliet, Rosalinde K. E., additional

Published
2017
Full Text
View/download PDF

149. Rationally derived drug combinations with the novel Mcl-1 inhibitor EU-5346 in breast cancer.

Author

Vallet, Sonia, Fan, Fengjuan, Malvestiti, Stefano, Pecherstorfer, Martin, Sattler, Martin, Schneeweiss, Andreas, Schulze-Bergkamen, Henning, Opferman, Joseph T., Cardone, Michael H., Jäger, Dirk, and Podar, Klaus

Abstract

Purpose: Recent studies have emphasized a key role for the anti-apoptotic Bcl-2 family member Mcl-1 in conferring tumor cell survival and drug resistance in breast cancer (BC). Mcl-1 inhibitors, such as the BH3-mimetic EU-5346, therefore represent an exciting new class of targeting agents and are a current focus of widespread cancer-drug development efforts.Methods: ONCOMINE analysis was utilized to compare expression profiles of Bcl-2 family members across all major BC subgroups. Potential toxicities of EU-5346 were evaluated using iPS-generated cardiomyocytes, blood cells and astrocytes. The anti-BC cell activity of EU-5346-based therapies was evaluated using [3H]-thymidine uptake and spheroid-forming assays as well as immunoblotting and the Chou-Talalay method. Protein level-based activity of EU-5346, the specific anti-Bcl-2 inhibitor ABT-199 and the specific anti-Bcl-xL inhibitor WEHI-539 was verified in Mcl-1Δ/null versus Mcl-1wt/wt MEFs.Results: We previously demonstrated significant anti-tumor activity of EU-5346 in all BC subtypes. Our present results go further and suggest that EU-5346 may induce limited adverse events such as cardiotoxicity, hematotoxicity, and neurotoxicity, frequently observed with other BH3 mimetics. As demonstrated by our mathematical scoring model, the prediction of EU-5643-induced IC50 not only relies on the protein level of Mcl-1 but also on Bak, Bim, and Noxa. Synergistic anti-BC activity of low-dose EU-5346 with the BH3 mimetics ABT-199 or WEHI-539 was observed only in those BC cells expressing Bcl-2 or Bcl-xL, respectively. Similarly, when combined with tamoxifen or trastuzumab, low-dose EU-5346 induced significant anti-BC activity in hormone receptor positive or Her2-positive BC cells, respectively. Finally, EU-5346 in combination with paclitaxel induced synergistic anti-BC activity in both paclitaxel-sensitive and paclitaxel-resistant TNBC cells.Conclusion: These data strongly support the further clinical development of EU-5346 to improve BC patient survival. [ABSTRACT FROM AUTHOR]

Published
2019
Full Text
View/download PDF

150. Publisher Correction: JunB is a key regulator of multiple myeloma bone marrow angiogenesis

Author

Fan, Fengjuan, Malvestiti, Stefano, Vallet, Sonia, Lind, Judith, Garcia-Manteiga, Jose Manuel, Morelli, Eugenio, Jiang, Qinyue, Seckinger, Anja, Hose, Dirk, Goldschmidt, Hartmut, Stadlbauer, Andreas, Sun, Chunyan, Mei, Heng, Pecherstorfer, Martin, Bakiri, Latifa, Wagner, Erwin F., Tonon, Giovanni, Sattler, Martin, Hu, Yu, Tassone, Pierfrancesco, Jaeger, Dirk, and Podar, Klaus

Published
2024
Full Text
View/download PDF

Catalog

Books, media, physical & digital resources
See catalog results