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10,428 results on '"Heirman AN"'

153. Data from Intratumoral Delivery of TriMix mRNA Results in T-cell Activation by Cross-Presenting Dendritic Cells

Author

Karine Breckpot, Kris Thielemans, Carlo Heirman, Véronique Flamand, Lukasz Bialkowski, Kevin Van der Jeught, Stephanie Du Four, Cleo Goyvaerts, Daphné Benteyn, Sarah Maenhout, Lode Goethals, Katrijn Broos, Dries Renmans, and Sandra Van Lint

Abstract

Modulating the activity of tumor-infiltrating dendritic cells (TiDC) provides opportunities for novel cancer interventions. In this article, we report on our study of the uptake of mRNA by CD8α+ cross-presenting TiDCs upon its intratumoral (i.t.) delivery. We exploited this property to deliver mRNA encoding the costimulatory molecule CD70, the activation stimuli CD40 ligand, and constitutively active Toll-like receptor 4, referred to as TriMix mRNA. We show that TiDCs are reprogrammed to mature antigen-presenting cells that migrate to tumor-draining lymph nodes (TDLN). TriMix stimulated antitumor T-cell responses to spontaneously engulfed cancer antigens, including a neoepitope. We show in various mouse cancer models that i.t. delivery of TriMix mRNA results in systemic therapeutic antitumor immunity. Finally, we show that the induction of antitumor responses critically depends on TiDCs, whereas it only partially depends on TDLNs. As such, we provide a platform and a mechanistic rationale for the clinical testing of i.t. administration of TriMix mRNA. Cancer Immunol Res; 4(2); 146–56. ©2015 AACR.

Published
2023
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154. Supplementary Figures 1 and 2 from Intratumoral Delivery of TriMix mRNA Results in T-cell Activation by Cross-Presenting Dendritic Cells

Author

Karine Breckpot, Kris Thielemans, Carlo Heirman, Véronique Flamand, Lukasz Bialkowski, Kevin Van der Jeught, Stephanie Du Four, Cleo Goyvaerts, Daphné Benteyn, Sarah Maenhout, Lode Goethals, Katrijn Broos, Dries Renmans, and Sandra Van Lint

Abstract

Supplementary Fig. S1. Delivery of TriMix mRNA to the tumor reprograms TiDCs. Supplementary Fig. S2. Delivery of TriMix mRNA to tumors induces tumor-specific CTLs.

Published
2023
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155. Decisional Conflict and Decision Regret in Head and Neck Oncology: A Systematic Review and Meta-Analysis.

Author

Heirman AN, Arends CR, de Jel DVC, Dirven R, van der Molen L, Halmos GB, van den Brekel MWM, and Stuiver MM

Subjects
Humans, Quality of Life, Head and Neck Neoplasms psychology, Decision Making, Emotions, Conflict, Psychological
Abstract

Importance: Head and neck cancer (HNC) often requires treatment with a major impact on quality of life. Treatment decision-making is often challenging, as it involves balancing survival against the preservation of quality of life and choosing among treatments with comparable outcomes but variation in morbidity and adverse events; consequently, the potential for decisional conflict (DC) and decision regret (DR) is high., Objectives: To summarize the literature on DC and DR in HNC, to give an overview of its prevalence and extent, and to advise on clinical practice and future research., Data Sources: Embase, Web of Science, MEDLINE, and PsycINFO were searched up to February 24, 2023, including all years of publication., Study Selection: Eligible studies addressed DC and/or DR as primary or secondary outcomes with any instrument in HNC, except cutaneous tumors. Two mutually blinded researchers conducted screening and inclusion with support of an artificial intelligence assistant and conducted risk of bias (ROB) assessment., Data Extraction and Synthesis: The Preferred Reporting Items for Systematic Review and Meta-Analyses guidelines were followed for data extraction. ROB assessments were done using Critical Appraisal Skills Programme (qualitative) and CLARITY (quantitative). Meta-analysis with a random-effects model was used to obtain pooled prevalence estimates for DC and DR when at least 4 sufficiently clinically homogeneous studies were available., Main Outcomes and Measures: Prevalence of DC (qualitative, Decisional Conflict Scale, SURE questionnaire) and DR (qualitative, study-specific questionnaires, Decision Regret Scale, Shame and Stigma Scale)., Results: Overall, 28 studies were included, with 16 included in meta-analyses for DR prevalence. The pooled prevalence of clinically relevant DR above the cutoff score for validated questionnaires (11 studies; 2053 participants) was 71% (95% CI, 58%-82%; I2 = 94%), while for study-specific questionnaires (5 studies; 674 participants) it was 11% (95% CI, 5%-22%; I2 = 92%). Only 4 studies investigated DC, showing a prevalence of 22.6% to 47.5% above cutoff values. Derived overarching themes found in qualitative studies were preparation, shared decision-making roles, information, time pressure, stress of diagnosis, and consequences., Conclusions and Relevance: Although limited data on DC and DR were available, the studies performed indicated that DC and DR are highly prevalent issues in HNC. Results suggest that study-specific questionnaires underestimated DR. The findings underscore the rationale to improve counseling and shared decision-making for this patient population.

Published
2024
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164. The public health benefit and burden of mass drug administration programs in Vietnamese schoolchildren: Impact of mebendazole.

Author

Sam Debaveye, Claudia Virginia Gonzalez Torres, Delphine De Smedt, Bert Heirman, Shane Kavanagh, and Jo Dewulf

Subjects
Arctic medicine. Tropical medicine, RC955-962, Public aspects of medicine, RA1-1270
Abstract

BACKGROUND:Mass anthelmintic drug administration is recommended in developing countries to address infection by soil-transmitted helminthiases (STH). We quantified the public health benefit of treatment with mebendazole in eight million Vietnamese children aged 5-14 years from 2006 to 2011. This was compared to the environmental impact of the pharmaceutical supply chain of mebendazole, as the resource use and emissions associated with pharmaceutical production can be associated with a public health burden, e.g. through emissions of fine particulate matter. METHODOLOGY:Through Markov modelling the disability due to STH was quantified for hookworm, Ascaris lumbricoides and Trichuris trichiura. For each worm type, four levels of intensity of infection were included: none, light, medium and heavy. The treatment effect on patients was quantified in Disability-Adjusted Life Years (DALYs). The public health burden induced by the pharmaceutical supply chain of mebendazole was quantified in DALYs through Life Cycle Assessment. PRINCIPAL FINDINGS:Compared to 'no treatment', the modelled results of five-year treatment averted 116,587 DALYs (68% reduction) for the three worms combined and largely driven by A. lumbricoides. The main change in DALYs occurred in the first year of treatment, after which the results stabilized. The public health burden associated with the pharmaceutical supply chain was 6 DALYs. CONCLUSIONS:The public health benefit of the Mass Drug Administration (MDA) averted substantially more DALYs than those induced by the pharmaceutical supply chain. These results were verified in a sensitivity analysis. The starting prevalence for each worm was the most sensitive model parameter. This methodology is useful for policymakers interested in a holistic approach towards the public health performance of MDA programs, enveloping both the treatment benefit received by the patient and the public health burden associated with the resource consumption and environmental emissions of the pharmaceutical production and supply chain.

Published
2018
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172. Evaluating Application Vulnerability to Soft Errors in Multi-level Cache Hierarchy

Author

Ma, Zhe, Carlson, Trevor, Heirman, Wim, Eeckhout, Lieven, Hutchison, David, editor, Kanade, Takeo, editor, Kittler, Josef, editor, Kleinberg, Jon M., editor, Mattern, Friedemann, editor, Mitchell, John C., editor, Naor, Moni, editor, Nierstrasz, Oscar, editor, Pandu Rangan, C., editor, Steffen, Bernhard, editor, Sudan, Madhu, editor, Terzopoulos, Demetri, editor, Tygar, Doug, editor, Vardi, Moshe Y., editor, Weikum, Gerhard, editor, Alexander, Michael, editor, D’Ambra, Pasqua, editor, Belloum, Adam, editor, Bosilca, George, editor, Cannataro, Mario, editor, Danelutto, Marco, editor, Di Martino, Beniamino, editor, Gerndt, Michael, editor, Jeannot, Emmanuel, editor, Namyst, Raymond, editor, Roman, Jean, editor, Scott, Stephen L., editor, Traff, Jesper Larsson, editor, Vallée, Geoffroy, editor, and Weidendorfer, Josef, editor

Published
2012
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173. Supplemental Figures S1-S7 from Loss of RASSF4 Expression in Multiple Myeloma Promotes RAS-Driven Malignant Progression

Author

Elke De Bruyne, Jérôme Moreaux, Karin Vanderkerken, Eline Menu, Kim De Veirman, Leo A. van Grunsven, Karine Breckpot, Dirk Hose, Andrew Cakana, Carlo Heirman, Nicolas Robert, Anke Maes, Alboukadel Kassambara, Hui Lui, Stefaan Verhulst, Ken Maes, and Eva De Smedt

Abstract

Supplemental Figure 1 shows the prognostic value of the classical RASSF proteins RASSF1, RASSF3, RASSF5 and RASSF6 in MM patients. Supplemental Figure S2 shows the cellular localization of RASSF4. Supplemental Figure S3 demonstrates the inducible doxycycline-dependent overexpression of human RASSF4 and provides additional evidence for the anti-myeloma activity of RASSF4 overexpression in human cell lines. Supplemental Figure S4 provides a comparison of the RASSF4 expression levels of the primary MM cells (n=10) and a selected panel of HMCL (n=9) obtained through microarray analysis. Supplemental Figure S5 shows additional data on the effect of RASSF4 overexpression on tumor development and the confirmation of RASSF4 overexpression on protein level. Supplemental Figure S6 provides an overview of the top 20 differentially expressed genes between all control and RASSF4 overexpressing human multiple myeloma cell lines and subsequent pathway enrichment analysis of the genes downregulated after RASSF4 overexpression. Supplemental Figure S7 provides additional evidence for the anti-myeloma activity of trametinib in combination with the HDACi quisinostat or panobinostat and shows the effect of the HDACi panobinostat and/or the MEK1/2 inhibitor trametinib on RASSF4 mRNA expression.

Published
2023
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174. Data from Loss of RASSF4 Expression in Multiple Myeloma Promotes RAS-Driven Malignant Progression

Author

Elke De Bruyne, Jérôme Moreaux, Karin Vanderkerken, Eline Menu, Kim De Veirman, Leo A. van Grunsven, Karine Breckpot, Dirk Hose, Andrew Cakana, Carlo Heirman, Nicolas Robert, Anke Maes, Alboukadel Kassambara, Hui Lui, Stefaan Verhulst, Ken Maes, and Eva De Smedt

Abstract

RAS mutations occur frequently in multiple myeloma (MM), but apart from driving progression, they can also stimulate antitumor effects by activating tumor-suppressive RASSF proteins. Although this family of death effector molecules are often silenced in cancers, functional data about RASSF proteins in MM are lacking. Here, we report that RASSF4 is downregulated during MM progression and correlates with a poor prognosis. Promoter methylation analysis in human cell lines revealed an inverse correlation between RASSF4 mRNA levels and methylation status. Epigenetic modulating agents restored RASSF4 expression. Enforced expression of RASSF4 induced G2-phase cell-cycle arrest and apoptosis in human cell lines, reduced primary MM cell viability, and blocked MM growth in vivo. Mechanistic investigations showed that RASSF4 linked RAS to several pro-death pathways, including those regulated by the kinases MST1, JNK, and p38. By activating MST1 and the JNK/c-Jun pathway, RASSF4 sensitized MM cells to bortezomib. Genetic or pharmacological elevation of RASSF4 levels increased the anti-MM effects of the clinical relevant MEK1/2 inhibitor trametinib. Kinome analysis revealed that this effect was mediated by concomitant activation of the JNK/c-Jun pathway along with inactivation of the MEK/ERK and PI3K/mTOR/Akt pathways. Overall, our findings establish RASSF4 as a tumor-suppressive hub in MM and provide a mechanistic rationale for combining trametinib with HDAC inhibitors or bortezomib to treat patients with tumors exhibiting low RASSF4 expression.Significance: These findings provide a mechanistic rationale for combining trametinib with HDAC inhibitors or bortezomib in patients with multiple myeloma whose tumors exhibit low RASSF4 expression. Cancer Res; 78(5); 1155–68. ©2017 AACR.

Published
2023
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175. Supplemental Tables S1, S4 and S5 from Loss of RASSF4 Expression in Multiple Myeloma Promotes RAS-Driven Malignant Progression

Author

Elke De Bruyne, Jérôme Moreaux, Karin Vanderkerken, Eline Menu, Kim De Veirman, Leo A. van Grunsven, Karine Breckpot, Dirk Hose, Andrew Cakana, Carlo Heirman, Nicolas Robert, Anke Maes, Alboukadel Kassambara, Hui Lui, Stefaan Verhulst, Ken Maes, and Eva De Smedt

Abstract

Supplemental Table S1 summarizes the patient characteristics. Supplemental Table S4 provides an overview of all kinases differentially phosphorylated in RASSF4 overexpressing cells treated with trametinib compared to parental cells treated with trametinib and/or RASSF4 overexpressing cells. Supplemental Table S5 summarizes significance and combination index (CI) values calculated for the different drug concentrations used in the combination experiments.

Published
2023
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176. Supplemental materials and methods, supplemental references and supplemental figure legends from Loss of RASSF4 Expression in Multiple Myeloma Promotes RAS-Driven Malignant Progression

Author

Elke De Bruyne, Jérôme Moreaux, Karin Vanderkerken, Eline Menu, Kim De Veirman, Leo A. van Grunsven, Karine Breckpot, Dirk Hose, Andrew Cakana, Carlo Heirman, Nicolas Robert, Anke Maes, Alboukadel Kassambara, Hui Lui, Stefaan Verhulst, Ken Maes, and Eva De Smedt

Abstract

Information about material and methods, that further support the date described in this article. Additional references and legends to the supplmental figures are also provided.

Published
2023
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177. Supplemental Table S2 from Loss of RASSF4 Expression in Multiple Myeloma Promotes RAS-Driven Malignant Progression

Author

Elke De Bruyne, Jérôme Moreaux, Karin Vanderkerken, Eline Menu, Kim De Veirman, Leo A. van Grunsven, Karine Breckpot, Dirk Hose, Andrew Cakana, Carlo Heirman, Nicolas Robert, Anke Maes, Alboukadel Kassambara, Hui Lui, Stefaan Verhulst, Ken Maes, and Eva De Smedt

Abstract

List of differentially expressed genes between all control and RASSF4 overexpressing human multiple myeloma cell lines

Published
2023
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179. Supplementary Figure 2 from Proinflammatory Characteristics of SMAC/DIABLO-Induced Cell Death in Antitumor Therapy

Author

Karine Breckpot, Joeri L. Aerts, Kris Thielemans, Carlo Heirman, Tomas Bos, Iain A. McNeish, Anje Cauwels, Sarah Maenhout, Cleo Goyvaerts, Sandra Van Lint, and Perpetua U. Emeagi

Abstract

PDF file - 117K, Uptake of LV-tSMAC transduced dying human melanoma cells enables dendritic cells to activate tumor-infiltrating lymphocytes.

Published
2023
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186. Supplemental Table S3 from Loss of RASSF4 Expression in Multiple Myeloma Promotes RAS-Driven Malignant Progression

Author

De Smedt, Eva, primary, Maes, Ken, primary, Verhulst, Stefaan, primary, Lui, Hui, primary, Kassambara, Alboukadel, primary, Maes, Anke, primary, Robert, Nicolas, primary, Heirman, Carlo, primary, Cakana, Andrew, primary, Hose, Dirk, primary, Breckpot, Karine, primary, van Grunsven, Leo A., primary, De Veirman, Kim, primary, Menu, Eline, primary, Vanderkerken, Karin, primary, Moreaux, Jérôme, primary, and De Bruyne, Elke, primary

Published
2023
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187. Supplemental Figures S1-S7 from Loss of RASSF4 Expression in Multiple Myeloma Promotes RAS-Driven Malignant Progression

Author

De Smedt, Eva, primary, Maes, Ken, primary, Verhulst, Stefaan, primary, Lui, Hui, primary, Kassambara, Alboukadel, primary, Maes, Anke, primary, Robert, Nicolas, primary, Heirman, Carlo, primary, Cakana, Andrew, primary, Hose, Dirk, primary, Breckpot, Karine, primary, van Grunsven, Leo A., primary, De Veirman, Kim, primary, Menu, Eline, primary, Vanderkerken, Karin, primary, Moreaux, Jérôme, primary, and De Bruyne, Elke, primary

Published
2023
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188. Data from Loss of RASSF4 Expression in Multiple Myeloma Promotes RAS-Driven Malignant Progression

Author

De Smedt, Eva, primary, Maes, Ken, primary, Verhulst, Stefaan, primary, Lui, Hui, primary, Kassambara, Alboukadel, primary, Maes, Anke, primary, Robert, Nicolas, primary, Heirman, Carlo, primary, Cakana, Andrew, primary, Hose, Dirk, primary, Breckpot, Karine, primary, van Grunsven, Leo A., primary, De Veirman, Kim, primary, Menu, Eline, primary, Vanderkerken, Karin, primary, Moreaux, Jérôme, primary, and De Bruyne, Elke, primary

Published
2023
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189. Supplemental materials and methods, supplemental references and supplemental figure legends from Loss of RASSF4 Expression in Multiple Myeloma Promotes RAS-Driven Malignant Progression

Author

De Smedt, Eva, primary, Maes, Ken, primary, Verhulst, Stefaan, primary, Lui, Hui, primary, Kassambara, Alboukadel, primary, Maes, Anke, primary, Robert, Nicolas, primary, Heirman, Carlo, primary, Cakana, Andrew, primary, Hose, Dirk, primary, Breckpot, Karine, primary, van Grunsven, Leo A., primary, De Veirman, Kim, primary, Menu, Eline, primary, Vanderkerken, Karin, primary, Moreaux, Jérôme, primary, and De Bruyne, Elke, primary

Published
2023
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190. Supplemental Tables S1, S4 and S5 from Loss of RASSF4 Expression in Multiple Myeloma Promotes RAS-Driven Malignant Progression

Author

De Smedt, Eva, primary, Maes, Ken, primary, Verhulst, Stefaan, primary, Lui, Hui, primary, Kassambara, Alboukadel, primary, Maes, Anke, primary, Robert, Nicolas, primary, Heirman, Carlo, primary, Cakana, Andrew, primary, Hose, Dirk, primary, Breckpot, Karine, primary, van Grunsven, Leo A., primary, De Veirman, Kim, primary, Menu, Eline, primary, Vanderkerken, Karin, primary, Moreaux, Jérôme, primary, and De Bruyne, Elke, primary

Published
2023
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