11 results on '"Lub S"'
Search Results
2. Functional properties of CD138- and CD138+ cells in Multiple Myeloma: Study in the 5T33MM model
- Author
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Van Valckenborgh, Els, Lub, S., Xu, Dehui, De Bruyne, Elke, Menu, Eline, Agarwal, P., Jernberg-Wiklund, Helena, Vanderkerken, Karin, and Hematology
- Subjects
multiple myeloma ,CD138 ,immune system diseases ,hemic and lymphatic diseases - Abstract
Multiple myeloma (MM) contains a heterogenous mix of tumor cells including CD138- and CD138+ cells. While some studies described that CD138- cells are a minor population containing MM clonogenic and therapy-resistant cells, others show that only CD138+ cells are able to proliferate and engraft. These studies clearly demonstrate that phenotypical and functional different tumor populations exist, but results are controversial. We investigated CD138- and CD138+ tumor populations in the murine syngeneic 5T33MM model. Both in vitro (clonogenic assay) and in vivo engraftment studies suggest that both populations form colonies and induce MM disease in a syngeneic environment, albeit CD138+ cells more apparent than CD138- cells. Real-time PCR for Blimp-1 and bcl-6 indicate that CD138- cells are less differentiated than CD138+ cells. We investigated in vitro the sensitivity of CD138- and CD138+ cells to drugs (bortezomib (Bz), MG132, melphalan, LBH589, 17AAG) by measuring cell viability and caspase3/7 activation. CD138- cells tend to be more resistant to drugs. Subsequently, we investigated, the phenotype of 5T33MM cells after in vivo treatment with Bz. The percentage of CD138- 5T33MM cells was significantly increased when mice were treated with Bz compared to vehicle. Preliminary results indicate that CD138- cells express more ABCG2, an ABC transporter involved in resistance. In conclusion, both CD138+ and CD138- cells are important in MM development with the CD138- cells being more therapy resistant indicating that CD138- MM cells should be included in further investigations.
- Published
- 2011
3. Practical use of mercury porosimetry in the study of porous solids
- Author
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Moscou, L., primary and Lub, S., additional
- Published
- 1981
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4. Characterization of Carbon Black Structure by Mercury Penetration
- Author
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Moscou, L., primary, Lub, S., primary, and Bussemaker, O. K. F., primary
- Published
- 1971
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5. Role of a medical student neuro-society organized neurosurgical conference: The Glasgow neuro experience.
- Author
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Ashraf M, Ismahel H, Lub S, Gardee A, Evans VE, Middleton EES, Chaudhary A, Cheema HA, Shahid A, Salloum LA, Szilagyi-Nagy E, Omar S, Mathieson C, Baird TA, O'Kane R, and Ashraf N
- Abstract
Background: Entering neurosurgical training in the United Kingdom demands extensive prior commitment and achievement, despite little to no exposure to the specialty in medical school. Conferences run by student "neuro-societies" offer a means to bridge this gap. This paper describes one student-led neuro-society's experience of curating a 1-day national neurosurgical conference supported by our neurosurgical department., Methods: A pre-and post-conference survey was distributed to attendees to ascertain baseline opinions and conference impact using a five-point Likert Scale, and free text questions explored medical students' opinions of neurosurgery and neurosurgical training. The conference offered four lectures and three workshops; the latter provided practical skills and networking opportunities. There were also 11 posters displayed throughout the day., Results: 47 medical students participated in our study. Post-conference, participants were more likely to understand what a neurosurgical career involves and how to secure training. They also reported increased knowledge about neurosurgery research, electives, audits, and project opportunities. Respondents enjoyed the workshops provided and suggested the inclusion of more female speakers in future., Conclusion: Neurosurgical conferences organized by student neuro-societies successfully address the gap between a lack of neurosurgery exposure and a competitive training selection. These events give medical students an initial understanding of a neurosurgical career through lectures and practical workshops; attendees also gain insight into attaining relevant achievements and have an opportunity to present research. Student neuro-society-organized conferences have the potential to be adopted internationally and used as a tool to educate on a global level and greatly aid medical students who are aspiring neurosurgeons., Competing Interests: There are no conflicts of interest., (Copyright: © 2023 Surgical Neurology International.)
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- 2023
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6. Glasgow Neuro Society 2021 Conference Proceedings.
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Ashraf M, Ismahel H, Lub S, Middleton E, Chaudhary A, Gardee A, Salloum LA, Szilagyi-Nagy E, Wales R, Omar S, Baird TA, O'Kane R, Holden J, Abdelsadg M, Burr P, Decruz AB, Badran K, Amato-Watkins A, Alakandy L, Boardman R, Nicely L, Tandon V, Banerjee S, Keenlyside A, Hughes M, Ho JW, Sieradzki J, Phan EPM, MacDougall NJJ, Bashir ABBA, Hutton DL, Doley ASF, Oochit KK, Kontorinis G, and Wong YY
- Published
- 2022
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7. Novel strategies to target the ubiquitin proteasome system in multiple myeloma.
- Author
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Lub S, Maes K, Menu E, De Bruyne E, Vanderkerken K, and Van Valckenborgh E
- Subjects
- Animals, Humans, Multiple Myeloma metabolism, Antineoplastic Agents pharmacology, Molecular Targeted Therapy, Multiple Myeloma drug therapy, Proteasome Endopeptidase Complex drug effects, Ubiquitin-Protein Ligases antagonists & inhibitors, Ubiquitination drug effects
- Abstract
Multiple myeloma (MM) is a hematological malignancy characterized by the accumulation of plasma cells in the bone marrow (BM). The success of the proteasome inhibitor bortezomib in the treatment of MM highlights the importance of the ubiquitin proteasome system (UPS) in this particular cancer. Despite the prolonged survival of MM patients, a significant amount of patients relapse or become resistant to therapy. This underlines the importance of the development and investigation of novel targets to improve MM therapy. The UPS plays an important role in different cellular processes by targeted destruction of proteins. The ubiquitination process consists of enzymes that transfer ubiquitin to proteins targeting them for proteasomal degradation. An emerging and promising approach is to target more disease specific components of the UPS to reduce side effects and overcome resistance. In this review, we will focus on different components of the UPS such as the ubiquitin activating enzyme E1, the ubiquitin conjugating enzyme E2, the E3 ubiquitin ligases, the deubiquitinating enzymes (DUBs) and the proteasome. We will discuss their role in MM and the implications in drug discovery for the treatment of MM.
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- 2016
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8. Inhibiting the anaphase promoting complex/cyclosome induces a metaphase arrest and cell death in multiple myeloma cells.
- Author
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Lub S, Maes A, Maes K, De Veirman K, De Bruyne E, Menu E, Fostier K, Kassambara A, Moreaux J, Hose D, Leleu X, King RW, Vanderkerken K, and Van Valckenborgh E
- Subjects
- Antineoplastic Agents, Alkylating pharmacology, Blotting, Western, Cdc20 Proteins metabolism, Cell Proliferation drug effects, Gene Expression Profiling, Humans, Immunoenzyme Techniques, Multiple Myeloma drug therapy, Multiple Myeloma metabolism, Tumor Cells, Cultured, Anaphase-Promoting Complex-Cyclosome antagonists & inhibitors, Apoptosis drug effects, Carbamates pharmacology, Cell Cycle Checkpoints drug effects, Diamines pharmacology, Melphalan pharmacology, Mitosis drug effects, Multiple Myeloma pathology
- Abstract
The anaphase promoting complex/cyclosome (APC/C) is an ubiquitin ligase involved in cell cycle. During the metaphase-anaphase transition the APC/C is activated by Cdc20. The aim of this study is to elucidate the importance and therapeutic potential of APC/C and its co-activator Cdc20 in multiple myeloma (MM). Gene expression analysis revealed that Cdc20 was expressed at higher levels in gene expression-based high-risk MM patients. Moreover, high Cdc20 expression correlated with poor prognosis. Treatment of human myeloma cell lines with proTAME, an APC/C inhibitor, resulted in an accumulation of APC/CCdc20 substrate cyclin B1 and an accumulation of cells in metaphase. Moreover we observed a significant dose-dependent decrease in viability and increase in apoptosis in MM cells upon proTAME treatment. The induction of apoptosis was accompanied with caspase 3, 8, 9 and PARP cleavage. A similar metaphase arrest and induction of apoptosis were obtained with specific knockdown of Cdc20. In addition, we demonstrated the accumulation of Bim was partially responsible for the observed cell death. Combining proTAME with another APC/C inhibitor apcin or the alkylating agent melphalan resulted in enhanced anti-MM activity. This study suggests that the APC/C and its co-activator Cdc20 could be a new and promising target especially in high-risk MM patients.
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- 2016
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9. Increased resistance to proteasome inhibitors in multiple myeloma mediated by cIAP2--implications for a combinatorial treatment.
- Author
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Fristedt Duvefelt C, Lub S, Agarwal P, Arngården L, Hammarberg A, Maes K, Van Valckenborgh E, Vanderkerken K, and Jernberg Wiklund H
- Subjects
- Apoptosis drug effects, Apoptosis physiology, Azocines administration & dosage, Azocines pharmacology, Baculoviral IAP Repeat-Containing 3 Protein, Benzhydryl Compounds administration & dosage, Benzhydryl Compounds pharmacology, Bortezomib administration & dosage, Bortezomib pharmacology, Case-Control Studies, Cell Line, Tumor, Drug Resistance, Neoplasm, Drug Synergism, HEK293 Cells, Humans, Inhibitor of Apoptosis Proteins biosynthesis, Inhibitor of Apoptosis Proteins genetics, Multiple Myeloma pathology, NF-kappa B metabolism, TNF Receptor-Associated Factor 3 deficiency, TNF Receptor-Associated Factor 3 genetics, TNF Receptor-Associated Factor 3 metabolism, Ubiquitin-Protein Ligases biosynthesis, Ubiquitin-Protein Ligases genetics, Antineoplastic Combined Chemotherapy Protocols pharmacology, Inhibitor of Apoptosis Proteins antagonists & inhibitors, Inhibitor of Apoptosis Proteins metabolism, Multiple Myeloma drug therapy, Multiple Myeloma enzymology, Proteasome Inhibitors pharmacology, Ubiquitin-Protein Ligases antagonists & inhibitors, Ubiquitin-Protein Ligases metabolism
- Abstract
Despite the introduction of new treatment options for multiple myeloma (MM), a majority of patients relapse due to the development of resistance. Unraveling new mechanisms underlying resistance could lead to identification of possible targets for combinatorial treatment. Using TRAF3 deleted/mutated MM cell lines, we evaluated the role of the cellular inhibitor of apoptosis 2 (cIAP2) in drug resistance and uncovered the plausible mechanisms underlying this resistance and possible strategies to overcome this by combinatorial treatment. In MM, cIAP2 is part of the gene signature of aberrant NF-κB signaling and is heterogeneously expressed amongst MM patients. In cIAP2 overexpressing cells a decreased sensitivity to the proteasome inhibitors bortezomib, MG132 and carfilzomib was observed. Gene expression analysis revealed that 440 genes were differentially expressed due to cIAP2 overexpression. Importantly, the data imply that cIAPs are rational targets for combinatorial treatment in the population of MM with deleted/mutated TRAF3. Indeed, we found that treatment with the IAP inhibitor AT-406 enhanced the anti-MM effect of bortezomib in the investigated cell lines. Taken together, our results show that cIAP2 is an important factor mediating bortezomib resistance in MM cells harboring TRAF3 deletion/mutation and therefore should be considered as a target for combinatorial treatment.
- Published
- 2015
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10. Multiple myeloma induces Mcl-1 expression and survival of myeloid-derived suppressor cells.
- Author
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De Veirman K, Van Ginderachter JA, Lub S, De Beule N, Thielemans K, Bautmans I, Oyajobi BO, De Bruyne E, Menu E, Lemaire M, Van Riet I, Vanderkerken K, and Van Valckenborgh E
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- Animals, Cell Line, Tumor, Disease Progression, Humans, Mice, Mice, Inbred C57BL, Multiple Myeloma genetics, Multiple Myeloma pathology, Myeloid Cell Leukemia Sequence 1 Protein genetics, Myeloid Cell Leukemia Sequence 1 Protein metabolism, Myeloid Cells metabolism, Myeloid Cells pathology, Survival Analysis, Multiple Myeloma metabolism, Myeloid Cell Leukemia Sequence 1 Protein biosynthesis
- Abstract
Myeloid-derived suppressor cells (MDSC) are contributing to an immunosuppressive environment by their ability to inhibit T cell activity and thereby promoting cancer progression. An important feature of the incurable plasma cell malignancy Multiple Myeloma (MM) is immune dysfunction. MDSC were previously identified to be present and active in MM patients, however little is known about the MDSC-inducing and -activating capacity of MM cells. In this study we investigated the effects of the tumor microenvironment on MDSC survival. During MM progression in the 5TMM mouse model, accumulation of MDSC in the bone marrow was observed in early stages of disease development, while circulating myeloid cells were increased at later stages of disease. Interestingly, in vivo MDSC targeting by anti-GR1 antibodies and 5-Fluorouracil resulted in a significant reduced tumor load in 5TMM-diseased mice. In vitro generation of MDSC was demonstrated by increased T cell immunosuppressive capacity and MDSC survival was observed in the presence of MM-conditioned medium. Finally, increased Mcl-1 expression was identified as underlying mechanism for MDSC survival. In conclusion, our data demonstrate that soluble factors from MM cells are able to generate MDSC through Mcl-1 upregulation and this cell population can be considered as a possible target in MM disease.
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- 2015
- Full Text
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11. The IGF-1 receptor inhibitor picropodophyllin potentiates the anti-myeloma activity of a BH3-mimetic.
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Bieghs L, Lub S, Fostier K, Maes K, Van Valckenborgh E, Menu E, Johnsen HE, Overgaard MT, Larsson O, Axelson M, Nyegaard M, Schots R, Jernberg-Wiklund H, Vanderkerken K, and De Bruyne E
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- Animals, Apoptosis drug effects, Biomimetic Materials administration & dosage, Biomimetic Materials pharmacology, Biphenyl Compounds administration & dosage, Cell Line, Tumor, Drug Synergism, Humans, Mice, Mice, Inbred C57BL, Multiple Myeloma metabolism, Multiple Myeloma pathology, Nitrophenols administration & dosage, Piperazines administration & dosage, Piperazines pharmacology, Podophyllotoxin administration & dosage, Podophyllotoxin pharmacology, Sulfonamides administration & dosage, Antineoplastic Combined Chemotherapy Protocols pharmacology, Biphenyl Compounds pharmacology, Multiple Myeloma drug therapy, Nitrophenols pharmacology, Podophyllotoxin analogs & derivatives, Receptor, IGF Type 1 antagonists & inhibitors, Sulfonamides pharmacology
- Abstract
The ABT-analogous 737, 263 and 199 are BH3 mimetics showing potent anti-myeloma (MM) activity, but only on defined molecular subgroups of MM patients presenting a Bcl-2high/Mcl-1low profile. IGF-1 is a major survival factor in MM regulating the expression of Bcl-2 proteins and might therefore be a resistance factor to these ABT-analogous. We first show that IGF-1 protected human MM cell lines (HMCLs) against ABT-737. Concurrently, the IGF-1 receptor inhibitor picropodophyllin (PPP) synergistically sensitized HMCL, primary human MM and murine 5T33MM cells to ABT-737 and ABT-199 by further decreasing cell viability and enhancing apoptosis. Knockdown of Bcl-2 by shRNA protected MM cells to ABT-737, while Mcl-1 shRNA sensitized the cells. PPP overcame the Bcl-2 dependency of ABT-737, but failed to completely overcome the protective effect of Mcl-1. In vivo, co-treatment of 5T33MM bearing mice significantly decreased tumor burden and prolonged overall survival both in a prophylactic and therapeutic setting. Interestingly, proteasome inhibitor resistant CD138- 5T33MM cells were more sensitive to ABT-737, whereas PPP alone targeted the CD138+ cells more effectively. After co-treatment, both subpopulations were targeted equally. Together, the combination of an IGF-1R inhibitor and an ABT-analogue displays synergistic anti-myeloma activity providing the rational for further (pre)clinical testing.
- Published
- 2014
- Full Text
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