Sien Bevers - Academia.edu (original) (raw)

Papers by Sien Bevers

Research paper thumbnail of The Combination of the CDK4/6 Inhibitor, Palbociclib, With the Vitamin D3 Analog, Inecalcitol, Has Potent In Vitro and In Vivo Anticancer Effects in Hormone-Sensitive Breast Cancer, But Has a More Limited Effect in Triple-Negative Breast Cancer

Frontiers in Endocrinology

Active vitamin D3, 1,25-dihydroxyvitamin D3 [1,25(OH)2D3], and its synthetically derived analogs ... more Active vitamin D3, 1,25-dihydroxyvitamin D3 [1,25(OH)2D3], and its synthetically derived analogs possess potent anticancer properties. In breast cancer (BC) cells, 1,25(OH)2D3 blocks cell proliferation and induces apoptosis through different cell-type specific mechanisms. In this study, we evaluated if the combination of the potent vitamin D3 analog, inecalcitol, with a selective CDK4/6 inhibitor, palbociclib, enhanced the antiproliferative effects of both single compounds in hormone-sensitive (ER+) BC, for which palbociclib treatment is already approved, but also in triple-negative BC (TNBC). Inecalcitol and palbociclib combination treatment decreased cell proliferation in both ER+ (T47D-MCF7) and TNBC (BT20-HCC1143-Hs578T) cells, with a more pronounced antiproliferative effect in the former. In ER+ BC cells, the combination therapy downregulated cell cycle regulatory proteins (p)-Rb and (p)-CDK2 and blocked G1-S phase transition of the cell cycle. Combination treatment upregulated...

Research paper thumbnail of PATH-20. Spatial Mapping of Therapy-Induced, Pathological Changes in Glioblastoma at Single-Cell Resolution

Neuro-Oncology

Glioblastoma (GBM) remains a highly malignant, intrinsically resistant and inevitably recurring b... more Glioblastoma (GBM) remains a highly malignant, intrinsically resistant and inevitably recurring brain tumor with dismal prognosis. The aggressiveness and lack of effective GBM treatments can be attributed to the highly heterogeneous and plastic nature of GBM tumor cells, which easily confer resistance to standard-of-care (SOC) therapy. While tumor progression has also been attributed to interactions with the tumor microenvironment, quantitative data describing these interactions are still largely missing. Here, we used high-dimensional, multiplexed immunohistochemistry to map evolutions in the spatial, single-cell tissue architecture of 120 paired adult GBM tumor samples derived from 60 patients at diagnosis (ND) and upon recurrence (REC) following SOC treatment. We mapped the spatial distribution of a multitude of GBM tumoral subtypes across this multicentric cohort, through which we identified a high level of heterogeneity defined by specific tumoral niches within and across patie...

Research paper thumbnail of Towards more accurate preclinical glioblastoma modelling: reverse translation of clinical standard of care in a glioblastoma mouse model

IntroductionContrarily to clinical trials, where glioblastoma (GBM) patients are usually heavily ... more IntroductionContrarily to clinical trials, where glioblastoma (GBM) patients are usually heavily pre-treated (surgery, radiotherapy (RT) and temozolomide (TMZ)) before receiving the experimental therapies, in preclinical GBM studies experimental treatments have mostly been administered as monotherapy or combined with a very limited part of the clinical standard of care. This discrepancy can explain the failed clinical translation of preclinically successful treatments. This study is aimed at evaluating the feasibility and survival impact of the clinical standard of care in glioma-bearing mice. Methods. Neurospheres CT-2A tumor-bearing mice were treated with fluorescence-guided tumor resection, focal RT and oral TMZ.ResultsThe implementation of postoperative intensive care treatment reduced surgical mortality by approximately 50% and increased experimental cost-effectiveness. Partial and total tumor resection significantly prolonged survival, the latter showing the strongest effect. ...

Research paper thumbnail of Immunocompetent Mouse Models in the Search for Effective Immunotherapy in Glioblastoma

Cancers, 2020

Simple Summary Glioblastoma (GBM) remains the most aggressive brain tumor. Treatment typically in... more Simple Summary Glioblastoma (GBM) remains the most aggressive brain tumor. Treatment typically includes surgery and radio/chemotherapy, but in spite of intensive treatment, virtually all tumors recur within the time-frame of months with insufficient and unsuccessful second line options. This clinical reality is in contrast to preclinical animal experiments, which often show successful outcomes of novel immunotherapeutic approaches. This discrepancy is largely explained by the small number of animal models and their limited capacity to mimic the complexity of the human disease. Moreover, new treatment options are typically administered as single treatments in animal models, whereas patients receive them in combination with standard-of-care. In this review, we provide an overview of the existing mouse models for GBM research and how each of them mimic (parts of) the human disease spectrum. As such we provide an overview of the advantages and limitations of the currently available opti...

Research paper thumbnail of The Combination of the CDK4/6 Inhibitor, Palbociclib, With the Vitamin D3 Analog, Inecalcitol, Has Potent In Vitro and In Vivo Anticancer Effects in Hormone-Sensitive Breast Cancer, But Has a More Limited Effect in Triple-Negative Breast Cancer

Frontiers in Endocrinology

Active vitamin D3, 1,25-dihydroxyvitamin D3 [1,25(OH)2D3], and its synthetically derived analogs ... more Active vitamin D3, 1,25-dihydroxyvitamin D3 [1,25(OH)2D3], and its synthetically derived analogs possess potent anticancer properties. In breast cancer (BC) cells, 1,25(OH)2D3 blocks cell proliferation and induces apoptosis through different cell-type specific mechanisms. In this study, we evaluated if the combination of the potent vitamin D3 analog, inecalcitol, with a selective CDK4/6 inhibitor, palbociclib, enhanced the antiproliferative effects of both single compounds in hormone-sensitive (ER+) BC, for which palbociclib treatment is already approved, but also in triple-negative BC (TNBC). Inecalcitol and palbociclib combination treatment decreased cell proliferation in both ER+ (T47D-MCF7) and TNBC (BT20-HCC1143-Hs578T) cells, with a more pronounced antiproliferative effect in the former. In ER+ BC cells, the combination therapy downregulated cell cycle regulatory proteins (p)-Rb and (p)-CDK2 and blocked G1-S phase transition of the cell cycle. Combination treatment upregulated...

Research paper thumbnail of PATH-20. Spatial Mapping of Therapy-Induced, Pathological Changes in Glioblastoma at Single-Cell Resolution

Neuro-Oncology

Glioblastoma (GBM) remains a highly malignant, intrinsically resistant and inevitably recurring b... more Glioblastoma (GBM) remains a highly malignant, intrinsically resistant and inevitably recurring brain tumor with dismal prognosis. The aggressiveness and lack of effective GBM treatments can be attributed to the highly heterogeneous and plastic nature of GBM tumor cells, which easily confer resistance to standard-of-care (SOC) therapy. While tumor progression has also been attributed to interactions with the tumor microenvironment, quantitative data describing these interactions are still largely missing. Here, we used high-dimensional, multiplexed immunohistochemistry to map evolutions in the spatial, single-cell tissue architecture of 120 paired adult GBM tumor samples derived from 60 patients at diagnosis (ND) and upon recurrence (REC) following SOC treatment. We mapped the spatial distribution of a multitude of GBM tumoral subtypes across this multicentric cohort, through which we identified a high level of heterogeneity defined by specific tumoral niches within and across patie...

Research paper thumbnail of Towards more accurate preclinical glioblastoma modelling: reverse translation of clinical standard of care in a glioblastoma mouse model

IntroductionContrarily to clinical trials, where glioblastoma (GBM) patients are usually heavily ... more IntroductionContrarily to clinical trials, where glioblastoma (GBM) patients are usually heavily pre-treated (surgery, radiotherapy (RT) and temozolomide (TMZ)) before receiving the experimental therapies, in preclinical GBM studies experimental treatments have mostly been administered as monotherapy or combined with a very limited part of the clinical standard of care. This discrepancy can explain the failed clinical translation of preclinically successful treatments. This study is aimed at evaluating the feasibility and survival impact of the clinical standard of care in glioma-bearing mice. Methods. Neurospheres CT-2A tumor-bearing mice were treated with fluorescence-guided tumor resection, focal RT and oral TMZ.ResultsThe implementation of postoperative intensive care treatment reduced surgical mortality by approximately 50% and increased experimental cost-effectiveness. Partial and total tumor resection significantly prolonged survival, the latter showing the strongest effect. ...

Research paper thumbnail of Immunocompetent Mouse Models in the Search for Effective Immunotherapy in Glioblastoma

Cancers, 2020

Simple Summary Glioblastoma (GBM) remains the most aggressive brain tumor. Treatment typically in... more Simple Summary Glioblastoma (GBM) remains the most aggressive brain tumor. Treatment typically includes surgery and radio/chemotherapy, but in spite of intensive treatment, virtually all tumors recur within the time-frame of months with insufficient and unsuccessful second line options. This clinical reality is in contrast to preclinical animal experiments, which often show successful outcomes of novel immunotherapeutic approaches. This discrepancy is largely explained by the small number of animal models and their limited capacity to mimic the complexity of the human disease. Moreover, new treatment options are typically administered as single treatments in animal models, whereas patients receive them in combination with standard-of-care. In this review, we provide an overview of the existing mouse models for GBM research and how each of them mimic (parts of) the human disease spectrum. As such we provide an overview of the advantages and limitations of the currently available opti...