The Experts below are selected from a list of 1983 Experts worldwide ranked by ideXlab platform
Robert P Coppes - One of the best experts on this subject based on the ideXlab platform.
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clinical management of salivary gland hypofunction and xerostomia in head and neck cancer patients successes and barriers
International Journal of Radiation Oncology Biology Physics, 2010Co-Authors: Arjan Vissink, Kirsten H Limesand, Siri Beier Jensen, Linda S. Elting, Robert P Coppes, James B Mitchell, Bruce J Baum, Johannes A. Langendijk, Mary E ReylandAbstract:The most significant long-term complication of radiotherapy in the head-and-neck region is Hyposalivation and its related complaints, particularily xerostomia. This review addresses the pathophysiology underlying irradiation damage to salivary gland tissue, the consequences of radiation injury, and issues contributing to the clinical management of salivary gland hypofunction and xerostomia. These include ways to (1) prevent or minimize radiation injury of salivary gland tissue, (2) manage radiation-induced Hyposalivation and xerostomia, and (3) restore the function of salivary gland tissue damaged by radiotherapy.
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keratinocyte growth factor prevents radiation damage to salivary glands by expansion of the stem progenitor pool
Stem Cells, 2008Co-Authors: Isabelle M A Lombaert, Robert P Coppes, Jeanette F Brunsting, Pieter K Wierenga, Harm H Kampinga, Gerald De HaanAbstract:Irradiation of salivary glands during radiotherapy treatment of patients with head and neck cancer evokes persistent Hyposalivation. This results from depletion of stem cells, which renders the gland incapable of replenishing saliva to produce acinar cells. The aim of this study was to investigate whether it is possible to expand the salivary gland stem/progenitor cell population, thereby preventing acinar cell depletion and subsequent gland dysfunction after irradiation. To induce cell proliferation, keratinocyte growth factor (DeltaN23-KGF, palifermin) was administered to C57BL/6 mice for 4 days before and/or after local irradiation of salivary glands. Salivary gland vitality was quantified by in vivo saliva flow rates, morphological measurements, and a newly developed in vitro salisphere progenitor/stem cell assay. Irradiation of salivary glands led to a pronounced reduction in the stem cells of the tissues, resulting in severe Hyposalivation and a reduced number of acinar cells. DeltaN23-KGF treatment for 4 days before irradiation indeed induced salivary gland stem/progenitor cell proliferation, increasing the stem and progenitor cell pool. This did not change the relative radiation sensitivity of the stem/progenitor cells, but, as a consequence, an absolute higher number of stem/progenitor cells and acinar cells survived after radiation. Postirradiation treatment with DeltaN23-KGF also improved gland function, and this effect was much more pronounced in DeltaN23-KGF pretreated animals. Post-treatment with DeltaN23-KGF seemed to act through accelerated expansion of the pool of progenitor/stem cells that survived the irradiation treatment. Overall, our data indicate that DeltaN23-KGF is a promising drug to enhance the number of salivary gland progenitor/stem cells and consequently prevent radiation-induced Hyposalivation. Disclosure of potential conflicts of interest is found at the end of this article.
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keratinocyte growth factor prevents radiation damage to salivary glands by expansion of the stem progenitor pool
Stem Cells, 2008Co-Authors: Isabelle M A Lombaert, Robert P Coppes, Jeanette F Brunsting, Pieter K Wierenga, Harm H Kampinga, Gerald De HaanAbstract:Irradiation of salivary glands during radiotherapy treatment of patients with head and neck cancer evokes persistent Hyposalivation. This results from depletion of stem cells, which renders the gland incapable of replenishing saliva to produce acinar cells. The aim of this study was to investigate whether it is possible to expand the salivary gland stem/ progenitor cell population, thereby preventing acinar cell depletion and subsequent gland dysfunction after irradiation. To induce cell proliferation, keratinocyte growth factor (N23-KGF, palifermin) was administered to C57BL/6 mice for 4 days before and/or after local irradiation of salivary glands. Salivary gland vitality was quantified by in vivo saliva flow rates, morphological measurements, and a newly developed in vitro salisphere progenitor/stem cell assay. Irradiation of salivary glands led to a pronounced reduction in the stem cells of the tissues, resulting in severe Hyposalivation and a reduced number of acinar cells. N23-KGF treatment for 4 days before irradiation indeed induced salivary gland stem/progenitor cell proliferation, increasing the stem and progenitor cell pool. This did not change the relative radiation sensitivity of the stem/progenitor cells, but, as a consequence, an absolute higher number of stem/ progenitor cells and acinar cells survived after radiation. Postirradiation treatment with N23-KGF also improved gland function, and this effect was much more pronounced in N23-KGF pretreated animals. Post-treatment with N23-KGF seemed to act through accelerated expansion of the pool of progenitor/stem cells that survived the irradiation treatment. Overall, our data indicate that N23-KGF is a promising drug to enhance the number of salivary gland progenitor/stem cells and consequently prevent radiationinduced Hyposalivation. STEM CELLS 2008;26:2595–2601 Disclosure of potential conflicts of interest is found at the end of this article.
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oral sequelae of head and neck radiotherapy
Critical Reviews in Oral Biology & Medicine, 2003Co-Authors: Arjan Vissink, J Jansma, F K L Spijkervet, Fred R Burlage, Robert P CoppesAbstract:In addition to anti-tumor effects, ionizing radiation causes damage in normal tissues located in the radiation portals. Oral complications of radiotherapy in the head and neck region are the result of the deleterious effects of radiation on, e.g., salivary glands, oral mucosa, bone, dentition, masticatory musculature, and temporomandibular joints. The clinical consequences of radiotherapy include mucositis, Hyposalivation, taste loss, osteoradionecrosis, radiation caries, and trismus. Mucositis and taste loss are reversible consequences that usually subside early post-irradiation, while Hyposalivation is normally irreversible. Furthermore, the risk of developing radiation caries and osteoradionecrosis is a life-long threat. All these consequences form a heavy burden for the patients and have a tremendous impact on their quality of life during and after radiotherapy. In this review, the radiation-induced changes in healthy oral tissues and the resulting clinical consequences are discussed.
Isabelle M A Lombaert - One of the best experts on this subject based on the ideXlab platform.
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distinct long term effects of precision x radiation on reflex saliva flow rate and tissue integrity in a preclinical model of chronic Hyposalivation
bioRxiv, 2020Co-Authors: Syed Mohammed Musheer Aalam, Ishaq Viringipurampeer, Matthew C Walb, Erik J Tryggestad, Chitra Priya Emperumal, Jianning Song, Rajan Saini, Isabelle M A Lombaert, Jann N Sarkaria, Joaquin J GarciaAbstract:Chronic salivary hypofunction and xerostomia are common side effects of radiation therapy which is an essential component in the curative management in patients with head & neck cancers. Over the years, improvements in delivery techniques such as image-guided intensity modulated radiation therapy have led to improvement in cancer management but chronic Hyposalivation continues to be a challenge that causes long-term health implications resulting in compromised quality of life. Recent advances in salivary stem cell research promise new frontier in the treatment of radiation-induced Hyposalivation by initiating regeneration of radiation-damaged salivary parenchymal cells. Lack of a standard preclinical immunodeficient model to assess radiation-induced changes objectively and quantitatively in salivary flow rates will impede rapid progress towards the development of cellular therapies for chronic salivary dysfunction and attendant xerostomia. Herein, we report the first fully characterized novel cone-beam computed tomography (CBCT)-guided precision ionizing radiation (IR) induced chronic Hyposalivation model in radiosensitive, immunodeficient transgenic NSG-SGM3 mice expressing three human cytokines including c-KIT ligand/stem cell factor. Additionally, we also report a novel and instantaneous method to objectively assess the kinetics of pilocarpine-stimulated salivary flowrate. Comprehensive structural and functional characterization of salivary glands revealed previously unknown and highly complex gender, age, IR dose and salivary gland subtype-specific effects of salivary-ablative precision IR.
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keratinocyte growth factor prevents radiation damage to salivary glands by expansion of the stem progenitor pool
Stem Cells, 2008Co-Authors: Isabelle M A Lombaert, Robert P Coppes, Jeanette F Brunsting, Pieter K Wierenga, Harm H Kampinga, Gerald De HaanAbstract:Irradiation of salivary glands during radiotherapy treatment of patients with head and neck cancer evokes persistent Hyposalivation. This results from depletion of stem cells, which renders the gland incapable of replenishing saliva to produce acinar cells. The aim of this study was to investigate whether it is possible to expand the salivary gland stem/progenitor cell population, thereby preventing acinar cell depletion and subsequent gland dysfunction after irradiation. To induce cell proliferation, keratinocyte growth factor (DeltaN23-KGF, palifermin) was administered to C57BL/6 mice for 4 days before and/or after local irradiation of salivary glands. Salivary gland vitality was quantified by in vivo saliva flow rates, morphological measurements, and a newly developed in vitro salisphere progenitor/stem cell assay. Irradiation of salivary glands led to a pronounced reduction in the stem cells of the tissues, resulting in severe Hyposalivation and a reduced number of acinar cells. DeltaN23-KGF treatment for 4 days before irradiation indeed induced salivary gland stem/progenitor cell proliferation, increasing the stem and progenitor cell pool. This did not change the relative radiation sensitivity of the stem/progenitor cells, but, as a consequence, an absolute higher number of stem/progenitor cells and acinar cells survived after radiation. Postirradiation treatment with DeltaN23-KGF also improved gland function, and this effect was much more pronounced in DeltaN23-KGF pretreated animals. Post-treatment with DeltaN23-KGF seemed to act through accelerated expansion of the pool of progenitor/stem cells that survived the irradiation treatment. Overall, our data indicate that DeltaN23-KGF is a promising drug to enhance the number of salivary gland progenitor/stem cells and consequently prevent radiation-induced Hyposalivation. Disclosure of potential conflicts of interest is found at the end of this article.
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keratinocyte growth factor prevents radiation damage to salivary glands by expansion of the stem progenitor pool
Stem Cells, 2008Co-Authors: Isabelle M A Lombaert, Robert P Coppes, Jeanette F Brunsting, Pieter K Wierenga, Harm H Kampinga, Gerald De HaanAbstract:Irradiation of salivary glands during radiotherapy treatment of patients with head and neck cancer evokes persistent Hyposalivation. This results from depletion of stem cells, which renders the gland incapable of replenishing saliva to produce acinar cells. The aim of this study was to investigate whether it is possible to expand the salivary gland stem/ progenitor cell population, thereby preventing acinar cell depletion and subsequent gland dysfunction after irradiation. To induce cell proliferation, keratinocyte growth factor (N23-KGF, palifermin) was administered to C57BL/6 mice for 4 days before and/or after local irradiation of salivary glands. Salivary gland vitality was quantified by in vivo saliva flow rates, morphological measurements, and a newly developed in vitro salisphere progenitor/stem cell assay. Irradiation of salivary glands led to a pronounced reduction in the stem cells of the tissues, resulting in severe Hyposalivation and a reduced number of acinar cells. N23-KGF treatment for 4 days before irradiation indeed induced salivary gland stem/progenitor cell proliferation, increasing the stem and progenitor cell pool. This did not change the relative radiation sensitivity of the stem/progenitor cells, but, as a consequence, an absolute higher number of stem/ progenitor cells and acinar cells survived after radiation. Postirradiation treatment with N23-KGF also improved gland function, and this effect was much more pronounced in N23-KGF pretreated animals. Post-treatment with N23-KGF seemed to act through accelerated expansion of the pool of progenitor/stem cells that survived the irradiation treatment. Overall, our data indicate that N23-KGF is a promising drug to enhance the number of salivary gland progenitor/stem cells and consequently prevent radiationinduced Hyposalivation. STEM CELLS 2008;26:2595–2601 Disclosure of potential conflicts of interest is found at the end of this article.
Jeanette F Brunsting - One of the best experts on this subject based on the ideXlab platform.
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keratinocyte growth factor prevents radiation damage to salivary glands by expansion of the stem progenitor pool
Stem Cells, 2008Co-Authors: Isabelle M A Lombaert, Robert P Coppes, Jeanette F Brunsting, Pieter K Wierenga, Harm H Kampinga, Gerald De HaanAbstract:Irradiation of salivary glands during radiotherapy treatment of patients with head and neck cancer evokes persistent Hyposalivation. This results from depletion of stem cells, which renders the gland incapable of replenishing saliva to produce acinar cells. The aim of this study was to investigate whether it is possible to expand the salivary gland stem/progenitor cell population, thereby preventing acinar cell depletion and subsequent gland dysfunction after irradiation. To induce cell proliferation, keratinocyte growth factor (DeltaN23-KGF, palifermin) was administered to C57BL/6 mice for 4 days before and/or after local irradiation of salivary glands. Salivary gland vitality was quantified by in vivo saliva flow rates, morphological measurements, and a newly developed in vitro salisphere progenitor/stem cell assay. Irradiation of salivary glands led to a pronounced reduction in the stem cells of the tissues, resulting in severe Hyposalivation and a reduced number of acinar cells. DeltaN23-KGF treatment for 4 days before irradiation indeed induced salivary gland stem/progenitor cell proliferation, increasing the stem and progenitor cell pool. This did not change the relative radiation sensitivity of the stem/progenitor cells, but, as a consequence, an absolute higher number of stem/progenitor cells and acinar cells survived after radiation. Postirradiation treatment with DeltaN23-KGF also improved gland function, and this effect was much more pronounced in DeltaN23-KGF pretreated animals. Post-treatment with DeltaN23-KGF seemed to act through accelerated expansion of the pool of progenitor/stem cells that survived the irradiation treatment. Overall, our data indicate that DeltaN23-KGF is a promising drug to enhance the number of salivary gland progenitor/stem cells and consequently prevent radiation-induced Hyposalivation. Disclosure of potential conflicts of interest is found at the end of this article.
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keratinocyte growth factor prevents radiation damage to salivary glands by expansion of the stem progenitor pool
Stem Cells, 2008Co-Authors: Isabelle M A Lombaert, Robert P Coppes, Jeanette F Brunsting, Pieter K Wierenga, Harm H Kampinga, Gerald De HaanAbstract:Irradiation of salivary glands during radiotherapy treatment of patients with head and neck cancer evokes persistent Hyposalivation. This results from depletion of stem cells, which renders the gland incapable of replenishing saliva to produce acinar cells. The aim of this study was to investigate whether it is possible to expand the salivary gland stem/ progenitor cell population, thereby preventing acinar cell depletion and subsequent gland dysfunction after irradiation. To induce cell proliferation, keratinocyte growth factor (N23-KGF, palifermin) was administered to C57BL/6 mice for 4 days before and/or after local irradiation of salivary glands. Salivary gland vitality was quantified by in vivo saliva flow rates, morphological measurements, and a newly developed in vitro salisphere progenitor/stem cell assay. Irradiation of salivary glands led to a pronounced reduction in the stem cells of the tissues, resulting in severe Hyposalivation and a reduced number of acinar cells. N23-KGF treatment for 4 days before irradiation indeed induced salivary gland stem/progenitor cell proliferation, increasing the stem and progenitor cell pool. This did not change the relative radiation sensitivity of the stem/progenitor cells, but, as a consequence, an absolute higher number of stem/ progenitor cells and acinar cells survived after radiation. Postirradiation treatment with N23-KGF also improved gland function, and this effect was much more pronounced in N23-KGF pretreated animals. Post-treatment with N23-KGF seemed to act through accelerated expansion of the pool of progenitor/stem cells that survived the irradiation treatment. Overall, our data indicate that N23-KGF is a promising drug to enhance the number of salivary gland progenitor/stem cells and consequently prevent radiationinduced Hyposalivation. STEM CELLS 2008;26:2595–2601 Disclosure of potential conflicts of interest is found at the end of this article.
Pieter K Wierenga - One of the best experts on this subject based on the ideXlab platform.
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keratinocyte growth factor prevents radiation damage to salivary glands by expansion of the stem progenitor pool
Stem Cells, 2008Co-Authors: Isabelle M A Lombaert, Robert P Coppes, Jeanette F Brunsting, Pieter K Wierenga, Harm H Kampinga, Gerald De HaanAbstract:Irradiation of salivary glands during radiotherapy treatment of patients with head and neck cancer evokes persistent Hyposalivation. This results from depletion of stem cells, which renders the gland incapable of replenishing saliva to produce acinar cells. The aim of this study was to investigate whether it is possible to expand the salivary gland stem/progenitor cell population, thereby preventing acinar cell depletion and subsequent gland dysfunction after irradiation. To induce cell proliferation, keratinocyte growth factor (DeltaN23-KGF, palifermin) was administered to C57BL/6 mice for 4 days before and/or after local irradiation of salivary glands. Salivary gland vitality was quantified by in vivo saliva flow rates, morphological measurements, and a newly developed in vitro salisphere progenitor/stem cell assay. Irradiation of salivary glands led to a pronounced reduction in the stem cells of the tissues, resulting in severe Hyposalivation and a reduced number of acinar cells. DeltaN23-KGF treatment for 4 days before irradiation indeed induced salivary gland stem/progenitor cell proliferation, increasing the stem and progenitor cell pool. This did not change the relative radiation sensitivity of the stem/progenitor cells, but, as a consequence, an absolute higher number of stem/progenitor cells and acinar cells survived after radiation. Postirradiation treatment with DeltaN23-KGF also improved gland function, and this effect was much more pronounced in DeltaN23-KGF pretreated animals. Post-treatment with DeltaN23-KGF seemed to act through accelerated expansion of the pool of progenitor/stem cells that survived the irradiation treatment. Overall, our data indicate that DeltaN23-KGF is a promising drug to enhance the number of salivary gland progenitor/stem cells and consequently prevent radiation-induced Hyposalivation. Disclosure of potential conflicts of interest is found at the end of this article.
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keratinocyte growth factor prevents radiation damage to salivary glands by expansion of the stem progenitor pool
Stem Cells, 2008Co-Authors: Isabelle M A Lombaert, Robert P Coppes, Jeanette F Brunsting, Pieter K Wierenga, Harm H Kampinga, Gerald De HaanAbstract:Irradiation of salivary glands during radiotherapy treatment of patients with head and neck cancer evokes persistent Hyposalivation. This results from depletion of stem cells, which renders the gland incapable of replenishing saliva to produce acinar cells. The aim of this study was to investigate whether it is possible to expand the salivary gland stem/ progenitor cell population, thereby preventing acinar cell depletion and subsequent gland dysfunction after irradiation. To induce cell proliferation, keratinocyte growth factor (N23-KGF, palifermin) was administered to C57BL/6 mice for 4 days before and/or after local irradiation of salivary glands. Salivary gland vitality was quantified by in vivo saliva flow rates, morphological measurements, and a newly developed in vitro salisphere progenitor/stem cell assay. Irradiation of salivary glands led to a pronounced reduction in the stem cells of the tissues, resulting in severe Hyposalivation and a reduced number of acinar cells. N23-KGF treatment for 4 days before irradiation indeed induced salivary gland stem/progenitor cell proliferation, increasing the stem and progenitor cell pool. This did not change the relative radiation sensitivity of the stem/progenitor cells, but, as a consequence, an absolute higher number of stem/ progenitor cells and acinar cells survived after radiation. Postirradiation treatment with N23-KGF also improved gland function, and this effect was much more pronounced in N23-KGF pretreated animals. Post-treatment with N23-KGF seemed to act through accelerated expansion of the pool of progenitor/stem cells that survived the irradiation treatment. Overall, our data indicate that N23-KGF is a promising drug to enhance the number of salivary gland progenitor/stem cells and consequently prevent radiationinduced Hyposalivation. STEM CELLS 2008;26:2595–2601 Disclosure of potential conflicts of interest is found at the end of this article.
Harm H Kampinga - One of the best experts on this subject based on the ideXlab platform.
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keratinocyte growth factor prevents radiation damage to salivary glands by expansion of the stem progenitor pool
Stem Cells, 2008Co-Authors: Isabelle M A Lombaert, Robert P Coppes, Jeanette F Brunsting, Pieter K Wierenga, Harm H Kampinga, Gerald De HaanAbstract:Irradiation of salivary glands during radiotherapy treatment of patients with head and neck cancer evokes persistent Hyposalivation. This results from depletion of stem cells, which renders the gland incapable of replenishing saliva to produce acinar cells. The aim of this study was to investigate whether it is possible to expand the salivary gland stem/progenitor cell population, thereby preventing acinar cell depletion and subsequent gland dysfunction after irradiation. To induce cell proliferation, keratinocyte growth factor (DeltaN23-KGF, palifermin) was administered to C57BL/6 mice for 4 days before and/or after local irradiation of salivary glands. Salivary gland vitality was quantified by in vivo saliva flow rates, morphological measurements, and a newly developed in vitro salisphere progenitor/stem cell assay. Irradiation of salivary glands led to a pronounced reduction in the stem cells of the tissues, resulting in severe Hyposalivation and a reduced number of acinar cells. DeltaN23-KGF treatment for 4 days before irradiation indeed induced salivary gland stem/progenitor cell proliferation, increasing the stem and progenitor cell pool. This did not change the relative radiation sensitivity of the stem/progenitor cells, but, as a consequence, an absolute higher number of stem/progenitor cells and acinar cells survived after radiation. Postirradiation treatment with DeltaN23-KGF also improved gland function, and this effect was much more pronounced in DeltaN23-KGF pretreated animals. Post-treatment with DeltaN23-KGF seemed to act through accelerated expansion of the pool of progenitor/stem cells that survived the irradiation treatment. Overall, our data indicate that DeltaN23-KGF is a promising drug to enhance the number of salivary gland progenitor/stem cells and consequently prevent radiation-induced Hyposalivation. Disclosure of potential conflicts of interest is found at the end of this article.
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keratinocyte growth factor prevents radiation damage to salivary glands by expansion of the stem progenitor pool
Stem Cells, 2008Co-Authors: Isabelle M A Lombaert, Robert P Coppes, Jeanette F Brunsting, Pieter K Wierenga, Harm H Kampinga, Gerald De HaanAbstract:Irradiation of salivary glands during radiotherapy treatment of patients with head and neck cancer evokes persistent Hyposalivation. This results from depletion of stem cells, which renders the gland incapable of replenishing saliva to produce acinar cells. The aim of this study was to investigate whether it is possible to expand the salivary gland stem/ progenitor cell population, thereby preventing acinar cell depletion and subsequent gland dysfunction after irradiation. To induce cell proliferation, keratinocyte growth factor (N23-KGF, palifermin) was administered to C57BL/6 mice for 4 days before and/or after local irradiation of salivary glands. Salivary gland vitality was quantified by in vivo saliva flow rates, morphological measurements, and a newly developed in vitro salisphere progenitor/stem cell assay. Irradiation of salivary glands led to a pronounced reduction in the stem cells of the tissues, resulting in severe Hyposalivation and a reduced number of acinar cells. N23-KGF treatment for 4 days before irradiation indeed induced salivary gland stem/progenitor cell proliferation, increasing the stem and progenitor cell pool. This did not change the relative radiation sensitivity of the stem/progenitor cells, but, as a consequence, an absolute higher number of stem/ progenitor cells and acinar cells survived after radiation. Postirradiation treatment with N23-KGF also improved gland function, and this effect was much more pronounced in N23-KGF pretreated animals. Post-treatment with N23-KGF seemed to act through accelerated expansion of the pool of progenitor/stem cells that survived the irradiation treatment. Overall, our data indicate that N23-KGF is a promising drug to enhance the number of salivary gland progenitor/stem cells and consequently prevent radiationinduced Hyposalivation. STEM CELLS 2008;26:2595–2601 Disclosure of potential conflicts of interest is found at the end of this article.