12 results on '"Dillingh, JH"'
Search Results
2. Growth factor treatment prior to low-dose total body irradiation increases donor cell engraftment after bone marrow transplantation in mice
- Author
-
Noach, EJK, Ausema, A, Dillingh, JH, Dontje, B, Weersing, E, Akkerman, [No Value], Vellenga, E, Haan, GC, Guided Treatment in Optimal Selected Cancer Patients (GUTS), and Stem Cell Aging Leukemia and Lymphoma (SALL)
- Subjects
EX-VIVO ,MYELOABLATIVE CONDITIONING REGIMEN ,LONG-TERM ENGRAFTMENT ,PROGENITOR CELLS ,HEMATOPOIETIC STEM-CELLS ,MURINE MARROW ,TOLERANCE ,COLONY-STIMULATING FACTOR ,CHIMERISM ,THERAPY - Abstract
Low-toxicity conditioning regimens prior to bone marrow transplantation (BMT) are widely explored. We developed a new protocol using hematopoietic growth factors prior to low-dose total body irradiation (TBI) in recipients of autologous transplants to establish high levels of long-term donor cell engraftment. We hypothesized that treatment of recipient mice with growth factors would selectively deplete stem cells, resulting in successful long-term donor cell engraftment after transplantation. Recipient mice were treated for 1 or 7 days with growth factors (stem cell factor [SCF] plus interleukin 11 [IL-11], SCF plus Flt-3 ligand [FL], or granulocyte colony-stimulating factor [G-CSF]) prior to low-dose TBI (4 Gy). Donor cell chimerism was measured after transplantation of congenic bone marrow cells. High levels of donor cell engraftment were observed in recipients pretreated for 7 days with SCF plus IL-11 or SCF plus FL. Although 1-day pretreatments with these cytokines initially resulted in reduced donor cell engraftment, a continuous increase in time was observed, finally resulting in highly significantly increased levels of donor cell contribution. In contrast, G-CSF treatment showed no beneficial effects on long-term engraftment. In vitro stem cell assays demonstrated the effect of cytokine treatment on stem cell numbers. Donor cell engraftment and number of remaining recipient stem cells after TBI were strongly inversely correlated, except for groups treated for 1 day with SCIF plus IL-11 or SCF plus FL. We conclude that long-term donor cell engraftment can be strongly augmented by treatment of recipient mice prior to low-dose TBI with hematopoietic growth factors that act on primitive cells.
- Published
- 2002
3. Comparison of different busulfan analogues for depletion of hematopoietic stem cells and promotion of donor-type chimerism in murine bone marrow transplant recipients
- Author
-
Westerhof, GR, Ploemacher, RE, Boudewijn, A, Blokland, [No Value], Dillingh, JH, McGown, AT, Hadfield, JA, Dawson, MJ, Down, JD, Hematology, and Groningen University Institute for Drug Exploration (GUIDE)
- Subjects
INTERSTRAND CROSS-LINKING ,ALKYLATING DRUGS ,CONDITIONING REGIMENS ,TOTAL-BODY IRRADIATION ,CYCLOPHOSPHAMIDE ,DIMETHANESULFONATE ESTERS ,DNA ,CHRONIC MYELOID-LEUKEMIA ,FREQUENCY-ANALYSIS ,HIGH-DOSE THERAPY - Abstract
Busulfan (1,4-butanediol dimethanesulfonate, BU) is relatively unique among other standard chemotherapy compounds in its ability to deplete noncycling primitive stem cells in the host and consequently to allow for high levels of long-term, donor-type engraftment after bone marrow transplantation (BMT), Such a property explains why this drug can be used as an alternative to total body irradiation in preparative regimes for BMT, However, as with radiation, BU conditioning is still troubled by severe toxicities that limit its applications to suboptimal drug doses. These problems stress the need for other BMT-conditioning drugs that are better tolerated and more selectively targeted toward normal and malignant hematopoietic stem cells. We have therefore compared the effects of various novel dimethanesulfonate compounds (related to BU) in terms of their toxicity to different stem cell subsets in vivo and in vitro and their ability to provide for long-term donor bone marrow engraftment using the congenic glucose-6-phosphate isomerase type 1 marker. Introduction of a benzene or cyclohexane ring in some of these drugs affords rigidity to the molecule and restricts the spatial positioning of the alkylating groups, Among 25 different compounds thus far tested at single doses, PL63 [cis-1,2-(2-hydroxyethyl) cyclohexane dimethanesulfonate] proved to be the most effective in providing for hematopoietic engraftment, The trans-isomer of the same compound gave significantly less engraftment and was comparable with the effects of dimethylbusulfan and Hepsulfam. The engraftment data correlated well with the depletion of different bone marrow stem cell subsets in the host as measured using the cobblestone area forming cell assay. The extent of stem cell depletion could not be explained on the basis of the distance and orientation of the two alkylating groups. Pharmacokinetic data, however, indicate that there is a correlation between biological activity and plasma levels reached, The diverse cytotoxic effects shown by these novel analogues of BU have provided a basis for relating biological activity with pharmacokinetic properties rather than with structural properties such as distance and orientation of the two alkylating groups, The identification of highly active compounds such as PL63 offers an opportunity for further developing other closely related drugs for potential application in clinical BMT conditioning therapy.
- Published
- 2000
4. Reduction of heat-induced haemotoxicity in a hyperthermic purging protocol of murine acute myeloid leukaemic stem cells by AcSDKP
- Author
-
Wierenga, PK, Dillingh, JH, and Konings, AWT
- Subjects
INVITRO ,haemopoiesis ,bone marrow transplantation ,ACUTE MYELOBLASTIC-LEUKEMIA ,PROLIFERATION ,HEMATOPOIETIC PROGENITORS ,Goralatide ,BONE-MARROW TRANSPLANTATION ,hyperthermia ,MICE ,purging ,AUTOLOGOUS MARROW ,SENSITIVITY ,AcSDKP ,TERM REPOPULATING ABILITY ,TETRAPEPTIDE ACSDKP - Abstract
The tetrapeptide AcSDKP (Goralatide) is a cytokine with known inhibitory effects on cell proliferation, Many purging agents used in autologous bone marrow transplantation protocols, including hyperthermia, preferentially kill cycling cells. A pretreatment with Goralatide offers a possibility to reduce the haemotoxicity in many purging settings. The impact of Goralatide on the hyperthermic purging protocol was investigated in normal and myeloid leukaemic (SA8) murine cells. The median survival time after transplantation (i.e. leukaemia incidences) was used as an in vivo parameter to determine the effects on leukaemic cells. The hyperthermic effect on normal and leukaemic cells was also investigated in vitro using the cobblestone area-forming cell (CAFC) assay. A heat treatment of 90 min at 43 degrees C resulted in a 4-log depletion of leukaemic stem cells. For normal progenitor cells (CFU-GM) a 2-log cell kill was shown. The reduction in proliferative activity of the CFU-GM after an 8 h incubation with 10(-9) M Goralatide resulted in a decrease in the heat sensitivity of the progenitor subset to approximately a 1-log cell kill, The leukaemic precursor cells seem insensitive to Goralatide inhibition, implicating an increase in the therapeutic window of the hyperthermic purging protocol. Finally, simulated remission bone marrow (5% leukaemic blasts) was incubated with Goralatide followed by a heat treatment of 90 min at 43 degrees C. Lethally irradiated (10 Gy) mice transplanted with heat-treated remission bone marrow (10(6) normal bone marrow cells versus 5x10(4) leukaemic cells) died of aplasia while Goralatide-pretreated remission bone marrow could rescue the irradiated mice without revealing leukaemic engraftment, These findings confirmed the enhanced protection against hyperthermia of the normal haemopoietic subsets by Goralatide and thus increased the success of the hyperthermic purging protocol.
- Published
- 1997
5. Conditioning regimens using growth factors prior to low dose tbi enhance engraftment of murine stem cells after bone marrow transplantations
- Author
-
Noach, EJK, primary, Ausema, A, additional, Dillingh, JH, additional, Vellenga, E, additional, and de Haan, G, additional
- Published
- 2000
- Full Text
- View/download PDF
6. Relationships between ablation of distinct haematopoietic cell subsets and the development of donor bone marrow engraftment following recipient pretreatment with different alkylating drugs
- Author
-
Down, JD, primary, Boudewijn, A, additional, Dillingh, JH, additional, Fox, BW, additional, and Ploemacher, RE, additional
- Published
- 1994
- Full Text
- View/download PDF
7. Comment on: 'Efficacy of topical tacrolimus for oral lichen planus: real-life experience in a retrospective cohort of patients with a review of the literature' by Ribero et al. (2015).
- Author
-
Delli K, Dillingh JH, Spijkervet FK, and Vissink A
- Subjects
- Administration, Topical, Humans, Immunosuppressive Agents, Lichen Planus, Retrospective Studies, Lichen Planus, Oral, Tacrolimus
- Published
- 2016
- Full Text
- View/download PDF
8. Is there an effect of intranasal insulin on development and behaviour in Phelan-McDermid syndrome? A randomized, double-blind, placebo-controlled trial.
- Author
-
Zwanenburg RJ, Bocca G, Ruiter SA, Dillingh JH, Flapper BC, van den Heuvel ER, and van Ravenswaaij-Arts CM
- Subjects
- Administration, Intranasal, Adolescent, Child, Child Development, Child, Preschool, Chromosome Deletion, Chromosome Disorders drug therapy, Chromosome Disorders genetics, Chromosomes, Human, Pair 22 genetics, Double-Blind Method, Female, Humans, Infant, Insulin administration & dosage, Insulin adverse effects, Male, Nerve Tissue Proteins genetics, Chromosome Disorders rehabilitation, Insulin therapeutic use, Social Skills
- Abstract
Phelan-McDermid syndrome (PMS) or 22q13.3 deletion syndrome is a rare neurodevelopmental disorder with at least 60 children and 35 adults diagnosed in the Netherlands. Clinical features are moderate to severe intellectual disability and behavioural problems in the autism spectrum. Other researchers had observed a beneficial effect of intranasal insulin on development and behaviour in a pilot study in six children with PMS. To validate this effect, we conducted a randomized, double-blind, placebo-controlled clinical trial using a stepped-wedge design. From March 2013 to June 2015, 25 children aged 1-16 years with a molecularly confirmed 22q13.3 deletion including the SHANK3 gene participated in the clinical trial for a period of 18 months. Starting 6 months before the trial, children were systematically assessed for cognitive, language and motor development and for adaptive, social and emotional behaviour every 6 months. The second, third and fourth assessments were followed by daily nose sprays containing either intranasal insulin or intranasal placebo for a 6-month period. A fifth assessment was done directly after the end of the trial. Intranasal insulin did not cause serious adverse events. It increased the level of developmental functioning by 0.4-1.4 months per 6-month period, but the effect was not statistically significant in this small group. We found a stronger effect of intranasal insulin, being significant for cognition and social skills, for children older than 3 years, who usually show a decrease of developmental growth. However, clinical trials in larger study populations are required to prove the therapeutic effect of intranasal insulin in PMS.
- Published
- 2016
- Full Text
- View/download PDF
9. Growth factor treatment prior to low-dose total body irradiation increases donor cell engraftment after bone marrow transplantation in mice.
- Author
-
Noach EJ, Ausema A, Dillingh JH, Dontje B, Weersing E, Akkerman I, Vellenga E, and de Haan G
- Subjects
- Animals, Bone Marrow Cells, Cell Division drug effects, Female, Growth Substances administration & dosage, Growth Substances therapeutic use, Hematopoietic Stem Cells drug effects, Liver cytology, Male, Mice, Mice, Inbred C57BL, Radiation Dosage, Spleen cytology, Transplantation, Homologous methods, Bone Marrow Transplantation methods, Graft Survival drug effects, Growth Substances pharmacology, Whole-Body Irradiation methods
- Abstract
Low-toxicity conditioning regimens prior to bone marrow transplantation (BMT) are widely explored. We developed a new protocol using hematopoietic growth factors prior to low-dose total body irradiation (TBI) in recipients of autologous transplants to establish high levels of long-term donor cell engraftment. We hypothesized that treatment of recipient mice with growth factors would selectively deplete stem cells, resulting in successful long-term donor cell engraftment after transplantation. Recipient mice were treated for 1 or 7 days with growth factors (stem cell factor [SCF] plus interleukin 11 [IL-11], SCF plus Flt-3 ligand [FL], or granulocyte colony-stimulating factor [G-CSF]) prior to low-dose TBI (4 Gy). Donor cell chimerism was measured after transplantation of congenic bone marrow cells. High levels of donor cell engraftment were observed in recipients pretreated for 7 days with SCF plus IL-11 or SCF plus FL. Although 1-day pretreatments with these cytokines initially resulted in reduced donor cell engraftment, a continuous increase in time was observed, finally resulting in highly significantly increased levels of donor cell contribution. In contrast, G-CSF treatment showed no beneficial effects on long-term engraftment. In vitro stem cell assays demonstrated the effect of cytokine treatment on stem cell numbers. Donor cell engraftment and number of remaining recipient stem cells after TBI were strongly inversely correlated, except for groups treated for 1 day with SCF plus IL-11 or SCF plus FL. We conclude that long-term donor cell engraftment can be strongly augmented by treatment of recipient mice prior to low-dose TBI with hematopoietic growth factors that act on primitive cells.
- Published
- 2002
- Full Text
- View/download PDF
10. Comparison of different busulfan analogues for depletion of hematopoietic stem cells and promotion of donor-type chimerism in murine bone marrow transplant recipients.
- Author
-
Westerhof GR, Ploemacher RE, Boudewijn A, Blokland I, Dillingh JH, McGown AT, Hadfield JA, Dawson MJ, and Down JD
- Subjects
- Animals, Bone Marrow Cells cytology, Bone Marrow Cells drug effects, Bone Marrow Transplantation immunology, Busulfan pharmacokinetics, Busulfan toxicity, Graft Survival drug effects, Graft Survival immunology, Hematopoietic Stem Cells immunology, Immunosuppressive Agents toxicity, Male, Mice, Mice, Inbred BALB C, Mice, Inbred C57BL, Structure-Activity Relationship, Transplantation Chimera, Bone Marrow Transplantation methods, Busulfan analogs & derivatives, Hematopoietic Stem Cells drug effects, Immunosuppressive Agents pharmacology, Transplantation Conditioning methods
- Abstract
Busulfan (1,4-butanediol dimethanesulfonate, BU) is relatively unique among other standard chemotherapy compounds in its ability to deplete noncycling primitive stem cells in the host and consequently to allow for high levels of long-term, donor-type engraftment after bone marrow transplantation (BMT). Such a property explains why this drug can be used as an alternative to total body irradiation in preparative regimes for BMT. However, as with radiation, BU conditioning is still troubled by severe toxicities that limit its applications to suboptimal drug doses. These problems stress the need for other BMT-conditioning drugs that are better tolerated and more selectively targeted toward normal and malignant hematopoietic stem cells. We have therefore compared the effects of various novel dimethanesulfonate compounds (related to BU) in terms of their toxicity to different stem cell subsets in vivo and in vitro and their ability to provide for long-term donor bone marrow engraftment using the congenic glucose-6-phosphate isomerase type 1 marker. Introduction of a benzene or cyclohexane ring in some of these drugs affords rigidity to the molecule and restricts the spatial positioning of the alkylating groups. Among 25 different compounds thus far tested at single doses, PL63 [cis-1,2-(2-hydroxyethyl) cyclohexane dimethanesulfonate] proved to be the most effective in providing for hematopoietic engraftment. The transisomer of the same compound gave significantly less engraftment and was comparable with the effects of dimethylbusulfan and Hepsulfam. The engraftment data correlated well with the depletion of different bone marrow stem cell subsets in the host as measured using the cobblestone area forming cell assay. The extent of stem cell depletion could not be explained on the basis of the distance and orientation of the two alkylating groups. Pharmacokinetic data, however, indicate that there is a correlation between biological activity and plasma levels reached. The diverse cytotoxic effects shown by these novel analogues of BU have provided a basis for relating biological activity with pharmacokinetic properties rather than with structural properties such as distance and orientation of the two alkylating groups. The identification of highly active compounds such as PL63 offers an opportunity for further developing other closely related drugs for potential application in clinical BMT conditioning therapy.
- Published
- 2000
11. Reduction of heat-induced haemotoxicity in a hyperthermic purging protocol of murine acute myeloid leukaemic stem cells by AcSDKP.
- Author
-
Wierenga PK, Dillingh JH, and Konings AW
- Subjects
- Acute Disease, Animals, Bone Marrow Purging, Female, Hematologic Diseases pathology, Hematopoiesis physiology, Leukemia, Myeloid pathology, Mice, Tumor Cells, Cultured, Growth Inhibitors therapeutic use, Hematologic Diseases prevention & control, Hyperthermia, Induced, Oligopeptides therapeutic use
- Abstract
The tetrapeptide AcSDKP (Goralatide) is a cytokine with known inhibitory effects on cell proliferation. Many purging agents used in autologous bone marrow transplantation protocols, including hyperthermia, preferentially kill cycling cells. A pretreatment with Goralatide offers a possibility to reduce the haemotoxicity in many purging settings. The impact of Goralatide on the hyperthermic purging protocol was investigated in normal and myeloid leukaemic (SA8) murine cells. The median survival time after transplantation (i.e. leukaemia incidences) was used as an in vivo parameter to determine the effects on leukaemic cells. The hyperthermic effect on normal and leukaemic cells was also investigated in vitro using the cobblestone area-forming cell (CAFC) assay. A heat treatment of 90 min at 43 degrees C resulted in a 4-log depletion of leukaemic stem cells. For normal progenitor cells (CFU-GM) a 2-log cell kill was shown. The reduction in proliferative activity of the CFU-GM after an 8 h incubation with 10(-9) M Goralatide resulted in a decrease in the heat sensitivity of the progenitor subset to approximately a 1-log cell kill. The leukaemic precursor cells seem insensitive to Goralatide inhibition, implicating an increase in the therapeutic window of the hyperthermic purging protocol. Finally, simulated remission bone marrow (5% leukaemic blasts) was incubated with Goralatide followed by a heat treatment of 90 min at 43 degrees C. Lethally irradiated (10 Gy) mice transplanted with heat-treated remission bone marrow (10(6) normal bone marrow cells versus 5 x 10(4) leukaemic cells) died of aplasia while Goralatide-pretreated remission bone marrow could rescue the irradiated mice without revealing leukaemic engraftment. These findings confirmed the enhanced protection against hyperthermia of the normal haemopoietic subsets by Goralatide and thus increased the success of the hyperthermic purging protocol.
- Published
- 1997
- Full Text
- View/download PDF
12. Stem cell factor has contrasting effects in combination with 5-fluorouracil or total-body irradiation on frequencies of different hemopoietic cell subsets and engraftment of transplanted bone marrow.
- Author
-
Down JD, de Haan G, Dillingh JH, Dontje B, and Nijhof W
- Subjects
- Animals, Male, Mice, Mice, Inbred C57BL, Bone Marrow Transplantation, Fluorouracil pharmacology, Hematopoietic Stem Cells drug effects, Stem Cell Factor pharmacology, Whole-Body Irradiation
- Abstract
The effect of stem cell factor (SCF) given at 24, 12 and 2 h before either 5-fluorouracil (5-FU) or total-body irradiation (TBI) was investigated on a range of bone marrow hemopoietic cell subsets that included primitive stem cells capable of long-term repopulation in bone marrow transplant (BMT) recipients. At 24 h after treatment, the femoral content of transient and permanent repopulating stem cell subsets was assessed from the frequency of early- and late-developing cobblestone area-forming cells (CAFCs) growing in stroma-associated cultures. At this time untreated 3 x 10(6) congenically marked donor bone marrow cells (B6-Gpi-Ia-->B6-Gpi-Ib) were transplanted and the level of erythroid engraftment was followed over 1 year. Analysis of the frequencies of CAFCs in host bone marrow after treatment with SCF demonstrated a remarkable increase in the number of early-developing CAFC subsets by about 10-fold. At the same time SCF conferred a sensitization of these subsets after treatment with 5-FU, which indicated an enhanced proliferative activity. The SCF-induced increase in the number of progenitor cells, however, was the more dominant process in the irradiated animals, resulting in less overall depletion of CAFCs. These contrasting results provide an explanation for the sensitization by SCF of 5-FU-induced lethality and its converse protection against radiation-induced lethality as reported by others. Nevertheless, the number of the more primitive CAFC subsets appearing at 28 and 35 days in culture and their sensitivity to 5-FU or radiation remained unaffected by this short SCF treatment. The number of CAFCs that remained in the bone marrow largely predicted the subsequent patterns of donor marrow engraftment in the treated BMT recipients: SCF enhanced short-term engraftment after treatment with 5-FU while it reduced the need for short-term engraftment after irradiation. Only irradiation afforded long-term engraftment through depletion of primitive host stem cells, and this was moderately improved by prior treatment with SCF.
- Published
- 1997
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