Jens Pietzsch | Helmholtz-Zentrum Dresden Rossendorf (original) (raw)
Papers by Jens Pietzsch
Ejc Supplements, Jul 1, 2008
Endocrine-related Cancer, Jun 1, 2022
Aggressive pheochromocytomas and paragangliomas (PPGLs) are difficult to treat, and molecular tar... more Aggressive pheochromocytomas and paragangliomas (PPGLs) are difficult to treat, and molecular targeting is being increasingly considered, but with variable results. This study investigates established and novel molecular-targeted drugs and chemotherapeutic agents for the treatment of PPGLs in human primary cultures and murine cell line spheroids. In PPGLs from 33 patients, including 7 metastatic PPGLs, we identified germline or somatic driver mutations in 79% of cases, allowing us to assess potential differences in drug responsivity between pseudohypoxia-associated cluster 1-related (n = 10) and kinase signaling-associated cluster 2-related (n = 14) PPGL primary cultures. Single anti-cancer drugs were either more effective in cluster 1 (cabozantinib, selpercatinib, and 5-FU) or similarly effective in both clusters (everolimus, sunitinib, alpelisib, trametinib, niraparib, entinostat, gemcitabine, AR-A014418, and high-dose zoledronic acid). High-dose estrogen and low-dose zoledronic acid were the only single substances more effective in cluster 2. Neither cluster 1- nor cluster 2-related patient primary cultures responded to HIF-2a inhibitors, temozolomide, dabrafenib, or octreotide. We showed particular efficacy of targeted combination treatments (cabozantinib/everolimus, alpelisib/everolimus, alpelisib/trametinib) in both clusters, with higher efficacy of some targeted combinations in cluster 2 and overall synergistic effects (cabozantinib/everolimus, alpelisib/trametinib) or synergistic effects in cluster 2 (alpelisib/everolimus). Cabozantinib/everolimus combination therapy, gemcitabine, and high-dose zoledronic acid appear to be promising treatment options with particularly high efficacy in SDHB-mutant and metastatic tumors. In conclusion, only minor differences regarding drug responsivity were found between cluster 1 and cluster 2: some single anti-cancer drugs were more effective in cluster 1 and some targeted combination treatments were more effective in cluster 2.
Codon Publications eBooks, Dec 5, 2017
ABSTRACT The worldwide incidence of malignant melanoma is steadily increasing, suggesting a proba... more ABSTRACT The worldwide incidence of malignant melanoma is steadily increasing, suggesting a probable melanoma “epidemic.” From a clinical point of view, malignant melanoma still is an unpredictable disease and, once in the advanced stage, allows only scarce therapeutic options. There is an urgent need to identify, characterize, and validate informative biomarkers, biomarker patterns, or surrogate markers in order to not only improve early diagnosis of melanoma but also for differential diagnosis, staging, prognosis, therapy selection, and therapy monitoring. In this chapter, an update on the ongoing debate on serologic and histologic markers such as lactate dehydrogenase, tyrosinase, S100 family of calcium-binding proteins, cyclooxygenase-2, matrix metalloproteinases, and stem and/or progenitor cell markers are presented, and novel, innovative, and promising trends currently being explored are discussed.
Molecules, Feb 17, 2018
on the occasion of his 65th birthday.
Advanced Therapeutics
Nonsteroidal anti‐inflammatory drugs (NSAIDs) are the most widely used therapeutics against pain,... more Nonsteroidal anti‐inflammatory drugs (NSAIDs) are the most widely used therapeutics against pain, fever, and inflammation; additionally, antitumor properties are reported. NSAIDs reduce the synthesis of prostaglandins by inhibiting the cyclooxygenase (COX) isoforms COX‐1 and COX‐2. As nonselective inhibition is associated with off‐target effects, strategies to achieve selectivity for the clinically preferred isoform COX‐2 are of high interest. The modification of NSAIDs using carborane clusters as phenyl mimetics is reported to alter the selectivity profile through size exclusion. Inspired by these findings, isonimesulide and its carborane derivatives are prepared. The biological screening shows that the carborane containing compounds exhibit a stronger antitumor potential compared to nimesulide and isonimesulide. Furthermore, the replacement of the phenyl ring of isonimesulide with a carborane moiety resulted in a shift of the COX activity from nonactive to COX‐active compounds.
ChemMedChem
The presence of inflammatory mediators in the tumor microenvironment, such as cytokines, growth f... more The presence of inflammatory mediators in the tumor microenvironment, such as cytokines, growth factors or eicosanoids, indicate cancer‐related inflammatory processes. Targeting these inflammatory mediators and related signal pathways may offer a rational strategy for the treatment of cancer. This study focuses on the incorporation of metabolically stable, sterically demanding, and hydrophobic dicarba‐closo‐dodecaboranes (carboranes) into dual cyclooxygenase‐2 (COX‐2)/5‐lipoxygenase (5‐LO) inhibitors that are key enzymes in the biosynthesis of eicosanoids. The di‐tert‐butylphenol derivative tebufelone represents a selective dual COX‐2/5‐LO inhibitor. The incorporation of meta‐ or para‐carborane into the tebufelone scaffold resulted in eight carborane‐based tebufelone analogs that show no COX inhibition but 5‐LO inhibitory activity in vitro. Cell viability studies on HT29 colon adenocarcinoma cells revealed that the observed antiproliferative effect of the para‐carborane analogs of t...
International Journal of Molecular Sciences, Dec 2, 2022
This article is an open access article distributed under the terms and conditions of the Creative... more This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY
International Journal of Molecular Sciences
Although chronic inflammation inhibits bone healing, the healing process is initiated by an infla... more Although chronic inflammation inhibits bone healing, the healing process is initiated by an inflammatory phase. In a well-tuned sequence of molecular events, pro-inflammatory cytokines are secreted to orchestrate the inflammation response to injury and the recruitment of progenitor cells. These events in turn activate the secretion of anti-inflammatory signaling molecules and attract cells and mediators that antagonize the inflammation and initiate the repair phase. Sulfated glycosaminoglycanes (sGAG) are known to interact with cytokines, chemokines and growth factors and, thus, alter the availability, duration and impact of those mediators on the local molecular level. sGAG-coated polycaprolactone-co-lactide (PCL) scaffolds were inserted into critical-size femur defects in adult male Wistar rats. The femur was stabilized with a plate, and the defect was filled with either sGAG-containing PCL scaffolds or autologous bone (positive control). Wound fluid samples obtained by microdialy...
Advanced Therapeutics
The selective inhibition of enzymes that catalyze the conversion of arachidonic acid to inflammat... more The selective inhibition of enzymes that catalyze the conversion of arachidonic acid to inflammatory eicosanoids represents a promising approach for cancer therapy. This study, therefore, focuses on the incorporation of metabolically stable, sterically demanding, and hydrophobic carboranes into existing dual cycloxygenase‐2 (COX‐2)/5‐lipoxygenase (5‐LO) inhibitors that are key enzymes in the biosynthesis of eicosanoids. Here, the first carborane‐containing dual COX‐2/5‐LO inhibitors derived from RWJ‐63556 are presented. The replacement of the fluorophenyl moiety by meta‐ or para‐carborane resulted in five carborane‐containing derivatives 3, 6, 9, 13, and 17 that show high inhibitory activities toward COX‐2 and 5‐LO in vitro. Cell viability studies on the A375 melanoma cell line revealed that meta‐carborane derivative 3 shows higher anticancer activity compared to RWJ‐63556 based on accumulation of lipid droplets in the cells due to blockage of the COX‐2 and 5‐LO pathways, indicating...
Journal of the American Chemical Society
36. Jahrestagung der Deutschen Gesellschaft für Klinische Mikrozirkulation und Hämorheologie (DGKMH), 2017
All source data and scripts for publication: "Tumor irradiation in mice with a laser-acceler... more All source data and scripts for publication: "Tumor irradiation in mice with a laser-accelerated proton beam"
Source data for all figures of publication: "Tumor irradiation in mice with a laser-accelera... more Source data for all figures of publication: "Tumor irradiation in mice with a laser-accelerated proton beam". Folder structure according to figures.
Materials Science and Engineering: C, 2020
This is a PDF file of an article that has undergone enhancements after acceptance, such as the ad... more This is a PDF file of an article that has undergone enhancements after acceptance, such as the addition of a cover page and metadata, and formatting for readability, but it is not yet the definitive version of record. This version will undergo additional copyediting, typesetting and review before it is published in its final form, but we are providing this version to give early visibility of the article. Please note that, during the production process, errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.
Clinical Hemorheology and Microcirculation, 2019
Biomaterials coated with artificial extracellular matrices (aECM) are intended to support the hea... more Biomaterials coated with artificial extracellular matrices (aECM) are intended to support the healing of critical size bone defects. This pilot study investigated (i) the feasibility of dual-tracer PET/CT imaging for functional characterization of biomaterial-assisted bone healing in a rat femoral defect model and (ii) the bone healing ability of polycaprolactone-colactide (PCL) scaffolds, coated with various aECM consisting of collagen type I (Col) and glycosaminoglycans (GAGs) such as chondroitin sulfate (CS) or polysulfated hyaluronan (sHA3). [ 18 F]FDG and [ 18 F]fluoride PET 4 and 8 weeks after implantation of aECM-coated PCL scaffolds, which provide an in vivo measure of cellular activation and bone mineralization, respectively, combined with CT imaging (in vivo/ex vivo) and histological/immunohistochemical investigations (ex vivo) showed that coating with CS in particular is beneficial for bone healing. The possible involvement of COX-2 and TGase 2, key enzymes of inflammation and ECM remodeling, in these processes offers starting points for targeted adjuvant therapy in the course of various bone healing phases. Our investigations show the feasibility of the selected dual-tracer approach for PET/CT imaging. In principle, this approach can be extended by further PET tracers for the functional characterization of physiological processes such as hypoxia/reperfusion or selected molecular players.
![Research paper thumbnail of Evaluation of [99mTc]Tc(CO)3+ moiety labeled alpha-melanocyte stimulating hormone derived peptide conjugates for potential melanoma imaging](https://attachments.academia-assets.com/116646570/thumbnails/1.jpg)
](Nuclear Medicine and Biology, 2019
Clinical Hemorheology and Microcirculation, 2019
In this third in a series of reviews on adjuvant drug-assisted bone healing, further possibilitie... more In this third in a series of reviews on adjuvant drug-assisted bone healing, further possibilities of influencing the healing process are discussed. Local and systemic modulation of bone metabolism is considered during use of a number of drugs with completely different indications, which are characterized by a pleiotropic spectrum of action. These include drugs used to treat lipid disorders (HMG-CoA reductase inhibitors), hypertension (ACE inhibitors), osteoporosis (bisphosphonates), cancer (proteasome inhibitors) and others. Possibilities of their application in the support of bone healing are discussed.
Ejc Supplements, Jul 1, 2008
Endocrine-related Cancer, Jun 1, 2022
Aggressive pheochromocytomas and paragangliomas (PPGLs) are difficult to treat, and molecular tar... more Aggressive pheochromocytomas and paragangliomas (PPGLs) are difficult to treat, and molecular targeting is being increasingly considered, but with variable results. This study investigates established and novel molecular-targeted drugs and chemotherapeutic agents for the treatment of PPGLs in human primary cultures and murine cell line spheroids. In PPGLs from 33 patients, including 7 metastatic PPGLs, we identified germline or somatic driver mutations in 79% of cases, allowing us to assess potential differences in drug responsivity between pseudohypoxia-associated cluster 1-related (n = 10) and kinase signaling-associated cluster 2-related (n = 14) PPGL primary cultures. Single anti-cancer drugs were either more effective in cluster 1 (cabozantinib, selpercatinib, and 5-FU) or similarly effective in both clusters (everolimus, sunitinib, alpelisib, trametinib, niraparib, entinostat, gemcitabine, AR-A014418, and high-dose zoledronic acid). High-dose estrogen and low-dose zoledronic acid were the only single substances more effective in cluster 2. Neither cluster 1- nor cluster 2-related patient primary cultures responded to HIF-2a inhibitors, temozolomide, dabrafenib, or octreotide. We showed particular efficacy of targeted combination treatments (cabozantinib/everolimus, alpelisib/everolimus, alpelisib/trametinib) in both clusters, with higher efficacy of some targeted combinations in cluster 2 and overall synergistic effects (cabozantinib/everolimus, alpelisib/trametinib) or synergistic effects in cluster 2 (alpelisib/everolimus). Cabozantinib/everolimus combination therapy, gemcitabine, and high-dose zoledronic acid appear to be promising treatment options with particularly high efficacy in SDHB-mutant and metastatic tumors. In conclusion, only minor differences regarding drug responsivity were found between cluster 1 and cluster 2: some single anti-cancer drugs were more effective in cluster 1 and some targeted combination treatments were more effective in cluster 2.
Codon Publications eBooks, Dec 5, 2017
ABSTRACT The worldwide incidence of malignant melanoma is steadily increasing, suggesting a proba... more ABSTRACT The worldwide incidence of malignant melanoma is steadily increasing, suggesting a probable melanoma “epidemic.” From a clinical point of view, malignant melanoma still is an unpredictable disease and, once in the advanced stage, allows only scarce therapeutic options. There is an urgent need to identify, characterize, and validate informative biomarkers, biomarker patterns, or surrogate markers in order to not only improve early diagnosis of melanoma but also for differential diagnosis, staging, prognosis, therapy selection, and therapy monitoring. In this chapter, an update on the ongoing debate on serologic and histologic markers such as lactate dehydrogenase, tyrosinase, S100 family of calcium-binding proteins, cyclooxygenase-2, matrix metalloproteinases, and stem and/or progenitor cell markers are presented, and novel, innovative, and promising trends currently being explored are discussed.
Molecules, Feb 17, 2018
on the occasion of his 65th birthday.
Advanced Therapeutics
Nonsteroidal anti‐inflammatory drugs (NSAIDs) are the most widely used therapeutics against pain,... more Nonsteroidal anti‐inflammatory drugs (NSAIDs) are the most widely used therapeutics against pain, fever, and inflammation; additionally, antitumor properties are reported. NSAIDs reduce the synthesis of prostaglandins by inhibiting the cyclooxygenase (COX) isoforms COX‐1 and COX‐2. As nonselective inhibition is associated with off‐target effects, strategies to achieve selectivity for the clinically preferred isoform COX‐2 are of high interest. The modification of NSAIDs using carborane clusters as phenyl mimetics is reported to alter the selectivity profile through size exclusion. Inspired by these findings, isonimesulide and its carborane derivatives are prepared. The biological screening shows that the carborane containing compounds exhibit a stronger antitumor potential compared to nimesulide and isonimesulide. Furthermore, the replacement of the phenyl ring of isonimesulide with a carborane moiety resulted in a shift of the COX activity from nonactive to COX‐active compounds.
ChemMedChem
The presence of inflammatory mediators in the tumor microenvironment, such as cytokines, growth f... more The presence of inflammatory mediators in the tumor microenvironment, such as cytokines, growth factors or eicosanoids, indicate cancer‐related inflammatory processes. Targeting these inflammatory mediators and related signal pathways may offer a rational strategy for the treatment of cancer. This study focuses on the incorporation of metabolically stable, sterically demanding, and hydrophobic dicarba‐closo‐dodecaboranes (carboranes) into dual cyclooxygenase‐2 (COX‐2)/5‐lipoxygenase (5‐LO) inhibitors that are key enzymes in the biosynthesis of eicosanoids. The di‐tert‐butylphenol derivative tebufelone represents a selective dual COX‐2/5‐LO inhibitor. The incorporation of meta‐ or para‐carborane into the tebufelone scaffold resulted in eight carborane‐based tebufelone analogs that show no COX inhibition but 5‐LO inhibitory activity in vitro. Cell viability studies on HT29 colon adenocarcinoma cells revealed that the observed antiproliferative effect of the para‐carborane analogs of t...
International Journal of Molecular Sciences, Dec 2, 2022
This article is an open access article distributed under the terms and conditions of the Creative... more This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY
International Journal of Molecular Sciences
Although chronic inflammation inhibits bone healing, the healing process is initiated by an infla... more Although chronic inflammation inhibits bone healing, the healing process is initiated by an inflammatory phase. In a well-tuned sequence of molecular events, pro-inflammatory cytokines are secreted to orchestrate the inflammation response to injury and the recruitment of progenitor cells. These events in turn activate the secretion of anti-inflammatory signaling molecules and attract cells and mediators that antagonize the inflammation and initiate the repair phase. Sulfated glycosaminoglycanes (sGAG) are known to interact with cytokines, chemokines and growth factors and, thus, alter the availability, duration and impact of those mediators on the local molecular level. sGAG-coated polycaprolactone-co-lactide (PCL) scaffolds were inserted into critical-size femur defects in adult male Wistar rats. The femur was stabilized with a plate, and the defect was filled with either sGAG-containing PCL scaffolds or autologous bone (positive control). Wound fluid samples obtained by microdialy...
Advanced Therapeutics
The selective inhibition of enzymes that catalyze the conversion of arachidonic acid to inflammat... more The selective inhibition of enzymes that catalyze the conversion of arachidonic acid to inflammatory eicosanoids represents a promising approach for cancer therapy. This study, therefore, focuses on the incorporation of metabolically stable, sterically demanding, and hydrophobic carboranes into existing dual cycloxygenase‐2 (COX‐2)/5‐lipoxygenase (5‐LO) inhibitors that are key enzymes in the biosynthesis of eicosanoids. Here, the first carborane‐containing dual COX‐2/5‐LO inhibitors derived from RWJ‐63556 are presented. The replacement of the fluorophenyl moiety by meta‐ or para‐carborane resulted in five carborane‐containing derivatives 3, 6, 9, 13, and 17 that show high inhibitory activities toward COX‐2 and 5‐LO in vitro. Cell viability studies on the A375 melanoma cell line revealed that meta‐carborane derivative 3 shows higher anticancer activity compared to RWJ‐63556 based on accumulation of lipid droplets in the cells due to blockage of the COX‐2 and 5‐LO pathways, indicating...
Journal of the American Chemical Society
36. Jahrestagung der Deutschen Gesellschaft für Klinische Mikrozirkulation und Hämorheologie (DGKMH), 2017
All source data and scripts for publication: "Tumor irradiation in mice with a laser-acceler... more All source data and scripts for publication: "Tumor irradiation in mice with a laser-accelerated proton beam"
Source data for all figures of publication: "Tumor irradiation in mice with a laser-accelera... more Source data for all figures of publication: "Tumor irradiation in mice with a laser-accelerated proton beam". Folder structure according to figures.
Materials Science and Engineering: C, 2020
This is a PDF file of an article that has undergone enhancements after acceptance, such as the ad... more This is a PDF file of an article that has undergone enhancements after acceptance, such as the addition of a cover page and metadata, and formatting for readability, but it is not yet the definitive version of record. This version will undergo additional copyediting, typesetting and review before it is published in its final form, but we are providing this version to give early visibility of the article. Please note that, during the production process, errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.
Clinical Hemorheology and Microcirculation, 2019
Biomaterials coated with artificial extracellular matrices (aECM) are intended to support the hea... more Biomaterials coated with artificial extracellular matrices (aECM) are intended to support the healing of critical size bone defects. This pilot study investigated (i) the feasibility of dual-tracer PET/CT imaging for functional characterization of biomaterial-assisted bone healing in a rat femoral defect model and (ii) the bone healing ability of polycaprolactone-colactide (PCL) scaffolds, coated with various aECM consisting of collagen type I (Col) and glycosaminoglycans (GAGs) such as chondroitin sulfate (CS) or polysulfated hyaluronan (sHA3). [ 18 F]FDG and [ 18 F]fluoride PET 4 and 8 weeks after implantation of aECM-coated PCL scaffolds, which provide an in vivo measure of cellular activation and bone mineralization, respectively, combined with CT imaging (in vivo/ex vivo) and histological/immunohistochemical investigations (ex vivo) showed that coating with CS in particular is beneficial for bone healing. The possible involvement of COX-2 and TGase 2, key enzymes of inflammation and ECM remodeling, in these processes offers starting points for targeted adjuvant therapy in the course of various bone healing phases. Our investigations show the feasibility of the selected dual-tracer approach for PET/CT imaging. In principle, this approach can be extended by further PET tracers for the functional characterization of physiological processes such as hypoxia/reperfusion or selected molecular players.
Nuclear Medicine and Biology, 2019
Clinical Hemorheology and Microcirculation, 2019
In this third in a series of reviews on adjuvant drug-assisted bone healing, further possibilitie... more In this third in a series of reviews on adjuvant drug-assisted bone healing, further possibilities of influencing the healing process are discussed. Local and systemic modulation of bone metabolism is considered during use of a number of drugs with completely different indications, which are characterized by a pleiotropic spectrum of action. These include drugs used to treat lipid disorders (HMG-CoA reductase inhibitors), hypertension (ACE inhibitors), osteoporosis (bisphosphonates), cancer (proteasome inhibitors) and others. Possibilities of their application in the support of bone healing are discussed.