A5035843992- Virus-based gene therapy research
- Cancer Research and Treatments
- Cancer, Hypoxia, and Metabolism
- RNA Interference and Gene Delivery
- Radiopharmaceutical Chemistry and Applications
- Mesenchymal stem cell research
- Glioma Diagnosis and Treatment
- Advanced Radiotherapy Techniques
- Ultrasound and Hyperthermia Applications
- Thyroid Cancer Diagnosis and Treatment
- Cancer Cells and Metastasis
- Nanoplatforms for cancer theranostics
- Prostate Cancer Treatment and Research
Ludwig-Maximilians-Universität München
2019-2023
LMU Klinikum
2019-2023
Background: Several clinical and experimental studies have implicated thyroid hormones in cancer progression. Cancer-relevant effects, including stimulation of tumor growth new blood vessel formation by angiogenesis, are thought to be mediated a nonclassical signaling pathway initiated through integrin αvβ3 expressed on cells proliferating endothelium. In an earlier study, we established mesenchymal stem (MSCs), important contributors the fibrovascular network tumors, as hormone-dependent...
The innate tumor homing potential of mesenchymal stem cells (MSCs) has been used for a targeted delivery the theranostic sodium iodide symporter (NIS) transgene into solid tumors. We have previously shown that external beam radiotherapy (EBRT) results in enhanced recruitment NIS-expressing MSCs human hepatocellular carcinoma (HuH7). In parallel, tumor-associated cytokine TGFB1 becomes strongly upregulated HuH7 tumors response to EBRT.We therefore evaluated effects combining focused EBRT (5...
Lipo-oligomers, post-functionalized with ligands to enhance targeting, represent promising new vehicles for the tumor-specific delivery of therapeutic genes such as sodium iodide symporter (NIS). Due its trapping activity, NIS is a powerful theranostic tool diagnostic imaging and application radionuclides. 124I PET allows non-invasive monitoring in vivo biodistribution functional expression, 131I enables cytoreduction. In our experimental design, we used epidermal growth factor receptor...
Sodium iodide symporter (NIS) gene transfer for active accumulation of in tumor cells is a powerful theranostic strategy facilitating both diagnostic and therapeutic application radioiodide. In glioblastoma (GBM), the blood-brain barrier (BBB) presents an additional delivery nucleic acid nanoparticles. present study, we designed dual-targeted NIS plasmid DNA complexes containing targeting ligands transferrin receptor (TfR) epidermal growth factor (EGFR), thus providing potential transport...
New treatment strategies are urgently needed for glioblastoma (GBM)-a tumor resistant to standard-of-care with a high risk of recurrence and extremely poor prognosis. Based on their intrinsic tropism, adoptively applied mesenchymal stem cells (MSCs) can be harnessed deliver the theranostic sodium/iodide symporter (NIS) deep into microenvironment. Interleukin-6 (IL-6) is multifunctional, highly expressed cytokine in GBM microenvironment including recruited MSCs. MSCs engineered drive NIS...
Abstract Purpose: Mesenchymal stem cells (MSC) have emerged as cellular-based vehicles for the delivery of therapeutic genes in cancer therapy based on their inherent tumor-homing capability. As theranostic gene, sodium iodide symporter (NIS) represents a successful target noninvasive radionuclide-based imaging and therapy. In this study, we applied genetically engineered MSCs tumor-targeted NIS gene transfer experimental glioblastoma (GBM)—a tumor with an extremely poor prognosis....
Abstract The sodium iodide symporter (NIS) mediates the active transport of into thyroid follicular cells, providing basis for use radioiodide diagnostic imaging and therapy differentiated cancer also non-thyroidal tumors after tumor-selective NIS gene transfer. Based on their excellent tumor-homing capacity, mesenchymal stem cells (MSCs) can be employed as delivery vehicles. Transgenic expression in genetically engineered MSCs allows noninvasive functional well therapeutic application 131I....
<p>Supplementary Figure 1: Radioiodide uptake of GL261 brain tumors after systemic MSC-mediated NIS reporter gene delivery in comparison to thyroid as endogenous NIS-expressing organ assessed by 124I PET/CT imaging. Results are expressed mean value ± SEM.Supplementary 2: Ex vivo analysis non-target organs NIS-MSC delivery. (A) and Neomycin (B; selection marker NIS-MSCs) mRNA expression was detected qPCR liver, spleen, kidney lung application showed no above the background level...
<p>Supplementary Figure 1: Radioiodide uptake of GL261 brain tumors after systemic MSC-mediated NIS reporter gene delivery in comparison to thyroid as endogenous NIS-expressing organ assessed by 124I PET/CT imaging. Results are expressed mean value ± SEM.Supplementary 2: Ex vivo analysis non-target organs NIS-MSC delivery. (A) and Neomycin (B; selection marker NIS-MSCs) mRNA expression was detected qPCR liver, spleen, kidney lung application showed no above the background level...
<div>AbstractPurpose:<p>The innate tumor homing potential of mesenchymal stem cells (MSCs) has been used for a targeted delivery the theranostic sodium iodide symporter (<i>NIS</i>) transgene into solid tumors. We have previously shown that external beam radiotherapy (EBRT) results in enhanced recruitment <i>NIS-</i>expressing MSCs human hepatocellular carcinoma (HuH7). In parallel, tumor-associated cytokine TGFB1 becomes strongly upregulated HuH7 tumors...
<div>AbstractPurpose:<p>Mesenchymal stem cells (MSC) have emerged as cellular-based vehicles for the delivery of therapeutic genes in cancer therapy based on their inherent tumor-homing capability. As theranostic gene, sodium iodide symporter (<i>NIS)</i> represents a successful target noninvasive radionuclide-based imaging and therapy. In this study, we applied genetically engineered MSCs tumor-targeted <i>NIS</i> gene transfer experimental glioblastoma...
<div>AbstractPurpose:<p>The innate tumor homing potential of mesenchymal stem cells (MSCs) has been used for a targeted delivery the theranostic sodium iodide symporter (<i>NIS</i>) transgene into solid tumors. We have previously shown that external beam radiotherapy (EBRT) results in enhanced recruitment <i>NIS-</i>expressing MSCs human hepatocellular carcinoma (HuH7). In parallel, tumor-associated cytokine TGFB1 becomes strongly upregulated HuH7 tumors...
<div>AbstractPurpose:<p>Mesenchymal stem cells (MSC) have emerged as cellular-based vehicles for the delivery of therapeutic genes in cancer therapy based on their inherent tumor-homing capability. As theranostic gene, sodium iodide symporter (<i>NIS)</i> represents a successful target noninvasive radionuclide-based imaging and therapy. In this study, we applied genetically engineered MSCs tumor-targeted <i>NIS</i> gene transfer experimental glioblastoma...
<p>Supplementary Figure S1. Cell viability after EW-7197 treatment. The of SMAD-NIS-MSCs was not affected by treatment with different concentrations the selective TGFB signaling inhibitor or without 10 ng/ml TGFB1 for 24 h as determined MTT assay. Data are presented percent untreated controls from four independent experiments (means {plus minus} SEM).</p>
<p>Supplementary Figure S2. Immunofluorescence staining of proliferating cells (Ki67) and blood vessels (CD31). analysis for Ki67 (green) CD31 (red) showed no difference in proliferation as well vessel density resected tumors mice treated with radiation SMAD-NIS MSC followed by 131I treatment compared to therapy receiving CMV-NIS-MSCs or irradiated injected MSCs NaCl non-irradiated only (A-C). Slides were counterstained Hoechst nuclear stain one representative image is shown each (20Ã-...
<p>Supplementary Figure S2. Immunofluorescence staining of proliferating cells (Ki67) and blood vessels (CD31). analysis for Ki67 (green) CD31 (red) showed no difference in proliferation as well vessel density resected tumors mice treated with radiation SMAD-NIS MSC followed by 131I treatment compared to therapy receiving CMV-NIS-MSCs or irradiated injected MSCs NaCl non-irradiated only (A-C). Slides were counterstained Hoechst nuclear stain one representative image is shown each (20Ã-...
<p>Supplementary Figure S1. Cell viability after EW-7197 treatment. The of SMAD-NIS-MSCs was not affected by treatment with different concentrations the selective TGFB signaling inhibitor or without 10 ng/ml TGFB1 for 24 h as determined MTT assay. Data are presented percent untreated controls from four independent experiments (means {plus minus} SEM).</p>
The sodium iodide symporter (NIS) is the operational molecule that has allowed efficient treatment of thyroid malignancies by administration 131I for over 70 years. Various vector-driven approaches are currently under investigation to introduce NIS gene into non-thyroidal tumors in order more broadly apply this effective anticancer therapy. One such system makes use genetically engineered mesenchymal stem cells (MSC) as therapy vehicles delivery solid tumors. MSCs show an innate ability home...