Search results for "Heterograft"
showing 10 items of 38 documents
Efficacy of CAR-T immunotherapy in MET overexpressing tumors not eligible for anti-MET targeted therapy
2022
Abstract Background Aberrant activation of the MET receptor in cancer is sustained by genetic alterations or, more frequently, by transcriptional upregulations. A fraction of MET-amplified or mutated tumors are sensible to MET targeting agents, but their responsiveness is typically short-lasting, as secondary resistance eventually occurs. Since in the absence of genetic alterations MET is usually not a tumor driver, MET overexpressing tumors are not/poorly responsive to MET targeted therapies. Consequently, the vast majority of tumors exhibiting MET activation still represent an unmet medical need. Methods Here we propose an immunotherapy strategy based on T lymphocytes expressing a Chimeri…
High expression of QSOX1 reduces tumorogenesis, and is associated with a better outcome for breast cancer patients.
2012
International audience; ABSTRACT: INTRODUCTION: The gene quiescin/sulfhydryl oxidase 1, QSOX1, encodes an enzyme directed to the secretory pathway and excreted into the extracellular space. QSOX1 participates in the folding and stability of proteins and thus could regulate the biological activity of its substrates in the secretory pathway and/or outside the cell. The involvement of QSOX1 in oncogenesis has been studied primarily in terms of its differential expression in systemic studies. QSOX1 is overexpressed in prostate cancers and in pancreatic adenocarcinoma. In contrast, QSOX1 gene expression is repressed in endothelial tumors. In the present study, we investigated the role of QSOX1 i…
Hybrid Chelator-Based PSMA Radiopharmaceuticals: Translational Approach
2021
(1) Background: Prostate-specific membrane antigen (PSMA) has been extensively studied in the last decade. It became a promising biological target in the diagnosis and therapy of PSMA-expressing cancer diseases. Although there are several radiolabeled PSMA inhibitors available, the search for new compounds with improved pharmacokinetic properties and simplified synthesis is still ongoing. In this study, we developed PSMA ligands with two different hybrid chelators and a modified linker. Both compounds have displayed a promising pharmacokinetic profile. (2) Methods: DATA5m.SA.KuE and AAZTA5.SA.KuE were synthesized. DATA5m.SA.KuE was labeled with gallium-68 and radiochemical yields of various…
High-Temperature Sintering of Xenogeneic Bone Substitutes Leads to Increased Multinucleated Giant Cell Formation: In Vivo and Preliminary Clinical Re…
2014
The present preclinical and clinical study assessed the inflammatory response to a high-temperature–treated xenogeneic material (Bego-Oss) and the effects of this material on the occurrence of multinucleated giant cells, implantation bed vascularization, and regenerative potential. After evaluation of the material characteristics via scanning electron microscopy, subcutaneous implantation in CD-1 mice was used to assess the inflammatory response to the material for up to 60 days. The clinical aspects of this study involved the use of human bone specimens 6 months after sinus augmentation. Established histologic and histomorphometric analysis methods were applied. After implantation, the mat…
Tissue engineered pre-vascularized buccal mucosa equivalents utilizing a primary triculture of epithelial cells, endothelial cells and fibroblasts
2015
Artificial generated buccal mucosa equivalents are a promising approach for the reconstruction of urethral defects. Limiting in this approach is a poor blood vessel supply after transplantation, resulting in increased morbidity and necrosis. We generated a pre-vascularized buccal mucosa equivalent in a tri-culture of primary buccal epithelial cells, fibroblasts and microvascular endothelial cells, using a native collagen membrane as a scaffold. A successful pre-vascularization and dense formation of capillary-like structures at superficial areas was demonstrated. The lumen size of pre-formed blood vessels corresponded to the capillary size in vivo (10-30 μm). Comparing native with a highly …
Balancing Passive and Active Targeting to Different Tumor Compartments Using Riboflavin-Functionalized Polymeric Nanocarriers
2017
Riboflavin transporters (RFTs) and the riboflavin carrier protein (RCP) are highly upregulated in many tumor cells, tumor stem cells, and tumor neovasculature, which makes them attractive targets for nanomedicines. Addressing cells in different tumor compartments requires drug carriers, which are not only able to accumulate via the EPR effect but also to extravasate, target specific cell populations, and get internalized by cells. Reasoning that antibodies are among the most efficient targeting systems developed by nature, we consider their size (-10-15 nm) to be ideal for balancing passive and active tumor targeting. Therefore, small, short-circulating (10 kDa, -7 nm, t1/2 - 1 h) and large…
Exosome-mediated crosstalk between chronic myelogenous leukemia cells and human bone marrow stromal cells triggers an Interleukin 8-dependent surviva…
2014
Chronic myelogenous leukemia (CML) is a myeloproliferative disorder characterized by the Bcr-Abl oncoprotein with constitutive tyrosine kinase activity. Exosomes are nanovesicles released by cancer cells that are involved in cell-to-cell communication thus potentially affecting cancer progression. It is well known that bone marrow stromal microenvironment contributes to disease progression through the establishment of a bi-directional crosstalk with cancer cells. Our hypothesis is that exosomes could have a functional role in this crosstalk. Interleukin-8 (IL 8) is a proinflammatory chemokine that activates multiple signalling pathways downstream of two receptors (CXCR1 and CXCR2). We demon…
Outcomes of complex femorodistal sequential autologous vein and biologic prosthesis composite bypass grafts
2014
Objective Femorodistal autologous vein bypass proves to be the preferred surgical therapy for long arterial occlusions and provides excellent early and long-term results in critical lower limb ischemia. Whenever vein length was insufficient and two distal outflow arteries were present, a sequential composite bypass configuration was chosen with human umbilical vein (HUV) or ovine collagen prosthesis (Omniflow II; Bio Nova International Pty Ltd, North Melbourne, Australia) as the proximal prosthetic part of the bypass. Single-center experience with this technique regarding limb salvage, graft function, secondary reinterventions, and biodegeneration is presented. Methods Between January 1998 …
The Role of Immunohistochemistry in Rhabdomyosarcoma Diagnosis Using Tissue Microarray Technology and a Xenograft Model
2015
Rhabdomyosarcomas (RMS) may resemble other non-myogenic sarcomas and malignant rhabdoid tumor (MRT). Alveolar rhabdomyosarcoma (ARMS) often harbors a typical translocation, but embryonal rhabdomyosarcoma (ERMS) lacks any specific rearrangement. Histopathology is not always sufficient for an unequivocal diagnosis, necessitating ancillary studies, including immunohistochemistry (IHC). Sixteen genetically tested RMS and two MRT were xenografted and followed in successive passages. Tissue microarrays were constructed including samples from original and xenograft tumors. Desmin, myogenin, CK, EMA, INI1, LSD1, AP2 beta, fibrillin-2, HMGA2, nestin, and SIRT1 were tested using immunohistochemical s…
SIRT1 prevents genotoxic stress-induced p53 activation in acute myeloid leukemia
2014
SIRT1 is an important regulator of cellular stress response and genomic integrity. Its role in tumorigenesis is controversial. Whereas sirtuin 1 (SIRT1) can act as a tumor suppressor in some solid tumors, increased expression has been demonstrated in many cancers, including hematologic malignancies. In chronic myeloid leukemia, SIRT1 promoted leukemia development, and targeting SIRT1 sensitized chronic myeloid leukemia progenitors to tyrosine kinase inhibitor treatment. In this study, we investigated the role of SIRT1 in acute myeloid leukemia (AML). We show that SIRT1 protein, but not RNA levels, is overexpressed in AML samples harboring activating mutations in signaling pathways. In FMS-l…