Search results for "XENOGRAFT"
showing 10 items of 161 documents
Theileria parasites secrete a prolyl isomerase to maintain host leukocyte transformation
2015
Infectious agents develop intricate mechanisms to interact with host cell pathways and hijack their genetic and epigenetic machinery to change host cell phenotypic states. Among the Apicomplexa phylum of obligate intracellular parasites, which cause veterinary and human diseases, Theileria is the only genus that transforms its mammalian host cells. Theileria infection of bovine leukocytes induces proliferative and invasive phenotypes associated with activated signalling pathways, notably JNK and AP-1 (ref. 2). The transformed phenotypes are reversed by treatment with the theilericidal drug buparvaquone. We used comparative genomics to identify a homologue of the peptidyl-prolyl isomerase PI…
Recombinant human erythropoietin increases the radiosensitivity of xenografted human tumours in anaemic nude mice
2001
Purpose: The effect of recombinant human erythropoietin (Epo) on the radiosensitivity of human tumour xenografts growing in anaemic nude mice was studied. Methods and materials: Anaemia was induced by total body irradiation (TBI) of mice prior to tumour transplantation. The development of anaemia was prevented by Epo (1000 U/kg s.c.) given 3 times weekly starting 2 weeks prior to TBI (5 Gy). Epo treatment did not influence the growth rate of the tumours, which were transplanted into the subcutis of the hind leg of mice. Thirteen days after TBI (tumour volume of approx. 40 mm3), a single-dose irradiation (12 Gy) of the tumour was performed resulting in a growth delay with subsequent regrowth…
Suppressor of cytokine signaling 3 sensitizes anaplastic thyroid cancer to standard chemotherapy
2009
We previously showed that cancer cells from papillary, follicular, and anaplastic thyroid carcinomas produce interleukin-4 and interleukin-10, which counteract the cytotoxic activity of conventional chemotherapy through the up-regulation of antiapoptotic molecules. Here, we identify Janus kinase/signal transducers and activators of transcription (STAT) and phosphatidyl inositol 3-kinase (PI3K)/AKT as the down-stream pathways through which these cytokines confer resistance to cell death in thyroid cancer. We found that the absence of suppressors of cytokine signaling (SOCS) molecules allows the propagation of the survival signaling. Exogenous expression of SOCS1, SOCS3, and SOCS5 in the high…
Compromised nuclear envelope integrity drives TREX1-dependent DNA damage and tumor cell invasion
2021
Although mutations leading to a compromised nuclear envelope cause diseases such as muscular dystrophies or accelerated aging, the consequences of mechanically induced nuclear envelope ruptures are less known. Here, we show that nuclear envelope ruptures induce DNA damage that promotes senescence in non-transformed cells and induces an invasive phenotype in human breast cancer cells. We find that the endoplasmic reticulum (ER)-associated exonuclease TREX1 translocates into the nucleus after nuclear envelope rupture and is required to induce DNA damage. Inside the mammary duct, cellular crowding leads to nuclear envelope ruptures that generate TREX1-dependent DNA damage, thereby driving the …
Cholesterol Starvation and Hypoxia Activate the FVII Gene via the SREBP1-GILZ Pathway in Ovarian Cancer Cells to Produce Procoagulant Microvesicles
2019
AbstractInteraction between the transcription factors, hypoxia-inducible factor (HIF1α and HIF2α) and Sp1, mediates hypoxia-driven expression of FVII gene encoding coagulation factor VII (fVII) in ovarian clear cell carcinoma (CCC) cells. This mechanism is synergistically enhanced in response to serum starvation, a condition possibly associated with tumor hypoxia. This transcriptional response potentially results in venous thromboembolism, a common complication in cancer patients by producing procoagulant extracellular vesicles (EVs). However, which deficient serum factors are responsible for this characteristic transcriptional mechanism is unknown. Here, we report that cholesterol deficien…
Influence of the Use of a Collagen Membrane Placed on the Bone Window after Sinus Floor Augmentation—An Experimental Study in Rabbits
2021
Background: We studied the influence on healing of a resorbable membrane covering the osteotomy site after maxillary sinus grafting, evaluated in different regions of the augmented area. Methods: Maxillary sinus augmentation was performed in 24 New Zealand rabbits. Osteotomy, 4 × 6 mm, were performed bilaterally. A collagenated cortico-cancellous porcine bone was used to fill the elevated region. A collagen membrane was randomly placed over the osteotomy site on one side (MG), and the other side was left uncovered (NMG). The animals were euthanized after 2, 4, and 8 weeks
The mitotic kinase Aurora-A promotes distant metastases by inducing epithelial-to-mesenchymal transition in ERα+ breast cancer cells
2013
In this study, we demonstrate that constitutive activation of Raf-1 oncogenic signaling induces stabilization and accumulation of Aurora-A mitotic kinase that ultimately drives the transition from an epithelial to a highly invasive mesenchymal phenotype in estrogen receptor α-positive (ERα(+)) breast cancer cells. The transition from an epithelial- to a mesenchymal-like phenotype was characterized by reduced expression of ERα, HER-2/Neu overexpression and loss of CD24 surface receptor (CD24(-/low)). Importantly, expression of key epithelial-to-mesenchymal transition (EMT) markers and upregulation of the stemness gene SOX2 was linked to acquisition of stem cell-like properties such as the ab…
The Influence of Hyaluronic Acid Biofunctionalization of a Bovine Bone Substitute on Osteoblast Activity In Vitro
2021
Bovine bone substitute materials (BSMs) are used for oral bone regeneration. The objective was to analyze the influence of BSM biofunctionalization via hyaluronic acid (HA) on human osteoblasts (HOBs). BSMs with ± HA were incubated with HOBs including HOBs alone as a negative control. On days 3, 7 and 10, cell viability, migration and proliferation were analyzed by fluorescence staining, scratch wound assay and MTT assay. On days 3, 7 and 10, an increased cell viability was demonstrated for BSM+ compared with BSM− and the control (each p ≤ 0.05). The cell migration was enhanced for BSM+ compared with BSM− and the control after day 3 and day 7 (each p ≤ 0.05). At day 10, an accelerated wound…
Capturing colorectal cancer inter-tumor heterogeneity in patient-derived xenograft (PDX) models
2019
Patient‐derived xenograft (PDX) models have become an important asset in translational cancer research. However, to provide a robust preclinical platform, PDXs need to accommodate the tumor heterogeneity that is observed in patients. Colorectal cancer (CRC) can be stratified into four consensus molecular subtypes (CMS) with distinct biological and clinical features. Surprisingly, using a set of CRC patients, we revealed the partial representation of tumor heterogeneity in PDX models. The epithelial subtypes, the largest subgroups of CRC subtype, were very ineffective in establishing PDXs, indicating the need for further optimization to develop an effective personalized therapeutic approach …
Endothelin-1-Mediated Drug Resistance in EGFR-Mutant Non-Small Cell Lung Carcinoma.
2020
Abstract Progression on therapy in non-small cell lung carcinoma (NSCLC) is often evaluated radiographically, however, image-based evaluation of said therapies may not distinguish disease progression due to intrinsic tumor drug resistance or inefficient tumor penetration of the drugs. Here we report that the inhibition of mutated EGFR promotes the secretion of a potent vasoconstrictor, endothelin-1 (EDN1), which continues to increase as the cells become resistant with a mesenchymal phenotype. As EDN1 and its receptor (EDNR) is linked to cancer progression, EDNR-antagonists have been evaluated in several clinical trials with disappointing results. These trials were based on a hypothesis that…