Breast cancer is a leading cause of cancer-related deaths. Anemia is common in breast cancer patients and can be treated with blood transfusions or with recombinant erythropoietin (EPO) to stimulate red blood cell production. Clinical studies have indicated decreased survival in some groups of cancer patients treated with EPO. Numerous tumor cells express the EPO receptor (EPOR), posing a risk that EPO treatment would enhance tumor growth, but the mechanisms involved in breast tumor progression are poorly understood.Here, we have examined the functional role of the EPO-EPOR axis in pre-clinical models of breast cancer. EPO induced the activation of PI3K/AKT and MAPK pathways in human breast cancer cell lines. EPOR knockdown abrogated human tumor cell growth, induced apoptosis through Bim, reduced invasiveness, and caused downregulation of MYC expression. EPO-induced MYC expression is mediated through the PI3K/AKT and MAPK pathways, and overexpression of MYC partially rescued loss of cell proliferation caused by EPOR downregulation. In a xenotransplantation model, designed to simulate recombinant EPO therapy in breast cancer patients, knockdown of EPOR markedly reduced tumor growth.Thus, our experiments in vitro and in vivo demonstrate that functional EPOR signaling is essential for the tumor-promoting effects of EPO and underline the importance of the EPO-EPOR axis in breast tumor progression.

No abstract

Intra-bone marrow transplantation (IBMT) has been adapted for mouse models to improve the seeding efficiency of transplanted hematopoietic stem and progenitor cells. Commonly used injection volumes for IBMT into the tibia differ between 10 and 40 μL even though considerable amounts of injected cells leak into the blood circulation immediately after injection. Injection of 3 μL trypan blue into the tibia of dead BALB/c mice showed staining in large vessels of hind limbs, even without supporting circulation. We therefore tested the effective capacity of the medullary cavity of dissected tibiae and femora of different mouse strains by bioluminescence imaging after injection of luciferase expressing cells. Cell leakage was already observed at 3 μL of injection volume and the measured emission rate increased significantly when 5 and 10 μL of volume with the same cell concentration were injected. Surprisingly, increasing injection volumes containing constant cell amounts resulted in comparable emission rates, suggesting a similar amount of leaked and absorbed cells independent of the injection volume. However, the absorption of a specific amount of injected cells could not be confirmed, as the ratio of leaked to absorbed cells was similar between IBMT that were performed with a constant injection volume containing either low or high cell amounts. In summary, for optimal cell transplantation via IBMT in mice we suggest to inject a high concentrated cell suspension with a maximum injection volume of 3 μL.

Background Gastrointestinal perforation is commonly seen in emergency departments. The perforation of the stomach is an emergency situation that requires immediate surgical treatment. The necessary surgical skills require regular practical training. Owing to patient`s safety, in vivo training opportunities in medicine are restricted. Animal tissue especially porcine tissue, is commonly used for surgical training. Due to its limiting factors, artificial training models are often to be preferred. Many artificial models are on the market but to our knowledge, none that mimic the haptic- and sewing properties of a stomach wall at the same time. In this study, an open source silicone model of a gastric perforation for training of gastric sewing was developed that attempts to provide realistic haptic- and sewing behaviour. Methods To simulate the layered structure of the human stomach, different silicone materials were used to produce three different model layups. The production process was kept as simple as possible to make it easily reproducible. A needle penetration setup as well as a systematic haptic evaluation were developed to compare these silicone models to a real porcine stomach in order to identify the most realistic model. Results A silicone model consisting of three layers was identified as being the most promising and was tested by clinical surgeons. Conclusions The presented model simulates the sewing characteristics of a human stomach wall, is easily reproducible at low-costs and can be used for practicing gastric suturing techniques. Trial registrations Not applicable.

No abstract