Projects / Programmes
Molecular mechanism of action of the recombinant human erythropoietin on cancerous cells
| Code |
Science |
Field |
Subfield |
| 3.04.00 |
Medical sciences |
Oncology |
|
| Code |
Science |
Field |
| B200 |
Biomedical sciences |
Cytology, oncology, cancerology |
| B726 |
Biomedical sciences |
Clinical biology |
| P004 |
Natural sciences and mathematics |
Biochemistry, Metabolism |
erythropoietin, breast cancer, chemotherapy, anemia
Researchers (1)
| no. |
Code |
Name and surname |
Research area |
Role |
Period |
No. of publicationsNo. of publications |
| 1. |
21407 |
PhD Sabina Berne |
Biotechnology |
Head |
2007 - 2008 |
165 |
Organisations (1)
Abstract
Anemia (a decreased number of erythrocytes in a bloodstream) is a common complication of the treatment of cancer patients and is related to the effects of chemotherapy or radiation. To correct this condition, patients receive packed red blood cell transfusions or injections of erythropoietin (Epo), a hormone that promotes red blood cell production. With the development of recombinant human erythropoietin (rHuEpo) in the 1980's, it became the leading drug for the treatment of anemia. However, it was soon discovered that Epo acts also in nonhemopoietic organs. The presence of Epo and its receptor (EpoR) has been demonstrated in various tissues and in many types of cancer and cancerous cell-lines. This finding, and insufficient knowledge about the role of EpoR in cancerous tissue, raised a question about the adequacy of the rHuEpo treatment in cancer patients. Two recently accomplished clinical studies have pointed out a decreased survival of the cancer patients receiving rHuEpo in comparison to those receiving transfusion. Therefore, it is necessary to perform a detailed analysis of the effects of the rHuEpo support therapy in cancer patients, as well as to investigate the molecular mechanisms of action of rHuEpo on cancerous cell.
The present study will include female patients with metastatic breast cancer, whose anemia is related to the effects of chemotherapy. To correct anemia half of the subjects will be assigned to receive rHuEpo and half of the subjects will, at least once, receive packed red blood cell transfusion. Twice (before and between treatment with rHuEpo/ transfusion) blood samples and metastatic biopsy will be taken. Within the framework of this study we will determine the level of serum Epo, analyze the global gene expression and transfer of the Epo signal in signaling pathways, and attempt to elucidate the action of rHuEpo on cancerous cells on the molecular and cellular level. This research will give groundwork for new guidelines in the usage of rHuEpo as a support therapy in cancer patients treated with chemotherapy.
Significance for science
This postdoctoral project has introduced a new field of research addressing the mechanism of action of recombinant human erythropoietin (rHuEpo) on the molecular basis in the metastatic breast cancer patients. All the clinical studies up to date analyzed only the survival rate / disease progression and specific molecular markers like erythropoietin and its receptor. Studies that addressed the molecular mechanisms have been performed on cell lines or on animal models, giving results that can only predict the mechanisms in cancer patients.
Due to the extensiveness of the study our research continuous within the framework of basic research project of Asst. Prof. N. Debeljak (J3-0124) and with the work of two young researchers (K. Španinger and N. Trošt). The study is designed with the aim to provide integral and detailed answers to important molecular questions regarding the mechanisms of action of recombinant human erythropoietin (rHuEpo) on the signaling transduction, gene regulation in cancerous tissue and effect on endogenous Epo levels.
Significance for the country
The research is performed in a collaboration with physicians at the Institute of Oncology Ljubljana, who will be informed in full with the results and findings of the presented study. A direct cooperation of researchers and physicians enables fast transfer of research findings and knowledge from laboratories to clinical practice; what in the end also affects the quality and efficacy of treatment of cancer patients.
Within postdoctoral project we successfully developed a procedure for separation of tumor from normal cells in fine needle aspiration biopsies on the basis of gradient centrifugation. The method is suitable also for diagnostic purposes, where further analyses of tumor cell populations are needed for better treatment options (in eg. responsiveness to chemotherapy and similar) and the presence of normal cells is undesirable.
For research purposes we employed a new technique for determination of rHuEpo in urine and blood samples by isoelectric focusing (IEF). Thus far the method was used for confirmation of rHuEpo doping usage in sport and it was not available in Slovenia. Although the method is very complex, it enables the differentiation of various Epo forms (endogenous vs. recombinant hormone) in blood and urine and could be used for routine monitoring of hormone state in anemic cancer patients and patients with kidney malfunction.
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