Project

Discipline

circulating tumor cells; magnetic nanoparticles; immunomodulation; natural killer cells; anesthetics; breast cancer

Lead
This is a project with a clinical, translational and engineering part, focusing on circulating tumor cells. In a randomised controlled trial the possible immunomodulatory effect of the volatile anaesthetic sevoflurane will be tested in patients undergoing breast cancer surgery. The kinetic of circulating tumor cells in the postoperative phase will be assessed as primary endpoint. In parallel, cancer cell capturing-nanoparticles will be engineered and extensively tested in vitro, which would allow a transfer from 'the bench to the bedside' in the near future.
Lay summary
Karzinomzellen können sich jederzeit aus dem Tumorverbund lösen und in die Blutstrombahn gelangen und damit an einen anderen Ort gelangen, wo möglicherweise eine Metastase gebildet wird. Daher ist es nicht erstaunlich, dass immer mehr Studien zeigen, dass die Präsenz von zirkulierenden Tumorzellen (CTC) mit einer eher ungünstigen Prognose korreliert. Insbesondere während der operative Entfernung eines Tumors ist damit zu rechnen, dass durch die Manipulation Tumorzellen freigesetzt werden und in die Blutbahn gelangen. Dies ist jedoch bis anhin kaum untersucht worden, ebenso nicht der mögliche Einfluss der Anästhesie auf diese CTC. Es ist bekannt, dass Narkosemittel die Immunabwehr beeinflussen. In früheren klinischen Studien in der Anästhesie konnte unser Forschungsteam zeigen, dass Narkosegase (volatile Anästhetika wie zum Beispiel Sevofluran) im Gegensatz zu Anästhetika, die in die Vene appliziert werden wie Propofol, einen entzündungshemmenden Einfluss nach ausgedehnter Chirurgie ausüben, und somit die Komplikationsrate positiv beeinflussen. Hingegen ist nicht bekannt, ob sich dieser positive Einfluss auch auf die Präsenz von Tumorzellen auswirkt. Dieses Gesuch enthält eine klinische Studie sowie ein Entwicklungsprojekt, beim dem einerseits Kliniker sowie translationale und Materialwissenschaftler involviert sind. Ziel der klinischen Studie ist es, bei 232 Frauen mit Mamma Karzinom, die sich in Allgemeinänästhesie einer operativen Entfernung des Tumors unterziehen, entweder Sevofluran oder aber Propofol als Anästhetikum einzusetzen. Dabei wird untersucht, ob die Art des Anästhetikums die Anzahl CTC nach der Operation beeinflusst. In einem Teilprojekt sollen zudem magnetische Nanopartikel hergestellt werden, die im Labor getestet werden. Sie könnten eingesetzt werden, um CTC, insbesondere solche, die während der Operation von Karzinomen entstehen, aus dem Blut zu entfernen.

Direct link to Lay Summary

Last update: 11.04.2015

Active participation

Number	Title	Start	Funding scheme

When cells detach from a primary tumor they may reach the vascular compartment either by direct invasion or through the lympathic system. Once in the blood they are carried to distant sites, adhere there and manifest as metastases if they grow to be a new tumor mass. At the same time tumor may recur locally. Manipulation through the process of surgery may trigger the release of tumor cells. Recent studies have pointed out the importance of circulating tumor cells (CTC) as reliable surrogate markers for cancer prognosis. The presence of CTC correlates with inferior outcomes as far as tumor recurrence and/or metastasis is concerned. However, information about CTC in the perioperative phase of tumor surgery is limited. The influence of anesthetics, which have clearly been shown to have an immunomodulatory effect in general, on tumor cell release into the blood compartment, has not yet been elucidated. It is known that the activity of natural killer (NK) cells, an important element of immunological tumor defense, is compromised by anesthesia drugs. While the conclusion of several studies is that the choice of anesthetics has an impact on CTC and cancer prognosis, the quality of these data is limited due to their retrospective character and the small sample size of the trials. Therefore, our group - with a broad expertise in the area of anesthetics and innate immunity - would like to further explore the immunomodulatory effect of general anesthetics in the perioperative phase in cancer surgery using the design of an adequately powered randomized clinical trial. Additionally, a potentially effective intervention using magnetic nanoparticles to eliminate CTC in blood will be explored. This proposal encompasses 3 aims:-To perform a randomized controlled trial in 232 patients undergoing breast cancer surgery, randomizing for 2 anesthesia regimens (volatile (sevoflurane) versus intravenous (propofol) anesthetic). Primary endpoint is the number of CTC in the respective group in the postoperative phase at 3 time points (immediately after surgery, 2nd and 4th postoperative day). Based on in vitro data we hypothesize that there are less CTC present in the sevoflurane than in the propofol arm.-To analyze NK cells of the study subjects with regard to cell number and activity in relation to the anesthetic used in the respective randomization arm. Our hypothesis is that both anesthetics attenuate NK cell activity, but sevoflurane to a lesser degree.-To engineer highly magnetic nanoparticles, which interact with surface antigens such as epithelial cell adhesion molecule (EpCAM, CD326) and eliminate breast cancer cells from blood by application of a magnet. The current application allows us to bridge between clinical, translational and engineering approaches for an area, which is considered highly innovative in the world of anesthesiology. We believe it is important to know which anesthesia regimen is superior to support the combined efforts of surgery, chemotherapy, radiation therapy and targeted therapies since thousands of patients undergo anesthesia for cancer surgery daily. Additionally, specifically designed nanoparticles could be a tool to purify CTC from the blood of patients undergoing cancer surgery in the future and thereby improve the anesthesiological care for cancer patients. Altogether the proposed strategies would offer the advantage of an inexpensive benefit for the patient.