Does stimulation with human gonadotropins and gonadotropin-releasing hormone agonist enhance and accelerate the developmental capacity of oocytes in human ovarian tissue xenografted into severe combined immunodeficient mice?

OBJECTIVE: To assess the capacity of human frozen-thawed ovarian follicles matured in xenografts to form metaphase II (MII) oocytes after xenotransplantation and exogenous stimulation. DESIGN: Prospective controlled animal study. SETTING: University hospital gynecology research unit. PATIENT(S): Ovarian fragments were obtained from 17 women with malignant diseases who wished to cryopreserve ovarian tissue for later pregnancy before chemotherapy. ANIMAL(S): Eighty-eight female severe combined immunodeficient (SCID) mice. INTERVENTION(S): Cryopreserved human ovarian tissue was grafted into oophorectomized SCID mice. The mice were divided into three groups: Group A received hMG alone every 2 days for a maximum of 24 weeks; group B additionally received nRH agonist (GnRHa) every 4 weeks; and group C was an untreated control group. MAIN OUTCOME MEASURE(S): Follicular density, morphology, proliferation, oocyte maturation, malignant cell contamination. RESULT(S): Follicle survival and development were similar in all three groups. No significant interactions between the stimulation protocols and grafting duration were noted. Three MII oocytes were observed in grafted follicles. Two MII oocytes were harvested without stimulation. None of the mice showed signs of reintroduced malignancy, nor did microscopic evaluation of the grafts raise any suspicion of residual malignant disease. CONCLUSION(S): After xenotransplantation, human primordial follicles can be matured to MII oocytes even without stimulation. Administering human gonadotropin and GnRHa does not enhance the developmental capacity of xenografted oocytes. The optimal stimulation schedule for grafted tissue remains unknown.

Visualisation of tumour regression after local chemotherapy with magnetic nanoparticles - a pilot study.

UNLABELLED: Magnetic drug targeting (MDT) is a new locoregional chemotherapy method that increases the drug dose in the tumour region, while simultaneously reducing the overall dose through the application of chemotherapeutic-bound superparamagnetic nanoparticles, which are focused by an external magnetic field to the desired body compartment. An important factor in this kind of therapy is the vascularisation of the targeted tumour. In this pilot study, the visualisation of the tumour-vascularisation before and after MDT was investigated. MATERIALS AND METHODS: In a rabbit VX-2 tumour model, mitoxantrone bound to Fe(3)O(4)-nanoparticles was applied through the femoral artery close to the tumour. The visualisation of vascularisation and tumour size before and after MDT was performed using a biplane angiographic system (Siemens Axiom Artis dBA) to obtain conventional angiographic series with a standard iodine contrast agent. In addition, cross-sectional images were obtained with the new technique of flat panel detector computed tomography (FD-CT) called DYNA-CT. RESULTS: The tumours and the supplying vessels were clearly displayed by FD-CT before and after MDT. The tumours of the study group showed considerable size reductions and the angiography showed a drastic reduction of the tumour supporting vessels following MDT. CONCLUSION: MDT leads to significant tumour size reductions within several weeks after a single administration of chemotherapy. In this pilot study, FD-CT offered an excellent possibility to monitor the vascularisation and the size of the tumours before and after MDT.

Delivery of superparamagnetic nanoparticles for local chemotherapy after intraarterial infusion and magnetic drug targeting.

BACKGROUND: Superparamagnetic nanoparticles are currently used as contrast agents for magnetic resonance imaging. These particles can also be used as drug carriers for local chemotherapy, called magnetic drug targeting. Using an external magnetic field, colloidal nanoparticles can be directed to a specific body compartment (i.e. tumor). MATERIALS AND METHODS: After magnetic drug targeting in an experimental rabbit model with a VX2 squamous cell carcinoma, tumor tissue was extracted and embedded in paraffin for histology and X-ray imaging. RESULTS: The distribution of magnetic nanoparticles was detected holistically with X-ray imaging and in detail using Prussian blue staining of histological cross sections. CONCLUSION: The biodistribution of magnetic nanoparticles can be visualized with X-ray imaging and histologically confirmed.

Targeting cancer cells: magnetic nanoparticles as drug carriers.

Magnetic drug targeting employing nanoparticles as carriers is a promising cancer treatment avoiding side effects of conventional chemotherapy. We used iron oxide nanoparticles covered by starch derivatives with phosphate groups which bound mitoxantrone as chemotherapeutikum. In this letter we show that a strong magnetic field gradient at the tumour location accumulates the nanoparticles. Electron microscope investigations show that the ferrofluids can be enriched in tumour tissue and tumour cells.

Magnetic drug targeting--biodistribution of the magnetic carrier and the chemotherapeutic agent mitoxantrone after locoregional cancer treatment.

Magnetic Drug Targeting means the specific delivery of chemotherapeutic agents to their desired targets, e.g. tumors, by using magnetic nanoparticles (ferrofluids) bound to these agents and an external magnetic field which is focused on the tumor. This type of target directed drug injection attempts to concentrate a pharmacologic agent by enhancing its efficacy while simultaneously minimizing deleterious side effects. In previous studies, we have been able to demonstrate the efficacy of this type of localized intraarterial chemotherapy in VX2 squamous cell carcinoma among rabbits [Alexiou, C., Arnold, W., Klein, R.J., Parak, F.G., Hulin, P., Bergemann, C., Erhardt, W., Wagenpfeil, S. and Lübbe, A.S. "Locoregional cancer treatment with Magnetic Drug Targeting", Cancer Res. 60 (2000) 6641-6648]. In the present investigation, we have studied the biodistribution of ferrofluids and chemotherapeutic agent by measuring the amount in the tumor, peritumoral area, various organs and body fluids (e.g. blood and urine), with and without Magnetic Drug Targeting. We compared results to that of administering a chemotherapeutic agent soley. An external magnetic field was directed toward the tumor for 60 min. Biodistribution of ferrofluids in the tumor was investigated using histological cross sections and measured semi-quantitatively using 123I-labeled nanoparticles and quantitatively by the use of radioactive 59Fe-ferrofluids. Mitoxantrone was quantitatively measured using HPLC-analysis. The strength of the external magnetic field was 0.6 Tesla (permanent magnet) in the 123iodine study and 1.7 Tesla (electromagnet) in the 59Fe-study and HPLC-analysis. The concentration of the ferrofluids (FFs) in the tumor region i.e. the tumor tissue and the surrounding area, which was under the influence of an external magnetic field, was found to be much higher than in the absence of one. In contrast to systemic chemotherapy, a much higher concentration of mitoxantrone in the tumor and the peritumoral area (region surrounding the tumor < or = 1 cm), by using only 50% and 20% of the normal dose was seen. Thus, the higher concentration of mitoxantrone could explain the therapeutic efficacy of Magnetic Drug Targeting in treatment of VX2 squamous cell carcinoma in rabbits in our previous studies with the advantage of no adverse clinical side effects.