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Institute
Summary
Background: Combination chemotherapies of platinum compounds with alkylating agents have been the standard treatment for patients with advanced ovarian carcinoma over the last decades. The recent development of taxans has added a group of new promising agents; however, long-term results are not yet available. Platin derivates have proven to be an indispensable part in combination chemotherapies for ovarian carcinoma. The dose intensity of cisplatin is, however, still a matter of debate. We report on the long-term results of a prospective randomized trial comparing two dosages of cisplatin combined with treosulfan in patients with advanced epithelial ovarian cancer. Patients and Methods: Between 1988 and 1995, 125 patients with ovarian cancer (FIGO stage II–IV) were randomized to receive 4 cycles (28-day intervals) of either cisplatin 100 mg/m2 (high dose, HD) or 50 mg/m2 (low dose, LD) in combination with 5 g/m2 treosulfan after primary cytoreductive surgery. Postoperative residual tumor was absent in 39 patients (HD: 16; LD: 23), < 2 cm in 61 patients (HD: 36; LD: 25) and > 2 cm in 25 patients (HD: 13; LD: 12). 65 and 60 patients received HD and LD cisplatin, respectively. Second-look surgery was optional. Results:The overall response rate was 70.0% (HD: 70.9%; LD: 68.9%). Pathological complete response (CR) was seen in 45 patients (37.5%), clinical CR in 23 patients (19.2%), partial response (PR) in 16 patients (13.3%), stable disease (SD) in 2 patients, and progression of disease (PD) in 34 patients (28.3%). 5 patients were not assessable for response. Overall median survival was 25.6 (HD: 26.9, LD: 25.2) months. The overall disease-free survival for responders was 19.6 and 24.7 months (HD and LD, respectively). HD chemotherapy did not result in any significant survival benefit in completely resected patients: HD: 39.8 months versus LD: 49.5 months. In suboptimally debulked patients (residual tumor < 2 cm), median survival was 24.1 months (HD) versus 22.6 months (LD). In patients with residual tumors > 2 cm median survival was 14.6 months (HD) versus 15.5 months (LD). Significantly less side effects were seen in the LD group: anemia (p = 0.008); nephrotoxicity (p = 0.014); alopecia (p = 0.017). Conclusions: Our data suggest that LD cisplatin-based chemotherapy is as effective as HD chemotherapy in patients with advanced epithelial ovarian cancer, but is far less toxic.
Copyright © 2000 S. Karger GmbH, Freiburg
BACKGROUND
Despite radical surgery and the introduction of novel chemotherapeutic agents, the prognosis of ovarian cancer remains poor. Since in the past the potential role of gonadotropins in the induction and progression of ovarian cancer has been discussed, we conjugated doxorubicin to human chorionic gonadotropin (hCG) in order to specifically target ovarian cancer cells.
MATERIALS AND METHODS
Doxorubicin was conjugated to hCG via glutaraldehyde. 48 hours post seeding, NIH:OVCAR 3 cells were treated with various concentrations of hCG-conjugated and non-conjugated doxorubicin for 2 hours. Cells were cultured for a total of 168 hours. Cell growth was monitored by a crystal violet assay.
RESULTS
Conjugating doxorubicin to hCG resulted in an average specific uptake of 22 mol doxorubicin per mol protein (range 3.0-43.3 mol). Incubating NIH:OVCAR 3 cells for 2 hours with the conjugate led to a more than 8 fold increase of the IC50 values compared to non-conjugated doxorubicin (0.55 microM versus 4.43 microM). The antiproliferative activity of both conjugated and free doxorubicin was detectable up to 168 hours post treatment.
CONCLUSIONS
The present experiments clearly demonstrate a more than 8-fold increase in cytotoxicity of the conjugates compared to free doxorubicin. It was also shown that this effect was not restricted to an acute toxic event but that it resulted in a prolonged antiproliferative activity.
Hessel, V. ; Löwe, H. ; Haverkamp, V. ; Wille, Ch. ; Ehrfeld, W. ; Lutz, N. ; Möllmann, Klaus-Peter ; Pinno, Frank ; Herweck, Th.
Wahlverhalten von Schülern der Sekundarstufe II im Fach Physik seit 1990 im bundesweiten Vergleich
(2000)
Max Planck legte 1900 mit dem nach ihm benannten Strahlungsgesetz das quantitative Fundament zu so genannten Wärmebildsystemen. 100 Jahre später gibt es — mit bedingt durch Fortschritte in der Halbleitertechnologie und Mikrosystemtechnik — Infrarotkameras, mit denen sowohl die von Planck untersuchten Strahlungsgesetze zur Hohlraumstrahlung als auch allgemein wissenschaftliche und technische Anwendungen der Temperaturstrahlung von Körpern untersucht werden können. Darüber hinaus bieten sich solche Systeme auch für didaktische Zwecke an, da physikalische Gesetzmäßigkeiten mit Energieaustauschprozesssen aus sehr vielen Gebieten der Physik durch eine etwas andere, physikalische Sehweise visualisiert und damit für Lehrzwecke eingesetzt werden können.
Das ist ein seltsam wunderbares Zeichen! Ein Streifzug durch die Kulturgeschichte des Regenbogens
(2000)