Anti-proliferative effects of 1,2-diphenylethane oestrogens and anti-oestrogens on human breast cancer cells

Summary The anti-tumour activities of 1,2-diphenylethane oestrogens (hexoestrol and orthohexoestrol) and anti-oestrogens (metahexoestrol, tetramethylHES, and metatetramethylHES) were studied on the human MCF-7 and MDA-MB-231 breast cancer cell lines. On the E₂R-positive MCF-7 cell line, all test compounds exhibited a dose-dependent inhibition of cell proliferation, but no correlation between anti-proliferative activity and binding affinity for the E₂R was found. Tested on the E₂R-negative MDA-MB-231 cell line, metahexoestrol also showed dose-dependent inhibitory effects, but higher concentrations were necessary than on the MCF-7 cell line. From this it is concluded that the anti-proliferative effect is specific and at least partially mediated via the E₂R. Combination of metahexoestrol (10^–6M) with E₂ (10^–9 to 10^–7M) gave no rescue effect. It is therefore suggested that this compound might be useful for therapy in the presence of high oestrogen levels, i.e. in pre-menopausal patients. The test compounds (10^–8 to 10^–6M) could rescue the inhibitory effect of tamoxifen (10^–6M) in a dose-dependent manner, except in the cases of metahexoestrol (10^–6M) and tetramethylHES (10^–6M). The latter compound exhibited a strongly additive effect at this concentration.Abbrevations E₂ 17-oestradiol - E₂R oestradiol receptor - DMBA 9,10-dimethyl-1,2-benzanthracene - NMU nitrosomethylurea - IMEM improved minimum essential medium - DCC dextran coated charcoal - hexoestrol meso-3,4-bis(4-hydroxyphenyl)hexane - metahexoestrol meso-3,4-bis(3-hydroxyphenyl)hexane - orthohexoestrol meso-3,4-bis(2-hydroxyphenyl)hexane - tetramethylHES 1,1,2,2-tetramethyl-1,2-bis(4-hydroxyphenyl)ethane - metatetramethylHES 1,1,2,2-tetramethyl-1,2-bis(3-hydroxyphenyl)ethane - C₂NCS DCC-treated new-born calf serum - EDTA ethylenediaminetetraacetic acid - PBS phosphate buffered saline - TED Tris-EDTA-dithiothreitol - Tris tris(hydroxymethyl)aminomethane - TCA trichloroacetic acid Dedicated to Prof. Dr. H. Schönenberger on the occasion of his 60th birthdaySupported by grants of the Deutsche Forschungsgemeinschaft (SFB 234-85) and the Verband der Chemischen Industrie, Fonds der Chemischen IndustrieGranted by the Deutscher Akademischer Austauschdienst     

Reliability of sensor-based real-time workflow recognition in laparoscopic cholecystectomy

Purpose

Laparoscopic cholecystectomy is a very common minimally invasive surgical procedure that may be improved by autonomous or cooperative assistance support systems. Model-based surgery with a precise definition of distinct procedural tasks (PT) of the operation was implemented and tested to depict and analyze the process of this procedure.

Methods

Reliability of real-time workflow recognition in laparoscopic cholecystectomy ( \(n=10\) cases) was evaluated by continuous sensor-based data acquisition. Ten PTs were defined including begin/end preparation calots’ triangle, clipping/cutting cystic artery and duct, begin/end gallbladder dissection, begin/end hemostasis, gallbladder removal, and end of operation. Data acquisition was achieved with continuous instrument detection, room/table light status, intra-abdominal pressure, table tilt, irrigation/aspiration volume and coagulation/cutting current application. Two independent observers recorded start and endpoint of each step by analysis of the sensor data. The data were cross-checked with laparoscopic video recordings serving as gold standard for PT identification.

Results

Bland–Altman analysis revealed for 95 % of cases a difference of annotation results within the limits of agreement ranging from \(-\) 309 s (PT 7) to +368 s (PT 5). Laparoscopic video and sensor data matched to a greater or lesser extent within the different procedural tasks. In the majority of cases, the observer results exceeded those obtained from the laparoscopic video. Empirical knowledge was required to detect phase transit.

Conclusions

A set of sensors used to monitor laparoscopic cholecystectomy procedures was sufficient to enable expert observers to reliably identify each PT. In the future, computer systems may automate the task identification process provided a more robust data inflow is available.     

Entwicklung neuer Antiöstrogene vom Typ des 3,3′-Dihydroxy-α,β-diäthylstilbens und ihre Prüfung am DMBA-induzierten,hormonabhängigen Mammacarcinom der SD-Ratte

Zusammenfassung Die Verlagerung der phenolischen OH-Gruppen des Diäthylstilböstrols in die 3,3-position (trans-3,3-Dihydroxy-,-diäthylstilben, Verb. Nr. III) führt unter Erhaltung der Rezeptoraffinität zu einer starken Abnhme der östrogenen Wirkung. III hemmt in vitro die östradiol-Rezeptor-Wechselbeziehung kompetitiv und antagonisiert in vivo bei der Maus die uterotrope Wirkung des Östrons. In Versuchen am DMBA-induzierten, hormonabhängigen Mammacarcinom der Ratte kommt es, unter III-Einwirkung dosisabhägig zu einer starken Abnahme von Tumorgröße und-zahl, die durch die antiöstrogenen Eigenschaften von III bedingt, ist. Der Austausch der ,-ständigen Äthylreste in III durch andere Alkylketten führt zu keiner weiteren, Steigerung der antiöstrogenen und tumorhemmenden, Wirkung.

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Abkürzungen trans-4,4-DES trans-4,4-Dihydroxy-,-diäthylstilben (Diäthylstilböstrol DAB 7) - I trans-3,3-Dihydroxy-,-dimethylstilben - II cis-3,3-Dihydroxy-,-diäthylstilben - III trans-3,3-Dihydroxy-,-diäthylstilben - IV trans-3,3-Dihydroxy-,-di-n-propylstilben - V trans-3,3-Dihydroxy-,-di-n-butylstilben - VI trans-2,2-Dihydroxy-,-diäthylstilben - DCC Dextran Coated, Charcoal - DMBA 7,12-Dimethylbenz-[a]-anthracen - TRIS Tris-(hydroxymethyl)-aminomethan - EDTA Äthylendiamintetraessigsäure - E2 Östradiol - ³H-E2 Östradiol [2,4,6,7-³H]; 90–115 Ci/mmol (New England Nuclear, Dreieichenhain/Frankfurt) - PPO 2,5-Diphenyloxazol - Dimethyl-POPOP p-Bis-2-(4-methyl-5-phenyl-oxazoyl)-benzol - K _d Dissoziationskonstante des Östradiol-Rezeptor-Komplexes - K _i Dissoziationskonstante des Inhibitor-Rezeptor-Komplexes - SDS Natriumdodecylsulfat - TCA Trichloressigsäure Der Deutschen Forschungsgemeinschaft, und dem Verband der Chemischen Industrie-Fonds der Chemischen Industrie — danken wir für die Förderung dieser UntersuchungenFrau G. Braun und Frau J. Garamvölgy danken wir für ihre wertvolle MitarbeitEin Teil der Untersuchungen wurde im Institut für Pharmazie, und Lebensmittelchemie der Universität München durchgeführtHerrn Prof. Dr. Heinrich Thies zum 75. Geburtstag gewidmet     

Untersuchungen zur mammatumorhemmenden Wirkung von cis-Bis(glycylglycinethylester)platin(II)chlorid

Studies on the Mammary Tumor Inhibiting Effect of cis-Dichlorobis(glycylglycinethylester)platinum(II) In vivo, cis-dichlorodiammineplatinum(II) (1) and cis-dichlorobis(glycylglycinethylester)platinum(II) (2) inhibit the DMBA-induced hormone dependent mammary carcinoma of the SD rat. In vitro, a marked effect on the DNA synthesis of mammary tumor cells and an inhibition of the ³H-E₂ receptor interaction can be demonstrated. A binding to DNA and an inhibition of the proliferation stimulating effect of endogenous estrogens by blocking the hormone receptors are discussed as modes of action.     

Empfehlungen zu urogynäkologischer Diagnostik und Therapie

Ohne Zusammenfassung     

Episiotomie versus Damm-Scheidenriss — Eine prospektive Studie

Schlu?folgerung Solange keine zwingenden Indikationen vorliegen, sollte versucht werden die Episiotomie m?glichst zu vermeiden (7, 8). Erscheint eine Episiotomie erforderlich, so ist die mediane Episiotomie zu favorisieren (2, 4).