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R Gust

Publications and source records attributed to R Gust.

67 records · Page 4Linked to original sources
PubMed1990

Tumor inhibiting [1,2-bis(fluorophenyl)ethylenediamine]platinum(II) complexes, III: Evaluation of the mammary tumor inhibiting properties.

Diastereomeric diaqua[1,2-bis(4-fluorophenyl)ethylenediamine]platinum(II) sulfates and nitrates produce a strong inhibition of the hormone-dependent MXT-M 3.2 mammary carcinoma of the B6D2F1 mouse. Besides an interference in the DNA synthesis in analogy to cisplatin a lowering of the estrogen level due to an interference in steroid biosynthesis is suggested as the mode of action. In contrast to the R,R/S,S configurated diaqua[1,2-bis(4-fluorophenyl)ethylenediamine]platinum(II) salts the corresponding R,S configurated compounds are also markedly active on the hormone-independent MXT-Ovex mammary carcinoma of the B6D2F1 mouse.

Animals↗
PubMed1990

[DL-1,2-bis(2-hydroxyphenyl)ethylenediamine]dichloroplatinum(II), a new compound for the therapy of ovarian cancer.

The synthesis of diastereoisomeric [1,2-bis(2-hydroxyphenyl)ethylenediamine]dichloroplatinum(II) complexes, DL-3-PtCl2 and meso-3-PtCl2, and their evaluation on the hormone-independent, human MDA-MB231 breast cancer cell line, on the cisplatin-sensitive and -resistant L1210 leukemia cell line, on the cisplatin-resistant human NIH:OVCAR 3 ovarian cancer cell line, on the P-388 leukemia of the mouse and on the cisplatin-sensitive and -resistant Ehrlich ascites tumor of the mouse are described. On all tumor models DL-3-PtCl2 produces a marked inhibitory effect. The diastereoisomer meso-3-PtCl2 is less active and more toxic. It is striking that DL-3-PtCl2 leads to a pronounced inhibition of all cisplatin-resistant tumors. At non-toxic concentrations DL-3-PtCl2 produces cytocidal effects on the NIH:OV-CAR 3 cell line. Therefore DL-3-PtCl2 is of interest for further evaluation for the therapy of ovarian cancer.

Animals↗
PubMed1990

Aqua[1-(2,6-dichloro-4-hydroxyphenyl)-2- phenylethylenediamine](sulfato)platinum-(II) complexes with variable substituents in the 2-phenyl ring. 1. Synthesis and antitumor and estrogenic properties.

Erythro- and threo-configurated aqua[1-(2,6-dichloro-4-hydroxyphenyl)-2- phenylethylenediamine](sulfato)platinum(II) complexes with variable substituents in the 2-phenyl ring (2-PtSO4 to 9-PtSO4: H, 4-F, 3-OH, 4-OH, 2,6-F2, 2,6-Cl2, 2-F/4-OH, 2-Cl/4-OH) were synthesized and tested for estrogenic and antitumor activities. The ligands were obtained by a three-step reaction. The stilbenes were reacted with a mixture of IN3 and NaN3 to yield the respective 1,2-diazido-1,2-diphenylethanes. The subsequent reduction with LiAlH4 led to the corresponding 1,2-diphenyl-ethylenediamines. The (sulfato)platinum(II) complexes were synthesized by reaction of Ag2SO4 with the diiodo complexes, which had been obtained by coordination of the diamines with K2PtI4. Two complexes, erythro-8-PtSO4 and erythro-9-PtSO4, possess antitumor and estrogenic effects and are therefore of interest for the therapy of breast cancer.

Animals↗
PubMed1989

Tumor inhibiting properties of stereoisomeric [1,2-bis(3-hydroxyphenyl)ethylenediamine]dichloroplatinum(II)-compl exe s, Part I: Synthesis.

The synthesis of the stereoisomeric 1,2-bis(3-hydroxyphenyl)ethylenediamines (1-4) from meso-1,2-bis(2-hydroxyphenyl)ethylenediamine and 3-methoxybenzaldehyde by a diaza-Cope-rearrangement and subsequent ether cleavage with BBr3 and their conversion into the [1,2-bis(3-hydroxyphenyl)ethylenediamine]dichloroplatinum(II)-complexes with K2PtCl4 (1-PtCl2 - 4-PtCl2) is described.

Antineoplastic Agents↗
PubMed1989

Tumor inhibiting properties of stereoisomeric [1,2-bis(3-hydroxyphenyl) ethylenediamine]dichloroplatinum(II)-complexes, Part II: Biological properties.

The activity of stereoisomeric [1,2-bis(3-hydroxyphenyl)ethylenediamine] dichloroplatinum(II)-complexes (1-PtCl2,R,S; 2-PtCl2, R,R/S,S; 3-PtCl2, R,R; 4-PtCl2, S,S) on several tumor models (MDA-MB 231 breast cancer cell line; P 388 leukemia, mouse; L 1210 leukemia, mouse; L 5222 leukemia, rat; Ehrlich ascites tumor, mouse--wildtype; cisplatin-, etoposide-, cyclophosphamide-, and daunomycin-resistant, resp.) is described. For comparison the analogous [1,2-bis(4-hydroxyphenyl)ethylendiamine]dichloroplatinum (II)-complexes (5-PtCl2, R, S; 6-PtCl2, R,R/S,S; 7-PtCl2, R,R; 8-PtCl2, S,S) and cisplatin are used. 1-PtCl2 to 4-PtCl2 (OH in 3,3'-positions) show their maximum antitumor effect at lower doses than 5-PtCl2 to 8-PtCl2 (OH in 4,4'-positions). 2-PtCl2 and 6-PtCl2 (R,R/S,S) are more active than 1-PtCl2 and 5-PtCl2 (R,S). 4-PtCl2 and 8-PtCl2 (S,S) are superior to 3-PtCl2 and 7-PtCl2 (R,R). On the L 5222 leukemia 2-PtCl2 (R,R/S,S), 4-PtCl2 (S,S) and 8-PtCl2 (S,S) markedly surpass cisplatin. Strong effects are produced by 2-PtCl2 to 4-PtCl2 on the Ehrlich ascites tumor (wildtype, cisplatin-, etoposide-, cyclophosphamide-, and daunomycin-resistant, resp.). The combination of 4-PtCl2 with cisplatin results in a weakly synergistic effect.

Animals↗
PubMed1989

[Adequate respiratory therapy in polytrauma in the prehospital phase by pulse oximetry monitoring].

As a result of recent medical development, the pulse oximetry enables the emergency-doctor to carry out an objective and continuous respiratory monitoring. In a prospective study we showed the consequences of this new procedure for prehospital respiratory therapy and the following posttraumatic development of polytraumatized patients. In 1988 within 6 months we carried out a continuous monitoring of 13 severely polytraumatized patients in the prehospital period using the pulse oximeter Nellcor N-10 and Pulsat. In order to see the posttraumatic respiratory complications, we studied the respiratory therapy of the following 3 days as well as the course of disease until the patients' release of the hospital. 38% of the patients were intubated immediately after the accident and further 12% before arriving at the hospital. The oxygen inhalation therapy of 63% spontaneously breathing patients and the mechanical ventilation patterns of 80% of the ventilated patients were modified in the prehospital period, because 60% of the patients with standard mechanical ventilation showed hypoxygenations. During the first 3 posttraumatic days 23% of the patients died the the number of mechanical ventilated patients increased from 46% to 54% because of surgical interventions. A respiratory therapy of more than 3 days was applied on 40% of the surviving patients, with 20% receiving mechanical ventilation. Thereby no primarily respiratory complications could be seen. While not being decisive for immediate intubation, monitoring with a pulse oximeter used by the emergency-doctor plays an essential part in carrying out an effective control and dosage of the therapy.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1988

Influence of ring substituents on the antitumor effect of dichloro(1,2-diphenylethylenediamine)platinum(II) complexes.

Diastereomeric para-substituted dichloro(1,2-diphenylethylenediamine)platinum(II) complexes were synthesized and tested for their antitumor activity on the human MDA-MB 231 breast cancer cell line and the P 388 leukemia of the mouse. An interaction with the DNA was demonstrated by UV difference spectroscopy. The D,L configurated, 4-fluoro-substituted complex was the most active.

Animals↗
PubMed1988

Ring-substituted [1,2-bis(4-hydroxyphenyl)ethylenediamine]dichloroplatinum (II) complexes: compounds with a selective effect on the hormone-dependent mammary carcinoma.

[1,2-Bis(4-hydroxyphenyl)ethylenediamine]dichloroplatinum (II) complexes with one substituent in the 2-position (CH3, CF3, F, Cl, Br, I: meso- and d,l-1-PtCl2, meso-(3-5)-PtCl2, meso-(7 and 8)-PtCl2) or two substituents in the 2,6-positions (CH3, Cl: meso-2-PtCl2, meso- and d,l-6-PtCl2) in both benzene rings were synthesized and tested for estrogenic and cytotoxic activities. Two complexes (meso-6-PtCl2 and meso-7-PtCl2) possess both effects. In comparative tests on estrogen receptor positive and negative mammary tumors in cell culture (MCF 7, ER+ and MDA-MB 231, ER-) and in animals (MXT, ER+ and MXT, ER-, mouse), meso-6-PtCl2 shows a selective effect on the estrogen receptor positive mammary carcinoma. A further increase of efficacy was achieved with the water-soluble (sulfato)platinum(II) derivative (meso-6-PtSO4). On the DMBA-induced hormone dependent mammary carcinoma of the SD rat, meso-6-PtSO4 is significantly more active than its ligand (meso-6) and cisplatin.

Animals↗
PubMedDate not supplied

Third generation antitumor platinum(II) complexes of the [1-(fluoro/difluorophenyl)-2-phenylethylenediamine]platinum(II) type.

The diastereomeric 1-(fluoro/difluorophenyl)-2-phenylethylene-diamines (4-fluoro: erythro-1/threo-1; 2,4-difluoro: erythro-2/-threo-2; 2,6-difluoro: erythro-3/threo-3) and the diastereomeric 1-(4-fluorophenyl)-2-(3-hydroxyphenyl)ethylenediamines (erythro-4/-threo-4) were synthesized from appropriately substituted stilbenes by reaction with IN3 and subsequent LiAlH4 reduction. Coordination of the 1,2-diphenylethylenediamines to platinum was carried out by use of K2PtI4. The water-soluble aquasulfato-platinum(II) complexes (erythro/threo-1-PtSO4-erythro/threo-4-PtSO4) were obtained from the diiodoplatinum(II) complexes by reaction with Ag2SO4. Additionally erythro/threo-1-PtSO4 and erythro/threo-4-PtSO4 were transformed into the dichloroplatinum(II) complexes (erythro/threo-1-PtCl2, erythro/threo-4-PtCl2) by treatment with KCl. In contrast to the less effective erythro-configurated sulfatoplatinum(II) complexes the threo-analogues showed comparable or even superior activities to cisplatin on the human MDA-MB-231 breast cancer cell line. On the MXT-M-3.2 breast cancer of the mouse only erythro- and threo-4-PtSO4 caused similar effects like cisplatin. The strong inhibitory effect of the diastereomeric sulfatoplatinum(II) complexes on the P-388 leukemia of the mouse was equal to that of cisplatin. On the latter tumor threo-4-PtCl2 was the most active among the less toxic dichloroplatinum(II) derivatives.

Animals↗
PubMedDate not supplied

Vascular remodeling in experimentally induced subacute canine pulmonary hypertension.

We quantified in vivo pulmonary vascular remodeling in a large animal model of pulmonary hypertension (PH). In group PH (n = 6), 3 mg/kg dehydromonocrotaline (DHMC) was administered to 12-week-old beagles via a right atrial injection. Eight weeks after DHMC in group PH, pulmonary artery pressure increased significantly (P < .05) from 18 +/- 2 mm Hg at baseline to 30 +/- 4 mm Hg. Medial wall thickness and medial wall area as a percentage of total vessel diameter or area was significantly higher (P < .05) in group PH (29 +/- 9% and 48 +/- 12%) than in a control group (n = 5) (7 +/- 1% and 14 +/- 1%). Neointimal proliferation was observed in 42% of pulmonary arterioles in the PH group but never in the control group. We conclude that a single injection of DHMC in young beagles, in addition to the development of moderate degrees of PH after 8 weeks, causes significant pulmonary vascular remodeling, with features similar to those observed in patients with primary PH.

Acute Disease↗