Subrenal capsule assay of fresh human tumors: problems and pitfalls.

The 6 day subrenal capsule (SRC) assay was performed in normal mice using 20 fresh human non-small cell lung cancers and nine fresh ovarian cancers. Different multi-agent chemotherapy regimens administered intravenously on days 2 + 3 of the assay were evaluated for activity against these two tumor types. Macroscopic results measured via an ocular microscope showed high activity for some combinations as well as for single agents.

[The CRF test in psychiatry. Preliminary studies].

The HPA axis exploration in the endogenous depressions indicates an hyperactivity of this system. But the reason of this perturbation is not definite. The corticotropin-releasing factor (CRF) test has been described from research work carried out by Vale et al.

Synthesis, characterization, and quantitation of para-hydroxymethadone, a metabolite of methadone in the rat.

To demonstrate a p-hydroxylation process in the metabolism of methadone, we have synthesized para-hydroxymethadone and characterized it by spectroscopy (IR, 13C-NMR, mass spectrometry) and chromatography (thin layer chromatography, gas-liquid chromatography, and HPLC). para-Hydroxymethadone was isolated by HPLC from the urine of rats treated with (R,S)-methadone. para-Hydroxymethadone in the urine and in the bile represents 1.

A lymphotropic prodrug of L-dopa: synthesis, pharmacological properties, and pharmacokinetic behavior of 1,3-dihexadecanoyl-2-[(S)-2-amino-3-(3,4-dihydroxyphenyl)prop anoyl] propane-1,2,3-triol.

A glyceride derivative of L-Dopa, 1,3-dihexadecanoyl-2-[(S)-2-amino-3-(3,4-dihydroxyphenyl)propan oyl] propane-1,2,3-triol (1), was synthesized and tested as an orally administrable prodrug endowed with lymphotropic properties. In the oxotremorine and reserpine tests, 1 exhibited an anti-Parkinsonian activity of longer duration than L-Dopa. The time course of concentration of 1 in the intestinal lymph of rat was determined and compared to that of L-Dopa.

[Replacement of both cruciate ligaments with a single transplant from the extensor system. Bicross quadricipital ligamentoplasty].

The authors describe a new procedure for replacement of both cruciate ligaments. They use a single anterior approach and a unique transplant, consisting of a long band including part of the patellar tendon, part of the patella and part of the quadriceps tendon. The technique is indicated in some cases of major instability of the knee.

Investigation of a new murine model of regional lymph node metastasis: characteristics of the model and applications.

The RC tumor, originally a renal adenocarcinoma very sensitive to different classes of chemotherapeutic agents, maintained in CDF 1 mice, was examined for its ability to metastasize. When inoculated into the foot (with 10(7) tumor cells), bulky metastases developed in the popliteal and para-aortic lymph nodes, in a constant and reproducible pattern, producing a massive microscopic invasion of the liver, the lungs and the spleen. The antigenicity tests demonstrated a low immunogenicity of the tumor.

Characterization of the activity of alpha/beta-triglycidylurazol (TGU; NSC-332488): a new antineoplastic compound.

The antitumour properties of alpha/beta-triglycidylurazol (TGU) were investigated on various transplantable mouse tumour systems. A high rate of cures of P388 and L1210 leukaemias was obtained with this compound. TGU also had an antitumour effect against B16 melanoma, the colon 38 tumour and the advanced RC renal carcinoma, producing a total regression of the tumour.

Lack of mutagenicity of diphenylhydantoin in in vitro short-term tests.

The mutagenicity of diphenylhydantoin (DPH) and its major metabolite, 5-(p-hydroxyphenyl)-5-phenylhydantoin (HPPH), has been re-evaluated by the Ames test using Salmonella typhimurium and, for DPH only, by an in vitro cytogenetic test with human lymphocytes and a turbidimetric assay of tubulin polymerization. As negative results were obtained in all test systems used here, one has to conclude that DPH is devoid of mutagenic properties.

Chemosensitivity of human melanoma xenografts in immunocompetent mice and its histological evaluation.

In the subrenal capsule assay, the immuno-competent mice used have a host immune response to the graft which may introduce a bias in the determination of tumour size. A study was therefore conducted to verify the quality of the correlation that could exist between "macroscopical" and "microscopical" evaluation. A histological study of 12 different tumours treated with cis-Pt, L-PAM, DTIC, vindesine, BCNU or TGU demonstrated that a cellular host immune response was observed in 11 out of the 12 control groups and was uneven in the treated groups.

Preclinical evaluation of the anti tumour activity of new epoxyde derivatives.

As a follow-up to our initial results on the antineoplastic activity of alpha-1,3,5-triglycidyl-s-triazinetrione (alpha TGT, NSC-296934, Teroxirone), many new epoxyde derivatives were tested against murine tumours, mostly against P388 leukaemia, to determine their antineoplastic role and to characterize their specific effect against tumour cells in vivo, as well as to select an analogue with higher anti-cancer properties and superior pharmacological properties. Triglycidyl urazol (TGU, NSC-332488) showed the highest therapeutic activity and a good level of water-solubility which makes this agent a good candidate for phase-one clinical trials.

Structure-activity relationships of phenytoin-like anticonvulsant drugs.

A limited series of compounds structurally related to phenytoin has been tested in the maximal electroshock seizure (MES) test in order to define the impact on their antiepileptic activity of reducing the ability to form a hydrogen bond. A net stepwise decrease of the anticonvulsant activity was observed when the hydantoin ring structure was altered into succinimide and pyrrolidinone and when these rings were N-methylated. The pharmacological data analyzed in terms of structure-activity relationships (SAR) indicate the importance of the capability of forming hydrogen bonds.

Investigation of the antitumor activity of new epoxide derivatives. Part II: N-glycidylated oxo-nitrogen heterocycles.

A number of N-glycidyl compounds derived from oxo-substituted nitrogen heterocycles such as diazines, triazines, diazoles, triazoles as well as condensed ring systems containing these units have been synthesised. All products were tested for their antitumor activity against leukaemia in the mouse. Almost all of the approx.

Investigation of the antitumor activity of new epoxide derivatives. Part I: s-Triazinetrione derivatives.

The noteworthy cytostatic activity of triglycidyl-s-triazinetrione and the planned clinical testing of this new active substance induced us to subject this class of substances to closer examination. By chemical reaction of one of the three glycidyl groups present it was possible to introduce wide variations in the properties of the compounds, whilst still retaining the active principle. A number of these substances possessed very high antitumor activity as revealed in the leukemia screening test (P 388; mouse).

Natural history of colorectal carcinoma with untreated liver metastases.

In a series of 474 patients operated on for colonic and rectal carcinoma, 65 were shown to have hepatic metastases. Factors influencing spontaneous survival were evaluated in 56 patients. This study emphasizes the dominant role of the amount of liver involvement.