Rhône-Poulenc

About: Rhône-Poulenc is a based out in . It is known for research contribution in the topics: Alkyl & Catalysis. The organization has 8909 authors who have published 8934 publications receiving 182241 citations. The organization is also known as: Rhone-Poulenc.

Continual reassessment methods in phase I trials of the combination of two drugs in oncology.

Abstract: Most phase I trials in oncology use standard methods for treating successive groups of patients with increasing doses in order to determine the maximum tolerated dose (MTD). These methods have been criticized because they treat many patients at suboptimal dose levels, and do not provide an accurate estimation of the best dose level. Continual reassessment methods for the study of toxicity in single agent phase I trials have recently been advocated since they present many advantages over traditional methods. Although the advantages of these methods are recognized by most clinical investigators, their use is not widespread and their advantages have not yet been universally accepted. A maximum likelihood continual reassessment method was conducted retrospectively and compared to the originally planned standard method in a two drug combination phase I trial in order to study its applicability in this setting. Calculations from the binomial distributions and simulations were used for identifying the MTD, for the proportion of patients treated at the MTD or at one dose level just below, and for the proportion of patients treated at doses above the MTD. If the new method had been applied in this study, the MTD would have been reached much earlier, since, most of the time, higher dose levels were recommended. This result shows the feasibility of the new method in a two-drug setting and its use should be encouraged since fewer patients are treated at suboptimal dose levels or at dose levels above the MTD.

Preclinical antitumor activity of CI-994

Abstract: CI-994 [aka: acetyldinaline; PD 123654; 4-acetylamino-N-(2'aminophenyl)-benzamide] (Figure 1) is a novel antitumor agent with a unique mechanism of action. It is the acetylated metabolite of dinaline, a compound previously identified as having cytotoxic and cytostatic activity against several murine and human xenograft tumor models. CI-994 had activity against 8/8 solid tumors tested (log cell kills at the highest non-toxic dose): pancreatic ductal adenocarcinoma #02 (4.7); pancreatic adenocarcinoma #03 (3.0; 1/6 cures); colon adenocarcinoma #38 (1.6); colon adenocarcinoma #51/A (1.1); mammary adenocarcinoma #25 (1.7); mammary adenocarcinoma #17/ADR (0.5); Dunning osteogenic sarcoma (4.0); and the human prostate carcinoma LNCaP (1.2). CI-994 had the same spectrum of activity in vivo as dinaline. It also behaved similarly in schedule comparison/toxicity trials. Prolonged administration with lower drug doses was more effective than short-term therapy at higher individual doses. If doses were kept between 40 and 60 mg/kg/injection, prolonged administration (> 50 days) was tolerated with no gross toxicity. Doses > or = 90 mg/kg/injection caused lethality after 4-5 days of administration. The maximum tolerated total dose was also increased with smaller individual doses administered for prolonged intervals. Clinical Phase I trials are ongoing with this agent.

Use of fibroblast growth factors to stimulate bone growth

Abstract: The present invention provides therapeutic compositions for the prevention and treatment of pathological conditions involving bone and dental tissue. The present invention also provides a method to promote bone repair and/or growth for the treatment of pathological conditions involving bone tissue, for example, osteoporosis, Paget's disease, osteopetrosis, and periodontal disease and fracture repair, and healing of bone defects by administering FGF-1 to an animal or human in need of said treatment.

Structure of nosiheptide, a polythiazole-containing antibiotic

Abstract: NOSIHEPTIDE is a metabolite with a strong antibiotic action which has been isolated from Streptomyces actuosus (F. Benazet et al., unpublished). Studies of its antibiotic spectrum and cross-resistance suggested that it belonged to the thiostrepton family1; chemical analyses and further chemical degradation confirmed this view. From analytical and spectroscopic data (NMR 1H, 13C and 15N) the general formula C51H43N13O12S6 was assigned (A. Brun, H. Depaire, G. Lukacs and J. P. Thomas, unpublished). Unfortunately no M+ peak can be extracted from its mass spectrum (electron impact). Some parts of the molecule have been identified after degradation by different techniques, namely one L-threonine, one hydroxypyridine, five thiazoles and one indole ring (A. Brun, H. Depaire, G. Lukacs, and J. P. Thomas, unpublished). Nothing could be deduced about the sixth sulphur atom. At least twenty antibiotics are known to contain thiazole rings (for instance bleomycins2, bacitracin A2, and althiomycin3), but among those containing five thiazole rings only two molecular structures are known: thiostrepton, by X-ray analysis4 and 13C NMR spectroscopy, and siomycin A, by comparing its NMR spectrum with that of thiostrepton5. To obtain the complete structure of nosiheptide, we undertook an X-ray analysis.