ABSTRACT
BACKGROUND: The sap from Euphorbia peplus, commonly known as petty spurge in the U.K. or radium weed in Australia, has been used as a traditional treatment for a number of cancers. OBJECTIVE: To determine the effectiveness of E. peplus sap in a phase I/II clinical study for the topical treatment of basal cell carcinomas (BCC), squamous cell carcinomas (SCC) and intraepidermal carcinomas (IEC). METHODS: Thirty-six patients, who had refused, failed or were unsuitable for conventional treatment, were enrolled in a phase I/II clinical study. A total of 48 skin cancer lesions were treated topically with 100-300 µL of E. peplus sap once daily for 3 days. RESULTS: The complete clinical response rates at 1 month were 82% (n = 28) for BCC, 94% (n = 16) for IEC and 75% (n = 4) for SCC. After a mean follow-up of 15 months these rates were 57%, 75% and 50%, respectively. For superficial lesions < 16 mm, the response rates after follow-up were 100% for IEC (n = 10) and 78% for BCC (n = 9). CONCLUSIONS: The clinical responses for these relatively unfavourable lesions (43% had failed previous treatments, 35% were situated in the head and neck region and 30% were > 2 cm in diameter), are comparable with existing nonsurgical treatments. An active ingredient of E. peplus sap has been identified as ingenol mebutate (PEP005). This clinical study affirms community experience with E. peplus sap, and supports further clinical development of PEP005 for the treatment of BCC, SCC and IEC.
Subject(s)
Carcinoma in Situ/drug therapy , Carcinoma, Basal Cell/drug therapy , Carcinoma, Squamous Cell/drug therapy , Euphorbiaceae , Plant Extracts/therapeutic use , Skin Neoplasms/drug therapy , Administration, Topical , Adult , Aged , Aged, 80 and over , Carcinoma in Situ/pathology , Carcinoma, Basal Cell/pathology , Carcinoma, Squamous Cell/pathology , Cohort Studies , Humans , Middle Aged , Phytotherapy/methods , Skin Neoplasms/pathologySubject(s)
Antipyrine/pharmacokinetics , Piperidines/pharmacology , Adult , Cisapride , Drug Interactions , Female , Humans , Male , Middle AgedABSTRACT
Three 16-aryloxy analogues of PGF2alpha are potent, full agonists on the isolated rabbit jejunum. Their actions are more prolonged than that of PGF2alpha, and radioactive tracer studies with one of the analogues reveal a slower wash-out of the analogue compared to PGF2alpha, under superfusion conditions. During the prolonged contractile response diminished responses to PGF2alpha were obtained: this effect was investigated in terms of receptor desensitization. The actions of these analogues were also investigated on the isolated guinea-pig ileum and the rabbit oviduct in vivo.
Subject(s)
Jejunum/drug effects , Muscle, Smooth/drug effects , Prostaglandins F, Synthetic/pharmacology , Prostaglandins F/pharmacology , Animals , Chemical Phenomena , Chemistry , Dose-Response Relationship, Drug , Fallopian Tubes , Female , Guinea Pigs , Ileum/drug effects , Muscle Contraction/drug effects , Prostaglandins E/administration & dosage , Prostaglandins F/administration & dosage , Prostaglandins F, Synthetic/administration & dosage , RabbitsABSTRACT
The interaction between delta9-tetrahydrocannabinol (THC) and PGE1 was studied using two pharmacological parameters-the rate of passage of a charcoal meal through mouse small intestine and the abdominal constriction response in the mouse. PGE1 administered intraperitoneally produced a dose-dependent decrease in intestinal motility, and this effect was antagonized by low (0.25 mg/kg) doses of THC and potentiated by higher doses of THC (1 mg/kg). Kinetic analysis suggested that the interaction was of a mixed but predominantly competitive type. PGF2alpha produced an increase in intestinal motility but this was not dose-dependent. THC antagonized the effect of PGF2alpha in a dose-dependent manner suggestive of a physiological antagonism. THC (0.25-2 mg/kg) antagonized the dose-dependent PGE1 abdominal constriction response in a fashion which suggested a mixed (though mainly competitive) antagonism. It would ssem, therefore, that on the two pharmacological parameters studied THC appears to be interacting with PGE1 at the same receptor site. Although the doses of THC used are within the range of those used in man, it is not implied that these results are necessarily implicated in the psychoactivity of the drug.
Subject(s)
Analgesia , Cannabis/pharmacology , Dronabinol/pharmacology , Gastrointestinal Motility/drug effects , Prostaglandins E/antagonists & inhibitors , Animals , Binding, Competitive , Female , Kinetics , Mice , Prostaglandins E/pharmacology , Prostaglandins F/antagonists & inhibitorsABSTRACT
After oral administration to mice, delta9-tetrahydrocannabinol (THC) and cannabinol (CBN) caused a dose-dependent suppression of the abdominal constriction response to formic acid. Cannabinol was 50 times less active than THC and cannabidiol (CBD) was without effect. The effects of THC and CBN were additive. CBD antagonised the antinociceptive effects of both THC and CBN in a dose-dependent manner.
