The effect of prostaglandin synthesis inhibitors and diphosphonates on tumour-mediated osteolysis

Previous studies have shown that the prostaglandin synthesis inhibitor indomethacin reduced osteolysis produced by the experimental VX2 carcinoma, probably by inhibiting the stimulation of osteoclasts by prostaglandin E2. This study was carried out to determine whether prostaglandin inhibitors affect the tumour osteolysis produced by human mammary carcinoma as well as the VX2 carcinoma. The effect of diphosphonates on reducing tumour osteolysis was also investigated, since diphosphonates directly affect bone resorption. The results indicated that various non-steroidal, anti-inflammatory agents which inhibit prostaglandin synthesis reduced the osteolysis produced by human mammary or rabbit VX2 carcinomas. The diphosphonate compounds also produced a significant inhibition of tumour osteolysis. The results confirm the findings of Powles and his colleagues (1) that aspirin (also a prostaglandin synthesis inhibitor) reduced the osteolysis induced by human mammary carcinoma. It is suggested that these agents be evaluated as adjuvant therapy in patients with apparently 'early' mammary cancer in a controlled clinical trial.     

Anxiety after a heart attack

An objective measurement of anxiety at defined intervals after the onset of acute cardiac symptoms was made in 203 men admitted to the Coronary Care Unit, Royal Infirmary of Edinburgh, and in 83 patients in a Teesside coronary survey. Of the Teesside patients, 50 were treated at home, 22 were admitted initially to a coronary care unit, and 11 were admitted directly to a general medical ward. In the Edinburgh patients the level of anxiety was high early in the illness, fell rapidly, and rose again towards the end of their stay in hospital. At 4 months it was that of a normal population. After transfer from the coronary care unit the group was not more anxious than other patients in the ward. Reaction to the illness was unrelated to its physical severity. Patients who reacted badly at the beginning were less likely to return to work. The pattern of anxiety in the Teesside patients resembled that of the Edinburgh group, and reaction to illness was largely independent of physical aspects. Treatment in hospital, either through a coronary care unit initially or in a medical ward, did not increase emotional distress. At 3 months patients treated initially in a coronary care unit were less anxious than the others. Throughout the period of study the Teesside patients were more anxious than the Edinburgh patients and outcome was not related to anxiety. Social and environmental differences may account for this.     

Carcinogenicity of benzo-ring derivatives of benzo(a)pyrene on mouse skin

Benzo(a)pyrene (BP) and several benzo-ring derivatives of BP were tested for carcinogenic activity in mice by topical application of each compound once every 2 weeks for 60 weeks. Chronic treatment of C57BL/6J mice with (+/-)-trans-7,8-dihydroxy-7,8-dihydrobenzo(a)pyrene (0.025 to 0.10 micronmole/application) indicated that the dihydrodiol was slightly more active as a complete carcinogen than the parent hydrocarbon BP. 7,8-Dihydroxy-7,8,9,10-tetrahydro-benzo(a)pyrene, a compound related to (+/-)-trans-7,8-dihydroxy-7,8-dihydrobenzo(a)pyrene but which lacks the double bond at position 9,10, was inactive as a carcinogen on mouse skin. These results indicate the importance of the double bond at position 9,10 for the carcinogenic activity of (+/-)-trans-7,8-dihydroxy-7,8-dihydrobenzo(a)pyrene. Chronic treatment of mice with -.4 micronmole of the highly mutagenic (+/-)-7,beta,8alpha-dihydroxy-9alpha, 10alpha-epoxy-7,8,9,10-tetrahydrobenzo(a)pyrene, (+/-)-7beta,8alpha-dihydroxy-9beta, 10beta-epoxy-7,8,9,10-tetrahydrobenzo(a)pyrene, or 9,10-epoxy-7,8,9,10-tetrahydrobenzo(a)pyrene every 2 weeks for 60 weeks resulted in tumor incidences of 0, 8, and 4%, respectively, whereas BP at this dose caused a 100% tumor incidence. The high reactivity of the three epoxides may account for their inactivity or their weak carcinogenic activity on mouse skin.     

An origin of DNA replication from Lactococcus lactis bacteriophage c2

An origin of DNA relication was identified in the intergenic region between the early and late gene regions of prolate lactococcal phage c2. A DNA fragment containing this origin, designated ori, was shown to direct DNA replication in Lactococcus lactis but not in Escherichia coli. A comparison of ori with the corresponding regions of other prolate phages revealed strict conservation of the nucleotide sequence in one half of this intergenic region. This conserved region alone would not support DNA replication. No open reading frames were identified in the ori fragment, suggesting that host factors alone are sufficient to initiate DNA replication at ori. A novel class of lactococcal vectors and E. coli-L. lactis shuttle vectors based on ori have been constructed.