Effect of Polyphenolic Composition BP-C2 on Lung Carcinogenesis Induced by Urethane in Progeny of Irradiated Male BALB/c Mice.

We studied the effects of polyphenolic composition BP-C2, comprising molybdenum with lignin derivatives, on lung carcinogenesis induced by urethane in the progeny of F0 male BALB/c mice preconceptionally exposed to radiation in a dose of 1 Gy. The multiplicity of lung tumors in the progeny of irradiated mice was higher than in the progeny of non-irradiated male parents by 50% in females and 43% in males (p<0.05). In F1 mice (progeny of irradiated F0 male parents treated with BP-C2), the multiplicity of lung tumors was also higher, but this increase was less pronounced: 35% in females (p=0.3852) and 23% in males (p=0.0766). We have demonstrated that administration of BP-C2 to irradiated parents (F0) efficiently inhibits carcinogenesis in their F1 progeny. The use of BP-C2 in irradiated male parents and their progeny not only reduced the multiplicity of tumors, but also normalized body weights in the F1 progeny. Our study demonstrates potential of the polyphenolic composition BP-C2 for chemoprophylaxis of radiation-induced transgenerational carcinogenesis.

Comparative Study of Antitumor Efficiency of Intraperitoneal and Intravenous Cytostatics in Experimental Rats with Disseminated Ovarian Cancer.

Antitumor efficiencies of cytostatics dioxadet, cisplatin, mitomycin C, melphalan, and paclitaxel after a single intraperitoneal or intravenous injection in doses of 1.5, 4, 1.5, 2, and 5 mg/kg, respectively, were studied on the model of transplanted ovarian tumor in 124 rats. The antitumor effects were evaluated by the increase in median survival. Dioxadet, cisplatin, and melphalan injected intraperitoneally significantly prolonged the lifespan median - by 79, 88, and 114%, respectively, and were in fact ineffective, when injected intravenously. Intraperitoneal mitomycin C prolonged lifespan median by just 35%, intravenous - by 152%. Paclitaxel injected intraperitoneally and intravenously prolonged the lifespan median by 45 and 81%, respectively.

[Role of clock proteins in skin carcinogenesis in 14-month-old SHR mice maintained under disrupted light regimen].

Circadian rhythm disturbance promotes of carcinogenesis and is associated with changes in clock genes and proteins expression. In the current study we observed that continu- ous light exposure potentiated skin carcinogenesis induced by 7,12-dimethylbenz[a]anthracene and 12-0-tetradecanoylphor- bol-13-acetate while melatonin had opposite effect. Carcinogenic exposure decreased BMAL1 and CRYI- expression in the skin, CLOCK expression was upregulated and CRYl downregulated in tumor compared to normal skin. BMAL1 expression increased under disrupted light regimen; melatonin treatment affected CLOCK expression in tumors and CRYI in skin at the carcinogens application sites.

[Intraperitoneal chemotherapy--a method of improving treatment effectiveness in ovarian cancer].

The study or antitumor effects of dioxadet, cisplatin, melphalan, paclitaxel, mitomycin C, cyclophosphamide and gemcitabine at intraperitoneal (i.p.) and intravenous (i.v.) administration as monochemotherapy and polychemotherapy in a rat model of ascitic ovarian cancer was carried out in 244 female Wistar rats. Ovarian cancer was transplanted i.p. at a number of 1 x 10(7) tumor cells. The drugs were administered once in 48 hours after ovarian cancer transplantation i.p. or i.v. for monotherapy--in maximum tolerated doses, for i.p. polychemotherapy--in half doses from maximum tolerated doses. Antitumor effects of the treatment were estimated in increase in median survival time (MST) compared to control rats who were administered saline i.p. At i.p. administration dioxadet, cisplatin and melphalan increased MST by 79%, 88% and 144%, respectively, while at i.v. administration these drugs didn't affect MST. Mitomycin C and paclitaxel had stronger antitumor action at i.v. administration increasing MST by 152% and 81%, respectively, while at i.p. administration these drugs increased MST by 35 and 45%, respectively. Combinations dioxadet + cisplatin, dioxadet + cyclophosphamide and dioxadet + paclitaxel at i.p. administration increased MST by 305%, 277% and 133%, respectively, and had additive antitumor action compared to mono-effects of these drugs. Gemcitabine and combination dioxadet + gemcitabine at i.p. administration didn't significantly affect survival of rats with ovarian cancer. Intraperitoneal monochemotherapy and polychemotherapy could be more effective in the treatment of peritoneal carcinomatosis from ovarian cancer compared to systemic administration of the drugs.

[Therapeutic activity of gemcitabine in intracranial tumors].

Gemcitabine is known to exert a therapeutic effect on brain tumors despite the limited permeability of the blood-brain barrier (BBB). In our experimental research single intraperitoneal (i.p.) injection of gemcitabine 25 mg/kg provided increase in median survival of mice with intracranially transplanted Ehrlich carcinoma by 41-89% (p < 0.001). In this experimental model i.p. administration of gemcitabine (permeability of the BBB of less than 10%), carmustine (good permeability of the BBB), cyclophosphamide (poor permeability of the BBB) and cisplatin (doesn't penetrate through the BBB) increased median survival of mice by 88% (p < 0.001), 59% (p = 0.001), 35% (p = 0.005) and 18% (p = 0.302) respectively. Considering strong correlation between antitumor activity of the drugs (carmustine, cyclophosphamide and cisplatin) and their permeability of the BBB, efficacy of gemcitabine in intracranial tumors could be due to its wide range of therapeutic doses.

[Antitumor effect of dioxadet in intraperitoneal chemoperfusion treatment for advanced ovarian cancer in experimental setting].

The study of antitumor efficacy of dioxadet in chemoperfusion treatment of ascitic ovarian cancer was carried out in 125 Wistar female rats. Ovarian cancer was inoculated intraperitoneally at a number 1x10(7) tumor cells per rat. Intraperitoneal administration of dioxadet as well as chemoperfusion was performed once in 48 hours after the ovarian cancer inoculation. Dioxadet was used at maximal tolerated doses which were 1.5 mg/kg for intraperitoneal administration, 30 mg/kg for normothermic intraperitoneal chemoperfusion (IPEC), and 15 mg/kg for hyperthermic intraperitoneal chemoperfusion (HIPEC). Antitumor effects of dioxadet were estimated in increase of median survival. In the control group, where animals didn't receive any treatment, the median survival was 9 days. Increase of the median survival after intraperitoneal administration of dioxadet, IPEC and HIPEC with dioxadet was 211% (p=0,001), 244% (p=0,001) and 444% (p=0,001), respectively, compared to the control group. Hence, intraperitoneal chemoperfusion with dioxadet (normo- or hyperthermic) is more effective compared to standard intraperitoneal administration of the drug. At HIPEC with dioxadet potentiating antitumor action of hyperthermia and dioxadet on the ovarian cancer growth was achieved.

[Experimental technology of chemoperfusion treatment for abdominal carcinomatosis in ovarian cancer].

An experimental technology of normothermic intraperitoneal chemoperfusion and hyperthermic intraperitoneal chemoperfusion with cisplatin and dioxadet has been elaborated to treat abdominal carcinomatosis in ovarian cancer. Antitumor effects of the treatment were evaluated for the duration of animal life. Normothermic intraperitoneal chemoperfusion and hyperthermic intraperitoneal chemoperfusion with cisplatin and dioxadet in comparison with the standard intraperitoneal administration significantly increased the median life expectancy by 75-92%. Hyperthermic intraperitoneal chemoperfusion with dioxadet demonstrated potentiation of antitumor effect of hyperthermia and dioxadet. Experimental technology is recommended for testing new drugs and methods of chemoperfusion for malignant tumors affecting the peritoneum.

Enterotoxigenic Escherichia coli as a cause of paediatric diarrhoea in Ujung Pandang, Indonesia.

The importance of enterotoxigenic Escherichia coli (ETEC) as a cause of diarrhoea in eastern Indonesia was investigated in 74 children during the dry season in Ujung Pandang. Six of the children less than five years old with diarrhoea were infected with ETEC. One child was infected with tetracycline-resistant bacteria. The low prevalence of antibiotic resistance among ETEC in Indonesia is similar to that reported from Bangladesh, but very different from the situation in Thailand.

Seasonal variation of entertoxigenic Escherichia coli among children with diarrhoea in Bangkok.

ETEC which produced both LT and ST or LT alone were isolated from 7.4 percent (18/244) of children with diarrhoea treated at two hospitals in Bangkok, Thailand between May 1, 1980 and April 30, 1981. These enteric pathogens were only isolated from children with diarrhoea during the dry and the beginning of the wet season. Eighty-three percent (15/18) children infected with ETEC were infected with antibiotic resistant isolates. One hundred percent of LT + ST + E. coli and 76 percent (50/66) of LT + ST - E. coli were resistant to two or more antibiotics. Fourteen of 15 (93%) ETEC transferred antibiotic resistance and nine of 14 (64%) isolates which transferred resistance in bacterial conjugation experiments also transferred toxigenicity. This experience suggests that the widespread use of antibiotics in Thailand could increase the prevalence of antibiotic resistant enterotoxigenic bacteria.