HIPEC in patients with primary advanced ovarian cancer: Is there a role? A systematic review of short- and long-term outcomes.

A systematic review of the studies where HIPEC combined with cytoreductive surgery was used in patients with primary advanced ovarian cancer was performed to understand is there a role for this treatment modality not only in recurrent but in primary advanced ovarian cancer. The results are controversial but there is a strong trend for improvement of the long-term outcomes of patients with primary advanced ovarian cancer after HIPEC.

Radioprotective and Apoptotic Properties of a Combination of α-Tocopherol Acetate and Ascorbic Acid.

We studied radioprotective and apoptotic properties of a combination of α-tocopherol acetate and ascorbic acid. α-Tocopherol acetate (10 mg/kg body weight) or ascorbic acid (20 mg/kg) or combination of these agents in the same doses was orally administered to male rats at various terms before and after single whole-body exposure to γ-irradiation in the doses of 2 and 8 Gy. Irradiation increased the frequency of chromosome aberrations in bone marrow cells and plasma level of low-molecular-weight DNA. Vitamin combination administered before or after irradiation significantly reduced the frequency of chromosome aberrations by 2-2.5 times. Administration of this combination 10 min before irradiation 1.5-fold increased the content of low-molecular-weight DNA in blood plasma in comparison with the control animals exposed to radiation. The combination of α-tocopherol acetate and ascorbic acid produced radioprotective effects and enhanced apoptosis in irradiated cells.

[Hyperthermic intraperitoneal chemotherapy combined with cytoreductive procedure in patients with peritoneal pseudomyxoma].

AIM: To study the results of intraperitoneal chemoperfusion combined with cytoreductive procedure in patients with peritoneal pseudomyxoma. MATERIAL AND METHODS: For the period 2006--2015 seven patients with peritoneal pseudomyxoma underwent aggressive treatment using hyperthermic intraperitoneal chemoperfusion combined with cytoreductive procedure at the Department of General Oncology of N.N. Petrov Research Institute of Oncology. RESULTS: Two patients had postoperative complications. One of them died after 12 days postoperatively. Features of postoperative complications were predominantly determined by volume of cytoreduction. Advanced tumoral process caused death in 2 patients additionally. Other patients are still alive during 4--28 months after surgery. CONCLUSION: Hyperthermic intraperitoneal chemoperfusion combined with cytoreductive procedure is advisable for peritoneal pseudomyxoma to improve survival. Optimal cytoreduction should be developed in researches with large number of patients to decrease incidence of complications.

Toxicogenomic Effects in Rat Blood Leukocytes and Chemoprophylaxis of Radiation-Induced Carcinogenesis.

Toxicogenomic parameters were studied in the blood of female rats after exposure to ionizing γ-radiation in a dose of 4 Gy and chemoprophylaxis with α-difluoromethylornithine, eleutherococcus or leuzea extracts, which were used in animals with morphological manifestations of tumor growth under conditions of radiation-induced carcinogenesis. Life-time evaluation of toxicogenomic effects was carried out by express method for measurements of blood nucleotid DNA - fluorescent indication. The level of hyperaneu/polyploidy increased in the blood leukocytes of control rats 30 days after radiation exposure. A significant decrease of genotoxicity as a result of drug treatment in comparison with the number and multiplicity of tumors in irradiated animals was found only in the endocrine and reproductive organs of rats treated by eleutherococcus extract.

[Intraoperative intraperitoneal chemoperfusion treatment with cisplatin and dioxadet on a model of peritoneal carcinomatosis in ovarian cancer: safety and efficacy evaluation].

A comparative study of safety and efficacy of normothermic and hyperthermic intraperitoneal chemoperfusion (IPEC and HIPEC) with cisplatin and dioxadet was carried out in 143 female Wistar rats. Ovarian cancer was inoculated intraperitoneally (i.p.). In 48 hours after ovarian cancer inoculation the drugs were administered i.p. or IPEC and HIPEC with the drugs were performed using maximum tolerated doses (MTD). Content of cisplatin was determined in the perfusate and blood plasma during HIPEC with the drug. The leukocyte count was measured using veterinary hematologic analyzer in peripheral blood of rats at different time points after HIPEC with dioxadet. Efficacy of the treatment was estimated in increase in median survival time (MST). During HIPEC cisplatin was accumulated in the abdominal cavity in a considerable amount with minimal systemic absorption. HIPEC with dioxadet didn't significantly affect the leukocyte count in peripheral blood while i.p. administration of dioxadet suppressed leukopoiesis. MST of rats after IPEC with cisplatin was 37.5 days which was significantly higher compared to MST after i.p. administration of cisplatin (19.5 days, p = 0.037). HIPEC with dioxadet was the most effective regimen of treatment with MST of rats reaching 49 days which was significantly higher compared to MST after HIPEC with cisplatin (25.5 days, p = 0.002).

[CHEMOPERFUSION TECHNOLOGIES IN TREATMENT FOR MALIGNANT TUMORS].

The data of literature on possibility of the use of perfusion technologies in combined treatment for malignant tumors of different sites are presented. Possible complications during hyperthermic chemoperfusion are discussed and the effectiveness of this method is analyzed.

Simulation of Chemoperfusion Treatment for Abdominal Carcinomatosis.

Experimental perfusion system and technology for normothermic and hyperthermic intraperitoneal chemoperfusion are developed for the treatment of abdominal carcinomatosis in rats with transplanted ovarian cancer. MTD of cisplatin in normothermic intraperitoneal chemoperfusion and hyperthermic perfusion are 40 and 20 mg/kg, i.e. by 10- and 5-fold higher than the dose of this cytostatic for routine intraperitoneal injection. Normothermic intraperitoneal chemoperfusion with cisplatin increases median survival time by 200% (p=0.039) in comparison with intraperitoneal injection.

[Opportunities of intraoperative hyperthermic perfusion application in treatment of peritoneal carcinomatosis].

Normothermic intraperitoneal perfusion (IPEP) and hyperthermic intraperitoneal perfusion (HIPEP) were performed in 44 Wistar female rats with transplanted ascites tumor of the ovary. Opportunities of intraoperative hyperthermic perfusion application in treatment of peritoneal carcinomatosis. Antineoplastic affects were evaluated according to increase of animals' survival. IPEP and HIPEP increase median survival time by 78% (p=0.307) and 150% (p=0.005) respectively in comparison with conventional intraperitoneal introduction of physiological solution. Thus HIPEP has statistically more significant antineoplastic affect in vase of peritoneal carcinomatosis.

[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.

[Comparative effects of difluoromethylornithine and tincture of Siberian ginseng root on radiation carcinogenesis and life span in rats].

Influence of alpha-difluoromethylornithine (DFMO) and tincture of Siberian ginseng root (TSGR) on radiation carcinogenesis and life span in rats has been studied. The results of the study demonstrate that DFMO as well as TSGR significantly improved survival and decreased incidence and multiplicity of malignant and benign tumors in rats subjected to ionizing radiation. Beneficial effect on the rat survival rate and anticarcinogenic action of DFMO were more expressed compared with TSGR.

[Inhibitory effect of bioginseng on radiation-induced carcinogenesis in rats].

Influence of bioginseng (biotechnological pharmaceutical drug from ginseng radix culture) on radiation-induced carcinogenesis has been studied. LIO female rats were divided into 3 groups. Rats of the first group (n=25) were used as intact control and weren't exposed to any influence. Rats of the second (n=50) and third (n=50) groups were exposed to single total body gamma-irradiation at a dose of 4 Gy. Animals of the 2nd group weren't exposed to any influence after irradiation, while animals of the 3rd group were given bioginseng with tap water (20 ml/l) until the end of study (438 days). In the control group 22,7% of animals developed tumors. In the 2nd group (irradiated control) 70% of animals were bearing multiple tumors one third of which were malignant. Mammary gland tumors were most frequent. Compared to the 2nd group the 3rd group receiving irradiation and bioginseng demonstrated the decrease in tumor incidence by 24.5% and 2,4 rate of decrease in tumors number. For the malign tumors was observed the decrease by 26.8% and 2,9 times, accordingly. For the mammary tumors the decrease was by 23.0% and 2,0 times, for mammary adenocarcinomas by 23.4% and 3,5 times, accordingly. The incidence and number of endocrine and reproductive organs tumors was 20,9% and 5,6 times, accordingly. Therefore, bioginseng effectively inhibits carcinogenesis induced by ionizing radiation in female rats.

[Anticarcinogenic action of dietary supplement pheocarpin and its active component].

Anticarcinogenic action of dietary supplement Pheocarpin and its active component Natural Coniferous Complex (NCC), in particular, has been studied. Pheocarpin and NCC efficiently inhibited tumorigenesis in the mammary gland, large bowel, skin, cervix uteri and lungs. Pheocarpin offers considerable advantage as a means of reducing the risk of malignant disease.

[Study of an antioxidant dietary supplement "Karinat" in patients with benign breast disease]. / Izuchenie antioksidantnoi biologicheski aktivnoi dobavki k pishche "Karinat" u bol'nykh s fibroadenomatozom molochnykh zhelez.

A randomized double blind placebo-controlled trial of efficiency of a dietary supplement "Karinat" in patients with benign breast disease was carried out. Karinat contains beta-carotene 2.5 mg, alpha-tocopherol 5 mg, ascorbic acid 30 mg and garlic powder 150 mg per one tablet. Out of 66 patients, 33 patients were given karinat, 33 were given placebo. The patients reccived a tablet of karinal or placebo twice a day during 6 months. Examinations of the patients included clinical estimation of symptoms of mastopathy and dysalgomenorrhea, breast sonography and mammography. It was found that karinat reduced the severity of mastalgia, premenstrual syndrome, dysmenorrhea and algomenorrhea and caused regression of palpable symptoms of the breast fibromatosis. On the whole karinat had positive action in 75.8% that was significantly greater by 45.5% as compared with placebo. Karinat may be useful for the treatment of patients with benign breast disease.

Chemoprevention of mammary, cervix and nervous system carcinogenesis in animals using cultured Panax ginseng drugs and preliminary clinical trials in patients with precancerous lesions of the esophagus and endometrium.

The anticarcinogenic effects and mechanisms of the biotechnological drugs of Panax ginseng C.A. Meyer cultivated in Russia, bioginseng, panaxel and panaxel- 5, were studied. Bioginseng was produced from a tissue culture of ginseng root cultured on standard medium, whereas panaxel and panaxel-5 were produced from ginseng tissue root cultures using standard mediums enriched with 2-carboxyethylgermanium sesquioxide and 1-hydroxygermatran-monohydrate respectively. All three ginseng drugs inhibited the development of mammary tumors induced by intramammary injections of N-methyl-N-nitrosourea (MNU) in rats, the development of the brain and spinal cord tumors induced by transplacental administration of N-ethyl-N-nitrosourea (ENU) in rats, and the development of uterine, cervical and vaginal tumors induced by intravaginal applications of 7,12-dimethylbenz(a)anthracene (DMBA) in mice. The ginseng drugs induced the cytotoxic activity of macrophages in mice, enhanced T-lymphocyte rosette formation in guinea pigs exposed to cyclophosphamide, and stimulated the production of thyroid hormones in rats. These mechanisms may contribute to the anticarcinogenic action of the ginseng drugs. The organic germanium compounds present in panaxel and panaxel-5 did not potentiate the anticarcinogenic or immuno- stimulatory effects as much as biogeinseng. Preliminary clinical trials with panaxel and bioginseng were carried out in patients with precancerous lesions of the esophagus and endometrium. Panaxel was found to have a strong therapeutic effect in patients suffering from chronic erosive esophagitis. Bioginseng induced the regression of adenomatous-cystic hyperplasia of the endometrium in some patients. Thus, we conclude that the drugs of ginseng appear to hold considerable promise for future cancer chemoprevention.

[The inhibitory effect of water-soluble and liposomal beta-carotene on various models of carcinogenesis]. / Ingibiruiushchaia aktivnost' vodorastvorimogo i liposomal'nogo beta-karotina na razlichnykh modeliakh kantserogeneza.

The inhibitory effects of the newly-developed forms of beta-carotene--water-soluble and liposomal--have been studied in rats and mice bearing tumors induced in 4 models of carcinogenesis. Mammary tumors were induced by single injections of 1 mg methylnitrosourea into each gland. Esophageal tumors were induced in male rats by intragastric administration of 3 mg/kg methylbenzylnitrosoamine, thrice a week for 4 weeks. Tumors of the vagina and cervix uteri were induced by intravaginal painting with 25 mkg dimethylbenz(a)anthracene, twice a week for 6 weeks. Tumors of the lung were induced in female mice by intraperitoneal injection of 1 g/kg urethane, once a week for 6 weeks. With models I-III, animals received water-soluble beta-carotene (Aquiton-10) with drinking water (200 mg/I), on completion of carcinogen treatment and for another 9-12 months until the end of experiment. Urethane-treated mice received liposomal beta-carotene with drinking water (60 mg/l) 10 days before the beginning of carcinogen treatment and for another 6 months until the end experiment. Water-soluble beta-carotene failed to influence the carcinogenesis in the mammary gland and esophagus in rats; however, it significantly inhibited carcinoma development in murine vagina and cervix uteri (47.0%). Liposomal beta-carotene significantly inhibited lung adenomas (46.4%) and mammary carcinomas (55.6%) in urethane-treated mice.

[The inhibition of the development of experimental tumors of the cervix uteri and vagina by using tinctures of the cultured-cell biomass of the ginseng root and its germanium-selective stocks]. / Tormozhenie razvitiia éksperimental'nykh opukholei sheiki matki i vlagalishcha s pomoshch'iu nastoek biomassy kul'tiviruemykh kletok kornia zhen'shenia i ego germanii-selektivnykh shtammov.

The anticarcinogenic effects of bioginseng and two germanium-selective drugs produced by cultivating cells of ginseng radix (Panax ginseng C. A. Mey) in a conventional medium or in media containing organogermanium compounds were studied. Squamous-cell carcinomas of the uterus cervix and vagina were induced by intravaginal applications of 7,12-dimethylbenz(a)anthracene in mice. The drugs of ginseng were used orally or intravaginally during a long period of time of the postinitiation stage of carcinogenesis. All the drugs used locally effectively inhibited the development of induced carcinomas of the uterus cervix and vagina. When orally used, the drugs of ginseng exhibited only an insignificant tendency to inhibit the carcinogenesis of uterus cervix and vagina. The anticarcinogenic effects of the compared drugs were similar.

[Clinico-experimental study of using plant preparations from the flowers of Filipendula ulmaria (L.) Maxim for the treatment of precancerous changes and prevention of uterine cervical cancer]. / Kliniko-éksperimental'noe izuchenie vozmozhnostei primeneniia fitopreparatov iz tsvetkov labaznika viazolistnogo dlia lecheniia predrakovykh izmenenii i profilaktiki raka sheiki matki.

The paper reports the results of the experimental and clinical evaluation of the administration of drugs prepared from flowers of Filipendula ulmaria (L.) Maxim for cervical dysplasia and cancer treatment. Local administration of decoction resulted in a 39% drop in the frequency of squamous-cell carcinoma of the cervix and vagina induced in mice by 7,12-dimethyl-benz(a)anthracene treatment. Positive response was recorded in 32 patients (67%), including 25 cases (52%) of complete regression of dysplasia, out of 48 cases of cervical dysplasia treated with courses of ointment application. No recurrence was observed in 10 completely cured patients within 12 months.

[Inhibition of mammary gland carcinogenesis using a tincture from biomass of ginseng tissue culture]. / Podavlenie kantserogeneza molochnoi zhelezy s pomoshch'iu nastoiki iz biomassy kul'tury tkani zhen'shenia.

The influence of official drug bioginseng produced from cultivated cells of ginseng radix (Panax ginseng C. A. Mey) on carcinogenesis of the mammary gland was studied. Adenocarcinomas of the mammary gland were induced in rats by single intramammary injections of N-methyl-N-nitrosourea (MNU) at a dose of 1 mg per gland into the tissues of all 12 mammary glands. Bioginseng was given per os at a daily dose of 0.5 ml per rat for 27 weeks beginning 1 week after the MNU administration. Bioginseng and the control MNU-group decreased the incidence and multiplicity of the mammary gland tumors at 44 and 62% respectively. By radioimmune assay it was found that bioginseng normalised abnormally high level of estradiol in blood of rats treated by MNU.