[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.

[Synergism of antitumor activity of gemcitabine and dioxadet in mice with ascitic Ehrlich's tumor].

Antitumor activity of a new cytostatic drug combination of gemcitabine and dioxadet have been studied in 86 female SHR mice transplanted with 5 x 10(6) of ascitic Ehrlich's tumor cells each. All mice received a single injection of gemcitabine, dioxadet on combination 48 hams after tumor cells introduction. In first series, experimental animals received maximal tolerable dose of gemcitabine (25 mg/kg) and one half of dioxadet maximal tolerable dose (2.5 mg/kg). In the second series of experiments, the animals received 5 mg/kg of dioxadet along with the same gemcitabine dose. Effect of drugs was compared using the time to ascites detection, body weight increase, and survival time. Gemcitabine and dioxadet administered separately and in combination inhibited the growth of ascitic Ehrlich's tumor in the mice. In both series of experiments antineoplastic activity of gemcitabine and dioxadet combination was significantly higher in comparison to the control groups receiving these drugs separately. The highest antineoplastic activity of the gemcitabine and dioxadet combination was observed when the maximal tolerable doses of both drugs was applied. However, the tumor cells growth was also significantly inhibited in mice receiving half of dioxadet dose. Synergism of antitumor activity of gemcitabine and dioxadet was not accompanied by appreciable increase in toxicity.

[Antitumor activity of dioxadet compared with cisplatin on ascitic ovarian tumor in rats].

Antitumor activity of dioxadet in comparison with cisplatin was studied on the model of ascitic ovarian tumor in 32 female Wistar rats. Ascitic ovarian tumor was transplanted intraperitoneally 0.5 ml per rat dissolved by saline in ratio 1 to 4. Dioxadet (1.5 mg/kg b.w.) and cisplatin (4.0 mg/kg b.w.) were administered intraperitoneally at their single maximal tolerable doses 48 hours after tumor cells transplantation. For drug activity estimation time to ascites detection and survival time values were used. In control group without no treatment the time till ascites occurrence and median life span were 5.4 +/- 0.25 and 7.5 days, correspondingly. In comparison with the control group dioxadet increased the average time of ascites occurrence and median of life span by 30% and 113% (p < 0.05), cisplatin increased these parameters by 28% and 147% (p < 0.05). Hence, antitumor activity of dioxadet is comparable with cisplatin activity for intraperitoneal therapy of the ascitic ovarian tumor.

[Tumor growth index as an integral criterion for the efficacy of antineoplastic therapy under experimental conditions]. / Indeks rosta opukholi kak integral'nyi kriterii éffektivnosti protivoopukholevoi terapii v éksperimente.

An additional criterion is suggested for description of effectiveness of therapy of experimental tumors--tumor growth index. It is a ratio of area covered by the kinetic curve of tumor growth in the study group and that in control. The index is intended to describe the efficacy of therapy in terms of degree and duration of the effect.

[Chemobiokinetics of sarcolysin and its peptides with glutaminic acid]. / Khemobiokinetika sarkolizina i ego peptidnykh analogov s glutaminovoi kislotoi.

A 14C study of chemobiokinetics of sarcolysin and its peptides of glutaminic acid, dosage and routes of administration was conducted in intact rats and those bearing Walker's carcinoma. Similar in shape for peptides, kinetic curves differed from those found for sarcolysin. The rates of absorption and excretion of sarcolysin peptides in intraperitoneal and, particularly, oral administration were lower than those of sarcolysin. Tumor appeared to play a role in a higher rate of peptide excretion. While sarcolysin and its peptides distribution in organs and tissues was generally identical, time of peak radioactive concentration build-up was different. Time needed for accumulation and excretion of peptides from tumor was much longer than from other organs or tissues. Sarcolysin went chiefly to urine while peptides--to faeces.

[Measurement of calcium content in the blood and other biological fluids by Arsenazo III complexone]. / Izmerenie soderzhaniia kal'tsiia v syvorotke krovi i drugikh biologicheskikh zhidkostiakh kompleksonom Arsenazo III.

A method of photometric measurement of total calcium in the serum and other biological liquids using Arsenazo III color complexone is offered. Physicochemical characteristics of Arsenazo III (mol extinction, affinity for other ions, spectral characteristics, and its complex with calcium) are described. Calcium was measured in 750 normal subjects, its reference value was 2.15-2.75 mmol/liter, the mean value 2.47 mmole/liter. In semiautomated measurement CV% was about 5%. The reagent is convenient, particularly for automated analyzers; no other reagent are needed, it can be stored for a long time at room temperature, and gives stable results.

[Alkyl nitrosoureidodioxans and alkyl nitrosoureidopropane diols -- new groups of antitumor compounds]. / Alkilnitrozoureidodioksany i alkilnitrozoureidopropandioly -- novye gruppy protivoopukholevykh soedinenii.

1,3-dioxan- and 1,3-propane diol derivatives of alkyl nitrosourea have been synthesized and studied. Like other 2/chloroethylnitrosoureas, they exerted pronounced influence on a wide range of transplantable tumors, including those transplanted intracranially. Antitumor effect was found to depend on C5 and C2 atom substituent in the 1,3-dioxan cycle and 1,3-propane diol, respectively. The therapeutic effect and toxicity of 1,3-propane diol derivatives were higher than those of 1,3-dioxan. The substances lost all antitumor properties if a methyl group was substituted for the 2-chloroethyl one, even though a nitroso group was retained in their structure.

[Antitumor activity and toxicity of combined doxorubicin and disodium salt of methylene-1,1-diphosphonic acid]. / O protivoopukholevoi aktivnosti i toksichnosti kompleksa doksorubitsina s dinatrievoi sol'iu metilen-1,1-difosfonovoi kisloty.

In experiments using mice and rats with transplantable Ehrlich ascites tumors, sarcoma-180 and adenocarcinoma of Walker, antitumor activity of doxorubicin in combination with disodium salt of 1,1-methylenediphosphonic acid proved higher than that of doxorubicin alone. Most advantage was gained with daily treatment. The toxic effect of said complex treatment seemed to differ slightly from that of doxorubicin as judged on the basis of survival, changes in body mass and peripheral blood count.

[The pharmacological properties of preparations from the aziridinyl triazine group]. / Farmakologicheskie svoistva preparatov iz gruppy aziridiniltriazinov.

The results of experimental studies of three drugs from aziridinyltriazine group, dioxadet, trisadet, and furizil, are presented. These drugs exhibit a pronounced therapeutic effect against a broaden spectrum of tumors grafted in mice and rats. Toxic effect of the drugs is exhibited mainly in suppression of blood formation. Other side-effects are slightly pronounced. One of the drugs, dioxadet passed the I and II stages of clinical trials and is recommended for application in chemotherapy of malignant tumors.

[Basic and salvage pathways of NAD biosynthesis in organs of normal rats, tumor-bearing rats and in tumors]. / Osnovnoi i zapasnoi puti biosinteza NAD v organakh zdorovykh krys, krys-opukholenositelei i v opukholiakh.

The rates of quinolinic and nicotinic acids and nicotinamide utilization for NAD biosynthesis in organs of normal rats and those with lymphosarcoma of Pliss and Walker's carcinosarcoma were studied. All three compounds were shown to be NAD's precursors in the liver and kidneys of normal animals. Quinolinic acid failed to stimulate the increase in NAD concentration in the liver of Walker carcinosarcoma-bearing rats. An insignificant rise in NAD concentration was registered in the liver of rats with lymphosarcoma of Pliss following quinolinic acid treatment. The rates of nicotinic acid and nicotinamide utilization in the liver of tumor-bearing animals were lower than in healthy controls. Quinolinic acid utilization was the most intense in the kidney of rats with Walker's carcinosarcoma while nicotinic acid and nicotinamide were mostly utilized in the kidney of rats with lymphosarcoma of Pliss. None of the three precursors caused NAD concentration to rise in Walker's carcinosarcoma cells whereas nicotinamide injection was followed by an increase in NAD concentration in Pliss lymphosarcoma cells. To summarize, the neoplastic cells under study do not use the basic pathway of NAD biosynthesis and are characterized by different rates of nicotinic acid and nicotinamide utilization.