[Activity of the Russian antitumor compound chlonisol in models of eyelid tumors (experimental study)]. / Aktivnost' otechestvennogo protivoopukholevogo soedineniya khlonizol na modelyakh opukholei vek (eksperimental'noe issledovanie).

Eyelid tumors are the most common neoplasms in everyday ophthalmic practice and cover a wide range of benign and malignant lesions. Surgical methods, cryodestruction, laser therapy and radiation therapy are used in the treatment of malignant eyelid tumors. Chemotherapy does not occupy a prominent place in the treatment of malignant eyelid tumors, its use is limited to sensitive tumors. OBJECTIVE: To assess the antitumor activity of the Russian-developed chemical compound 2-[3-(2-chloroethyl)-3-nitrosoureido]-1.3-propandiol (chlonisol) on the models of transplantable tumors of various histogenesis implanted into the lower eyelid. MATERIAL AND METHODS: The study was carried out on 67 mice of lines 129/SN, BALB/c and C57BL/6 that had Ehrlich carcinoma, sarcoma 37, lymphosarcoma LIO-1 and B16 melanoma transplanted into the eyelid. Tumor transplantation was done by injecting 0.05 ml of sterile sodium chloride solution containing 106 cells of Ehrlich carcinoma, sarcoma 37, lymphosarcoma LIO-1, or 10% suspension of tumor tissue of B16 melanoma. The injection was performed into the right lower eyelid in the direction from the outer towards the inner corner of the eye using a thin needle (29G). Chlonisol was administered at the maximum tolerated dose of 20 mg/kg or at the lower dose of 15 mg/kg intraperitoneally 24 hours after tumor transplantation. RESULTS: In mice with Ehrlich carcinoma, sarcoma 37, lymphosarcoma LIO-1 and melanoma B16 transplanted under the skin of the lower eyelid, a single intraperitoneal injection of chlonisol at the dose of 20 or 15 mg/kg caused significant inhibition of tumor growth reaching 100%. Chlonisol significantly increased overall survival in animals with Ehrlich carcinoma (log rank test, p=0.0464), sarcoma 37 (log rank test, p<0.0001), lymphosarcoma LIO-1 (log rank test, p=0.0122) and B16 melanoma (log rank test, p<0.0001); the proportion of animals that were fully healed was 25, 78, 67 and 25%, respectively. CONCLUSION: Chlonisol has a pronounced antitumor effect in mice with Ehrlich carcinoma, sarcoma 37, lymphosarcoma LIO-1 and B16 melanoma transplanted into the eyelid.

[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.

[Combined effect of gemcitabine and lomustine in mice with intracranial transplanted lymphosarcoma LIO-1].

SHR mice with intracranial transplanted lymphosarcoma LIO-1 received a single intraperitoneal gemcitabine injection in maximal tolerated dose of 25 mg/kg or single maximal tolerated oral dose of lomustine, 50 mg/kg. Compared to control group gemcitabine injection increased the mice lifespan 1.4-fold (p < 0,01) and oral lomustine 1.6-fold (p < 0,01). The median lifespan of the mice receiving both gemcitabine and lomustine in maximal dose underwent a significant 3.3-fold increase (p < 0,01) compared to controls (2.4-fold compared to gemcitabine and 2.1-fold compared to lomustine group). Combined therapy didn't cause an increase of toxicity.

[Investigation of gemcitabine plus lomustine treatment in mice with transplantable lymphosarcoma LIO-1].

Efficiency of gemcitabine plus lomustine treatment of transplantable lymphosarcoma LIO-1 in mice was significantly higher than that of monotherapy. According to the area under the kinetic curve for tumor growth, antitumor action, for single maximum tolerable dose of gemcitabine 25 mg/kg body, rose 4.6 times (p < or = 0.001), for lomustine 50 mg/kg body,--2.9 times (p < or = 0.01). The combination involved moderately increased toxicity. Lethality rate for gemcitabine+lomustine, 50 mg/kg body each, was as low as one and a half times as compared with gemcitabine therapy alone, 50 mg/kg body, (30 and 20%, respectively). The antitumor action of the combination (50 mg/kg body), was 32 times that of gemcitabine 50 mg/kg body (p < or = 0.001) and lomustine 50 mg/kg body--30 times (p < or = 0.001).

[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.

Morphological studies of the metastatic process after LIO-1 tumor transplantation by different methods.

Variants of injection of LIO-1 lymphosarcoma cell suspension were studied. The number of animals with local metastases was higher after injection of LIO-1 cell suspension into the mouse paw sole. This method of tumor cell injection is suggested as the metastasizing model for experimental studies.

[Antineoplastic effect of glutapyrone in continual gamma-irradiation of rats]. / Izuchenie antikantserogennogo deistviia glutapirona pri khronicheskom gamma-obluchenii krys.

In experiments on rats (290 animals) exposed to chronic gamma-radiation with the total dose of 10.0 Gy it was detected that prescription of synthetic pharmaceutical of the dihydropyridine class--glutapyrone--together with drinking water during 6 months reduced the rate of malignant neoplasms from 26.5% in the control group to 13% in the treated animals. In radiation-exposed rats that received glutapyrone there was a narrowing of spectrum of the emerged neoplasms (connectively-tissual tumors only) as compared to the animals of the radiated control group, where blastomas of epithelium and lymphoid origin were also revealed. Low toxicity of glutapyrone and its anticarcinogenic action show the potential for this preparation to be used in practice.

[Antineoplastic activity of 5-fluorouracil upon transdermal adminstration using "Coletex" napkins]. / Protivoopukholevaia aktivnost' 5-ftoruratsila pri ego transdermal'nom vvedenii s pomoshch'iu salfetok "Koleteks".

The paper presents data on the effect of 5-fluorouracil (5-FU)-impregnated Coletex napkins on rats and mice with transplantable subcutaneous tumors of different histological patterns: Pliss lymphosarcoma, Walker carcinosarcoma and Ehrlich carcinoma. Since the napkins showed antitumor activity it is suggested that they might find application in treating a number of oncological pathologies, particularly, skin lesions and ulcerated and necrotized tumors.

[The occurrence of cataract in rats as one of the factors worsening the quality of their lives in the late periods after whole-body and partial irradiation]. / Vozniknovenie katarakty u krys kak odin iz faktorov ukhudsheniia kachestva ikh zhizni v otdalennye sroki posle obshchego i partsial'nogo oblucheniia.

A study was made of the formation of cataract in rats at remote times after whole-body and partial X irradiation. The whole-body radiation loses were 5 and 10 Gy (two fractions of 5 Gy at a 30-day interval). Partial exposure of the head and neck, as well as irradiation of chest were performed with doses of 5, 10 (two fractions at a 30-day interval) and 15 Gy (three 5 Gy fractions at a 30-day interval). It has been shown that cataract develops not only due to the direct effect of radiation on the eye, but also to indirect effect on the experimental animal body (with irradiation of the abdomen and diabetes development).

[Diabetes mellitus as a cause for the shortening of the longevity of locally irradiated rats]. / Sakharnyi diabet kak prichina sokrashcheniia prodolzhitel'nosti zhizni lokal'no obluchennykh krys.

A study was made of the development of remote radiation pathology of pancreas in male rats after local irradiation of abdomen with doses of 5, 10 (two fractions of 5 Gy at a 30-day interval) and 15 Gy (three fractions of 5 Gy at a 30-day interval). The clinical and morphological estimates show the dose-dependent development of diabetes mellitus and 1.8-fold shortening of the life span, as compared to biological control.

[Late sequelae of exposure to ionizing radiation with various LET's. Effect of dose rate and fractionation on changes in the life span of rats]. / Otdalennye posledstviia vozdeistviia ioniziruiushchego izlucheniia s raznoi LPE. Vliianie moshchnosti dozy i fraktsionirovaniia na izmenenie prodolzhitel'nosti zhizni krys.

In experiments with 2120 albino mongrel rats their life span was followed up after the effect of various types of radiation (for instance, gamma-neutron radiation of 0.9 MeV and gamma- and X-rays) at different exposure schedules (that is, whole-body irradiation with doses from LD0/30 to LD100/30 and fractionated at 24 and 72 hour intervals and dose--rates varying from 0.00042 Gy/min to 1.02 Gy/min). The type of radiation, the dose--rate, single and cumulative doses, the number of fractions and the interval between them were estimated with respect to their contribution to life span shortening.

[Long-term consequences of the effect of ionizing radiation of different LET. Relation of changes in the intensity of light scattering by blood lymphocytes in the early postradiation stages to the prolongation of the life of rats]. / Otdalennye posledstviia vozdeistviia ioniziruiushchego izlucheniia s raznoi LPE. Sootnoshenie mezhdu izmeneniiami intensivnosti svetorasseianiia limfotsitov krovi v rannie sroki posle oblucheniia i prodolzhitel'nost'iu zhizni krys.

Optic properties of rat blood were studied 24 h following gamma- or gamma-neutron-irradiation with different doses. A comparative analysis of the changes observed was performed in relation to life span of animals. It is concluded that remote effects of radiation can be prognosticated by changes in light scattering of the peripheral blood lymphocytes 24 h following irradiation.

[Parametric analysis of survival data for doubly irradiated animals]. / Parametricheskii analiz dannykh o vyzhivaemosti dvykratno obluchennykh zhivotnykh.

On the basis of their previously reported model of acute radiation sickness development the authors made a parametric analysis of the survival rate of mice after double exposure to ionizing radiation.

[Effect of gamma- and gamma-neutron irradiation on the composition of the metabolic amino acid pool, blood antiprotease activity and the life-span of animals]. / Vliianie gamma- i gamma-neitronnogo oblucheniia na sostav metabolicheskogo fonda aminokislot, antiproteaznuiu aktivnost' krovi i prodolzhitel'nost' zhizni zhivotnykh.

A study was made of the effect of gamma- and gamma-neutron-radiation, with neutron energy of 0.9 MeV, on the free amino acid composition and antiprotease activity of blood as well as on the life span of albino mongrel rats. The data obtained indicate that changes in the metabolic pool of blood amino acids and inhibitory capacity of blood with respect to alpha 2-macroglobulin depend upon the type and dose of radiation. An attempt is made to find a correlation between early changes in the metabolic pool of amino acids and antiprotease activity and the degree of life span shortening after gamma- and gamma-neutron irradiation.