**2.10 Drugs**

130 Advances in Cancer Therapy

of 4-5 mm in diameter) were intraperitoneally administrated with 100 mg of BSH per 1 kg of body weight. In 1 hour before euthanasia the mice were administrated with 3Н-thymidin (74 kBq/g of body weigh); as control administration saline was used Excised tumors were used for preparation of cytological preparations. Melanocytes were determined as cells containing more than 5 granules of melanin (Alberts, 1989). Analysis of kinetics of DNAsynthesizing cells was studied in preparations covered with "M" emulsion counting 3Нlabelled melanocytes. These parameters were separately assessed for peripheral and central

Alterations of the quantitative distribution through the cell cycle were also investigated. The distribution of tumor cells through the cell cycle was studied by flow DNA-cytofluorimetry

The BSH distribution was investigated in B-16 melanoma bearing male C57Bl/6 mice. The mice had a body weight (BW) of 17-20 g, the tumor was subcutaneously transplanted. BSH was administrated intraperitoneously. 2 dose groups were injected with 50 and 150 mg/kg body weight on 9-11-th day after subcutaneous tumor inoculation. In 3, 12 and 24 hours after administration tumors were excised (3 samples per time point). Tumor samples were used for preparation of cell nuclei suspension. This suspension was dyed with mixture of

During experiments with transplanted tumors three reciprocally perpendicular tumor's diameters were daily measured and evaluated tumors volumes taking tumor's shape as

V=(/6). d1. d2 . d3 (1)

For every temporary point tumor volume was normalized to it's volume at the beginning of exposure (V0) and then V1/V0 against time from the beginning of exposure curves were constructed depending on every dose D and for every concrete mouse at adequate control for it (D=0). The parameters of tumor growth delay (Td) and of time of tumor's volume

 TGI=SE/SK (2) where: SE. – area under tumor growth curve of experimental group, Sк – area under tumor

1

*i*

(3)

1

*i*

<sup>1</sup> 2 *<sup>n</sup> i i*

*V V S t* 

Where V- tumor volume, d1, d2, d3 – linear dimensions of ellipsoid, cm

Area under tumor growth curve was calculated as following:

duplication were evaluated from these curves as well as tumor growth index (2).

**2.8 Study of cell distribution through the cell cycle** 

zones.

ellipse:

on ICP-22 cytofluorimeter.

ethidium bromide and mitramicin (1:1).

**2.9 Assessment of tumor growth** 

growth curve of experimental group.

n – number of measurements,

where Vi - tumor volume at ith measurement,

ti – period between nearby measurements.

In our studies we have used the following medicines: [10B]-ВРА (Khoknlov, 2001, Kulakov, 2001, Kulakov, 2002) – 4-(dihidroxyboron)–L-phenilalane (BPA, KatChem, Chehia), Katchem, (Czechia), chemical purity of 98 % , degree of enrichment of 10В 99.7 %); borated ethers with D-fructose ([10B]-ВРА-F) and D-galactose ([10B]-ВРА-Gal); Na2 10B12H11SH - [10B]-BSH (Katchem, (Czechia) , chemical purity of 99 % ; degree of enrichment of 10В – 99.7 %; novel boroncontained compound KUG-1 (this is manufacturing code of compound), chemical purity of 99 % with natural boron and Dipentast® – Gd-DTPA based pharmaceutical with Gd content of 28.11% and semi-elimination period from site of injection - 556 min.).

The dogs were intravenously administrated with boron-containing compounds while the mice were administrated with boron-containing compounds intraperitoneally. Dipentast® was administrated intratumorally at uniform distribution (4-6 injection per tumor) both in NCT and PCT studies.
